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Sample records for hepatocellular tumor thrombus

  1. Tumor thrombus

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

    2014-01-01

    PURPOSE: Thrombosis in cancer may manifest itself as venous thromboembolic disease or tumor thrombosis (TT). We present our experience with incidentally detected TT on FDG PET/CT in 21 oncologic patients. PATIENTS AND METHODS: We retrospectively reviewed all FDG PET/CT examinations during a 5-year......-one patients were included; the most common malignancies were renal cell carcinoma (n=6), hepatocellular carcinoma (n=3), and lung cancer (n=3). Indication for the scan was initial staging (n=15) and suspected recurrence (n=6). Several vessels were affected, the most common was the inferior vena cava (n=14......), but most other major branches of the venous vasculature was represented, and some patients had thrombi in several vessels. FDG uptake was linear in 7 patients, linear with a dilated vessel in 6 patients, and focal in 7 patients. The mean SUVmax of the primary tumors was 10.3 (range, 2.6-31.2; median, 6...

  2. A single institution report of 19 hepatocellular carcinoma patients with bile duct tumor thrombus

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    Chotirosniramit A

    2017-03-01

    Full Text Available Anon Chotirosniramit, Akkaphod Liwattanakun, Worakitti Lapisatepun, Wasana Ko-iam, Trichak Sandhu, Sunhawit Junrungsee Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Background: Obstructive jaundice caused due to bile duct tumor thrombus (BDTT in a hepatocellular carcinoma (HCC patient is an uncommon event. This study reports our clinical experiences and evaluates the outcomes of HCC patients with BDTT in a single institution. Methods: A retrospective review of 19 HCC patients with secondary obstructive jaundice caused due to BDTT during a 15-year period was conducted. Results: At the time of diagnosis, 14 (73.7% patients had obstructive jaundice. Eighteen (94.7% patients were preoperatively suspected of “obstruction of the bile duct”. Sixteen patients (84.2% underwent a hepatectomy with curative intent, while two patients underwent removal of BDTT combined with biliary decompression and another patient received only palliative care as his liver reserve and general condition could not tolerate the primary tumor resection. The overall early recurrence (within 1 year after hepatectomy occurred in more than half (9/16, 56.3% of our patients. The 1-year survival rate of patients was 75% (12/16. The longest disease-free survival time was >11 years. Conclusion: Identification of HCC patients with obstructive jaundice is clinically important because proper treatment can offer an opportunity for a cure and favorable long-term survival. Keywords: hepatocellular carcinoma, biliary thrombosis, hepatectomy, recurrence, survival

  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. 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.

  5. Pilot study of local radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma

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    Yamada, Kazunari; Soejima, Toshinori; Sugimoto, Koji [Kobe Univ. (Japan). School of Medicine] [and others

    2001-04-01

    Patients suffering from hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) generally have a poor prognosis. We therefore conducted a prospective pilot trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) for PVTT in unresectable HCC. The aim of the study was to investigate the efficacy and toxicity of this preliminary trial regime and to explore RT guidelines for cirrhosis. Eight patients with unresectable HCC accompanied by first branch PVTT were entered into the study from February 1998 to December 1999. TACE was performed using Lipiodol, epirubicin hydrochloride and mytomycin followed by gelatin sponge cubes. RT was started 10-14 days following TACE. A total delivered dose of 60 Gy was given as daily 2 Gy fractions, with the clinical target volume defined as PVTT only. We observed a relationship between deterioration of liver function and the percent volume of the total liver receiving a dose exceeding 30 Gy (V{sub 30}). An objective response was observed in three of the eight patients. However, on follow-up angiograms the protrusion of PVTT into the main portal trunk was decreased in all cases. Deterioration of liver function was observed in all patients with V{sub 30} >40%. It is possible that this combined therapy prevents PVTT from spreading to the main trunk and that indicates a further benefit of TACE. Our results indicate that V{sub 30} constitutes a predictive test for the development of liver failure. More detailed evaluations of liver function and determination of the safe irradiation volume are necessary. (author)

  6. 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.

  7. A Case of Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Refractory to Epirubicin That Showed Marked Decrease in Tumor Markers after Transcatheter Arterial Infusion with Miriplatin

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    Hiroki Nishikawa

    2011-06-01

    Full Text Available Miriplatin, a cisplatin derivative with a high affinity for iodized ethyl esters of fatty acids from poppy seed oil, is a novel chemotherapeutic agent designed for use in the transarterial treatment of hepatocellular carcinoma (HCC. Here, we describe transcatheter arterial infusion (TAI using miriplatin to treat a case of advanced HCC with portal vein tumor thrombus (PVTT refractory to TAI with epirubicin. A 66-year-old man with advanced hepatitis C virus-related HCC with PVTT in the right lobe of the liver was treated with TAI with epirubicin suspended in iodized oil; however, tumor marker levels (alpha-fetoprotein and des-gamma-carboxy protein did not decrease. Next, he was treated twice with TAI with miriplatin suspended in iodized oil. The tumor marker levels markedly decreased to a nearly normal range and the size of the main tumor was markedly reduced according to dynamic computed tomography. No serious adverse events occurred during the course of treatment with TAI and miriplatin. Therefore, we suggest that TAI with miriplatin is a safe and effective treatment option for advanced HCCs refractory to TAI with epirubicin.

  8. 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.

  9. New macroscopic classification and back-flow thrombectomy for advanced hepatocellular carcinoma with portal vein tumor thrombus invading the contralateral second portal branch.

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    Fukumoto, Takumi; Kido, Masahiro; Takebe, Atsushi; Tanaka, Motofumi; Kinoshita, Hisoka; Kuramitsu, Kaori; Komatsu, Shohei; Tsugawa, Daisuke; Goto, Tadahiro; Asari, Sadaki; Toyama, Hirochika; Ajiki, Tetsuo; Ku, Yonson

    2017-09-01

    Patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) invading the portal trunk (Vp4) are poor surgical candidates because of the technical difficulties involved. To overcome the limitations, we developed a technique of back-flow thrombectomy (BFT) based on the inherent portal hemodynamics and the macroscopic form of PVTT. Forty-six patients with multiple HCC and Vp4 PVTT underwent hepatectomy with tumor thrombectomy. We used the BFT to treat 24 patients, 18 of whom had PVTT in the contralateral second portal branch. The form of PVTT was classified macroscopically into the floating and expansive types. The rate of complete removal by BFT of PVTT in the contralateral second portal branch was 89%. The patency rates at the thrombectomy site in all 46 patients and in the 24 BFT patients, 3 months after hepatectomy were 93 and 90%, respectively. The median OS of all 46 patients was 15 months, with 1- and 3-year OS rates of 58.5 and 17.1%, respectively. The median OS of the 24 patients treated with BFT vs. the 22 not treated with BFT was 14 and 15 months, respectively. BFT can expand the therapeutic time window for patients with HCC and deep-seated PVTT and may improve their survival.

  10. 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.

  11. Mass-forming intrahepatic cholangiocarcinoma with portal vein tumor thrombus and bile duct tumor thrombus: A case report.

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    Iwaki, Kentaro; Kaido, Toshimi; Yamamoto, Gen; Kamo, Naoko; Yagi, Shintaro; Taura, Kojiro; Uemoto, Shinji

    2017-01-01

    We report the first case of mass-forming intrahepatic cholangiocarcinoma (ICC) with portal vein tumor thrombus (PVTT) and bile duct tumor thrombus (BDTT), where the extrahepatic bile duct was preserved with thrombectomy. A 70-year-old male. Magnetic resonance imaging (MRI) showed the tumor extending from the hepatic hilum to the left hepatic duct with complete obstruction of the left hepatic duct and a defect at the left portal vein. We planned to perform extended left lobectomy, lymph node dissection, extra hepatic bile duct resection and reconstruction based on the diagnosis of mass-forming ICC with left portal vein and left hepatic duct infiltration (cT3N0M0 Stage III). Intraoperative cholangiography revealed a crab claw-like filling defect at the left hepatic duct, which suggested tumor thrombus. Accordingly, we performed thrombectomy. The margin of the left hepatic duct was tumor negative, so we performed extended left lobectomy, lymph node dissection and thrombectomy. Pathologically, the tumor was diagnosed as ICC (pT4N0M0 Stage IVA, vp3, b3). Tumors in the left hepatic duct and left portal vein proved to be tumor thrombus. The postoperative course was uneventful. He is doing well without recurrence. Thrombectomy is performed for hepatocellular carcinoma (HCC) with tumor thrombus. Furthermore, extrahepatic bile duct resection and reconstruction are recommended for ICC. In this case, intraoperative cholangiography was effective for precisely diagnosing. Thrombectomy could reduce surgical stress and prevent complications. Thrombectomy can be a valid option for ICC with tumor thrombus, as well as for HCC. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. 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.

  13. Left ventricular mass: A tumor or a thrombus diagnostic dilemma

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    U S Dinesh Kumar

    2016-01-01

    Full Text Available Left ventricular (LV mass is a rare condition, of which the most common is thrombus. Echocardiography is a very useful modality of investigation to evaluate the LV mass. We are reporting a case of LV mass presenting with neurological symptom. The diagnosis of this mass was dilemma as the echocardiographic features were favoring tumor as well as thrombi. Mass (a measuring 3.8 cm × 1.9 cm attached to the left ventricle apex appeared to be pedunculated tumor and mass (b measuring 2.4 cm × 1.8 cm attached to the chordae of anterior mitral leaflet resembled a thrombus or an embolized tumor entangled in the chordae. A differential diagnosis for the LV mass is thrombus, tumors such as fibroma, and vegetation. Preoperative detection of a thrombus leads to an alteration in surgical steps. A large and mobile thrombus with or without a hemodynamic alteration is an indication for surgical removal to prevent stroke, myocardial infarction, mesenteric ischemia, renal infarction, gangrene of the limbs, and mortality.

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

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    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.

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

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    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.

  16. Clot in Lung, Clot in Heart: A Case Report of Tumor-Like Thrombus in Right Atrium

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    Roshanak Habibi

    2017-04-01

    Full Text Available Tumor-like formation of thrombus in the right atrial cavity is rare. It may be mistaken for a myxoma. The exact pathophysiology of an isolated thrombus in the heart is still unclear. Management to prevent complications such as pulmonary thromboembolism depends on the clinical judgment of a cardiologist. This report describes a 76-year-old woman with right atrial thrombus causing subsequent pulmonary thromboembolism in right lung. She initially presented to us with pulmonary embolism, and later, an incidental finding of a mass in her right atrium revealed an association of thrombus in heart with thrombus in lung. The challenging management was to resect this thrombus which was fixed to atrial septum, and a trial of anticoagulation did not resolve it. Exact management of such incidental findings in right heart cavities is not well established. Some cases may benefit from resection of such formed fixed thrombus.

  17. Unusual Presentation of Testicular Cancer with Tumor Thrombus Extending to the Inferior Vena Cava

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    Marie Dusaud

    2015-01-01

    Full Text Available A 45-year-old man with a left testis tumor with a 25 mm para-aortic lymph node swelling, multiple bilateral pulmonary metastases, bilateral pulmonary embolism, and inferior vena cava (IVC thrombus underwent a radical orchidectomy in our institution. The thrombus extended from the left gonadal vein to the left renal vein to the IVC. The fluorine-18 fluorodeoxyglucose (f-FDG positron emission tomography (PET computerized tomography (CT demonstrated a hypermetabolic focus in the retroperitoneum and in the IVC thrombus. Before orchidectomy only lactate dehydrogenase (LDH was high but all the serum tumor markers increased postoperatively. The tumor was staged pT1N2M1aS1, which was an intermediate prognosis, based on the International Germ Cell Cancer Collaborative Group consensus (IGCCCG. After 4 courses of bleomycin, etoposide, and cisplatin (BEP chemotherapy the patient’s tumor markers normalized and the thrombus disappeared. There was only one residual retroperitoneal lymph node M1. Retroperitoneal lymph node dissection was performed. The pathological examination revealed only necrotic tissues. The patient has been disease-free since surgery.

  18. [Presurgical treatment of axitinib reduced operation risk by downsizing the vena cava tumor thrombus in advanced renal cell carcinomas: two case reports].

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    Hamada, Akihiro; Yamasaki, Toshinari; Negoro, Hiromitsu; Kobayashi, Takashi; Terada, Naoki; Sugino, Yoshio; Matsui, Yoshiyuki; Inoue, Takahiro; Kamba, Tomomi; Yoshimura, Koji; Ogawa, Osamu

    2014-12-01

    In cases of advanced renal cell carcinoma with inferior vena cava (IVC) thrombus, surgical resection of both tumor and thrombus contributes to the improvement of patient's prognosis, but the risk of perioperative complication is still high. We experienced two cases of advanced renal tumors with IVC tumor thrombus down-sized by presurgical treatment of axitinib. Axitinib treatment showed a marked tumor reduction effect without any severe adverse event. We could remove both tumor and thrombus without perioperative complications. In these two cases, downsizing of IVC thrombus enabled us to reduce the extent of the surgery.

  19. EUS-guided FNA of a portal vein thrombus in hepatocellular ...

    African Journals Online (AJOL)

    Portal vein thrombosis is a relatively rare but well-known complication of cirrhosis that has a prevalence of between 1% and 5.7%. On the contrary, in case of hepatocellular carcinoma (HCC), it is a much more frequent complication. In this paper, we presented three cases that had liver cirrhosis, mass and portal vein ...

  20. [Clinical analysis of renal cell carcinoma with intravenous tumor thrombus].

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    Kogawa, T; Sawada, Y; Narita, S; Tanaka, S; Sato, F; Kudo, S; Kitagawa, M; Suzuki, T

    1990-11-20

    We reviewed treatment and prognosis in 7 operative and 7 non-operative cases of renal cell carcinoma with venous tumor thrombosis formation, 14 cases in total. Treatment after around 1983 involved the use of biological response modifier (BRM), chiefly interferon (IFN), and operation by thoracoabdominal approach. Before that, chemotherapy, radiotherapy and operation by peritoneal approach were used, with many cases judged inoperable. Even in non-operative cases, life-prolongation was frequently achieved by embolization of the renal artery and administration of various BRMs. On the other hand, in cases judged operable which were always treated by resection, early postoperative death sometimes occurred. These facts brought home to us the difficulty of choosing appropriate treatment. Though it is hard to determine the relative merits of various treatments from the present data, since the series is small and contains cases from 1963 onwards, the clinical and pathological pictures should be carefully evaluated for each case, and the most suitable course of treatment should be selected individually. We describe a non-operative case in which a combined use of embolization, IFN-gamma and tumor necrosis factor (TNF) elicited a lasting partial response, and an operative case in which postoperative complications such as pulmonary infarction and renal failure occurred after operation under extracorporeal circulation and patient died at 2 months after operation.

  1. FDG PET/CT appearance of portal vein tumor thrombus in the gastric primitive neuroectodermal tumor: uncommon primary tumor site with rare finding.

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    Aras, Mustafa; Dede, Fuat; Dane, Faysal; Aktas, Bilge; Turoglu, Halil Turgut

    2013-01-01

    Gastric primitive neuroectodermal tumor (PNET) is a very rare tumor. There are only a few case reports in the literature. Although cases with FDG uptake in the portal venous tumor thrombus (PVTT) in different primary malignancies have been evaluated before, the coexistence of PNET and PVTT has not been reported yet. Herein, we report the case of a gastric PNET with PVTT, which resolved after 3 cycles of polychemotherapy except for a residual tumor focus in the gastric corpus.

  2. Hepatocellular carcinoma arising in adenoma: similar immunohistochemical and cytogenetic features in adenoma and hepatocellular carcinoma portions of the tumor

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    Paradis, Valerie; Pote, Nicolas; Jakate, Shriram; Ferrell, Linda D

    2016-01-01

    Well-differentiated hepatocellular carcinoma in non-cirrhotic liver can show morphological features similar to hepatocellular adenoma. In rare instances, hepatocellular carcinoma can arise in the setting of hepatocellular adenoma. This study compares the immunohistochemical and cytogenetic features of the hepatocellular adenoma-like and hepatocellular carcinoma portions of these tumors. Immunohistochemistry for β-catenin, glutamine synthetase, serum amyloid A protein, glypican-3, and heat-shock protein 70 was done in 11 cases of hepatocellular carcinoma arising in hepatocellular adenoma in non-cirrhotic liver. Tumors with nuclear β-catenin and/or diffuse glutamine synthetase were considered β-catenin activated. Fluorescence in situ hybridization (FISH) was done in nine cases for gains of chromosomes 1, 8 and MYC. There were seven men (33–75 years) and four women (29–65 years). Focal atypical morphological features were seen in hepatocellular adenoma-like areas in 7 (64%) cases. Hepatocellular adenoma-like areas showed features of inflammatory hepatocellular adenoma in 7 (64%) cases; 4 of these were also serum amyloid A-positive in the hepatocellular carcinoma portion. β-catenin activation, heat-shock protein 70 positivity, and chromosomal gains on FISH were seen in the hepatocellular adenoma portion in 55%, 40%, and 56% of cases, and 73%, 60%, and 78% of cases in the hepatocellular carcinoma portion, respectively. In conclusion, the hepatocellular adenoma-like portion of most cases of hepatocellular carcinoma arising in hepatocellular adenoma shows features typically seen in hepatocellular carcinoma such as focal morphological abnormalities, β-catenin activation, heat-shock protein 70 expression, and chromosomal gains. Hepatocellular adenoma-like areas in these tumors, especially in men and older women, may represent an extremely well-differentiated variant of hepatocellular carcinoma, whereas the morphologically recognizable hepatocellular carcinoma

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

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    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.

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

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    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.

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

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    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.

  6. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    Science.gov (United States)

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC.

  7. Surgical management of hepatocellular carcinoma with tumor thrombi in the inferior vena cava or right atrium.

    Science.gov (United States)

    Wakayama, Kenji; Kamiyama, Toshiya; Yokoo, Hideki; Kakisaka, Tatsuhiko; Kamachi, Hirofumi; Tsuruga, Yosuke; Nakanishi, Kazuaki; Shimamura, Tsuyoshi; Todo, Satoru; Taketomi, Akinobu

    2013-10-05

    The prognosis for advanced hepatocellular carcinoma (HCC) with tumor thrombi in the inferior vena cava (IVC) or right atrium (RA) is poor, and there is no established effective treatment for this condition. Thus study aimed to evaluate the efficacy of surgical resection and prognosis after surgery for such cases. Between January 1990 and December 2012, 891 patients underwent hepatectomy for HCC at our institution. Of these, 13 patients (1.5%) diagnosed with advanced HCC with tumor thrombi in the IVC or RA underwent hepatectomy and thrombectomy. Data detailing the surgical outcome were evaluated and recurrence-free and overall survival rates were calculated using the Kaplan-Meier method. Seven patients had an IVC thrombus and six had an RA thrombus. Extra-hepatic metastasis was diagnosed in 8 of 13 patients. Surgical procedures included three extended right lobectomies, three extended left lobectomies, five right lobectomies, and two sectionectomies. Right adrenal gland metastases were excised simultaneously in two patients. All IVC thrombi were removed under hepatic vascular exclusion and all RA thrombi were removed under cardiopulmonary bypass (CPB). Four patients (30.8%) experienced controllable postoperative complications, and there was no surgical mortality. The mean postoperative hospital stay for patients with IVC and RA thrombi was 23.6 ± 12.5 days and 21.2 ± 4.6 days, respectively. Curative resection was performed in 5 of 13 cases. The 1- and 3-year overall survival rates were 50.4%, and 21.0%, respectively, and the median survival duration was 15.3 months. The 1- and 3-year overall survival rates for patients who underwent curative surgical resection were 80.0% and 30.0%, respectively, with a median survival duration of 30.8 months. All patients who underwent curative resection developed postoperative recurrences, with a median recurrence-free survival duration of 3.8 months. The 1-year survival rate for patients who underwent noncurative surgery and had

  8. 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

  9. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

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    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.

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

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    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

  11. Preoperative multivariable prognostic models for prediction of survival and major complications following surgical resection of renal cell carcinoma with suprahepatic caval tumor thrombus.

    Science.gov (United States)

    Haddad, Ahmed Q; Leibovich, Bradley C; Abel, Edwin Jason; Luo, Jun-Hang; Krabbe, Laura-Maria; Thompson, Robert Houston; Heckman, Jennifer E; Merrill, Megan M; Gayed, Bishoy A; Sagalowsky, Arthur I; Boorjian, Stephen A; Wood, Christopher G; Margulis, Vitaly

    2015-09-01

    Surgical resection for renal cell carcinoma (RCC) with suprahepatic inferior vena cava tumor thrombus is associated with significant morbidity, yet there are currently no tools for preoperative prognostic evaluation. Our goal was to develop a preoperative multivariable model for prediction of survival and risk of major complications in patients with suprahepatic thrombi. We identified patients who underwent surgery for RCC with suprahepatic tumor thrombus extension from 2000 to 2013 at 4 tertiary centers. A Cox proportional hazard model was used for analysis of overall survival (OS) and logistic regression was used for major complications within 90 days of surgery (Clavien ≥ 3A). Nomograms were internally calibrated by bootstrap resampling method. A total of 49 patients with level III thrombus and 83 patients with level IV thrombus were identified. During median follow-up of 24.5 months, 80 patients (60.6%) died and 46 patients (34.8%) experienced major complication. Independent prognostic factors for OS included distant metastases at presentation (hazard ratio = 2.52, P = 0.002) and Eastern Cooperative Oncology Group (ECOG) performance status (hazard ratio = 1.84, Pmodels for the prediction of survival and major complications in patients with RCC who have a suprahepatic inferior vena cava thrombus. If externally validated, these tools may aid in patient selection for surgical intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Benign Hepatocellular Tumors in Children: Focal Nodular Hyperplasia and Hepatocellular Adenoma

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    Stéphanie Franchi-Abella

    2013-01-01

    Full Text Available Benign liver tumors are very rare in children. Most focal nodular hyperplasia (FNH remain sporadic, but predisposing factors exist, as follows: long-term cancer survivor (with an increasing incidence, portal deprivation in congenital or surgical portosystemic shunt. The aspect is atypical on imaging in two-thirds of cases. Biopsy of the tumor and the nontumoral liver is then required. Surgical resection will be discussed in the case of large tumors with or without symptoms. In the case of associated vascular disorder with portal deprivation, restoration of the portal flow will be discussed in the hope of seeing the involution of FNH. HepatoCellular Adenoma (HCA is frequently associated with predisposing factors such as GSD type I and III, Fanconi anemia especially if androgen therapy is administered, CPSS, and SPSS. Adenomatosis has been reported in germline mutation of HNF1-α. Management will depend on the presence of a predisposing factor and may include metabolic control, androgen therapy withdrawn, or closure of the shunt when appropriate. Surgery is usually performed on large lesions. In the case of adenomatosis or multiple lesions, surgery will be adapted. Close followup is required in all cases.

  13. CT Findings of Completely Regressed Hepatocellular Carcinoma with Main Portal Vein Tumor Thrombosis after Transcatheter Arterial Chemoembolization

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    Yoon, Jeong Hee; Kim, Hyo Cheol; Chung, Jin Wook; Jae, Hwan Jun; Park, Jae Hyung [Seoul National University Hospital, Seoul (Korea, Republic of); Yoon, Jung Hwan [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2010-02-15

    The objective of this study was to determine the sequential CT findings of controlled hepatocellular carcinoma (HCC) with main portal vein (MPV) thrombosis with the use of transcatheter arterial chemoembolization and additional intra-arterial cisplatin infusion. From January 2004 to September 2006, 138 patients with HCC invading MPV were referred to the angiography unit of our institution for chemoembolization and additional intra-arterial cisplatin infusion. Until August 2008, seven (5%) of 138 patients were followed-up and found not to have tumor recurrence. CT scans were retrospectively reviewed by two radiologists, focusing on the following parameters: the extent of portal vein thrombosis, the diameter of the affected portal vein, and enhancement of portal vein thrombosis. The extent of portal vein thrombosis at the initial presentation was variable: left portal vein (LPV) and MPV (n = 1), right portal vein (RPV) and MPV (n = 3), as well as RPV, LPV and MPV (n = 3). The extent and diameter of the affected portal vein decreased during follow-up examinations. In addition, the degree of enhancement for tumor thrombi and serum alpha-feto-protein levels decreased after the transcatheter arterial chemoembolization. Portal vein thrombosis was found to be completely resolved in one patient, whereas residual thrombus without viability was persistent in six patients. If chemoembolization is effective in patients with HCC that invades the portal vein, the extent and enhancement of portal vein thrombosis is reduced, but residual thrombosis frequently persists for months or years, without evidence of a viable tumor.

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

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    Kawashima, Mitsuhiko; Tokuuye, Koichi; Sumi, Minako; Kagami, Yashikazu; Murayama, Shigeyuki; Nakayama, Hidetsugu; Imai, Atsushi; Ando, Kou; Ikeda, Hiroshi [National Cancer Center, Tokyo (Japan)

    1997-09-01

    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)

  15. Tumor-derived exosomes elicit tumor suppression in murine hepatocellular carcinoma models and humans in vitro.

    Science.gov (United States)

    Rao, Quan; Zuo, Bingfeng; Lu, Zhen; Gao, Xianjun; You, Abin; Wu, Chenxuan; Du, Zhi; Yin, HaiFang

    2016-08-01

    Hepatocellular carcinoma (HCC) remains a global challenge due to high morbidity and mortality rates and poor response to treatment. Immunotherapy, based on introduction of dendritic cells (DCs) activated by tumor cell lysates as antigens ex vivo, shows limited response rates in HCC patients. Here, we demonstrate that tumor cell-derived exosomes (TEXs), displaying an array of HCC antigens, can elicit a stronger immune response than cell lysates in vitro and in vivo. Significant tumor growth inhibition was achieved in ectopic and orthotopic HCC mice treated with TEX-pulsed DCs. Importantly, the tumor immune microenvironment was significantly improved in orthotopic HCC mice treated by TEX-pulsed DCs, demonstrated by increased numbers of T lymphocytes, elevated levels of interferon-γ, and decreased levels of interleukin-10 and tumor growth factor-β in tumor sites. As expected, T cells played an essential role in the TEX-pulsed DC-mediated immune response. Notably, exosomes from HCC cells not only promoted HCC-specific cytolysis but also provided cross-protective effects against pancreatic cancer cells. Moreover, HCC-specific cytolysis, elicited by DCs pulsed with human HepG2 cell-derived exosomes, was observed across different human HCC cells irrespective of human leukocyte antigen types. HCC TEXs can potently carry HCC antigens, trigger a strong DC-mediated immune response, and improve the HCC tumor microenvironment. (Hepatology 2016;64:456-472). © 2016 by the American Association for the Study of Liver Diseases.

  16. Effect of ultrasound-guided percutaneous injection of cinobufotalin or anhydrous ethanol in treatment of portal vein tumor thrombus: a comparative analysis

    OpenAIRE

    JI Jianfeng; XIAO Qiujin; Deng, Xiaoli

    2016-01-01

    To investigate the effect of ultrasound-guided percutaneous injection of cinobufotalin or anhydrous ethanol in the treatment of portal vein tumor thrombus (PVTT) through a comparative analysis. MethodsA total of 56 patients with PVTT after liver cancer surgery, who were admitted to the 94th Hospital of PLA from October 2009 to December 2011, were enrolled. Among these patients, 27 underwent ultrasound-guided percutaneous injection of cinobufotalin (cinobufotalin group) and 29 underwent ultras...

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

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    Zhang, Wen, E-mail: wenzhangxiao@126.com; Yan, Zhiping, E-mail: Yan.zhiping@zs-hospital.sh.cn; Luo, Jianjun, E-mail: luo.jianjun@zs-hospital.sh.cn; Fang, Zhuting, E-mail: 470389481@qq.com; Wu, Linlin, E-mail: linlinzhifubao@126.com; Liu, QingXin, E-mail: liu.qingxin@zs-hospital.sh.cn; Qu, Xudong, E-mail: qu.xudong@zs-hospital.sh.cn; Liu, Lingxiao, E-mail: liu.lingxiao@zs-hospital.sh.cn; Wang, Jianhua, E-mail: wang.jianhua@zs-hospital.sh.cn [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

  18. Radiation Therapy for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

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    Park, Seung Gyu; Kim, Jin Hee; Byun, Sang Jun; Kim, Ok Bae; Hwang, Jae Seok; Oh, Young Kee; Choi, Tae Jin [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2011-03-15

    To evaluate the effectiveness of radiation therapy (RT) for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and to analyze the prognostic factors. From December 2004 to April 2009, 70 patients who had HCC with PVTT were treated with RT at Keimyung University Dongsan Medical Center. Nineteen patients whose total dose was below 30 Gy and one patient who underwent liver transplantation were excluded. The remaining 50 patients (45 males, 5 females; median age 55 years) were analyzed. According to the LCSGJ TNM stage, there were 27 patients (54.0%) with stage III and 23 (46.0%) with stage IV. Total dose of 30-54 Gy was administered (median 45). Thirty patients (60.0%) were treated with concurrent chemoradiation therapy (CCRT). The median follow-up duration was from 13.5 months (range, 3 to 70 months). The median survival time from the start of RT was 9 months. One-year and 2-year overall survival rates were 24.9% and 11.2%, respectively. At the follow-up time, three patients (6.0%) displayed no evidence of disease. Seven patients (14.0%) were alive with disease, and 40 (80.0%) patients had expired due to disease progression. CCRT was associated with worse survival than RT alone (p=0.034). Response to RT (p=0.037), CLIP stage (p=0.017), and TNM stage (p=0.041) were statistically significant prognostic factors. There was no radiation-induced liver disease. RT is an effective and safe modality for HCC with PVTT. Further studies such as prospective randomized trials are needed to confirm the role of RT for HCC with PVTT.

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

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    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.

  20. Low-dose steroid-induced tumor lysis syndrome in a hepatocellular carcinoma patient

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    Jin Ok Kim; Dae Won Jun; Hye Jin Tae; Kang Nyeong Lee; Hang Lak Lee; Oh Young Lee; Ho Soon Choi; Byung Chul Yoon; Joon Soo Hahm

    2015-01-01

    Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The p...

  1. [Kidney cancer with venal thrombus-principles of menagement].

    Science.gov (United States)

    Skiba, Ryszard; Syryło, Tomasz; Wieczorek, Andrzej; Zieliński, Henryk

    Frequency of renal cell carcinoma with tumor thrombus may reach up to 30% of cases. Epidemiologic data show that tumor thrombus by itself is not negative predictive factor. Meticulous preparation by analisis of high quality imaging, acurate preoperative patient and team preparation enables to make complete thrombus resection. In our analisis we propouse rules of holistic treatment for patients suffering from renal cell carcinoma with tumor thrombus. Applying of these rules results in satisfactory long term results.

  2. Multimodal Treatment of Hepatic Metastasis in the Form of a Bile Duct Tumor Thrombus from Pancreatic Acinar Cell Carcinoma: Case Report of Successful Resection after Chemoradiation Therapy

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    Hirotada Kittaka

    2012-07-01

    Full Text Available Pancreatic acinar cell carcinoma (ACC is a rare tumor, and its pathophysiology has not been well understood. Treatment strategies for hepatic metastasis originating from ACC remain controversial. We report the case of a 66-year-old woman who had undergone total pancreatectomy from ACC 7 years prior to clinical presentation. Contrast-enhanced computed tomography imaging revealed a tumorous lesion measuring 7 cm in length and 1 cm in diameter and extending along the intrahepatic bile duct (B6, which showed mild enhancement in the early phase and modest washout in the late phase. This lesion was diagnosed as hepatic metastasis primarily in the form of a bile duct tumor thrombus originating from the prior ACC by the pathological evaluation of the fine needle biopsy specimen. The patient underwent preoperative gemcitabine-based chemoradiation therapy followed by subsequent surgical resection, which included subsegmentectomy (S6 of the liver and complete removal of the bile duct tumor thrombus. The patient has had no recurrence during the past 8 months since her last surgery. Multimodal treatment including preoperative chemoradiation therapy might be beneficial especially for marginally resectable cases of ACC.

  3. [Vitamin D metabolism and signaling in human hepatocellular carcinoma and surrounding non-tumorous liver].

    Science.gov (United States)

    Horváth, Evelin; Balla, Bernadett; Kósa, János; Lakatos, Péter András; Lazáry, Áron; Németh, Dániel; Jozilan, Hasan; Somorácz, Áron; Korompay, Anna; Gyöngyösi, Benedek; Borka, Katalin; Kiss, András; Kupcsulik, Péter; Schaff, Zsuzsa; Szalay, Ferenc

    2016-11-01

    1,25-Dihydroxy vitamin D 3 mediates antitumor effects in hepatocellular carcinoma. We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D 3 -inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver. Snap-frozen tissues from 13 patients were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA expression was measured by RT-PCR, CYP24A1 protein was detected by immunohistochemistry. Expression of VDR and CYP27B1 was significantly lower in hepatocellular carcinoma compared with non-tumorous liver (pexpressed CYP24A1 mRNA, but neither of the non-tumorous liver. The gene activation was followed by CYP24A1 protein synthesis. The presence of CYP24A1 mRNA and the reduced expression of VDR and CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased bioavailability of 1,25-Dihydroxy vitamin D 3 , providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910-1918.

  4. Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma.

    Science.gov (United States)

    Xiao, Zhenyu; Chung, Haniee; Banan, Babak; Manning, Pamela T; Ott, Katherine C; Lin, Shin; Capoccia, Benjamin J; Subramanian, Vijay; Hiebsch, Ronald R; Upadhya, Gundumi A; Mohanakumar, Thalachallour; Frazier, William A; Lin, Yiing; Chapman, William C

    2015-05-01

    Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival times. The efficacy of current systemic therapies for HCC is limited. In this study, we used xenograft tumor models to investigate the use of antibodies that block CD47 and inhibit HCC tumor growth. Immunostaining of tumor tissue and HCC cell lines demonstrated CD47 over-expression in HCC as compared to normal hepatocytes. Macrophage phagocytosis of HCC cells was increased after treatment with CD47 antibodies (CD47mAbs) that block CD47 binding to SIRPα. Further, CD47 blockade inhibited tumor growth in both heterotopic and orthotopic models of HCC, and promoted the migration of macrophages into the tumor mass. Our results demonstrate that targeting CD47 by specific antibodies has potential immunotherapeutic efficacy in human HCC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

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    Li Fan

    2010-04-01

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

  6. 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...

  7. 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.

  8. Effect of ultrasound-guided percutaneous injection of cinobufotalin or anhydrous ethanol in treatment of portal vein tumor thrombus: a comparative analysis

    Directory of Open Access Journals (Sweden)

    JI Jianfeng

    2016-04-01

    Full Text Available To investigate the effect of ultrasound-guided percutaneous injection of cinobufotalin or anhydrous ethanol in the treatment of portal vein tumor thrombus (PVTT through a comparative analysis. MethodsA total of 56 patients with PVTT after liver cancer surgery, who were admitted to the 94th Hospital of PLA from October 2009 to December 2011, were enrolled. Among these patients, 27 underwent ultrasound-guided percutaneous injection of cinobufotalin (cinobufotalin group and 29 underwent ultrasound-guided percutaneous injection of anhydrous ethanol (anhydrous ethanol group. The clinical outcome and survival time were compared between the two groups after treatment, and the levels of total bilirubin (TBil, alanine aminotransferase (ALT, and aspartate aminotransferase (AST before and after treatment were compared. The t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, the rank sum test was used for comparison of ranked data, and the Kaplan-Meier method was used for survival analysis. ResultsThe response rate showed no significant difference between the cinobufotalin group and the anhydrous ethanol group (63.0% vs 58.6%, χ2=0.111, P>0.05. After treatment, the cinobufotalin group had significantly lower levels of TBil, ALT, and AST than the anhydrous ethanol group (t=2.24, 2.40, and 2.39, all P<0.05. The 6-month, 1-year, and 2-year survival rates showed no significant differences between the cinobufotalin group and the anhydrous ethanol group (81.5%/63.0%/29.6% vs 82.8%/586%/31.0%, χ2=0.016, 0.111, and 0.013, all P>0.05. ConclusionUltrasound-guided percutaneous injection of cinobufagin or anhydrous ethanol has similar short- and long-term effects in the treatment of PVTT and can inhibit the growth of tumor thrombus and prolong survival time, but cinobufagin is superior to anhydrous ethanol in the aspect of protecting liver function.

  9. TCP10L acts as a tumor suppressor by inhibiting cell proliferation in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zuo, Jie; Cai, Hao; Wu, Yanhua; Ma, Haijie; Jiang, Wei; Liu, Chao; Han, Dingding; Ji, Guoqing [State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433 (China); Yu, Long, E-mail: longyu@fudan.edu.cn [State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433 (China); Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 (China)

    2014-03-28

    Highlights: • TCP10L was down-regulated in clinical hepatocellular carcinoma (HCC). • Expression of TCP10L correlated significantly with tumor size and Milan criteria. • Overexpression of TCP10L attenuated growth of HCC cells both in vitro and in vivo. • Knocking down TCP10L promoted cell proliferation and tumorigenesis of HCC cells. - Abstract: TCP10L (T-complex 10 (mouse)-like) has been identified as a liver and testis-specific gene. Although a potential transcriptional suppression function of TCP10L has been reported previously, biological function of this gene still remains largely elusive. In this study, we reported for the first time that TCP10L was significantly down-regulated in clinical hepatocellular carcinoma (HCC) samples when compared to the corresponding non-tumorous liver tissues. Furthermore, TCP10L expression was highly correlated with advanced cases exceeding the Milan criteria. Overexpression of TCP10L in HCC cells suppressed colony formation, inhibited cell cycle progression through G0/G1 phase, and attenuated cell growth in vivo. Consistently, silencing of TCP10L promoted cell cycle progression and cell growth. Therefore, our study has revealed a novel suppressor role of TCP10L in HCC, by inhibiting proliferation of HCC cells, which may facilitate the diagnosis and molecular therapy in HCC.

  10. Acute heart failure caused by a giant hepatocellular metastatic tumor of the right atrium.

    Science.gov (United States)

    Dedeilias, Panagiotis; Nenekidis, Ioannis; Koukis, Ioannis; Anagnostakou, Vania; Paparizou, Niki; Zompolos, Spyros; Apostolakis, Efstratios

    2011-08-26

    We present a symptomatic 40-year-old cirrhotic man who presented with sudden onsets of syncope. Echocardiography revealed right ventricular outflow track obstruction caused by a huge right atrial mass. The tumor was surgically excised under cardiopulmonary bypass. Although no primary cancerous lesion in the liver was detected, histopathology revealed that the mass was a metastatic hepatocellular carcinoma. The aim of this report is to show the value of urgent preoperative computed tomography and its contribution in the operative strategy. The importance of urgent surgical treatment with tricuspid valve sparing tumor resection is emphasized even though the prognosis for such patients is dismal. We also discuss the further management options of such rare cases.

  11. Low-dose steroid-induced tumor lysis syndrome in a hepatocellular carcinoma patient

    Directory of Open Access Journals (Sweden)

    Jin Ok Kim

    2015-03-01

    Full Text Available Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC, but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE, radiofrequency thermal ablation (RFTA, and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone. The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition of tumor lysis syndrome. Although the patient received adequate hydration, severe metabolic acidosis and acute kidney injury progressed unabated. He finally developed multiple organ failure, and died 3 days after admission. This was a case of tumor lysis syndrome caused by administration of low-dose steroid in a patient with HCC.

  12. Low-dose steroid-induced tumor lysis syndrome in a hepatocellular carcinoma patient.

    Science.gov (United States)

    Kim, Jin Ok; Jun, Dae Won; Tae, Hye Jin; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Choi, Ho Soon; Yoon, Byung Chul; Hahm, Joon Soo

    2015-03-01

    Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition of tumor lysis syndrome. Although the patient received adequate hydration, severe metabolic acidosis and acute kidney injury progressed unabated. He finally developed multiple organ failure, and died 3 days after admission. This was a case of tumor lysis syndrome caused by administration of low-dose steroid in a patient with HCC.

  13. [Prognostic factors in renal cancer with venous thrombus survival analysis.

    Science.gov (United States)

    Pascual-Fernández, Angela; Calleja-Escudero, Jesús; Gómez de Segura, Cristina; Pesquera-Ortega, Laura; Taylor, James; Fajardo, José Antonio; González de Zárate, Javier; Monllor-Gisbert, Jesús; Cortiñas-González, José Ramón

    2017-07-01

    To analyze surgery for renal cancer with venous thrombus at different levels, perioperative complications and prognostic factors associated to overall, cancer-specific and disease-free survival. Retrospective analysis of 42 cases of renal cancer with venous thrombus performed between 2005 and 2015. The level reached by the thrombus was established according to the Mayo Clinic classification. Postoperative complications were staged according to Clavien-Dindo classification. Most frequent in males. Mean age 65.7 years. 16.6% were tumors with level II thrombus. Subcostal approach was performed in 58.9%. Extracorporeal circulation with cardiac arrest and hypothermia was established in 2 patients. Resection of metastatic disease was performed in 3 patients during radical nephrectomy. Reoperation was 2.3% while, perioperative mortality was 4.7%. 30% presented with metastases at diagnosis. Twenty patients progressed at 15.5 months (3-55). Overall survival was 60 months. The cancer-specific mortality was 75%. Disease-free survival was 30% at 55 months. Surgical treatment of renal cancer with venous thrombus requires a multidisciplinary management. The surgical technique varies according to the level reached by the venous thrombus. Tumor stage is the most important prognostic factor. Thrombus level influences prognosis, with longer survival for patients with tumor thrombus confined to the renal vein (pT3a) in comparison to tumors with thrombus in the atrium (pT3c).

  14. Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models.

    Science.gov (United States)

    Lu, Zhen; Zuo, Bingfeng; Jing, Renwei; Gao, Xianjun; Rao, Quan; Liu, Zhili; Qi, Han; Guo, Hongxing; Yin, HaiFang

    2017-10-01

    Dendritic cell (DC)-derived exosomes (DEXs) form a new class of vaccines for cancer immunotherapy. However, their potency in hepatocellular carcinoma (HCC), a life-threatening malignancy with limited treatment options in the clinic that responds poorly to immunotherapy, remains to be investigated. Exosomes derived from α-fetoprotein (AFP)-expressing DCs (DEXAFP) were investigated in three different HCC mouse models systemically. Tumor growth and microenvironment were monitored. DEXAFP elicited strong antigen-specific immune responses and resulted in significant tumor growth retardation and prolonged survival rates in mice with ectopic, orthotopic and carcinogen-induced HCC tumors that displayed antigenic and pathological heterogeneity. The tumor microenvironment was improved in DEXAFP-treated HCC mice, demonstrated by significantly more γ-interferon (IFN-γ)-expressing CD8+ T lymphocytes, elevated levels of IFN-γ and interleukin-2, and fewer CD25+Foxp3+ regulatory T (Treg) cells and decreased levels of interleukin-10 and transforming growth factor-β in tumor sites. Lack of efficacy in athymic nude mice and CD8+ T cell-depleted mice showed that T cells contribute to DEXAFP-mediated antitumor function. Dynamic examination of the antitumor efficacy and the immune microenvironment in DEXAFP-treated orthotopic HCC mice at different time-points revealed a positive correlation between tumor suppression and immune microenvironment. Our findings provide evidence that AFP-enriched DEXs can trigger potent antigen-specific antitumor immune responses and reshape the tumor microenvironment in HCC mice and thus provide a cell-free vaccine option for HCC immunotherapy. Lay summary: Dendritic cell (DC)-derived exosomes (DEXs) form a new class of vaccines for cancer immunotherapy. However, their potency in hepatocellular carcinoma (HCC) remains unknown. Here, we investigated exosomes from HCC antigen-expressing DCs in three different HCC mouse models and proved their feasibility

  15. 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.

  16. Tumor progression locus 2 ablation suppressed hepatocellular carcinoma development by inhibiting hepatic inflammation and steatosis in mice

    Science.gov (United States)

    Background: Tumor progression locus 2 (TPL2), a serine threonine kinase, functions as a critical regulator of inflammatory pathways and mediates oncogenic events. The potential role of Tpl2 in nonalcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) development remains unkn...

  17. 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.

  18. Metformin, a diabetes drug, eliminates tumor-initiating hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Tomoko Saito

    Full Text Available Metformin has been widely used as an oral drug for diabetes mellitus for approximately 60 years. Interestingly, recent reports showed that metformin exhibited an anti-tumor action in a wide range of malignancies including hepatocellular carcinoma (HCC. In the present study, we investigated its impact on tumor-initiating HCC cells. Metformin suppressed cell growth and induced apoptosis in a dose-dependent manner. Flow cytometric analysis showed that metformin treatment markedly reduced the number of tumor-initiating epithelial cell adhesion molecule (EpCAM(+ HCC cells. Non-adherent sphere formation assays of EpCAM(+ cells showed that metformin impaired not only their sphere-forming ability, but also their self-renewal capability. Consistent with this, immunostaining of spheres revealed that metformin significantly decreased the number of component cells positive for hepatic stem cell markers such as EpCAM and α-fetoprotein. In a xenograft transplantation model using non-obese diabetic/severe combined immunodeficient mice, metformin and/or sorafenib treatment suppressed the growth of tumors derived from transplanted HCC cells. Notably, the administration of metformin but not sorafenib decreased the number of EpCAM(+ cells and impaired their self-renewal capability. As reported, metformin activated AMP-activated protein kinase (AMPK through phosphorylation; however its inhibitory effect on the mammalian target of rapamycin (mTOR pathway did not necessarily correlate with its anti-tumor activity toward EpCAM(+ tumor-initiating HCC cells. These results indicate that metformin is a promising therapeutic agent for the elimination of tumor-initiating HCC cells and suggest as-yet-unknown functions other than its inhibitory effect on the AMPK/mTOR pathway.

  19. Identification of responders to sorafenib in hepatocellular carcinoma: is tumor volume measurement the way forward?

    Science.gov (United States)

    Bargellini, Irene; Scionti, Alessandra; Mismas, Valeria; Masi, Gianluca; Vivaldi, Caterina; Bartolozzi, Carlo; Sacco, Rodolfo

    2014-01-01

    Early assessment of hepatocellular carcinoma (HCC) response during sorafenib (SO) treatment is challenging, since tumor necrosis, extension and radiological appearance can be inhomogeneous. We evaluated the predictive value of different imaging criteria - such as Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), tumor density and volume variations - in the early follow-up of SO treatment. The study included 22 patients. CT images from baseline and 2 months were reviewed to assess response according to RECIST 1.1, mRECIST, EASL, Choi's criteria (decreased tumor density by ≥15%) and arterial-enhancing tumor volume ratio; α-fetoprotein (AFP) variations were expressed as AFP ratio. The response criteria and volume measurements were reproducible (k > 0.80). The overall disease control rate was 40.9% by EASL and mRECIST, and 27.3% by RECIST 1.1; a ≥15% decrease in tumor density was observed in 9 patients (40.9%). The mean volume ratio was 1.73 ± 2.12, the mean AFP ratio 14 ± 37. The 1-year survival rate was 65.9%. Volume ratio was the only predictive factor for survival, with 1-year cumulative survival rates of 90% for volume ratios ≤1.1 and of 45.4% for volume ratios >1.1 (p = 0.04). Tumor volume measurements are reproducible and might provide an early predictive marker of response in HCC patients treated with SO. © 2014 S. Karger AG, Basel.

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

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    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

  1. Synergistic anti-tumor efficacy of doxorubicin and flavopiridol in an in vivo hepatocellular carcinoma model.

    Science.gov (United States)

    Kwak, Min-Sun; Yu, Su Jong; Yoon, Jung-Hwan; Lee, Sung-Hee; Lee, Soo-Mi; Lee, Jeong-Hoon; Kim, Yoon Jun; Lee, Hyo-Suk; Kim, Chung Yong

    2015-11-01

    A previous study showed that flavopiridol increased doxorubicin sensitivity in hypoxic hepatocellular carcinoma (HCC) cells by increasing apoptosis through suppressing hypoxia-inducible N-myc downstream-regulated gene-1 (NDRG1) expression. However, this has not been investigated in an in vivo HCC model. Therefore, we aimed to elucidate whether the combination of doxorubicin and flavopiridol has a synergistic anti-tumor effect in an in vivo HCC model. An HCC mouse model was established by implanting C3H/He mouse with MH134 cells. Then, doxorubicin with or without flavopiridol was injected. The anti-tumor efficacy was assessed by evaluating tumor volumes, and the underlying mechanism was investigated by quantifying apoptotic cells, the Ki-67 proliferation index, and microvessel densities (MVDs). Immunohistochemistry of NDRG1 was performed to determine the underlying mechanism. Tumor growth was significantly suppressed in the doxorubicin + flavopiridol combination group compared to the other three groups. The percentage of apoptotic cells was significantly higher, and Ki-67-positive proliferating cells were significantly lower in the combination group compared to the other groups; however, MVDs were not significantly different across the groups. Increased apoptosis by flavopiridol occurred by suppressing hypoxia-inducible NDRG1 expression. These results show that a combination of doxorubicin and flavopiridol has a synergistic anti-tumor effect in an in vivo HCC model. This synergistic effect of combination therapy was attributed to increased apoptosis and decreased proliferation of tumor cells rather than decreased angiogenesis. These findings suggest that flavopiridol might be an effective adjuvant therapy to doxorubicin-resistant HCC cells by inducing apoptosis through suppression of NDRG1 expression.

  2. Colony-Stimulating Factor 1 Receptor Blockade Inhibits Tumor Growth by Altering the Polarization of Tumor-Associated Macrophages in Hepatocellular Carcinoma.

    Science.gov (United States)

    Ao, Jian-Yang; Zhu, Xiao-Dong; Chai, Zong-Tao; Cai, Hao; Zhang, Yuan-Yuan; Zhang, Ke-Zhi; Kong, Ling-Qun; Zhang, Ning; Ye, Bo-Gen; Ma, De-Ning; Sun, Hui-Chuan

    2017-08-01

    Colony-stimulating factor-1 (CSF-1) and its receptor, CSF-1R, regulate the differentiation and function of macrophages and play an important role in macrophage infiltration in the context of hepatocellular carcinoma. The therapeutic effects of CSF-1R blockade in hepatocellular carcinoma remain unclear. In this study, we found that CSF-1R blockade by PLX3397, a competitive inhibitor with high specificity for CSF-1R tyrosine kinase, significantly delayed tumor growth in mouse models. PLX3397 inhibited the proliferation of macrophages in vitro, but intratumoral macrophage infiltration was not decreased by PLX3397 in vivo Gene expression profiling of tumor-associated macrophages (TAM) showed that TAMs from the PLX3397-treated tumors were polarized toward an M1-like phenotype compared with those from vehicle-treated tumors. In addition, PLX3397 treatment increased CD8(+) T-cell infiltration, whereas CD4(+) T-cell infiltration was decreased. Further study revealed that tumor cell-derived CSF-2 protected TAMs from being depleted by PLX3397. In conclusion, CSF-1R blockade delayed tumor growth by shifting the polarization rather than the depletion of TAMs. CSF-1R blockade warrants further investigation in the treatment of hepatocellular carcinoma. Mol Cancer Ther; 16(8); 1544-54. ©2017 AACR. ©2017 American Association for Cancer Research.

  3. Knockout of the Nogo-B Gene Attenuates Tumor Growth and Metastasis in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Bo Zhu

    2017-07-01

    Full Text Available Human hepatocellular carcinoma (HCC is a malignant cancer. It is a challenge to develop anti-HCC drugs due to HCC's extreme aggressiveness and with the sensitivity of the liver to show severe adverse effects. More importantly, the precise mechanisms causing HCC pathogenicity are not known. Our previous study disclosed Nogo-B as a reticulon 4 (Rtn4 family member. In the present study, we first identified that Nogo-B played a critical role in HCC progression. We found, via in vitro and in vivo assays, that Nogo-B was expressed aberrantly in primary HCC tumor tissues and immortal HCC cells but was relatively scarce in the normal liver tissues or cells. Nogo-B knockout, via the CRISPR-Cas9 technique, resulted in significant suppression of HCC cell proliferation and tumor growth. Next-generation sequencing analysis showed that Nogo-B knockout have effects on interleukin-6 (IL-6 signaling pathway. Furthermore, we observed that IL-6 induced phosphorylation of STAT3 (pSTAT3 in wild-type HCC cells, but Nogo-B knockout could reduce IL-6–induced increase of pSTAT3, supporting that Nogo-B affects HCC tumor progression possibly via regulating the IL-6/STAT3 signaling pathway. In conclusion, Nogo-B is expressed aberrantly in HCCs and plays an oncogenic role. These findings support that Nogo-B may be a novel anti-HCC therapeutic target.

  4. Proton-beam therapy for hepatocellular carcinoma associated with portal vein tumor thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Sugahara, Shinji [Dept. of Radiation Oncology, Inst. of Clinical Medicine, Univ. of Tsukuba, Ibaraki (Japan); Research Center Hospital for Charged Particle Therapy, National Inst. of Radiological Sciences, Chiba (Japan); Nakayama, Hidetsugu; Mizumoto, Masashi; Tsuboi, Koji; Tokuuye, Koichi [Dept. of Radiation Oncology, Inst. of Clinical Medicine, Univ. of Tsukuba, Ibaraki (Japan); Fukuda, Kuniaki; Abei, Masato; Shoda, Junichi [Dept. of Gastroenterology, Inst. of Clinical Medicine, Univ. of Tsukuba, Ibaraki (Japan); Tokita, Mari [Alpert Medical School of Brown Univ., Providence, RI (United States); Matsuzaki, Yasushi [Dept. of Gastroenterology, Tokyo Medical Univ. Kasumigaura Hospital, Ibaraki (Japan); Thono, Eriko [Dept. of Radiology, Inst. of Clinical Medicine, Univ. of Tsukuba, Ibaraki (Japan)

    2009-12-15

    Background and purpose: the prognosis of patients with advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor, as effective treatment options are limited. The authors performed a retrospective review to evaluate the efficacy of proton-beam therapy (PBT) for patients presenting with PVTT in the setting of HCC. Patients and methods: between February 1991 and September 2005, 35 patients with HCC and tumor thrombi in the main trunk or major branches of the portal vein presented for consideration of PBT. Their tumor sizes ranged from 25 mm to 130 mm (median, 60 mm). A median total dose of 72.6 GyE in 22 fractions was delivered over 31 days to a target volume that encompassed both the primary hepatic lesion and the PVTT. Results: 32 patients were progression-free during a median follow-up period of 21 months (range, 2-88 months) and three patients experienced disease progression. Local progression-free survival rates were 46% at 2 years and 20% at 5 years, and the median local progression-free survival was 21 months. Acute toxicity {>=} grade 3 was observed in three patients, and no patient experienced late toxicity {>=} grade 3. None of the patients had to discontinue treatment as a result of toxicity. Conclusion: PBT improved local control and significantly prolonged survival in HCC patients with PVTT. (orig.)

  5. [A case of hepatocellular carcinoma with respiratory failure caused by widespread tumor microemboli].

    Science.gov (United States)

    Tanaka, Kosuke; Nakasya, Akio; Miyazaki, Masanori; Takao, Shinichiro; Higuchi, Nobito; Tanaka, Masatake; Tanaka, Yuki; Kato, Masaki; Kato, Kazuhiro; Takayanagi, Ryoichi; Aishima, Shinichi

    2011-10-01

    A 76-year-old man with hepatocellular carcinoma (HCC) was admitted to our hospital suffering from rapidly progressing dyspnea. Chest computed tomography on admission merely showed ground-glass patterns in both lung fields without thrombi in the pulmonary trunk. On the third day, pulmonary blood flow scintigraphy was performed because of progression of his dyspnea, and showed multiple defects indicating widespread thrombi in the peripheral pulmonary arteries. He died of respiratory failure on day 13. A needle necropsy revealed the presence of multiple foci of adenocarcinoma nests in the lungs, suggesting venous thrombi from the poorly differentiated HCC. Although HCC frequently metastasizes to the lung, patients with lung metastasis rarely result in respiratory failure. It is well known that some patients with adenocarcinoma including HCC can develop respiratory failure owing to pulmonary tumor thrombotic microangiopathy (PTTM). In our case, however, pathological examination showed widespread tumor microemboli in the lung, but no stenosis or fibrocellular intimal proliferation in the small arteries and arterioles, which are essential findings of PTTM. Although we concluded that the respiratory failure in this case was mainly caused by widespread tumor microemboli, it remains unclear why such dissemination rapidly developed.

  6. Aryl hydrocarbon receptor regulates histone deacetylase 8 expression to repress tumor suppressive activity in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Li-Ting; Chiou, Shyh-Shin; Chai, Chee-Yin; Hsi, Edward; Wang, Shen-Nien; Huang, Shau-Ku; Hsu, Shih-Hsien

    2017-01-31

    Histone deacetylase 8 (HDAC8), a unique member of class I histone deacetylases, shows remarkable correlation with advanced disease stage and multiple malignant tumors However, little is known about the contribution of HDAC8 to the tumorigenesis of hepatocellular carcinoma (HCC). The present study investigated the expression of HDAC8 regulated by the aryl hydrocarbon receptor (AHR) in HCC cell lines and tissues, and the roles of HDAC8 overexpression in cell proliferation, including potentially underlying mechanisms. We assessed the correlation between the clinic-pathological parameters and the expression of AHR and HDAC8. Further, we analyzed the AHR siRNA transfection and HDAC8 inhibitors to explore the functions of HDAC8 in HCC progression in vitro and in vivo. In a panel of 289 HCC patients, HDAC8 was shown to be highly correlated with AHR expression at both mRNA and protein levels. HCC patients with high AHR expression showed a shorter survival time than that with low AHR expression. We then found that the expression of both AHR and HDAC8 was significantly upregulated in both HCC cell lines and tumor tissues compared to human normal hepatocytes and matched non-tumor tissues. Furthermore, HDAC8 inhibition remarkably inhibited hepatoma cell proliferation and transformation activity via upregulation of RB1 in vitro and in vivo. Our data revealed an important role of the AHR-HDAC8 axis in promoting HCC tumorigenesis, thus identifying HDAC8 as a potential therapeutic target for HCC treatment.

  7. Impacts of clinicopathologic and operative factors on short-term and long-term survival in renal cell carcinoma with venous tumor thrombus extension: a multi-institutional retrospective study in Japan.

    Science.gov (United States)

    Hirono, Masanori; Kobayashi, Mikio; Tsushima, Tomoyasu; Obara, Wataru; Shinohara, Nobuo; Ito, Keiichi; Eto, Masatoshi; Takayama, Tatsuya; Fujii, Yasuhisa; Nishikido, Masaharu; Kimura, Go; Kishida, Takeshi; Takahashi, Masayuki; Miyao, Noriomi; Naya, Yukio; Abe, Takashige; Fujioka, Tomoaki; Ito, Kazuto; Naito, Seiji

    2013-10-02

    Although the percentage of patients with renal cell carcinoma (RCC) extending into venous systems is unexpectedly high, the prognostic impact and independency of venous tumor thrombus-related factors on overall survival (OS) remain controversial. Furthermore, the prognostic impact of various clinicopathologic factors including tumor thrombus-related factors on OS may change with elapsed years after the intervention and also with follow-up duration of participants. The aim of the study is to explore independent and universal predictive preoperative and intraoperative clinicopathologic factors on OS in patients with RCC extending into venous systems using subgroup analysis in terms of restricted follow-up duration and yearly-based survivors. Between 1980 and 2009, 292 patients diagnosed with RCC with venous tumor thrombus were retrospectively registered for this study. The prognostic impacts of various clinicopathologic and surgical treatment factors including levels of venous thrombus, venous wall invasion status and likelihood of aggressive cytoreductive operation, were investigated using Kaplan-Meier method and following multivariate Cox proportional hazards model for all patients and those still alive at 1, 2, and 3 years of follow-up. To investigate the impact of follow-up duration on the statistical analyses, multivariate logistic regression analyses were used to explore prognostic factors using restricted data until 1, 2, and 3 years of follow-up. The median follow-up duration was 40.4 months. The 5-year OS was 47.6%. Several independent predictive factors were identified in each subgroup analysis in terms of yearly-based survival and restricted follow-up duration. The presence of tumor thrombus invading to venous wall was independently related to OS in the full-range follow-up data and in survivors at 2 and 3 years of follow-up. Using restricted follow-up data until 1, 2, and 3 years of follow-up, many independent predictive factors changed with follow

  8. Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

    Science.gov (United States)

    Severi, Tamara; van Malenstein, Hannah; Verslype, Chris; van Pelt, Jos F

    2010-01-01

    Hepatocellular carcinoma (HCC) is a major health problem worldwide responsible for 500 000 deaths annually. A number of risk factors are associated with either the induction of the disease or its progression; these include infection with hepatitis B or C virus, alcohol consumption, non-alcoholic steatohepatitis and certain congenital disorders. In around 80% of the cases, HCC is associated with cirrhosis or advanced fibrosis and with inflammation and oxidative stress. In this review we focus firstly on the different risk factors for HCC and summarize the mechanisms by which each is considered to contribute to HCC. In the second part we look at the molecular processes involved in cancer progression. HCC development is recognized as a multistep process that normally develops over many years. Over this period several mutations accumulate in the cell and that stimulate malign transformation, growth, and metastatic behavior. Over the recent years it has become evident that not only the tumor cell itself but also the tumor microenviroment plays a major role in the development of a tumor. There is a direct link between the role of inflammation and cirrhosis with this microenviroment. Both in vitro and in vivo it has been shown that tumor formation and metastatic properties are linked to epithelial-mesenchymal transition (EMT), a process by which facillitates the tumor cell's attempts to migrate to a more favourable microenviroment. Several groups have analyzed the gene expression in HCC and its surrounding tissue by microarray and this has resulted in the molecular classification into a distinct number of classes. Here we also found a role for hypoxia induced gene expression leading to a clinically more aggressive gene expression in HCC. Molecular analysis also helped to identify important cellular pathways and possible therapeutic targets. The first molecule that in this way has shown clinical application for liver cancer is the multikinase inhibitor sorafenib, others

  9. Tumor-specific suicide gene therapy for hepatocellular carcinoma by transcriptionally targeted retroviral replicating vectors.

    Science.gov (United States)

    Lai, Y-H; Lin, C-C; Chen, S-H; Tai, C-K

    2015-02-01

    Replicating virus vectors are attractive tools for anticancer gene therapy, but the potential for adverse events due to uncontrolled spread of the vectors has been a major concern. To design a tumor-specific retroviral replicating vector (RRV), we replaced the U3 region of the RRV ACE-GFP with a regulatory sequence consisting of the hepatitis B virus enhancer II (EII) and human α-fetoprotein (AFP) core promoter to produce ACE-GFP-EIIAFP, a hepatocellular carcinoma (HCC)-targeting RRV. Similar to ACE-GFP, ACE-GFP-EIIAFP exhibited robust green fluorescent protein (GFP) expression in HCC cells and, most importantly, it exhibited HCC-specific replication and did not replicate in non-HCC tumor cells or normal liver cells. We sequenced the promoter region of ACE-GFP-EIIAFP collected from serial infection cycles to examine the genomic stability of the vector during its replicative spread, and found that the vector could retain the hybrid promoter in the genome for at least six infection cycles. In vitro studies revealed that ACE-CD-EIIAFP and ACE-PNP-EIIAFP, which express the yeast cytosine deaminase and Escherichia coli purine nucleoside phosphorylase, respectively, exert a highly potent cytotoxic effect on HCC cells in the presence of their respective prodrugs. In vivo, ACE-CD-EIIAFP-mediated suicide gene therapy efficiently suppressed HCC tumor growth and no detectable RRV signal was observed in extratumoral tissues. These results suggest that the tumor-specific, suicide-gene-encoding RRV may fulfill the promise of retroviral gene therapy for cancer.

  10. 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.

  11. Advances in clinical application of cryoablation therapy for hepatocellular carcinoma and metastatic liver tumor.

    Science.gov (United States)

    Hu, Ke-Qin

    2014-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Although surgical resection and liver transplantation are the curative treatments, many of HCC patients do not qualify for these curative therapies at the presentation. Thus, ablation therapies are currently important modalities in HCC treatment. Among currently available ablation therapies, cryoablation (ie, cryotherapy) is a novel local therapeutic modality. However, cryoablation has not been widely used as one of ablation therapies for HCC, because of historical concerns about risk of bleeding when cryotherapy is delivered by early generation of the argon-helium device. Nevertheless, with technological advances and increased clinical experience in the past decade, clinical application of cryoablation for HCC management has significantly increased. Accumulating data have demonstrated that cryoablation is highly effective in local tumor control with well-acceptable safety profile, and the overall survival is comparable with that of radiofrequency ablation in patients with tumors advances in clinical application of cryoablation therapy for HCC, including the related mechanisms and technology, clinical indications, efficacy and safety profiles, and future research directions.

  12. Comprehensive interventional treatment of hepatocellular carcinoma with portal vein tumor thrombosis

    Directory of Open Access Journals (Sweden)

    ZHU Xiaoli

    2015-06-01

    Full Text Available Portal vein tumor thrombosis (PVTT often occurs in advanced hepatocellular carcinoma (HCC patients. PVTT may cause tumor dissemination, liver failure, and portal hypertension, thus leading to intractable ascites, variceal rupture, and hepatic encephalopathy, which will result in a poor prognosis. According to the Barcelona Clinic Liver Cancer Staging System, sorafenib is recommended as the first-line treatment for advanced HCC with PVTT, but its application in China has been limited due to its mild efficacy and high price. Nowadays, interventional treatment is widely used in the treatment of advanced HCC with PVTT due to the advantages of minimal invasiveness and repeatability and shows good efficacy. At present, the main methods of interventional treatment include hepatic arterial infusion chemotherapy, transcatheter arterial chemoembolization (TACE, TACE combined with sorafenib, TACE combined with ablation, TACE combined with three-dimensional conformal radiotherapy, TACE combined with portal vein stent placement, endovascular implantation of iodine-125 seeds strand, and transjugular intrahepatic portosystemic shunt. It is pointed out that multimodality treatment is expected to achieve good efficacy in the treatment of advanced HCC with PVTT.

  13. Chrysin inhibited tumor glycolysis and induced apoptosis in hepatocellular carcinoma by targeting hexokinase-2.

    Science.gov (United States)

    Xu, Dong; Jin, Junzhe; Yu, Hao; Zhao, Zheming; Ma, Dongyan; Zhang, Chundong; Jiang, Honglei

    2017-03-20

    Hexokinase-2(HK-2) plays dual roles in glucose metabolism and mediation of cell apoptosis, making it an attractive target for cancer therapy. Chrysin is a natural flavone found in plant extracts which are widely used as herb medicine in China. In the present study, we investigated the antitumor activity of chrysin against hepatocellular carcinoma (HCC) and the role of HK-2 played for chrysin to exert its function. The expression of HK-2 in HCC cell line and tumor tissue was examined by western blotting and immunohistochemistry staining. The activities of chrysin against HCC cell proliferation and tumor glycolysis were investigated. Chrysin-induced apoptosis was analyzed by flow cytometry. The effect of chrysin on HK-2 expression and the underlying mechanisms by which induced HCC cell apoptosis were studied. In HK-2 exogenous overexpression cell, the changes of chrysin-induced cell apoptosis and glycolysis suppression were investigated. HCC cell xenograft model was used to confirm the antitumor activity of chrysin in vivo and the effect on HK-2 was tested in chrysin-treated tumor tissue. In contrast with normal cell lines and tissue, HK-2 expression was substantially elevated in the majority of tested HCC cell lines and tumor tissue. Owing to the decrease of HK-2 expression, glucose uptake and lactate production in HCC cells were substantially inhibited after exposure to chrysin. After chrysin treatment, HK-2 which combined with VDAC-1 on mitochondria was significantly declined, resulting in the transfer of Bax from cytoplasm to mitochondria and induction of cell apoptosis. Chrysin-mediated cell apoptosis and glycolysis suppression were dramatically impaired in HK-2 exogenous overexpression cells. Tumor growth in HCC xenograft models was significantly restrained after chrysin treatment and significant decrease of HK-2 expression was observed in chrysin-treated tumor tissue. Through suppressing glycolysis and inducing apoptosis in HCC, chrysin, or its derivative has

  14. 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

  15. Three-dimensional conformal radiotherapy for portal vein tumor thrombosis alone in advanced hepatocellular carcinoma

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    Lee, Ju Hye Kim Dong Hyun; Ki, Yong Kan; Kim, Dong Won; Kim, Won Taek; Heo, Jeong; Woo, Hyun Young [Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of); Nam, Ji Ho [Dept.of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2014-09-15

    We sought to evaluate the clinical outcomes of 3-dimensional conformal radiation therapy (3D-CRT) for portal vein tumor thrombosis (PVTT) alone in patients with advanced hepatocellular carcinoma. We retrospectively analyzed data on 46 patients who received 3D-CRT for PVTT alone between June 2002 and December 2011. Response was evaluated following the Response Evaluation Criteria in Solid Tumors. Prognostic factors and 1-year survival rates were compared between responders and non-responders. Thirty-seven patients (80.4%) had category B Child-Pugh scores. The Eastern Cooperative Oncology Group performance status score was 2 in 20 patients. Thirty patients (65.2%) had main or bilateral PVTT. The median irradiation dose was 50 Gy (range, 35 to 60 Gy) and the daily median dose was 2 Gy (range, 2.0 to 2.5 Gy). PVTT response was classified as complete response in 3 patients (6.5%), partial response in 12 (26.1%), stable disease in 19 (41.3%), and progressive disease in 12 (26.1%). There were 2 cases of grade 3 toxicities during or 3 months after radiotherapy. Twelve patients in the responder group (15 patients) received at least 50 Gy irradiation, but about 84% of patients in the non-responder group received less than 50 Gy. The 1-year survival rate was 66.8% in responders and 27.4% in non-responders constituting a statistically significant difference (p = 0.008). Conformal radiotherapy for PVTT alone could be chosen as a palliative treatment modality in patients with unfavorable conditions (liver, patient, or tumor factors). However, more than 50 Gy of radiation may be required.

  16. Serological and histological indices of hepatocellular carcinoma and tumor volume doubling time

    Science.gov (United States)

    SHINGAKI, NAOKI; TAMAI, HIDEYUKI; MORI, YOSHIYUKI; MORIBATA, KOSAKU; ENOMOTO, SHOTARO; DEGUCHI, HISANOBU; UEDA, KAZUKI; INOUE, IZUMI; MAEKITA, TAKAO; IGUCHI, MIKITAKA; KATO, JUN; ICHINOSE, MASAO

    2013-01-01

    Hepatocellular carcinoma (HCC) frequently develops in cirrhotic liver and is one of the most common malignancies worldwide. The tumor volume doubling time (TVDT) reflects the natural tumor growth rate and is an indicator of the biological malignant potential of a tumor. The present study aimed to elucidate the association between the serological and histological indices of HCC and TVDT. TVDT was analyzed for 53 HCCs by measuring the enlargement of the tumor diameter on dynamic computed tomography. Differences in TVDT were compared among histological grades of HCC differentiation. The α-fetoprotein (AFP) doubling time (T2AFP) for 44 HCCs with AFP levels >200 ng/ml was calculated and the differences in T2AFP were compared according to the histological grade of HCC differentiation and positivity for Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3). Among these 44 HCCs, the correlation between T2AFP and TVDT was analyzed for the 27 tumors for which TVDT could be calculated. The mean ± standard deviation (SD) TVDT in Edmondson grade 1 (Ed1), Ed2 and Ed3 HCC was 138.3±110.3, 94.9±91.5 and 32.2±20.8 days, respectively (P<0.05). The mean ± SD T2AFP in Ed2 and Ed3 HCC was 121.0±167.5 and 37.3±24.6 days, respectively (P<0.01). TVDT and T2AFP decreased with histological dedifferentiation of HCC. The mean ± SD T2AFP in the AFP-L3-positive and -negative groups was 63.2±101.2 and 191.9±209.9 days, respectively, with a statistically significant difference between the groups (P<0.01). A significant correlation was observed between T2AFP and TVDT (correlation coefficient, 0.70; P<0.01). A significant correlation was also observed among TVDT, serological indices and histological grades of HCC differentiation. A short T2AFP and/or AFP-L3-positivity were shown to reflect a poorly differentiated HCC histopathology and a higher malignant potential. PMID:24649280

  17. Primary liver tumors. Hepatocellular versus intrahepatic cholangiocellular carcinoma; Primaere Lebertumoren. Hepatozellulaeres vs. intrahepatisches cholangiozellulaeres Karzinom

    Energy Technology Data Exchange (ETDEWEB)

    Wengert, G.J.; Bickel, H.; Breitenseher, J.; Ba-Ssalamah, A. [Medizinische Universitaet Wien, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Allgemeines Krankenhaus, Wien (Austria)

    2015-01-01

    Hepatocellular carcinoma (HCC) and intrahepatic cholangiocellular carcinoma (ICC) are the most commonly occurring and important primary liver tumors. Originating from one pluripotent liver stem cell both tumor entities can occur in a cirrhotic liver and also in patients without cirrhosis. Several risk factors have been identified as causative for both carcinomas; therefore, tumor screening is advantageous, especially for high-risk patients who could be diagnosed in an early stage to allow curative treatment. Surgical resection, interventional procedures and transplantation are available as curative treatment options when diagnosed in time. Common characteristic features and morphology in cross-sectional imaging by ultrasound (US), multidetector computed tomography (CT) and magnetic resonance imaging (MRI) as well as screening aspects are presented and discussed. Recent findings show a better understanding of the carcinogenesis model of both liver tumors originating from one pluripotent liver stem cell. Further developments of modern cross-sectional imaging modalities, especially MRI in combination with diffusion-weighted imaging and intravenous administration of hepatocyte-specific contrast agents enable early detection, exact differentiation, staging and treatment evaluation of HCC and ICC In this article we discuss modern, multiparametric imaging modalities, which allow a complete and reliable diagnosis of the majority of these tumor entities. Contrast-enhanced MRI, using hepatocyte-specific contrast agents, is currently the most accurate procedure for the noninvasive diagnosis and treatment evaluation of HCC and ICC. (orig.) [German] Das hepatozellulaere Karziom (HCC) sowie das intrahepatische cholangiozellulaere Karzinom (ICC) zaehlen zu den wichtigsten primaeren Lebertumoren. Mit dem Ursprung aus einer pluripotenten Stammzelle koennen beide Tumorentitaeten bei bestehender, aber auch bei nicht bestehender Leberzirrhose auftreten. Im Folgenden werden

  18. An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma.

    Science.gov (United States)

    Kalinich, Mark; Bhan, Irun; Kwan, Tanya T; Miyamoto, David T; Javaid, Sarah; LiCausi, Joseph A; Milner, John D; Hong, Xin; Goyal, Lipika; Sil, Srinjoy; Choz, Melissa; Ho, Uyen; Kapur, Ravi; Muzikansky, Alona; Zhang, Huidan; Weitz, David A; Sequist, Lecia V; Ryan, David P; Chung, Raymond T; Zhu, Andrew X; Isselbacher, Kurt J; Ting, David T; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A

    2017-01-31

    Circulating tumor cells (CTCs) are shed into the bloodstream by invasive cancers, but the difficulty inherent in identifying these rare cells by microscopy has precluded their routine use in monitoring or screening for cancer. We recently described a high-throughput microfluidic CTC-iChip, which efficiently depletes hematopoietic cells from blood specimens and enriches for CTCs with well-preserved RNA. Application of RNA-based digital PCR to detect CTC-derived signatures may thus enable highly accurate tissue lineage-based cancer detection in blood specimens. As proof of principle, we examined hepatocellular carcinoma (HCC), a cancer that is derived from liver cells bearing a unique gene expression profile. After identifying a digital signature of 10 liver-specific transcripts, we used a cross-validated logistic regression model to identify the presence of HCC-derived CTCs in nine of 16 (56%) untreated patients with HCC versus one of 31 (3%) patients with nonmalignant liver disease at risk for developing HCC (P digital CTC scoring was not correlated with the standard HCC serum protein marker alpha fetoprotein (P = 0.57). Modeling the sequential use of these two orthogonal markers for liver cancer screening in patients with high-risk cirrhosis generates positive and negative predictive values of 80% and 86%, respectively. Thus, digital RNA quantitation constitutes a sensitive and specific CTC readout, enabling high-throughput clinical applications, such as noninvasive screening for HCC in populations where viral hepatitis and cirrhosis are prevalent.

  19. Multicenter validation study of a prognostic index for portal vein tumor thrombosis in hepatocellular carcinoma.

    Science.gov (United States)

    Yu, Jeong Il; Yoon, Sang Min; Park, Hee Chul; Kim, Jong Hoon; Kim, Tae Hyun; Park, Joong-Won; Seong, Jinsil; Lee, Ik Jae; Jang, Hong Seok; Kay, Chul Seung; Kim, Chul Yong; Chie, Eui Kyu; Kim, Jin Hee; Kim, Mi-Sook; Choi, Young Min

    2014-10-01

    We previously reported on a staging system and prognostic index (PITH) for portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) patients treated with radiotherapy (RT) at a single institution. The aim of this study is to validate the PITH staging system using data from patients at other institutions and to compare it with other published staging systems. A total of 994 HCC patients with PVTT who were treated with RT between 1998 and 2011 by the Korean Radiation Oncology Group were analyzed retrospectively. All patients were staged using the Cancer of the Liver Italian Program (CLIP), Japanese Integrated Staging (JIS), Okuda, and PITH staging systems, and survival data were analyzed. The likelihood ratio, Akaike information criteria (AIC), time-dependent receiver operating characteristics, and prediction error curve analysis were used to determine discriminatory ability for comparison of staging systems. The median survival was 9.2 months. Compared with the other staging systems, the PITH score gave the highest values for likelihood ratio and lowest AIC values, demonstrating that PITH may be a better prognostic model. Although the values were not significant and differences were not exceptional, the PITH score showed slightly better performance with respect to time-dependent area under curve and integrated Brier score of prediction error curve. The PITH staging system was validated in this multicenter retrospective study and showed better stratification ability in HCC patients with PVTT than other systems.

  20. Expression of PEG10 Is Associated with Poor Survival and Tumor Recurrence in Hepatocellular Carcinoma.

    Science.gov (United States)

    Bang, Heejin; Ha, Sang Yun; Hwang, Soo Hyun; Park, Cheol-Keun

    2015-10-01

    Paternally expressed gene 10 (PEG10), first identified as an imprinted gene, is paternally expressed and maternally silenced. In hepatocellular carcinoma (HCC), PEG10 has been identified as a potential target gene located within the amplified 7q21 locus. The purpose of this study was to investigate the expression of PEG10 protein in HCC and evaluate its prognostic significance. PEG10 protein expression was examined by immunohistochemistry in tumor tissues from 218 HCC patients undergoing curative resection. Furthermore, the relationships between PEG10 expression and clinicopathologic features or postoperative survival of HCC patients were evaluated. The median follow-up period was 119.8 months for survivors. PEG10 expression was observed in 148 of the 218 HCCs (67.9%) and was significantly correlated with younger age, female, higher Edmondson grade, microvascular invasion, intrahepatic metastasis, higher American Joint Committee on Cancer T-stage, and higher α-fetoprotein level. PEG10 expression was an independent predictor of early recurrence (p=0.013), and it showed an unfavorable influence on recurrence-free survival (p expression showed an unfavorable influence on overall survival (p=0.007) but was not an independent predictor of shorter overall survival (p=0.128). PEG10 protein could be a potential biomarker predicting early recurrence and recurrence-free survival in HCC patients after curative resection, even in those with normal serum α-fetoprotein levels.

  1. 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.

  2. 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.

  3. Left ventricular mural thrombus

    Energy Technology Data Exchange (ETDEWEB)

    Nixon, J.V.

    1983-08-01

    The identification of mural thrombus in patients with left ventricular aneurysm and mural thrombus probably warrants consideration of long-term anticoagulation. In patients with acute, large, anterior or anteroapical, transmural myocardial infarctions, serial noninvasive examinations are warranted to define a group of patients at high risk for the development of left ventricular aneurysm and/or mural thrombus. Anticoagulants should be considered in patients in whom mural thrombi develop as a complication of their infarction. Patients with congestive cardiomyopathy should be considered for long-term anticoagulation. These recommendations are all tempered by the realization that the use of anticoagulant therapy is not without its own risks. The decision to anticoagulate must be balanced against each individual patient's suitability for such therapy and the individual likelihood of the development of side effects.

  4. CXCR5+CD8+ T cells could induce the death of tumor cells in HBV-related hepatocellular carcinoma.

    Science.gov (United States)

    Jin, Yun; Lang, Cuicui; Tang, Jianzhong; Geng, Jiawei; Song, Haihan K; Sun, Zhiwei; Wang, Jinfeng

    2017-12-01

    The follicular CXCR5+CD8+ T cells have recently emerged as a critical cell type in mediating peripheral tolerance as well as antiviral immune responses during chronic infections. In this study, we investigated the function of CXCR5+CD8+ T cells in HBV-related hepatocellular carcinoma patients. Compared to CXCR5-CD8+ T cells, CXCR5+CD8+ T cells presented elevated PD-1 expression but reduced Tim-3 and CTLA-4 expression. Upon anti-CD3/CD28 stimulation, CXCR5+CD8+ T cells demonstrated higher proliferation potency than CXCR5-CD8+ T cells, especially after PD-1 blockade. CXCR5+CD8+ T cells also demonstrated significantly higher granzyme B synthesis and release, as well as higher level of degranulation. Tumor cells were more readily eliminated by CXCR5+CD8+ T cells than by CXCR5-CD8+ T cells. Interestingly, we found that B cells were more resistant to CXCR5+CD8+ T cell-mediated killing than tumor cells, possibly through IL-10-mediated protection. In addition, the CXCR5+CD8+ T cell-mediated cytotoxic effects on tumor cells could be significantly enhanced by PD-L1 blockade. Together, we presented that in patients with in HBV-related hepatocellular carcinoma, CXCR5+CD8+ T cells could mediate tumor cell death more potently than the CXCR5-CD8+ T cells in vitro while the autologous B cells were protected. Copyright © 2017. Published by Elsevier B.V.

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

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    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.

  6. 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.

  7. Rate of tumor growth predicts recurrence of hepatocellular carcinoma after liver transplantation in patients beyond Milan or UCSF criteria.

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    Hanouneh, I A; Macaron, C; Lopez, R; Aucejo, F; Zein, N N

    2011-12-01

    It is likely that some patients whose tumor burdens exceed the current transplant criteria have favorable tumor biology, and that these patients would have low risk of tumor recurrence after liver transplantation (LT). To assess the rate of tumor growth as selection criteria for LT in patients with hepatocellular carcinoma (HCC). We identified all patients who underwent LT for HCC in our institution from 2002 to 2008. Total tumor volume (TTV) was calculated as the sum of the volumes of all tumors on pretransplantation imaging [(4/3)πr3, where r is the maximum radius of each HCC]. The rate of tumor growth was calculated as per-month change in TTV on sequential pretransplantation imaging before any locoregional therapy. A Kaplan-Meier plot was constructed and Cox regression analysis performed. Ninety-two patients were included in the study. The median follow-up was 19.5 (range 10.7-30.7) months during which 12 patients (13%) experienced recurrence of HCC. Twenty-four patients (26%) had HCC beyond the Milan criteria, and the overall survival rate of the entire group was 72%. Higher pre-LT alpha-fetoprotein (hazard ratio [HR] 1.01; P=.001), poorly differentiated tumors (HR 13; P=.039), the presence of microvascular invasion (HR 7.9; P=.001), higher TTV (HR 1.03; P1.61 cm3/mo. Similarly, rate of tumor growth predicted HCC recurrence in those beyond the University of California of San Francisco (UCSF) criteria. Patients with slowly growing tumor who would be currently excluded from LT because tumor burden exceeds traditional Milan and UCSF criteria may have a favorable posttransplantation outcome. Copyright © 2011. Published by Elsevier Inc.

  8. [The effects of different clinicopathologic variables on serum protein fingerprint in hepatocellular carcinoma patients].

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    Huang, Cheng; Fan, Jia; Zhou, Jian; Liu, Yin-kun; Cui, Jie-feng

    2006-04-01

    To investigate the effects of different clinicopathologic variables on serum protein fingerprint in hepatocellular carcinoma (HCC) patients. Serum samples were collected from 112 HCC patients, Special serum protein or peptide spectra was determined by surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) measurement after treating the sample onto weak cation exchange (WCX2) protein chip for each case. The serum protein profiles were compared by BioMarker Wizard Software among the patients stratified according to gender, AFP, presence of portal vein tumor thrombus (PVTT), tumor size, tumor number, presence of cirrhosis, respectively. According to serum protein fingerprints of 112 HCC patients, a total of 100 protein peaks were identified at the m/z value ranging from 1100 to 30,000. (1) Sixteen significant differential proteins were found between the groups of HCC with single tumor and those with multiple tumors (P 3 cm and those with tumor size 5 cm and those with tumor size 10 cm and those with tumor size tumor thrombus (Ma-PVTT) and those without PVTT (N-PVTT); Only 2 significant differential protein were found between the groups of microscopic portal vein tumor thrombus (Mi-PVTT) and N-PVTT (P < 0.01); eight significant differential proteins were found between the groups of Ma-PVTT and Mi-PVTT (P < 0.01). (4) No significant differential protein was found when patients stratified according to gender, presence of cirrhosis and AFP. PVTT, tumor number and tumor size had significant effects on serum protein fingerprint, while no significant effect on serum protein from gender, presence of cirrhosis and AFP. The most profound impact on the serum protein was attained when cutoff was chosen to be presence of Ma-PVTT compared to less effect from Mi-PVTT and 5cm for tumor size.

  9. CDKN3 expression is negatively associated with pathological tumor stage and CDKN3 inhibition promotes cell survival in hepatocellular carcinoma.

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    Dai, Wei; Miao, Huilai; Fang, Shuo; Fang, Tao; Chen, Nianping; Li, Mingyi

    2016-08-01

    Aberrant expression of CDKN3 may be involved in carcinogenesis of liver cancer. The effect of CDKN3 on tumorigenesis and the molecular mechanisms involved have not been fully elucidated. Immunohistochemistry was performed to detect CDKN3 expression levels in tumor tissues. CDKN3 siRNA was used to knockdown CDKN3 in QGY7701 hepatocellular carcinoma (HCC) cells. Colony formation assay was used to measure the clonogenic capacity of the tumor cells. Cell viability was determined by MTT assay. Logistic regression was performed to analyze the association between CDKN3 expression level and the HCC clinical pathology index. The CDKN3 expression level was significantly decreased in HCC tumor tissues compared with normal liver tissue and liver cirrhosis tissue. Additionally, CDKN3 expression was negatively‑associated with the pathological stage of the tumor. Inhibition of CKDN3 promoted the clonogenic capacity and chemotherapeutic tolerance in HCC tissues compared with controls. Knockdown of CDKN3 resulted in downregulation of p53 and p21 protein levels, whereas, AKT serine/threonine kinase 1 expression was upregulated. Thus, CDKN3 expression may reduce the survival of tumor cells and alter the sensitivity to therapeutic agents via the AKT/P53/P21 signaling pathway. Therefore, CDKN3 may be involved in tumor differentiation and self-renewal.

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

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    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

  11. TRIM26 functions as a novel tumor suppressor of hepatocellular carcinoma and its downregulation contributes to worse prognosis

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    Wang, Yi, E-mail: wangyichenben@163.com [Department of General Surgery, The Affiliated Baoan Hospital of Southern Medical University, Shenzhen, Guangdong, 518101 (China); He, Du, E-mail: hdu1234@163.com [Department of Oncology, The Central Hospital of Enshi Autonomous of Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, 445000 (China); Yang, Liang, E-mail: yliang0689@163.com [Department of Oncology, Qianjiang Central Hospital, Qianjiang, Hubei, 433100 (China); Wen, Bo, E-mail: tjwb001@126.com [Department of Urology, The Affiliated Baoan Hospital of Southern Medical University, Shenzhen, Guangdong, 518101 (China); Dai, Jinfen, E-mail: brilliant_510@126.com [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060 (China); Zhang, Qian, E-mail: anny9655@126.com [Department of Immunology, School of Basic Medicine, Wuhan University, Wuhan, Hubei, 430071 (China); Kang, Jian, E-mail: 984190619@qq.com [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060 (China); He, Weiyang, E-mail: 996114664@qq.com [Department of Immunology, School of Basic Medicine, Wuhan University, Wuhan, Hubei, 430071 (China); Ding, Qianshan, E-mail: iamdqs@163.com [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060 (China); He, De, E-mail: 18938027146@126.com [Department of General Surgery, The Affiliated Baoan Hospital of Southern Medical University, Shenzhen, Guangdong, 518101 (China)

    2015-07-31

    Hepatocellular carcinoma (HCC) is the one of the most common malignancies worldwide and its prognosis is extremely poor. Tripartite motif (TRIM) proteins play crucial roles in cancer cell biology but the function of tripartite motif 26 (TRIM26) has not been investigated. We demonstrated that low expression level of TRIM26 in tumor samples was significantly correlated with worse prognosis in HCC patients. We also demonstrated its expression level was associated with several clinicopathologic features such as AFP level and T stage of HCC patients. Furthermore, we validated that TRIM26 was significantly downregulated in HCC tissue compared with normal liver tissue. To further clarify the functional role of TRIM26 in HCC, We confirmed that TRIM26 silencing can promote cancer cell proliferation, colony forming, migration and invasion in vitro with HCC cell lines HepG2 and Bel-7402. Then we utilized bioinformatic tool to predict gene influenced by TRIM26, showing TRIM26 could modulate gene sets about cancer cell metabolism. In conclusion, we proved that TRIM26 is a novel tumor suppressor modulating multiple metabolism-related pathways in HCC. To our best knowledge, this is the first study to investigate the function of TRIM26 in cancer biology. Our findings provide useful insight into the mechanism of HCC origin and progression. Moreover, TRIM26 may represent a novel therapeutic target for HCC. - Highlights: • TRIM26 is down-regulated in liver cancer samples and functions as a novel tumor suppressor. • Down-regulation of TRIM26 is associated with worse prognosis of hepatocellular carcinoma (HCC). • Knockdown of TRIM26 promotes the proliferation and metastasis of HCC cells. • TRIM26 may function in abnormal metabolic progress of HCC.

  12. S100P expression is a novel prognostic factor in hepatocellular carcinoma and predicts survival in patients with high tumor stage or early recurrent tumors.

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    Yuan, Ray-Hwang; Chang, Ko-Tung; Chen, Yu-Ling; Hsu, Hey-Chi; Lee, Po-Huang; Lai, Po-Lin; Jeng, Yung-Ming

    2013-01-01

    The calcium-binding protein S100P is expressed in a variety of human cancer cells and is important in cancer cell growth and invasion. Using differential display, we found S100P is overexpressed in human hepatocellular carcinoma (HCC). We examined the expression of 305 unifocal, primary HCC tumors using immunohistochemistry. The S100P protein was expressed in 173 of the 305 (56.7%) HCC tumors. The expression of S100P correlated with female sex (P = 0.0162), high serum α-fetoprotein level (P = 0.0001), high tumor grade (P = 0.0029), high tumor stage (P = 0.0319), the presence of the p53 mutation (P = 0.0032), and the absence of the β-catenin mutation (P = 0.0489). Patients with HCC tumors that expressed S100P were more likely to have early tumor recurrence (ETR) (P = 0.0189) and lower 5-year survival (P = 0.0023). The multivariate analysis confirmed that S100P expression was an independent prognostic factor in HCC. The combinatorial analysis showed an additive unfavorable prognostic interaction between S100P expression and the p53 mutation. In contrast, the β-catenin mutation was associated with better prognosis in both S100P-positive and -negative HCCs. Furthermore, S100P expression was a predictor of survival in HCC patients with high tumor stage or ETR (P = 0.0026 and P = 0.0002, respectively). Our study indicates the expression of the S100P protein is a novel independent predictor for poor prognosis in HCC, and it is also an unfavorable prognostic predictor in HCC patients with high tumor stage or ETR.

  13. Surgical treatment of a patient with diaphragmatic invasion by a ruptured hepatocellular carcinoma with biliary and portal venous tumor thrombi.

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    Maruyama, Hiroshi; Yoshida, Hiroshi; Hirakata, Atsushi; Matsutani, Takeshi; Yokoyama, Tadashi; Suzuki, Seiji; Matsushita, Akira; Sasajima, Koji; Kikuchi, Yuta; Uchida, Eiji

    2012-01-01

    We describe the surgical treatment of a patient with diaphragmatic invasion by a ruptured hepatocellular carcinoma (HCC) associated with biliary and portal venous tumor thrombi. A 67-year-old man was admitted because of jaundice (total serum bilirubin, 6.6 mg/dL). The serum concentration of alpha-fetoprotein was 236.1 ng/mL. The anti-hepatitis C virus antibodies were present in the serum. Computed tomography showed a large hypervascular mass in the right subphrenic region, surrounded by local effusion. Endoscopic retrograde cholangiography revealed dilatation of the left intrahepatic bile duct caused by biliary tumor thrombi extending from the right hepatic duct to the common bile duct. Endoscopic nasobiliary drainage was performed, and the total serum bilirubin level returned to the normal range. Angiography revealed a hypervascular tumor without extravasation of contrast medium in the right lobe and obstruction of the right anterior branch of the portal vein. Right hepatectomy was attempted 15 days after drainage. Severe invasion of the diaphragm by the ruptured HCC was detected. Bleeding of the ruptured HCC stopped spontaneously. Partial resection of the diaphragm was performed, followed by primary suture, without an artificial patch. Tumor thrombectomy was performed from the common bile duct. Macroscopic examination revealed that the ruptured HCC had invaded the diaphragm. Biliary and portal venous tumor thrombi were present. Histopathological examination showed a moderately differentiated HCC with biliary and portal venous tumor thrombi. The postoperative course was uneventful. The patient was discharged on postoperative day 14. Five months after the operation, local and intrahepatic recurrences of HCC were detected. Six months after operation, the patient died of liver failure. In conclusion, the outcome of a patient with diaphragmatic invasion by a ruptured HCC with biliary tumor thrombi was poor, even after curative hepatic resection.

  14. GIANT PROSTHETIC VALVE THROMBUS

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    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.

  15. Lobar Hepatocellular Carcinoma with Ipsilateral Portal Vein Tumor Thrombosis Treated with Yttrium-90 Glass Microsphere Radioembolization: Preliminary Results

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    M. Pracht

    2013-01-01

    Full Text Available Portal vein tumor thrombosis (PVTT is a common complication of hepatocellular carcinoma (HCC and has a negative impact on prognosis. This characteristic feature led to the rationale of the present trial designed to assess the efficacy and the safety of yttrium-90 glass-microsphere treatment for advanced-stage lobar HCC with ipsilateral PVTT. 18 patients with unresectable lobar HCC and ipsilateral PVTT were treated in our institution with 90Y-microS radioembolization. Patients were evaluated every 3 to 6 months for response, survival, and toxicity. Mean follow-up was 13.0 months (2.2–50.6. Outcomes were: complete response (n=2, partial response (n=13, stable disease (n=1, and progressive disease (n=2 giving a disease control rate of 88.9%. Four patients were downstaged. Treating lobar hepatocellular carcinoma with ipsilateral portal vein thrombosis with yttrium-90 glass-microsphere radioembolization is safe and efficacious. Further clinical trials are warranted to confirm these results and to compare 90Y-microS with sorafenib, taking into account not only survival but also the possibility of secondary surgery for putative curative intention after downstaging.

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

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    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.

  17. Disulfiram eradicates tumor-initiating hepatocellular carcinoma cells in ROS-p38 MAPK pathway-dependent and -independent manners.

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    Tetsuhiro Chiba

    Full Text Available Tumor-initiating cells (TICs play a central role in tumor development, metastasis, and recurrence. In the present study, we investigated the effect of disulfiram (DSF, an inhibitor of aldehyde dehydrogenase, toward tumor-initiating hepatocellular carcinoma (HCC cells. DSF treatment suppressed the anchorage-independent sphere formation of both HCC cells. Flow cytometric analyses showed that DSF but not 5-fluorouracil (5-FU drastically reduces the number of tumor-initiating HCC cells. The sphere formation assays of epithelial cell adhesion molecule (EpCAM(+ HCC cells co-treated with p38-specific inhibitor revealed that DSF suppresses self-renewal capability mainly through the activation of reactive oxygen species (ROS-p38 MAPK pathway. Microarray experiments also revealed the enrichment of the gene set involved in p38 MAPK signaling in EpCAM(+ cells treated with DSF but not 5-FU. In addition, DSF appeared to downregulate Glypican 3 (GPC3 in a manner independent of ROS-p38 MAPK pathway. GPC3 was co-expressed with EpCAM in HCC cell lines and primary HCC cells and GPC3-knockdown reduced the number of EpCAM(+ cells by compromising their self-renewal capability and inducing the apoptosis. These results indicate that DSF impaired the tumorigenicity of tumor-initiating HCC cells through activation of ROS-p38 pathway and in part through the downregulation of GPC3. DSF might be a promising therapeutic agent for the eradication of tumor-initiating HCC cells.

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

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    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.

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

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    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.

  20. Blood Serum Alpha Fetoprotein Enhancer Binding Protein, a Tumor Suppressor, Decreases in Chronic HBV Hepatitis Patients as Hepatocellular Cancer Appears

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    James N. Riggins

    2010-01-01

    Full Text Available Chronic hepatitis increases the risk of hepatocellular carcinoma (HCC. To test whether circulating proteins reflect hepatic carcinogenesis, sera from patients and controls were albumin depleted, enriched for glycoproteins, digested with trypsin, and subjected to reverse phase chromatography and tandem mass spectrometry. Alpha-fetoprotein enhancer binding protein (AFPebp, a tumor suppressor, was repeatedly identified in sera from chronic HBV hepatitis patients. We independently identified and quantified AFPebp with a deuterated, phenylisocyanate-labeled synthetic peptide standard. Elevated AFPebp levels in sera from chronic HBV hepatitis patients decreased as cancer developed. These data suggest that rising AFPebp levels in chronic HBV hepatitis may be protective, while falling levels may contribute to HCC development.

  1. Extrahepatic metastasis risk of hepatocellular carcinoma based on α-fetoprotein and tumor staging parameters at cross-sectional imaging

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    Yokoo T

    2017-10-01

    Full Text Available Takeshi Yokoo,1 Amish D Patel,1 Naama Lev-Cohain,1 Amit G Singal,2 Adam C Yopp,3 Ivan Pedrosa1 1Department of Radiology, 2Department of Internal Medicine, 3Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA Background: Extrahepatic metastases have important implications in the clinical management of hepatocellular carcinoma (HCC. The purpose of this study was to validate tumor staging parameters and serum AFP as risk factors of HCC metastasis.Patients and methods: In this retrospective case–control study, patients with a new diagnosis of HCC (N=236, median age 57 years (range 28–89 years, and male-to-female ratio of 183/53 were divided into a “no-met” group (N=101 without extrahepatic metastasis or a “met” group with extrahepatic metastases (N=135. Metastasis risk factors based on tumor staging parameters (size, number, infiltration, and vascular invasion and serum AFP level were calculated as odds ratio (OR. Sensitivities of the risk factors as metastasis screening tests were also calculated.Results: AFP >400 mg/mL, index tumor size >5 cm, and vascular invasion individually had strong association with metastasis, with OR (95% confidence interval of 11.5 (5.9–22.1, 17.7 (9.0–34.8, and 18.9 (8.2–43.9, respectively, but with moderate sensitivities as metastasis screening tests, with 71.9% (65.7–77.3, 75.6% (69.6–80.7, and 58.5% (52.1–64.7, respectively. Composite multiparametric criteria, eg, a logical union of 1 tumor size outside of Milan criteria, 2 AFP threshold >35 mg/mL, and 3 vascular invasion, had excellent OR up to 55.6 (13.0–237.1 with screening sensitivity 98.5% (95.8–99.6.Conclusion: Serum AFP, tumor size, and vascular invasion are strongly associated with extrahepatic metastasis of HCC, especially when combined into a multiparametric metastasis prediction criterion. Keywords: hepatocellular carcinoma, risk factor, α-fetoprotein, stage, metastasis

  2. The expression of a tumor suppressor gene JDP2 and its prognostic value in hepatocellular carcinoma patients.

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    Chen, Yao-Li; Chan, Shih-Hsuan; Lin, Ping-Yi; Chu, Pei-Yi

    2017-05-01

    The c-Jun dimerization protein 2 (JDP2) belongs to the activator protein-1 (AP-1) family and functions as a repressor of the AP-1 complex by dimerizing with other c-Jun proteins. Thus, JDP2 plays an important role in the repression of AP-1-driven biological processes, such as differentiation and proliferation. Recent studies have suggested that JDP2 may function as a tumor suppressor through its suppressive action against the AP-1 complex, which is known to drive oncogenic signals in several human malignancies. In this study, we used immunohistochemistry to examine the JDP2 expression in 211 cases of hepatocellular carcinoma (HCC) and analyzed the potential link of JDP2 expression to the clinicopathological features of HCC patients. Clinical parameter analysis showed that high expression of JDP2 was significantly correlated with smaller tumor size (P=.002) and early stage HCC (P=.039). Moreover, Kaplan-Meier survival analysis showed that high expression of JDP2 was significantly associated with better survival in HCC patients (P=.006). Taken together, our results showed that JDP2 may serve as a tumor suppressor in HCC and could therefore serve as a good prognostic marker for patients with HCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Decreased expression of PBLD correlates with poor prognosis and functions as a tumor suppressor in human hepatocellular carcinoma.

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    Li, Aimin; Yan, Qun; Zhao, Xinmei; Zhong, Jietao; Yang, Haiyun; Feng, Zhiqiang; Du, Yanlei; Wang, Yadong; Wang, Zenan; Wang, Hong; Zhou, Yongjian; Liu, Side; Nie, Yuqiang

    2016-01-05

    Recent accumulating genomic and proteomic data suggested that decreased expression of phenazine biosynthesis-like domain-containing protein (PBLD) was frequently involved in hepatocellular carcinoma (HCC). However, there is lack of systematical investigation focusing on its expression pattern, clinical relevance, and biological function. Here, we found that PBLD was frequently decreased in HCC tissues relative to adjacent non-tumorigenic liver tissues. This decreased expression was significantly associated with poor tumor differentiation and advanced tumor stage. Kaplan-Meier analysis further showed that recurrence-free survival and overall survival were significantly worse among patients with low PBLD expression. Moreover, multivariate analyses revealed that PBLD was an independent predictor of OS and RFS. This prognostic value of PBLD was further validated in another independent cohort. We also found PBLD inhibited HCC cell growth and invasion in vitro and tumor growth in vivo. Furthermore, forced expression of PBLD influenced multiple downstream genes related to MAPK, NF-κB, EMT, and angiogenesis signaling pathways. PBLD deletion was an independent predictor of poor prognosis in patients with HCC. Elevated PBLD expression may reduce HCC cell growth and invasion via inactivation of several tumorigenesis-related signaling pathways.

  4. High expression of G-protein signaling modulator 2 in hepatocellular carcinoma facilitates tumor growth and metastasis by activating the PI3K/AKT signaling pathway.

    Science.gov (United States)

    He, Xiao-Qin; Zhang, Yue-Feng; Yu, Jia-Jun; Gan, Yuan-Yuan; Han, Na-Na; Zhang, Mei-Xia; Ge, Wei; Deng, Jun-Jian; Zheng, Yong-Fa; Xu, Xi-Ming

    2017-03-01

    The aim of this study was to investigate the role of G-protein signaling modulator 2 in the carcinogenesis and progression of hepatocellular carcinoma. We previously showed that G-protein signaling modulator 2 was upregulated in hepatitis B virus-related hepatocellular carcinoma tissues through a hierarchical clustering analysis. With this study, we first assessed the expression pattern of G-protein signaling modulator 2 in hepatocellular carcinoma specimens and adjacent noncancerous tissues; clinical data were analyzed, along survival times, utilizing the Kaplan-Meier method. Moreover, the functions of G-protein signaling modulator 2 were examined using small-interfering RNAs in vitro. The results showed that G-protein signaling modulator 2 was clearly overexpressed in hepatocellular carcinoma tissues and cell lines and that the G-protein signaling modulator 2 expression level was related to tumor size and hepatitis B virus infection. Furthermore, G-protein signaling modulator 2 knockdown studies suggested that G-protein signaling modulator 2 accelerates cell growth, cell cycle, migration, and invasion and inhibits apoptosis, acting as an oncogene in hepatocellular carcinoma. Western blotting indicated that silencing of G-protein signaling modulator 2 in HepG2 and SMMC-7721 cells increased the expression levels of Bax, caspase-3, and E-cadherin, while notably suppressing the cyclin-dependent kinase 4, cyclin-dependent kinase 6, CyclinD1, Snail1, Vimentin, and matrix metallopeptidase 9 expression levels, compared with that in the control groups. In addition, we found that G-protein signaling modulator 2 can affect the expression of key proteins involved in protein kinase B activation. In conclusion, high expression of G-protein signaling modulator 2 was involved in the pathological processes of hepatocellular carcinoma through activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, which may provide an attractive potential diagnostic

  5. Visualization of right atrial thrombus associated with constrictive pericarditis by indium-111 oxine platelet imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, T.; Misawa, T.; Park, Y.D.; Uehara, T.; Hayashida, K.; Hayashi, M.

    1987-08-01

    A right atrial thrombus is not often seen and only a few reports of visualization have been described. We report a 44-yr-old man who had a large atrial thrombus associated with constrictive pericarditis. Two-dimensional echocardiography and computed tomography showed a large right atrial mass. Indium-111 oxine platelet deposition was demonstrated on the surface of thrombus by platelet imaging. Platelet imaging was useful for differential diagnosis from cardiac tumor, and as an indication for surgical treatment, since right atrial thrombus may have a high risk of pulmonary embolism or severe right heart failure.

  6. Total tumor volume predicts recurrence of hepatocellular carcinoma after liver transplantation in patients beyond Milan or UCSF criteria.

    Science.gov (United States)

    Macaron, C; Hanouneh, I A; Lopez, R; Aucejo, F; Zein, N N

    2010-12-01

    The aim of tumor-based selection criteria in patients with hepatocellular carcinoma (HCC) is to prevent orthotopic liver transplantation (OLT) in patients likely to experience recurrence and to maximize OLT opportunities for those with a high likelihood of cure. Our aim was to assess total tumor volume (TTV) as a selection criterion for OLT in patients with HCC beyond Milan or University of California San Francisco criteria. We identified patients who underwent OLT for HCC between 2002 and 2008. TTV was calculated as the sum of the volumes of all tumors on pretransplant imaging before any therapy [(4/3)πr(3), where r is the maximum radius of each HCC]. Univariable and multivariable Cox proportional hazards regression analysis was used to assess factors associated with recurrence of HCC. 107 patients were included in the study. The mean follow-up was 21 months (interquartile range, 11.8-32.5), during which 13 patients (12.1%) experienced recurrence of HCC. Twenty-nine patients (27.1%) had HCC beyond the Milan criteria. A TTV cutoff value of 33.5 cm(3) was chosen on the basis of the risk of recurrence by using a receiver operating characteristic curve. Patients beyond the Milan criteria with TTV <33.5 experienced less recurrence (13.3% vs 42.8%; P < .001) and higher survival (13.3% vs 57.1%; P = .006) than those who were beyond the Milan criteria with TTV ≥33.5. Similarly, TTV predicted HCC recurrence and survival in those beyond the UCSF criteria. TTV is useful in identifying patients at risk of tumor recurrence and poor survival among those with tumor burden beyond traditional criteria, and it may improve the selection of OLT candidates. Copyright © 2010 Elsevier Inc. All rights reserved.

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

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    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.

  8. 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 < .0001). Median survival times were 46.5 months, 16.9 months, and 11.1 months for groups 0, 1, and 2, respectively. Median survival times of 24.4 months and 12.5 months by Okuda scores of I and II, respectively, were achieved (mean, 25.8 months vs 13.1). Patients had median survival times of 20.5 months and 13.8 months according to Child class A and class B/C disease, respectively (mean, 22.7 months vs 13.6 months). Patients classified as having diffuse disease exhibited decreased survival and reduced tumor response. There were no life-threatening adverse events related to treatment. Use of 90Y microspheres (TheraSpheres) provides a safe and effective method of treatment for a broad spectrum of patients presenting with unresectable HCC. Further investigation is warranted.

  9. What to do when facing with atrial thrombus: Surgical treatment of five cases

    OpenAIRE

    Deser, Serkan Burc; Demirag, Mustafa Kemal

    2018-01-01

    Although atrial thrombuses are not very common, may represent as tumors. Urgentsurgery is indicated in patients to prevent pulmonary embolism, acute valveobstruction or heart failure. We review here the clinical features, epidemiology,diagnosis and treatment of five interesting cases with atrial thrombuses

  10. Dynamin 3: a new candidate tumor suppressor gene in hepatocellular carcinoma detected by triple combination array analysis

    Directory of Open Access Journals (Sweden)

    Inokawa Y

    2013-10-01

    Full Text Available Yoshikuni Inokawa,1 Shuji Nomoto,1 Mitsuhiro Hishida,1 Masamichi Hayashi,1 Mitsuro Kanda,1 Yoko Nishikawa,1 Shin Takeda,2 Michitaka Fujiwara,1 Masahiko Koike,1 Hiroyuki Sugimoto,1 Tsutomu Fujii,1 Goro Nakayama,1 Suguru Yamada,1 Chie Tanaka,1 Daisuke Kobayashi,1 Yasuhiro Kodera11Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya Japan; 2Department of Surgery, Nagoya Medical Center, Nagoya, JapanBackground: To identify genes associated with hepatocellular carcinoma (HCC pathogenesis, we developed a triple combination array strategy comprising methylation, gene expression, and single nucleotide polymorphism (SNP array analysis.Methods: Surgical specimens obtained from a 68-year-old female HCC patient were analyzed by triple combination array, and identified Dynamin 3 (DNM3 as a candidate tumor suppressor gene in HCC. Subsequently, samples from 48 HCC patients were evaluated for DNM3 methylation and expression status using methylation specific polymerase chain reaction (PCR; MSP and semi-quantitative reverse transcriptase (RT-PCR, respectively. The relationship between clinicopathological factors and DNM3 methylation status was also investigated.Results: DNM3 was shown to be hypermethylated (methylation value 0.879, range 0–1.0 in cancer tissue compared with adjacent normal tissue (0.213 by methylation array in the 68-year-old female patient. Expression arrays revealed decreased expression of DNM3 in cancerous tissue. SNP arrays revealed that the copy number of chromosome 1q24.3, in which DNM3 resides, was normal. MSP revealed hypermethylation of the DNM3 promoter region in 33 of 48 tumor samples. A trend toward decreased DNM3 expression was observed in patients with DNM3 promoter methylation (P = 0.189. Furthermore, patients with reduced expression of DNM3 in tumor tissues exhibited worse prognosis with decreased disease specific survival compared to patients without decreased expression (P = 0.014.Conclusion: The

  11. Adrenal Rest Tumor from the Greater Omentum Mimicking Exophytic Hepatocellular Carcinoma (HCC): A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyung Jo; Kim, Seong Hoon; Shin, Hyun Woong [Daegu Fatima Hospital, Daegu (Korea, Republic of); Park, Jae Bok [Catholic University of Daegu, Gyeongsan (Korea, Republic of); Jo, Hyun Chul; Son, Mi Young; Kim, Tae Bong [Daegu Veterans Hospital, Daegu (Korea, Republic of)

    2010-02-15

    Adrenal rest tumors are aberrant adrenocortical tissue which has been most commonly described in abdominal and pelvic sites. To our knowledge, there has been no previous description of an adrenal rest tumor of the greater omentum. We present a case of a pathologically confirmed adrenal rest tumor of the greater omentum in a 76-year- old man

  12. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or ...

  13. Circulating tumor cells with stem-like phenotypes for diagnosis, prognosis and therapeutic response evaluation in hepatocellular carcinoma.

    Science.gov (United States)

    Fan, Jia; Guo, Wei; Sun, Yun-Fan; Shen, Minna; Ma, Xiao-Lu; Wu, Jiong; Zhang, Chunyan; Zhou, Yan; Xu, Yang; Hu, Bo; Zhang, Min; Wang, Gang; Chen, Wei-Qin; Guo, Lin; Lu, Renquan; Zhou, Chao-Hui; Zhang, Xin; Shi, Ying-Hong; Qiu, Shuang-Jian; Pan, Bai-Shen; Cao, Ya; Zhou, Jian; Yang, Xin-Rong

    2018-01-26

    In present study, we assessed the clinical value of circulating tumor cells (CTCs) with stem-like phenotypes for diagnosis, prognosis and surveillance in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by an optimized QPCR-based detection platform. Differing subsets of CTCs were investigated, and a multimarker diagnostic CTC panel was constructed in a multicenter-patient study with independent validation (total n=1006), including healthy individuals, patients with chronic hepatitis B infection (CHB), liver cirrhosis (LC), benign hepatic lesion (BHL) and HBV-related HCC, with area under the receiver operating characteristic curve (AUC-ROC) reflecting diagnostic accuracy. The role of CTC panel in treatment response surveillance and its prognostic significance were further investigated. The AUC of CTC panel was 0.88 in training set [sensitivity=72·5%, specificity=95.0%, positive predictive value (PPV) =92.4, negative predictive value (NPV)=77.8] and 0.93 in validation set (sensitivity=82·1%; specificity=94.2%, PPV=89.9, NPV=89.3). This panel performed equally well in detecting early-stage and α-fetoprotein (AFP)-negative HCC, as well as differentiating HCC from CHB, LC and BHL. The CTC load was decreased significantly after tumor resection, and patients with persistently high CTC load showed a propensity of tumor recurrence after surgery. The prognostic significance of CTC panel in predicting tumor recurrence was further confirmed (training: HR=2.692, 95% CI, 1.617-4.483, P <0.001; validation: HR=3.127, 95% CI, 1.360-7.190, P =0.007). Our CTC panel showed high sensitivity and specificity in HCC diagnosis and could be a real-time parameter for risk prediction and treatment monitoring, enabling early decision-making to tailor effective antitumor strategies. Copyright ©2018, American Association for Cancer Research.

  14. Tumor markers for early diagnosis for brain metastasis of hepatocellular carcinoma: A case series and literature review for effective loco-regional treatment.

    Science.gov (United States)

    Kamimura, Kenya; Kobayashi, Yuji; Takahashi, Yoshifumi; Abe, Hiroyuki; Kumaki, Daisuke; Yokoo, Takeshi; Kamimura, Hiroteru; Sakai, Norihiro; Sakamaki, Akira; Abe, Satoshi; Takamura, Masaaki; Kawai, Hirokazu; Yamagiwa, Satoshi; Terai, Shuji

    2017-02-01

    Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately loco-regional treatment, including surgical resection and radiation therapy should be performed for better prognosis by preventing re-bleeding from the tumors.

  15. 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.)

  16. Metformin decreases IL-22 secretion to suppress tumor growth in an orthotopic mouse model of hepatocellular carcinoma.

    Science.gov (United States)

    Zhao, Dong; Long, Xi-Dai; Lu, Tian-Fei; Wang, Tao; Zhang, Wei-Wei; Liu, Yi-Xiao; Cui, Xiao-Lan; Dai, Hui-Juan; Xue, Feng; Xia, Qiang

    2015-06-01

    Epidemiological, preclinical and cellular studies in the last 5 years have shown that metformin exerts anti-tumoral properties, but its mode of action in cancer remains unclear. Here, we investigated the effects of metformin on a mouse hepatocellular carcinoma (HCC) model and tumor-associated T cell immune responses. Oral metformin administration led to a significant reduction of tumor growth, which was accompanied by decreased interleukin-22 (IL-22). Meanwhile, IL-22-induced STAT3 phosphorylation and upregulation of downstream genes Bcl-2 and cyclin D1 were inhibited by metformin. At the cellular level, metformin attenuated Th1- and Th17-derived IL-22 production. Furthermore, metformin inhibited de novo generation of Th1 and Th17 cells from naive CD4(+) cells. These observations were further supported by the fact that metformin treatment inhibited CD3/CD28-induced IFN-γ and IL-17A expression along with the transcription factors that drive their expression (T-bet [Th1] and ROR-γt [Th17], respectively). The effects of metformin on T cell differentiation were mediated by downregulated STAT3 and STAT4 phosphorylation via the AMP-activated kinase-mammalian target of rapamycin complex 1 pathway. Notably, metformin led to a reduction in glucose transporter Glut1 expression, resulting in less glucose uptake, which is critical to regulate CD4(+) T cell fate. Taken together, these findings provide evidence for the growth-inhibitory and immune-modulatory effects of metformin in HCC and thus, broaden our understanding about the action of metformin in liver cancer treatment. © 2014 UICC.

  17. Prognostic prediction across a gradient of total tumor volume in patients with hepatocellular carcinoma undergoing locoregional therapy

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    Lin Han C

    2010-12-01

    Full Text Available Abstract Background The size and number of tumors are important prognostic indicators for hepatocellular carcinoma (HCC. However, it is difficult to assess the prognosis for patients with a variable number and size of tumors. By combining these two factors, we investigated the role and prognostic accuracy of total tumor volume (TTV for HCC. Methods A total of 786 patients undergoing locoregional therapy (transarterial chemoembolization, percutaneous radiofrequency ablation and acetic acid or ethanol injection for HCC were prospectively evaluated. Results The mean and median TTV was 177 cm3 (range, 0.1-3,591 cm3 and 21 cm3, respectively. Of all, 38%, 29%, 15%, 7% and 11% of patients had TTV of 3, 10-50 cm3, 50-200 cm3, 200-500 cm3 and >500 cm3, respectively. TTV was significantly larger in patients with higher serum α-fetoprotein (AFP levels or with vascular invasion. The Child-Turcotte-Pugh score, performance status, vascular invasion, AFP level and TTV were significant independent prognostic predictors in the Cox proportional hazards model. After adjustment, patients with TTV 50-200 cm3 (relative risk [RR]: 1.74, p = 0.009, 200-500 cm3 (RR: 2.15, p = 0.006 and >500 cm3 (RR: 3.92, p 3. Conclusions TTV is a feasible prognostic predictor across a wide gradient and can be used to predict the mortality risk of HCC. Selecting appropriate cutoffs of TTV may help refine the design of cancer staging system and treatment planning. Future clinical trials of HCC may include this parameter for mortality risk stratification.

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

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    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.

  19. Mouse IP-10 Gene Delivered by Folate-modified Chitosan Nanoparticles and Dendritic/tumor Cells Fusion Vaccine Effectively Inhibit the Growth of Hepatocellular Carcinoma in Mice.

    Science.gov (United States)

    Hu, Zixi; Chen, Jiaojiao; Zhou, Sufang; Yang, Nuo; Duan, Siliang; Zhang, Zhenghua; Su, Jing; He, Jian; Zhang, Zhiyong; Lu, Xiaoling; Zhao, Yongxiang

    2017-01-01

    Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells. The combination of FA-chitosan/mIP-10 and DC/tumor cell fusion vaccine against hepatocellular carcinoma (HCC) effectively inhibited the growth of implanted HCC tumors and prolonged the survival of mice. The combination therapy significantly reduced myeloid-derived suppressor cells (MDSC) in mouse spleen, local tumor, and bone marrow while increasing tumor-specific IFN-γ responses. Furthermore, the combination therapy significantly inhibited tumor cell proliferation while promoting their apoptosis. Taken together, our data illustrate that the mIP-10 enhances the anti-tumor effect of DC/tumor cell fusion vaccine by alleviating the immunosuppressive tumor environment.

  20. Impact of Tumor Factors on Survival in Patients with Hepatocellular Carcinoma Classified Based on Kinki Criteria Stage B2.

    Science.gov (United States)

    Arizumi, Tadaaki; Minami, Tomohiro; Chishina, Hirokazu; Kono, Masashi; Takita, Masahiro; Yada, Norihisa; Hagiwara, Satoru; Minami, Yasunori; Ida, Hiroshi; Ueshima, Kazuomi; Kamata, Ken; Minaga, Kosuke; Komeda, Yoriaki; Takenaka, Mamoru; Sakurai, Toshiharu; Watanabe, Tomohiro; Nishida, Naoshi; Kudo, Masatoshi

    2017-01-01

    Tumors classified based on the Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) are heterogeneous in nature. Previously, the Kinki criterion was proposed for a more precise subclassification of tumors in BCLC-stage B. However, tumors in sub-stage B2 include various size and number of HCCs even with the Kinki criteria, which could lead to heterogeneity for overall survival (OS). In this study, we assessed how the size and number of tumors affect the OS and time to progression (TTP) in patients with Kinki criteria stage B2 tumors and treated with transarterial chemoembolization (TACE). Of 906 HCC patients treated with TACE at Kindai University Hospital, 236 patients with HCC considered as Kinki criteria stage B2 were examined. They were classified into the following 4 groups according to the maximum tumor diameter and number of tumors: B2a group, tumor size ≤6 cm and total number of tumors ≤6; B2b group, size ≤6 cm and number >6; B2c group, size >6 cm and number ≤6; and B2d group, size >6 cm and number >6. The OS and TTP of patients in each group were compared. There were 131 patients (55.5%) in the B2a group, 58 (24.6%) in the B2b group, 41 (17.4%) in the B2c group, and 6 (0.03%) in the B2d group. Comparison of the survivals revealed that the median OS was 2.8 years (95% CI 2.0-3.5) in the B2a group, 2.8 years (95% CI 2.0-3.3) in the B2b group, 1.9 years (95% CI 0.8-4.0) in the B2c group, and 2.3 years (95% CI 1.2-ND [no data]) in the B2d group, respectively (p = 0.896). The median TTP in B2a, B2b, B2c, and B2d sub-substage HCC were13.2, 12.1, 13.8, and 11.5 months, respectively (p = 0.047). The median TTP in B2a + B2c sub-substage patients was longer than that in B2b + B2d sub-substage HCC patients (14.0 months and 10.4 months; p = 0.002). No significant differences were observed in the OS among HCC patients subclassified based on the maximum tumor diameter and tumor number in Kinki criteria stage B2. Consequently, Kinki criteria

  1. 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

  2. MicroRNA-144-3p suppresses tumor growth and angiogenesis by targeting SGK3 in hepatocellular carcinoma.

    Science.gov (United States)

    Wu, Manya; Huang, Chaoyuan; Huang, Xinping; Liang, Rong; Feng, Yan; Luo, Xiaoling

    2017-10-01

    In our previous studies, the Illumine Soledad massively parallel signature sequencing of miRNomes in non‑tumor and hepatocellular carcinoma (HCC) tissues revealed that microRNA (miR)-144-3p was significantly downregulated in HCC, but its role in HCC development, especially angiogenesis, remains unclear. In this investigation, we found recovering miR‑144‑3p expression can significantly suppress the growth, migration and induced angiogenic capacity of HCC cells through both in vivo and in vitro experiments. Moreover, clinical correlation analysis showed that low expression of miR‑144‑3p was positively correlated to poor disease-free survival (DFS) of HCC patients. Mechanistically, serum and glucocorticoid kinase 3 (SGK3), the putative targets of miR‑144‑3p, was predicted by Target Scan database and identified to be suppressed by miR‑144‑3p so that inhibiting the activation of mTOR-VEGF downstream signals was activated by the phosphoinositide 3-kinase (PI3K)-independent pathway. Hence, we concluded that miR‑144‑3p, which is frequently downregulated in HCC, can inhibit proliferation, migration and repress angiogenesis by regulating SGK3 activation with PI3K independent signal pathway, and acts as a prognostic factor for HCC patients.

  3. Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway.

    Science.gov (United States)

    Zou, Xuejing; Liang, Jiyun; Sun, Jingyuan; Hu, Xiaoyun; Lei, Ling; Wu, Dehua; Liu, Li

    2016-08-01

    Drug resistance and hepatic dysfunction are the two major factors that limit the application of chemotherapy for hepatocellular carcinoma (HCC). It has been reported that allicin has the hepatic protective effect and antitumor activity. Hence allicin may be an ideal enhancer to chemotherapy regimen of HCC. In the present study, we demonstrated that allicin enhanced 5-fluorouracil (5-FU) inducing cytotoxicity in HCC cells. In vivo experiment, combined treatment group with allicin (5 mg/kg/d; every two days for 3 weeks) and 5-FU (20 mg/kg/d; 5 consecutive days) showed a dramatic inhibitory effect on the growth of HCC xenograft tumors in nude mice. The co-treatment group showed highly apoptotic level compared with 5-FU treated alone. Cells combined treatment with allicin and 5-FU increased intracellular reactive oxygen species (ROS) level, reduced mitochondrial membrane potential (ΔΨm), activated caspase-3 and PARP, and down-regulated Bcl-2 compared with DMSO, allicin and 5-FU treated alone. Moreover, the increase of activated caspase-3 and PARP was blocked by the ROS inhibitor antioxidant N-acetyl cysteine (NAC). In conclusion, this is the first study to demonstrate that allicin sensitized HCC cells to 5-FU induced apoptosis through ROS-mediated mitochondrial pathway. These results provided evidences for the combination used of allicin and 5-FU as a novel chemotherapy regimen in HCC. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  4. Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway

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    Xuejing Zou

    2016-08-01

    Full Text Available Drug resistance and hepatic dysfunction are the two major factors that limit the application of chemotherapy for hepatocellular carcinoma (HCC. It has been reported that allicin has the hepatic protective effect and antitumor activity. Hence allicin may be an ideal enhancer to chemotherapy regimen of HCC. In the present study, we demonstrated that allicin enhanced 5-fluorouracil (5-FU inducing cytotoxicity in HCC cells. In vivo experiment, combined treatment group with allicin (5 mg/kg/d; every two days for 3 weeks and 5-FU (20 mg/kg/d; 5 consecutive days showed a dramatic inhibitory effect on the growth of HCC xenograft tumors in nude mice. The co-treatment group showed highly apoptotic level compared with 5-FU treated alone. Cells combined treatment with allicin and 5-FU increased intracellular reactive oxygen species (ROS level, reduced mitochondrial membrane potential (ΔΨm, activated caspase-3 and PARP, and down-regulated Bcl-2 compared with DMSO, allicin and 5-FU treated alone. Moreover, the increase of activated caspase-3 and PARP was blocked by the ROS inhibitor antioxidant N-acetyl cysteine (NAC. In conclusion, this is the first study to demonstrate that allicin sensitized HCC cells to 5-FU induced apoptosis through ROS-mediated mitochondrial pathway. These results provided evidences for the combination used of allicin and 5-FU as a novel chemotherapy regimen in HCC.

  5. Association of decreased expression of the macrophage scavenger receptor MARCO with tumor progression and poor prognosis in human hepatocellular carcinoma.

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    Sun, Haoyu; Song, Jiaxi; Weng, Chenchun; Xu, Jing; Huang, Mei; Huang, Qiang; Sun, Rui; Xiao, Weihua; Sun, Cheng

    2017-05-01

    The macrophage receptor with collagenous structure (MARCO) belongs to the scavenger receptor family; however, few studies have assessed their potentials in modulating inflammatory signaling other than the typical function of pattern recognition and phagocytic clearance. Interestingly, RNA-Seq analyses of hepatocellular carcinoma (HCC) have identified MARCO as one of the top 30 differentially expressed genes between cancerous and adjacent noncancerous tissues. However, no research has been performed to study MARCO in liver cancer. MARCO protein expression was evaluated by immunostaining liver tissue specimens collected from 88 HCC patients, 10 liver cirrhosis patients, 6 metastatic patients, and 5 healthy controls. All sections were reviewed by blinded observers followed by the interpretation of integral optical density per area as a measure of protein intensity. We observed significantly decreased expression of MARCO in intratumoral tissues of HCC compared with expression in peritumoral tissues. The expression of MARCO declined progressively as the disease condition was aggravated, with the highest expression found in healthy controls and the lowest found in patients with HCC metastasis. Furthermore, MARCO expression decreased along with tumor progression. MARCO + cells co-localized with CD68 + cells, indicating predominant expression on macrophages. The overall survival rate was significantly increased in patients with high intratumoral MARCO expression compared with that of patients with low intratumoral MARCO expression. Our study is the first to demonstrate an association between MARCO expression and the progression and prognosis of HCC. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

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

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    Maruyama, Hitoshi, E-mail: maru-cib@umin.ac.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine 1-8-1, Inohana, Chuou-ku, Chiba 260-8670 (Japan); Takahashi, Masanori, E-mail: machat@aa.pial.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine 1-8-1, Inohana, Chuou-ku, Chiba 260-8670 (Japan); Ishibashi, Hiroyuki, E-mail: bashiish@yahoo.co.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine 1-8-1, Inohana, Chuou-ku, Chiba 260-8670 (Japan); Okabe, Shinichiro, E-mail: okabeshin1966@yahoo.co.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine 1-8-1, Inohana, Chuou-ku, Chiba 260-8670 (Japan); Yoshikawa, Masaharu, E-mail: yoshikawa@faculty.chiba-u.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine 1-8-1, Inohana, Chuou-ku, Chiba 260-8670 (Japan); Yokosuka, Osamu, E-mail: yokosukao@faculty.chiba-u.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine 1-8-1, Inohana, Chuou-ku, Chiba 260-8670 (Japan)

    2010-07-15

    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{sup 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.

  7. COH-203, a novel microtubule inhibitor, exhibits potent anti-tumor activity via p53-dependent senescence in hepatocellular carcinoma

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    Qi, Huan; Zuo, Dai-Ying; Bai, Zhao-Shi; Xu, Jing-Wen; Li, Zeng-Qiang [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang (China); Shen, Qi-Rong; Wang, Zhi-Wei [Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang (China); Zhang, Wei-Ge, E-mail: zhangweige2000@sina.com [Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang (China); Wu, Ying-Liang, E-mail: yingliang_1016@163.com [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang (China)

    2014-12-12

    Highlights: • COH-203 exhibits anti-hepatoma effects in vitro and in vivo with low toxicity. • COH-203 inhibits tubulin polymerization. • COH-203 induces mitotic arrest followed by mitotic slippage in BEL-7402 cells. • COH-203 induces p53-dependent senescence in BEL-7402 cells. - Abstract: 5-(3-Hydroxy-4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-3H-1, 2-dithiol-3-one (COH-203) is a novel synthesized analogue of combretastatin A-4 that can be classified as a microtubule inhibitor. In this study, we evaluated the anti-hepatoma effect of COH-203 in vitro and in vivo and explored the underlying molecular mechanisms. COH-203 was shown to be more effective in inhibiting the proliferation of liver cancer cells compared with normal liver cells. COH-203 also displayed potent anti-tumor activity in a hepatocellular carcinoma xenograft model without significant toxicity. Mechanistic studies demonstrated that treatment with COH-203 induced mitotic arrest by inhibiting tubulin polymerization in BEL-7402 liver cancer cells. Long-term COH-203 treatment in BEL-7402 cells led to mitotic slippage followed by senescence via the p14{sup Arf}–p53–p21 and p16{sup INK4α}–Rb pathways. Furthermore, suppression of p53 via pifithrin-α (p53 inhibitor) and p53-siRNA attenuated COH-203-induced senescence in BEL-7402 cells, suggesting that COH-203 induced senescence p53-dependently. In conclusion, we report for the first time that COH-203, one compound in the combretastatin family, promotes anti-proliferative activity through the induction of p-53 dependent senescence. Our findings will provide a molecular rationale for the development of COH-203 as a promising anti-tumor agent.

  8. Oxidative stress is closely associated with tumor angiogenesis of hepatocellular carcinoma.

    Science.gov (United States)

    Jo, Masayasu; Nishikawa, Taichiro; Nakajima, Tomoki; Okada, Yoshihisa; Yamaguchi, Kanji; Mitsuyoshi, Hironori; Yasui, Kohichiroh; Minami, Masahito; Iwai, Masaki; Kagawa, Keizo; Itoh, Yoshito; Yoshikawa, Toshikazu

    2011-06-01

    Oxidative stress (OS) plays an important role in the progression of chronic liver disease and hepatocarcinogenesis. However, the role of OS in the progression of hepatocellular carcinoma (HCC) is unclear. The aim of this study was to assess whether OS promotes angiogenesis in HCC. The expressions of vascular endothelial growth factor (VEGF), VEGF receptor2 (VEGFR2), and phosphorylated Akt were assessed, and microvessel density (MVD) and the cancer-associated fibroblast (CAF) population were examined by immunohistological staining in 55 HCC samples. The OS level in these tissues was assessed using 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (4-HNE) immunostaining, and an 8-OHdG enzyme-linked immunosorbent assay (ELISA). The expression and activation of angiogenic factors and the effect of growth stimulation of human umbilical vein endothelial cells (HUVECs) were also assessed in vitro, using HLE hepatoma-derived cells and conditioned medium with or without treatment with hydrogen peroxide (H₂O₂); a phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin; and an anti-oxidative agent, N-acetyl-L-cysteine (NAC). A higher OS grade was significantly associated with higher MVD, VEGF expression, Akt activity, and OS grade of CAFs, but not with the percentage of the CAF population in HCC tissues. Additionally, cancer cells constituted a major population of OS marker-positive cells in HCC tissues. In vitro, H₂O₂ treatment induced up-regulation of VEGF at both the mRNA and protein levels, activated Akt, and resulted in the proliferation of HUVECs; the addition of wortmannin and NAC counteracted the effects of OS. OS enhances the malignant potential of HCC through the stimulation of angiogenesis by activation of the Akt-VEGF pathway.

  9. Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria.

    Science.gov (United States)

    Yao, Francis Y; Mehta, Neil; Flemming, Jennifer; Dodge, Jennifer; Hameed, Bilal; Fix, Oren; Hirose, Ryutaro; Fidelman, Nicholas; Kerlan, Robert K; Roberts, John P

    2015-06-01

    We report on the long-term intention-to-treat (ITT) outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing downstaging to within Milan/United Network for Organ Sharing T2 criteria before liver transplantation (LT) since 2002 and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The downstaging subgroups include 1 lesion >5 and ≤8 cm (n = 43), 2 or 3 lesions at least one >3 and ≤5 cm with total tumor diameter ≤8 cm (n = 61), or 4-5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n = 14). In the downstaging group, 64 patients (54.2%) had received LT and 5 (7.5%) developed HCC recurrence. Two of the five patients with HCC recurrence had 4-5 tumors at presentation. The 1- and 2-year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the downstaging group versus 20.3% and 25.6% in the T2 group (P = 0.04). Kaplan-Meier's 5-year post-transplant survival and recurrence-free probabilities were 77.8% and 90.8%, respectively, in the downstaging group versus 81% and 88%, respectively, in the T2 group (P = 0.69 and P = 0.66, respectively). The 5-year ITT survival was 56.1% in the downstaging group versus 63.3% in the T2 group (P = 0.29). Factors predicting dropout in the downstaging group included pretreatment alpha-fetoprotein ≥1,000 ng/mL (multivariate hazard ratio [HR]: 2.42; P = 0.02) and Child's B versus Child's A cirrhosis (multivariate HR: 2.19; P = 0.04). Successful downstaging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post-transplant survival, comparable to those meeting T2 criteria without downstaging. Owing to the small number of patients with 4-5 tumors, further investigations are needed to confirm the efficacy of downstaging in this subgroup. © 2015 by the American Association for the Study of Liver Diseases.

  10. 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

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    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

  11. HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Aref AM

    2014-06-01

    Full Text Available Ahmed M Aref,1–3 Neil T Hoa,3 Lisheng Ge,3 Anshu Agrawal,4 Maria Dacosta-Iyer,5,6 Nils Lambrecht,5,6 Yi Ouyang,5,6 Andrew N Cornforth,7 Martin R Jadus5,6,8 1Biological Science Department, Modern Sciences and Arts University, Faculty of Dentistry, Cairo, Egypt; 2Southern California Institute for Research and Education, Veterans Affairs Medical Center, Long Beach, CA, USA; 3Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA, USA; 4Department of Medicine, Division of Basic and Clinical Immunology, University of California, Irvine, CA, USA; 5Pathology and Laboratory Medicine Department, Veterans Affairs Medical Center Long Beach, CA, USA; 6Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA; 7California Stem Cells, Inc., CA, USA; 8Neuro-Oncology Program, Chao Comprehensive Cancer Center, University of California, Irvine, CA, USA Background: Immunotherapy for human hepatocellular cancer (HCC is slowly making progress towards treating these fatal cancers. The identification of new antigens can improve this approach. We describe a possible new antigen, hepatocellular carcinoma-associated antigen-519/targeting protein for Xklp-2 (HCA519/TPX2, for HCC that might be beneficial for T-cell specific HCC immunotherapy. Methods: HCC was studied for the expression for 15 tumor-associated antigens considered useful for immunotherapy within three HCC cell lines (HepG2, Hep3B, and PLC/PRF/5, lymphocytes, non-cancerous livers, and clinical HCC. The expression of tumor antigenic precursor proteins (TAPPs messenger RNA was first screened by reverse transcriptase quantitative real-time polymerase chain reaction. Results: Four antigens (alpha fetoprotein, aspartyl/asparaginyl β-hydroxylase, glypican-3 and HCA519/TPX2 proved to be the best expressed TAPPs within the HCC specimens by molecular analyses. HCA519/TPX2 was detected by intracellular cell flow cytometry within HCC cell lines by using a specific

  12. Diagnostic Value of Preoperative Needle Biopsy for Tumor Grading Assessment in Hepatocellular Carcinoma.

    Science.gov (United States)

    Wang, Lijun; Wang, Jianguo; Zhang, Xuanyu; Li, Jie; Wei, Xuyong; Cheng, Jun; Ling, Qi; Xie, Haiyang; Zhou, Lin; Xu, Xiao; Zheng, Shusen

    2015-01-01

    Needle core biopsy (NCB) is one of the most widely used and accepted methods for the diagnosis of focal hepatic lesions. Although many studies have assessed the diagnostic accuracy of NCB in predicting the tumor grade, it is still under debate. To identify the influence of number of biopsies on NCB diagnostic accuracy. 153 patients with HCC were selected from patients who received preoperative NCB under the guidance of ultrasonography in our hospital. The diagnostic reference standard was the surgical pathologic diagnosis. Using a 3-tier grading scheme (well, moderate and poor), the accuracy of NCB has no significant differences among different number of passes in HCC ≤5 cm. For HCC >5≤8 cm, the increasing number of passes could increase the diagnostic accuracy (63.3%, 81.8%, and 84.8% for passes one, two, and three, respectively). While in HCC>8 cm, the diagnostic accuracy of passes one, two, and three were 62.1%, 69%, and 75.8%, respectively. The accuracy of NCB in assessing tumor grading associated with tumor size and number of passes. Meanwhile, a minimum of two passes should be performed to get better accuracy in patients with HCC >5 cm.

  13. Diagnostic Value of Preoperative Needle Biopsy for Tumor Grading Assessment in Hepatocellular Carcinoma.

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    Lijun Wang

    Full Text Available Needle core biopsy (NCB is one of the most widely used and accepted methods for the diagnosis of focal hepatic lesions. Although many studies have assessed the diagnostic accuracy of NCB in predicting the tumor grade, it is still under debate.To identify the influence of number of biopsies on NCB diagnostic accuracy.153 patients with HCC were selected from patients who received preoperative NCB under the guidance of ultrasonography in our hospital. The diagnostic reference standard was the surgical pathologic diagnosis.Using a 3-tier grading scheme (well, moderate and poor, the accuracy of NCB has no significant differences among different number of passes in HCC ≤5 cm. For HCC >5≤8 cm, the increasing number of passes could increase the diagnostic accuracy (63.3%, 81.8%, and 84.8% for passes one, two, and three, respectively. While in HCC>8 cm, the diagnostic accuracy of passes one, two, and three were 62.1%, 69%, and 75.8%, respectively.The accuracy of NCB in assessing tumor grading associated with tumor size and number of passes. Meanwhile, a minimum of two passes should be performed to get better accuracy in patients with HCC >5 cm.

  14. Differential expression of Axl in hepatocellular carcinoma and correlation with tumor lymphatic metastasis.

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    He, Ling; Zhang, Jianing; Jiang, Lili; Jin, Changgong; Zhao, Yongfu; Yang, Guang; Jia, Li

    2010-10-01

    Protein kinases play important roles in tumor development and progression. A variety of members of the signal transduction enzymes serve as targets for therapeutic intervention in cancer. The dysregulation of Axl receptor and its ligand growth arrest-specific 6 (Gas6) is implicated in the pathogenesis of several cancers. In this study, the differential expressions of Axl were investigated in mouse hepatocarcinoma cell lines Hca-F and Hca-P, which have high- and low-metastatic potential to lymph nodes. Experimental inhibition of Axl by siRNA assessed further the metastatic potential of Axl. The results showed that down-regulation of Axl expression attenuated Hca-F cells proliferation, migration, and invasion in vitro, as well as inhibited metastasis to peripheral lymph nodes in vivo. Further analysis demonstrated that the addition of exogenous Gas6 mediated the migration and invasion of Hca-F cells both in vitro and in vivo through Axl. Furthermore, Gas6 stimulation of Axl in Hca-F cells resulted primarily in the down-regulation of Cyr61, a member of the CCN protein family involved in tumor progression. These data suggest that Axl acts as a tumor lymphatic metastasis-associated gene, and may function partly through the regulation of Cyr61. © 2010 Wiley-Liss, Inc.

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

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    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.

  16. Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for Hepatocellular Carcinoma Recurrence After Liver Transplant.

    Science.gov (United States)

    Mehta, Neil; Heimbach, Julie; Harnois, Denise M; Sapisochin, Gonzalo; Dodge, Jennifer L; Lee, David; Burns, Justin M; Sanchez, William; Greig, Paul D; Grant, David R; Roberts, John P; Yao, Francis Y

    2017-04-01

    Several factors are associated with increased hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT), but no reliable risk score has been established to determine the individual risk for HCC recurrence. We aimed to develop and validate a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score for patients with HCC meeting Milan criteria by imaging. Predictors of recurrence were tested in a development cohort of 721 patients who underwent LT between 2002 and 2012 at 3 academic transplant centers (University of California-San Francisco; Mayo Clinic, Rochester; and Mayo Clinic, Jacksonville) to create the RETREAT score. This was subsequently validated in a cohort of 341 patients also meeting Milan criteria by imaging who underwent LT at the University of Toronto transplant center using the C concordance statistic and net reclassification index. Characteristics associated with post-LT HCC recurrence. A total of 1061 patients participated in the study; 77.8% (825) were men, and the median (IQR) age was 58.2 (53.3-63.9) years in the development cohort and 56.4 (51.7-61.0) years in the validation cohort (P development cohort of 721 patients (542 men), median α-fetoprotein (AFP) level at the time of LT was 8.3 ng/mL; 9.4% had microvascular invasion (n = 68), and 22.1% were beyond Milan criteria on explant (n = 159) owing to understaging by pretransplantation imaging. Cumulative probabilities of HCC recurrence at 1 and 5 years were 5.7% and 12.8%, respectively. On multivariable Cox proportional hazards regression, 3 variables were independently associated with HCC recurrence: microvascular invasion, AFP at time of LT, and the sum of the largest viable tumor diameter and number of viable tumors on explant. The RETREAT score was created using these 3 variables, with scores ranging from 0 to 5 or higher that were highly predictive of HCC recurrence (C statistic, 0.77). RETREAT was able to stratify 5-year post-LT recurrence risk

  17. Changes of Oxidative Stress, Glutathione, and Its Dependent Antioxidant Enzyme Activities in Patients with Hepatocellular Carcinoma before and after Tumor Resection.

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    Shao-Bin Cheng

    Full Text Available The changes in and relationship between oxidative stress and the glutathione (GSH antioxidant system in the plasma and tissues of patients with hepatocellular carcinoma (HCC before and after tumor resection have not been clearly determined. We investigated the changes in oxidative stress, GSH status and its dependent antioxidant enzyme activities in HCC patients before and after tumor resection, and to determine the association of oxidative stress with GSH and its dependent antioxidant enzyme activities in plasma and tissues. This study employed a cross-sectional design. Forty-four men and 16 women with HCC were recruited. Fasting blood was drawn on the day before the tumor resection and one month after the tumor resection. HCC tissue and adjacent normal liver tissue were obtained at the time of surgical resection. Patients had significantly increased plasma malondialdehyde (MDA and oxidized-low density lipoprotein levels but decreased GSH and oxidized GSH levels before tumor resection compared with the corresponding post-resection values. GSH and trolox equivalent antioxidant capacity (TEAC levels and activities of GSH peroxidase were significantly increased while MDA level was significantly lower in HCC tissue when compared with the adjacent normal tissue. The pre-resection plasma MDA level was significantly correlated with pre-resection plasma GSH concentration, and MDA level in HCC and adjacent normal tissues. Pre-resection plasma GSH concentration was significantly correlated with GSH and TEAC level in HCC tissue. HCC patients had increased oxidative stress, decreased GSH, and lower dependent antioxidant capacities before tumor resection. However, hepatocellular tumor had increased GSH and TEAC levels as well as GSH peroxidase activities which might protect itself against increased oxidative stress.

  18. Changes of Oxidative Stress, Glutathione, and Its Dependent Antioxidant Enzyme Activities in Patients with Hepatocellular Carcinoma before and after Tumor Resection.

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    Cheng, Shao-Bin; Liu, Hsiao-Tien; Chen, Sin-Yuan; Lin, Ping-Ting; Lai, Chia-Yu; Huang, Yi-Chia

    2017-01-01

    The changes in and relationship between oxidative stress and the glutathione (GSH) antioxidant system in the plasma and tissues of patients with hepatocellular carcinoma (HCC) before and after tumor resection have not been clearly determined. We investigated the changes in oxidative stress, GSH status and its dependent antioxidant enzyme activities in HCC patients before and after tumor resection, and to determine the association of oxidative stress with GSH and its dependent antioxidant enzyme activities in plasma and tissues. This study employed a cross-sectional design. Forty-four men and 16 women with HCC were recruited. Fasting blood was drawn on the day before the tumor resection and one month after the tumor resection. HCC tissue and adjacent normal liver tissue were obtained at the time of surgical resection. Patients had significantly increased plasma malondialdehyde (MDA) and oxidized-low density lipoprotein levels but decreased GSH and oxidized GSH levels before tumor resection compared with the corresponding post-resection values. GSH and trolox equivalent antioxidant capacity (TEAC) levels and activities of GSH peroxidase were significantly increased while MDA level was significantly lower in HCC tissue when compared with the adjacent normal tissue. The pre-resection plasma MDA level was significantly correlated with pre-resection plasma GSH concentration, and MDA level in HCC and adjacent normal tissues. Pre-resection plasma GSH concentration was significantly correlated with GSH and TEAC level in HCC tissue. HCC patients had increased oxidative stress, decreased GSH, and lower dependent antioxidant capacities before tumor resection. However, hepatocellular tumor had increased GSH and TEAC levels as well as GSH peroxidase activities which might protect itself against increased oxidative stress.

  19. Effect of recombinant human endostatin combined with hepatic artery interventional therapy on progression-free survival of patients with advanced hepatocellular carcinoma

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    HAO Mingzhi

    2016-01-01

    Full Text Available ObjectiveTo investigate the effect of recombinant human endostatin (Endostar combined with hepatic artery interventional therapy on the progression-free survival (PFS of patients with advanced hepatocellular carcinoma (HCC. MethodsA total of 86 patients with advanced HCC who were admitted to Fujian Provincial Tumor Hospital from March 2011 to May 2015 were selected and divided into treatment group and control group according to a matched pair design. The treatment group (43 patients was given Endostar combined with hepatic artery interventional therapy, and the control group (43 patients was given hepatic artery interventional therapy combined with oral administration of Ganfule. The chi-square test was applied for comparison of categorical data between the two groups, and the t-test was applied for comparison of continuous data between the two groups. The Kaplan-Meier method was applied for survival analysis, the Log-rank test was applied for univariate analysis, and Cox proportional hazards model was applied for multivariate analysis. ResultsThe median PFS in the treatment group and the control group was 154 d [95% confidence interval (CI: 94-214 d] and 70 d (95%CI: 39-101 d, respectively, with a significant difference between the two groups (χ2=10.741, P=0001. Univariate analysis showed that the severity of liver cirrhosis, number of tumors, and main portal vein tumor thrombus/inferior vena cava tumor thrombus were the prognostic factors for patients with advanced HCC (χ2=8.182, 9.150, and 6.565, P=0.004, 0.027, and 0.038; multivariate analysis showed that the severity of liver cirrhosis and main portal vein tumor thrombus/inferior vena cava tumor thrombus were the independent prognostic factors for PFS in patients with advanced HCC who were treated with Endostar combined with hepatic artery interventional therapy (P=0.028 and 0.013. ConclusionEndostar can effectively prolong the PFS of patients with advanced HCC after hepatic artery

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

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    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.

  1. Antimicrobial peptaibols, novel suppressors of tumor cells, targeted calcium-mediated apoptosis and autophagy in human hepatocellular carcinoma cells

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    Chen Xiu-Lan

    2010-02-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is one of the most common cancers in the world which is highly chemoresistant to currently available chemotherapeutic agents. Thus, novel therapeutic targets are needed to be sought for the successful treatment of HCC. Peptaibols, a family of peptides synthesized non-ribosomally by the Trichoderma species and other fungi, exhibit antibiotic activities against bacteria and fungi. Few studies recently showed that peptaibols exerted cytotoxicity toward human lung epithelial and breast carcinoma cells. However, the mechanism involved in peptaibol-induced cell death remains poorly understood. Results Here, we showed that Trichokonin VI (TK VI, a peptaibol from Trichoderma pseudokoningii SMF2, induced growth inhibition of HCC cells in a dose-dependent manner. It did not obviously impair the viability of normal liver cells at lower concentration. Moreover, the suppression of cell viability resulted from the programmed cell death (PCD with characteristics of apoptosis and autophagy. An influx of Ca2+ triggered the activation of μ-calpain and proceeded to the translocation of Bax to mitochondria and subsequent promotion of apoptosis. On the other hand, typically morphological characteristics consistent with autophagy were also observed by punctate distribution of MDC staining and the induction of LC3-II, including extensive autophagic vacuolization and enclosure of cell organelles by these autophagosomes. More significantly, specific depletion of Bak expression by small RNA interfering (siRNA could partly attenuate TK VI-induced autophagy. However, siRNA against Bax led to increased autophagy. Conclusion Taken together, these findings showed for the first time that peptaibols were novel regulators involved in both apoptosis and autophagy, suggesting that the class of peptaibols might serve as potential suppressors of tumor cells.

  2. Inhibition of CIP2A attenuates tumor progression by inducing cell cycle arrest and promoting cellular senescence in hepatocellular carcinoma.

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    Yang, Xue; Qu, Kai; Tao, Jie; Yin, Guozhi; Han, Shaoshan; Liu, Qingguang; Sun, Hao

    2018-01-08

    CIP2A is a recent identified oncogene that inhibits protein phosphatase 2A (PP2A) and stabilizes c-Myc in cancer cells. To investigate the potential oncogenic role and prognostic value of CIP2A, we comprehensively analyzed the CIP2A expression levels in pan-cancer and observed high expression level of CIP2A in majority cancer types, including hepatocellular carcinoma (HCC). Based on a validation cohort including 60 HCC and 20 non-tumorous tissue samples, we further confirmed the high mRNA and protein expression levels of CIP2A in HCC, and found high CIP2A mRNA expression level was associated with unfavorable overall and recurrence-free survival in patients with HCC. Mechanistic investigations revealed that inhibition of CIP2A significantly attenuated cellular proliferation in vitro and tumourigenicity in vivo. Bioinformatic analysis suggested that CIP2A might be involved in regulating cell cycle. Our experimental data further confirmed CIP2A knockdown induced cell cycle arrest at G1 phase. We found accumulated cellular senescence in HCC cells with CIP2A knockdown, companying expression changes of senescence associated proteins (p21, CDK2, CDK4, cyclin D1, MCM7 and FoxM1). Mechanistically, CIP2A knockdown repressed FoxM1 expression and induced FoxM1 dephosphorylation. Moreover, inhibition of PP2A by phosphatase inhibitor rescued the repression of FoxM1. Taken together, our results showed that CIP2A was highly expressed in HCC. Inhibition of CIP2A induced cell cycle arrest and promoted cellular senescence via repressing FoxM1 transcriptional activity, suggesting a potential anti-cancer target for patients with HCC. Copyright © 2017. Published by Elsevier Inc.

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

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    Li, Wei; Shen, Shiqiang; 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 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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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    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

  5. Analysis of association between HSP70 expression in tumor tissues and clinicopathological characteristics of HBV-related hepatocellular carcinoma

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    GAO Jialin

    2015-05-01

    Full Text Available ObjectiveTo investigate the relationship between heat shock protein 70 (HSP70 expression and clinicopathological characteristics of hepatitis virus B (HBV-induced hepatocellular carcinoma (HCC. MethodsStatistical analysis was conducted to explore the association between the data of HSP70 obtained from the gene expression omnibus (GEO and the clinicopathological characteristics of HCC. As for categorical data, frequency (proportion was used to describe and chi-square test or Fisher′s exact test was applied to analyze. Univariate and multivariate logistic regression analyses were used to investigate the relationship between HSP expression and the clinicopathological characteristics of HCC. The variables with a P value less than 0.10 were included for subsequent multivariate analysis. Results1 The percentage of the HCC patients whose primary tumor sizes were more than 5 cm was significantly higher in the group with high expression of HSPA4L, HSPA6, and HSPA13 than in the group with low expression (P<0.05; in comparison with the group with high expression of HSPA1A and HSPA6, the group with low expression had a significantly lower percentage of patients accompanied by liver cirrhosis (P<0.05; there was a significantly higher percentage of patients with alpha-fetoprotein (AFP levels more than 300 ng/ml in the group with high expression of HSPA5 and HSA13 compared with the group with low expression (P<0.01. 2 The survival rates of HCC patients with liver cirrhosis and/or primary tumor that was more than 5 cm significantly decreased (P<0.05. 3 Highly expressed HSPA4L might promote the growth of HCC (OR=1.019, 95% CI:1.006-10.032, P=0.003; the patients with high expression of HSPA1B might have a higher risk of developing multiple nodules (OR=1.002, 95%CI:1.000-1.004, P=0.003. ConclusionThe expression of HSPA4L and HSPA1B is, to some extent, associated with the clinicopathological characteristics of HCC, which might be a therapeutic target and

  6. Lidocaine Induces Apoptosis and Suppresses Tumor Growth in Human Hepatocellular Carcinoma Cells In Vitro and in a Xenograft Model In Vivo.

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    Xing, Wei; Chen, Dong-Tai; Pan, Jia-Hao; Chen, Yong-Hua; Yan, Yan; Li, Qiang; Xue, Rui-Feng; Yuan, Yun-Fei; Zeng, Wei-An

    2017-05-01

    Recent epidemiologic studies have focused on the potential beneficial effects of regional anesthetics, and the differences in cancer prognosis may be the result of anesthetics on cancer biologic behavior. However, the function and underlying mechanisms of lidocaine in hepatocellular carcinoma both in vitro and in vivo have been poorly studied. Human HepG2 cells were treated with lidocaine. Cell viability, colony formation, cell cycle, and apoptosis were assessed. The effects of lidocaine on apoptosis-related and mitogen-activated protein kinase protein expression were evaluated by Western blot analysis. The antitumor activity of lidocaine in hepatocellular carcinoma with or without cisplatin was investigated with in vitro experiments and also with animal experiments. Lidocaine inhibited the growth of HepG2 cells in a dose- and time-dependent manner. The authors also found that lidocaine arrested cells in the G0/G1 phase of the cell cycle (63.7 ± 1.7% vs. 72.4 ± 3.2%; P = 0.0143) and induced apoptosis (1.7 ± 0.3% vs. 5.0 ± 0.7%; P = 0.0009). Lidocaine may exert these functions by causing an increase in Bax protein and activated caspase-3 and a corresponding decrease in Bcl-2 protein through the extracellular signal-regulated kinase 1/2 and p38 pathways. More importantly, for the first time, xenograft experiments (n = 8 per group) indicated that lidocaine suppressed tumor development (P lidocaine vs. control) and enhanced the sensitivity of cisplatin (P = 0.0008; lidocaine plus cisplatin vs. cisplatin). The authors' findings suggest that lidocaine may exert potent antitumor activity in hepatocellular carcinoma. Furthermore, combining lidocaine with cisplatin may be a novel treatment option for hepatocellular carcinoma.

  7. Effect of 125I radioactive particle implantation combined with TACE treatment on serum markers apoptotic molecules in tumor tissue of patients with primary hepatocellular carcinoma

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    Jian-Feng Zou

    2016-06-01

    Full Text Available Objective: To analyze the effect of 125I radioactive particle implantation combined with TACE treatment on serum markers apoptotic molecules in tumor tissue of patients with pri mary hepatocellular carcinoma. Methods: Patients with primary hepatocellular carcinoma treated in our hospital from July 2012 to January 2015 were included for study and randomly divided into observation group and control group. Control group received TACE treatment alone, observation group received 125I radioactive particle implantation combined with TACE treatment, and then differences in serum marker levels and protein expression of apoptosisrelated genes in tumor tissue were compared between two groups. Results: Serum AFP, AFPL3 and GP73 values of observation group after treatment were lower than those of control group (P<0.05; serum GPC3, TGF-β1, DCP and AFU values of observation group after treatment were lower than corresponding indicator values of control group (P<0.05; protein expression levels of c-Met, telomerase and FasL of observation group after treatment were lower than those of control group, and protein expression levels of Fas and Caspase-3 were higher than those of control group (P<0.05; protein expression levels of p53 and Bax in liver cancer tissue of observation group after treatment were higher than those of control group, and protein expression levels of livin and Bcl-2 were lower than those of control group (P<0.05. Conclusions: 125I radioactive particle implantation combined with TACE treatment for patients with primary hepatocellular carcinoma can effectively inhibit liver cancer cell activity and promote liver cancer cell apoptosis.

  8. Update on Embolization Therapies for Hepatocellular Carcinoma.

    Science.gov (United States)

    Kishore, Sirish; Friedman, Tamir; Madoff, David C

    2017-06-01

    The purpose of the review is to summarize the latest applications for embolotherapy in the management of patients with HCC according to BCLC stage. While traditionally reserved for patients with unresectable HCC and stage B disease, there is an important role for embolization therapies in earlier stage patients as an adjunct to ablation, bridging, or downstaging therapy, as a means to improve safety of resection, and potentially as an arterial ablative option in the case of radioembolization. Newer applications of radioembolization such as radiation segmentectomy have the potential to provide cure in localized unifocal disease, and transarterial chemoembolization-portal vein embolization and radiation lobectomy may provide a combination of treatment and future liver remnant hypertrophy for planned hepatic resection. There is also an increasing role for embolization in the treatment of stage C disease, and recent data suggest it can be used in combination with sorafenib with the potential for survival benefit over sorafenib alone, even in the case of portal vein tumor thrombus. Embolization therapies play an increasingly important role in patients with BCLC stage A-C hepatocellular carcinoma. While different therapies may be offered on a patient-specific basis, there are limited prospective RCT data to support superiority of one technique over another.

  9. The minimal ablative margin of radiofrequency ablation of hepatocellular carcinoma (> 2 and < 5 cm) needed to prevent local tumor progression: 3D quantitative assessment using CT image fusion.

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    Kim, Young-Sun; Lee, Won Jae; Rhim, Hyunchul; Lim, Hyo K; Choi, Dongil; Lee, Ji Young

    2010-09-01

    The aim of this study was to elucidate the minimal ablative margin for percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) (> 2 and ablative margin quantitatively. Risk factors for local tumor progression (the thinnest ablative margin, tumor size, and the effect of hepatic vessels) were assessed by multivariate analysis. Patients underwent follow-up for 12.9-46.6 months (median, 28.1 months). The tumors were 2.1-4.8 cm (mean +/- SD, 2.7 +/- 0.6 cm) in diameter. The thinnest ablative margins ranged from 0 to 6 mm (1.0 +/- 1.4 mm). A 5-mm safety margin was achieved in only 2.7% (3/110) of cases. In 47.3% (52/110) of cases, vessel-induced indentation of the ablation zone contributed to the thinnest ablative margins. Local tumor progression was detected in 27.3% (30/110) of cases. Concordance between local tumor progression and the thinnest margin was observed in 83.3% (25/30) of cases. The incidence of concordant local tumor progression was 22.7% (25/110), 18.9% (10/53), 5.9% (2/34), and 0% (0/15) in tumors with the thinnest ablative margin of > or = 0, > or = 1, > or = 2, and > or = 3 mm, respectively. An insufficient ablative margin was the sole significant factor associated with local tumor progression. When the thickness of the ablative margin is evaluated by CT image fusion, a margin of 3 mm or more appears to be associated with a lower rate of local tumor progression after percutaneous RFA of HCC.

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

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    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

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

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    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.

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

    Science.gov (United States)

    Cao, Wen; Hu, Chao; Wu, Lingling; Xu, Liba; Jiang, Weizhe

    2016-10-01

    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. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  13. Genetic heterogeneity of hepatocellular carcinoma

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    Unsal, H.; Isselbacher, K.J. (Massachusetts General Hospital Cancer Center, Charlestown, MA (United States)); Yakicier, C.; Marcais, C.; Ozturk, M. (Institut National de la Sante et de la Recherche Medicale, Lyon (France)); Kew, M. (Univ. of Witwatersrand, Johannesburg (South Africa)); Volkmann, M. (Univ. of Heidelberg (Germany)); Zentgraf, H. (Deutsches Krebsforschungszentrum, Heidelberg (Germany))

    1994-01-18

    The authors studied 80 hepatocellular carcinomas from three continents for p53 gene (TP53) mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in tumors from Mozambique but not in tumors from South Africa, China, and Germany. Independent of geographic origin, most tumors were positive for HBV sequences. X gene coding sequences of HBV were detected in 78% of tumors, whereas viral sequences in the surface antigen- and core antigen-encoding regions were present in less than 35% of tumors. These observations indicate that hepatocellular carcinomas are genetically heterogeneous. Mozambican-types of hepatocellular carcinomas are characterized by a high incidence of p53 mutations related to aflatoxins. In other tumors, the rarity of p53 mutations combined with the frequent presence of viral X gene coding sequences suggests a possible interference of HBV with the wild-type p53 function.

  14. AFP mRNA level in enriched circulating tumor cells from hepatocellular carcinoma patient blood samples is a pivotal predictive marker for metastasis.

    Science.gov (United States)

    Jin, Junhua; Niu, Xiaojuan; Zou, Lihui; Li, Lin; Li, Shugang; Han, Jingli; Zhang, Peiying; Song, Jinghai; Xiao, Fei

    2016-08-01

    Circulating tumor cells (CTCs) quantification may be helpful for evaluating cancer dissemination, predicting prognosis and assessing therapeutic effectiveness and safety. In the present study, CTCs from blood samples of 72 patients with hepatocellular carcinoma (HCC) were enriched with anti-EpCAM nanoparticles. AFP mRNA level was detected by nested polymerase chain reaction (PCR) after enrichment of CTCs from HCC blood samples at 0, 3, 6, 9 and 12 months after hepatectomy, respectively. AFP mRNA expression in CTCs was positive in 43 patients (59.7%) and negative in 29 patients (40.3%) before hepatectomy. Among 43 patients with positive AFP mRNA expression in CTCs before hepatectomy, 10 and 11 were diagnosed as intrahepatic/extrahepatic metastasis before and after hepatectomy, respectively. In addition, these 21 patients with metastasis had persisting positive AFP mRNA of CTCs during the whole tested year. Specifically, 3 patients with AFP mRNA negative in CTCs before hepatectomy changed to be positive at 6 and 9 months, and 2 of them were diagnosed as metastasis 12 months after hepatectomy. We conclude that the positive AFP mRNA of CTCs can be a pivotal predictor for HCC metastasis before and after hepatectomy. The release of AFP expression from hepatocellular carcinoma cells into circulation must be a major source of HCC metastasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Deteriorated portal flow may cause liver failure in patients with hepatocellular carcinoma being treated with sorafenib.

    Science.gov (United States)

    Yamasaki, Akihiro; Umeno, Narihiro; Harada, Shigeru; Tanaka, Kosuke; Kato, Masaki; Kotoh, Kazuhiro

    2016-06-01

    We encountered two patients with hepatocellular carcinoma (HCC) who showed rapid progression of liver failure during sorafenib treatment. One had portal vein tumor thrombus (PVTT) and the other developed portal vein thrombosis (PVT) during the treatment, and both of them experienced the elevation of serum lactate dehydrogenase (LDH) concentration during the administration of sorafenib. Their clinical courses indicate that the liver failure might have been caused by sorafenib-induced liver hypoxia, being amplified in the circumstances with reduced portal flow. To our best knowledge, all the reported patients who achieved complete remission (CR) during sorafenib monotherapy had a condition that could decrease portal blood flow. We hypothesized that pathogenesis of disease may be similar in HCC patients who achieve CR and those who experience liver failure while on sorafenib. Sorafenib treatment of patients with HCC and deteriorated portal flow may be a double-edged sword.

  16. 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.

  17. Infiltrative Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis Treated With a Single High-Dose Y90 Radioembolization and Subsequent Liver Transplantation Without a Recurrence.

    Science.gov (United States)

    Dendy, Meaghan S; Camacho, Juan C; Ludwig, Johannes M; Krasinskas, Alyssa M; Knechtle, Stuart J; Kim, Hyun S

    2017-09-01

    Infiltrative hepatocellular carcinoma with macrovascular invasion is a relatively rare presentation and usually fatal disease. Both patients exceeded Milan and University of California-San Francisco (UCSF) criteria, and per Barcelona Clinic Liver Cancer group guidelines, they were enrolled in a prospective open-label radioembolization phase II trial that gave them optimized lobar doses of Yttrium-90 as solely the first-line therapy without concomitant or additional pharmacological or locoregional therapies. Three months after radioembolization, the patients demonstrated no residual viable disease on surveillance imaging. The patients were then followed up with serial imaging for 2 years in 3-month intervals, without documenting recurrence or extrahepatic disease. Finally, both patients underwent transplantation and after more than 20 months of imaging surveillance, no locoregional or systemic recurrence have been observed. We present, to our knowledge, the first 2 reports of transplantation after successfully downstaging infiltrative disease with portal vein tumoral thrombosis, which traditionally poses as a relative contraindication for resection or transplantation.

  18. 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......–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...

  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 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......-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...

  20. The meaning of gross tumor type in the aspects of cytokeratin 19 expression and resection margin in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Gong, Sung Chan; Cho, Mee-Yon; Lee, Sang Woo; Kim, Sung Hoon; Kim, Moon Young; Baik, Soon Koo

    2016-01-01

    There is no consensus on the safe resection margin in patients with hepatocellular carcinoma. Surgeons decide the extent of resection according to residual liver function and tumor location. We investigated the influence of resection margin on early recurrence with respect to gross tumor type and expression of cytokeratin 19 (CK19). We divided the patients into two groups based on the classification of The Korean Liver Cancer Study group as follows: group 1 included expanding and vaguely nodular types whereas group 2 included nodular with perinodular extension, multinodular confluent, and infiltrative types. We classified the resection margin as narrow (0.1-0.9 cm) or wide (greater than 1 cm). We compared clinicopathological features and CK19 positivity between the groups. Group 2 had a higher prevalence of gross portal vein invasion, microscopic portal vein invasion, microvessel invasion, satellite nodules, intrahepatic metastasis, multicentric occurrence, and positivity for CK19. Group 1 showed no difference in recurrence according to the resection margin; however, group 2 showed a higher recurrence rate in patients with a narrow resection margin compared with those with a wide resection margin (P = 0.047). Patients in group 2 with CK19 positivity showed a higher prevalence of microvessel invasion than those without CK19 (P = 0.026). Although our study has the limitation of a small number of cases, the data suggest that patients with hepatocellular carcinoma of expanding and vaguely nodular gross types may safely undergo surgical resection with a narrow resection margin and a low risk of early recurrence. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

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

    Directory of Open Access Journals (Sweden)

    Kenji Imai

    2017-09-01

    Full Text Available 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.

  2. Amiodarone inhibits arterial thrombus formation and tissue factor translation.

    Science.gov (United States)

    Breitenstein, A; Stämpfli, S F; Camici, G G; Akhmedov, A; Ha, H R; Follath, F; Bogdanova, A; Lüscher, T F; Tanner, F C

    2008-12-01

    In patients with coronary artery disease and reduced ejection fraction, amiodarone reduces mortality by decreasing sudden death. Because the latter may be triggered by coronary artery thrombosis as much as ventricular arrhythmias, amiodarone might interfere with tissue factor (TF) expression and thrombus formation. Clinically relevant plasma concentrations of amiodarone reduced TF activity and impaired carotid artery thrombus formation in a mouse photochemical injury model in vivo. PTT, aPTT, and tail bleeding time were not affected; platelet number was slightly decreased. In human endothelial and vascular smooth muscle cells, amiodarone inhibited tumor necrosis factor (TNF)-alpha and thrombin-induced TF expression as well as surface activity. Amiodarone lacking iodine and the main metabolite of amiodarone, N-monodesethylamiodarone, inhibited TF expression. Amiodarone did not affect mitogen-activated protein kinase activation, TF mRNA expression, and TF protein degradation. Metabolic labeling confirmed that amiodarone inhibited TF protein translation. Amiodarone impairs thrombus formation in vivo; in line with this, it inhibits TF protein expression and surface activity in human vascular cells. These pleiotropic actions occur within the range of amiodarone concentrations measured in patients, and thus may account at least in part for its beneficial effects in patients with coronary artery disease.

  3. Synergistic Inhibitory Effect of Traditional Chinese Medicine Astragaloside IV and Curcumin on Tumor Growth and Angiogenesis in an Orthotopic Nude-Mouse Model of Human Hepatocellular Carcinoma.

    Science.gov (United States)

    Zhang, Shuo; Tang, Decai; Zang, Wenhua; Yin, Gang; Dai, Jianguo; Sun, Y U; Yang, Zhijian; Hoffman, Robert M; Guo, Xiuxia

    2017-02-01

    The aim of the present study was to investigate the efficacy of the traditional Chinese medicine (TCM), astragaloside IV (AS-IV) and curcumin on tumor growth and angiogenesis in an orthotopic nude-mouse model of human hepatocellular carcinoma (HCC). We have previously shown the usefulness of orthotopic models of human cancer for evaluation of the efficacy of TCM. Nude mice with orthotopic HepG2 HCC were treated with vehicle control (0.01 ml/g normal saline), cisplatinum (2 mg/kg), AS-IV (20 mg/kg), curcumin (100 mg/kg) or AS-IV plus curcumin (20 mg/kg + 100 mg/kg). Tumor inhibition in each group was evaluated by tumor weight at autopsy. The effect of AS-IV and curcumin on tumor angiogenesis was assessed by CD34 staining and expression of fibroblast growth factor-2 (FGF2), matrix metalloproteinase 2 (MMP2), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), thrombosis-related factor tissue factor (TF) and coagulation factor VII (FVII), as well as microRNAs miR-122 and miR-221. AS-IV and curcumin alone and in combination significantly reduced mean tumor weight compared to vehicle control (pcurcumin alone. Expression of FGF2, MMP2, VEGF, HGF, TF and FVII was reduced by AS-IV and curcumin alone. AS-IV and curcumin alone up-regulated expression of miR-122 and down-regulated that of miR-221. The combination of AS-IV and curcumin demonstrated significant synergistic effects on microvessel count as well as on expression of angiogenic and thrombosis-related factors and microRNAs. The present study indicates future clinical potential of combination therapy with AS-IV and curcumin for HCC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. The lack of the organic cation transporter OCT1 at the plasma membrane of tumor cells precludes a positive response to sorafenib in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Geier, Andreas; Macias, Rocio I R; Bettinger, Dominik; Weiss, Johannes; Bantel, Heike; Jahn, Daniel; Al-Abdulla, Ruba; Marin, Jose J G

    2017-02-28

    Sorafenib is the drug of choice in the treatment of advanced hepatocellular carcinoma (HCC). Beneficial effects are limited by mechanisms of chemoresistance, which include downregulation and/or impaired function of plasma membrane transporters accounting for drug uptake. The organic cation transporter 1 (OCT1) plays a major role in sorafenib uptake and decreased expression in HCC has been associated with poorer response. The multicenter retrospective TRANSFER study involved tumor biopsies from 39 patients with advanced HCC and sorafenib therapy for ≥4 wk. Endpoint was the relationship between clinicopathological features and immunohistological result. Immunostaining was performed using specific primary anti-OCT1-head and anti-OCT1-tail antibodies. Tumors were classified according to a simplified staining score as absent, weak, moderate or strong, taking into account the localization of the staining at the plasma membrane as positive or negative. Results confirmed OCT1 downregulation in half of the cases investigated (10% absent, 38% weak). However, only one third of tumors expressing OCT1 displayed plasma membrane location (15% vs. 36% cytosolic expression). When comparing HCC with and without OCT1 expression, no different sorafenib response was found. When tumors expressing OCT1 at the plasma membrane were considered separately, a marked longer survival was found (Log Rank p<0.001). No association between OCT1 expression at the plasma membrane with tumor stage, previous treatment with TACE or radiological response was seen.In conclusion, these results indicate that the presence of OCT1 at the plasma membrane, rather than its expression levels, is related to better outcome of HCC patients treated with sorafenib.

  5. Intense 18F-FDG uptake in an organizing right atrial thrombus mimicking malignancy

    Directory of Open Access Journals (Sweden)

    Krishna G. Chaudhuri, MD

    2017-09-01

    Full Text Available We present a case of an intensely hypermetabolic intracavitary cardiac mass, standardized uptake values max 44.4, that was pathologically proved to be organizing and organized thrombus, negative for tumor. Our patient had previous right atrial mass resection 2 years prior that was pathologically described as either thrombus or infarcted atrial myxoma. She had since been on lifelong controlled anticoagulation; and on routine follow-up imaging, she had recurrent slow growth of a new right atrial mass. During a later hospital admission for chest pain, the mass was evaluated on both transthoracic and transesophageal echo cardiogram, which could not differentiate thrombus vs neoplasm. Cardiac magnetic resonance imaging was equivocal for mass enhancement. The patient underwent fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT evaluation, which revealed intensely hypermetabolic activity within the mass concerning for malignancy, potentially an aggressive tumor. Subsequently, the mass was surgically excised for pathological diagnosis.

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

    Science.gov (United States)

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

    2014-02-21

    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 (131I) against the human vascular endothelial growth factor (hVEGF). hVEGF siRNA was labeled with 131I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. 131I-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 131I-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. 131I-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 131I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with 131I-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 131I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control. EMF-guided 131I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging.

  7. 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.

  8. Vitamin B-6 Supplementation Could Mediate Antioxidant Capacity by Reducing Plasma Homocysteine Concentration in Patients with Hepatocellular Carcinoma after Tumor Resection.

    Science.gov (United States)

    Cheng, Shao-Bin; Lin, Ping-Ting; Liu, Hsiao-Tien; Peng, Yi-Shan; Huang, Shih-Chien; Huang, Yi-Chia

    2016-01-01

    Vitamin B-6 has a strong antioxidative effect. It would be useful to determine whether vitamin B-6 supplementation had effects on antioxidant capacities in patients with hepatocellular carcinoma (HCC) who had recently undergone tumor resection. Thirty-three HCC patients were randomly assigned to either the placebo (n = 16) group or the vitamin B-6 50 mg/d (n = 17) group for 12 weeks. Plasma pyridoxal 5'-phosphate, homocysteine, indicators of oxidative stress, and antioxidant capacities were measured. Plasma homocysteine in the vitamin B-6 group was significantly decreased at week 12, while the level of trolox equivalent antioxidant capacity (TEAC) was significantly increased at the end of the intervention period. Vitamin B-6 supplementation had a significant reducing effect on the change of plasma homocysteine (β = -2.4, p = 0.02) but not on the change of TEAC level after adjusting for potential confounders. The change of plasma homocysteine was significantly associated with the change of TEAC after adjusting for potential confounders (β = -162.0, p = 0.03). Vitamin B-6 supplementation seemed to mediate antioxidant capacity via reducing plasma homocysteine rather than having a direct antioxidative effect in HCC patients who had recently undergone tumor resection. The clinical trial number is NCT01964001, ClinicalTrials.gov.

  9. Development of a novel assay to quantify serum human telomerase reverse transcriptase messenger RNA and its significance as a tumor marker for hepatocellular carcinoma.

    Science.gov (United States)

    Miura, Norimasa; Maruyama, Shigeo; Oyama, Kenji; Horie, Yutaka; Kohno, Michimori; Noma, Eijiro; Sakaguchi, Seigo; Nagashima, Miki; Kudo, Masatoshi; Kishimoto, Yukihiro; Kawasaki, Hironaka; Hasegawa, Junichi; Shiota, Goshi

    2007-01-01

    Currently available tumor markers for hepatocellular carcinoma (HCC) are alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and Des-gamma-carboxy prothrombin (DCP). However, their positive rate can not surpass abdominal ultrasonography (US) as modalities to detect small HCC at early stage, resulting in a possible delay of its diagnosis. There is a need to develop an additional sensitive marker to improve the early detection of HCC. We here introduced a newly developed quantitative detection method for serum hTERT mRNA, which has a clinical significance in HCC diagnosis. Briefly, we examined its sensitivity and specificity in HCC diagnosis, clinical significance in comparison with other tumor markers, and its correlations with the clinical parameters. Serum hTERT mRNA showed higher values in patients with HCC than those with chronic liver diseases. hTERT mRNA expression independently correlated with clinical parameters such as differentiation degree (p < 0.001). The sensitivity/specificity of hTERT mRNA in HCC diagnosis showed 88.2/70.0%. hTERT mRNA proved to be expectedly superior to AFP mRNA , AFP and DCP in HCC diagnosis. Importantly, hTERT mRNA in serum correlated with that in HCC tissue. Thus, we report that serum hTERT mRNA is a novel and available marker for HCC diagnosis. Copyright 2007 S. Karger AG, Basel.

  10. Vitamin B-6 Supplementation Could Mediate Antioxidant Capacity by Reducing Plasma Homocysteine Concentration in Patients with Hepatocellular Carcinoma after Tumor Resection

    Directory of Open Access Journals (Sweden)

    Shao-Bin Cheng

    2016-01-01

    Full Text Available Vitamin B-6 has a strong antioxidative effect. It would be useful to determine whether vitamin B-6 supplementation had effects on antioxidant capacities in patients with hepatocellular carcinoma (HCC who had recently undergone tumor resection. Thirty-three HCC patients were randomly assigned to either the placebo (n=16 group or the vitamin B-6 50 mg/d (n=17 group for 12 weeks. Plasma pyridoxal 5′-phosphate, homocysteine, indicators of oxidative stress, and antioxidant capacities were measured. Plasma homocysteine in the vitamin B-6 group was significantly decreased at week 12, while the level of trolox equivalent antioxidant capacity (TEAC was significantly increased at the end of the intervention period. Vitamin B-6 supplementation had a significant reducing effect on the change of plasma homocysteine (β=-2.4, p=0.02 but not on the change of TEAC level after adjusting for potential confounders. The change of plasma homocysteine was significantly associated with the change of TEAC after adjusting for potential confounders (β=-162.0, p=0.03. Vitamin B-6 supplementation seemed to mediate antioxidant capacity via reducing plasma homocysteine rather than having a direct antioxidative effect in HCC patients who had recently undergone tumor resection. The clinical trial number is NCT01964001, ClinicalTrials.gov.

  11. Sorafenib enriches epithelial cell adhesion molecule-positive tumor initiating cells and exacerbates a subtype of hepatocellular carcinoma through TSC2-AKT cascade.

    Science.gov (United States)

    Guan, Dong-Xian; Shi, Jie; Zhang, Yang; Zhao, Jiang-Sha; Long, Ling-Yun; Chen, Tian-Wei; Zhang, Er-Bin; Feng, Yuan-Yuan; Bao, Wen-Dai; Deng, Yue-Zhen; Qiu, Lin; Zhang, Xue-Li; Koeffler, H Phillip; Cheng, Shu-qun; Li, Jing-Jing; Xie, Dong

    2015-12-01

    Sorafenib is a specific adenosine triphosphate-competitive RAF inhibitor used as a first-line treatment of advanced hepatocellular carcinoma (HCC). However, the responses are variable, reflecting heterogeneity of the disease, while the resistance mechanism remains poorly understood. Here, we report that sorafenib treatment can exacerbate disease progression in both patient-derived xenografts and cell line-derived xenografts and that the therapeutic effect of the drug inversely covaries to the ratio of epithelial cell adhesion molecule-positive cells, which may be tumor initiating cells in HCC. The TSC2-AKT cascade mediates this sorafenib resistance. In response to sorafenib treatment, formation of the TSC1/2 complex is enhanced, causing increased phosphorylation of AKT, which contributes to up-regulation of "stemness"-related genes in epithelial cell adhesion molecule-positive cells and enhancement of tumorigenicity. The expression of TSC2 negatively correlated with prognosis in clinical sorafenib therapy. Furthermore, all-trans retinoic acid decreased AKT activity, reduced the epithelial cell adhesion molecule-positive cell population enriched by sorafenib, and potentiated the therapeutic effect of sorafenib in the patient-derived xenograft model. Our findings suggest that a subtype of HCC is not suitable for sorafenib therapy; this resistance to sorafenib can be predicted by the status of TSC2, and agents inducing differentiation of tumor initiating cells (e.g., all-trans retinoic acid) should improve the prognosis of this subtype of HCC. © 2015 by the American Association for the Study of Liver Diseases.

  12. ANXA3/JNK Signaling Promotes Self-Renewal and Tumor Growth, and Its Blockade Provides a Therapeutic Target for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Man Tong

    2015-07-01

    Full Text Available Frequent tumor relapse in hepatocellular carcinoma (HCC has been commonly attributed to the presence of residual cancer stem cells (CSCs after conventional treatments. We have previously identified and characterized CD133 to mark a specific CSC subset in HCC. In the present study, we found endogenous and secretory annexin A3 (ANXA3 to play pivotal roles in promoting cancer and stem cell-like features in CD133+ liver CSCs through a dysregulated JNK pathway. Blockade of ANXA3 with an anti-ANXA3 monoclonal antibody in vitro as well as in human HCC xenograft models resulted in a significant reduction in tumor growth and self-renewal. Clinically, ANXA3 expression in HCC patient sera closely associated with aggressive clinical features. Our results suggest that ANXA3 can serve as a novel diagnostic biomarker and that the inhibition of ANXA3 may be a viable therapeutic option for the treatment of CD133+ liver-CSC-driven HCC.

  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. 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.

  15. 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.

  16. Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2

    OpenAIRE

    Huang, Bee-Piao; Lin, Chun-Shiang; Wang, Chau-Jong; Kao, Shao-Hsuan

    2017-01-01

    Tumor necrosis factor alpha (TNF?) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNF? on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNF? stimulus. We observed that HepG2 cell revealed a higher resistance to TNF?-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By usin...

  17. CD44 variant 9 is a potential biomarker of tumor initiating cells predicting survival outcome in hepatitis C virus-positive patients with resected hepatocellular carcinoma.

    Science.gov (United States)

    Kakehashi, Anna; Ishii, Naomi; Sugihara, Eiji; Gi, Min; Saya, Hideyuki; Wanibuchi, Hideki

    2016-05-01

    This study investigated whether the expression of CD44 variant 9 (CD44v9) might be a functional marker of tumor-initiating stem-like cells in primary hepatocellular carcinomas (HCCs) of hepatitis C virus (HCV)(+) patients and provide an indicator of patient survival, as well as associated mechanisms. A total of 90 HCV(+) HCC patients who underwent surgery from 2006 to 2011 were enrolled and monitored for 2-8 years. Expression of CD44v9 was validated immunohistochemically in all HCCs, followed by comparative proteome, survival, and clinicopathological analyses. CD44 variant 8--10 was further evaluated in diethylnitrosamine-induced HCCs of C57Bl/6J mice. Focally localized CD44v(+) cells with a membranous staining pattern were detected in human HCV(+) and mouse HCCs. CD44v9(+) cells of HCCs were predominantly negative for Ki67 and P-p38, indicating decrease of cell proliferation in the CD44v9(+) tumor cell population, likely to be related to suppression of intracellular oxidative stress due to activation of Nrf2-mediated signaling, DNA repair, and inhibition of xenobiotic metabolism. CD44v9 IHC evaluation in 90 HCV(+) HCC cases revealed that positive expression was significantly associated with poor overall and recurrence-free survival, a younger age, poor histological differentiation of HCCs, and high alkaline phosphatase levels compared with patients with negative expression. CD44v9 is concluded to be a potential biomarker of tumor-initiating stem-like cells and a prognostic marker in HCV(+) HCC patients associated with Nrf2-mediated resistance to oxidative stress. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  18. Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients.

    Science.gov (United States)

    Lim, Tae Seop; Kim, Do Young; Han, Kwang-Hyub; Kim, Hyon-Suk; Shin, Seung Hwan; Jung, Kyu Sik; Kim, Beom Kyung; Kim, Seung Up; Park, Jun Yong; Ahn, Sang Hoon

    2016-03-01

    As data on the effectiveness of tumor markers in detecting hepatocellular carcinoma (HCC) in cirrhotic patients are limited, we investigated the diagnostic accuracy of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3). This retrospective study enrolled 361 cirrhotic patients with HCC, and 276 cirrhotic patients without HCC occurrence. Most patients were men (n = 431, 67.7%); the median age was 57.0 years. The main etiology of chronic liver disease was chronic hepatitis B (n = 467, 73.3%). The sensitivity and specificity of combined three biomarkers was 87.0 and 60.1% in overall HCC, and 75.7 and 60.1% in early HCC, respectively (cutoff: 20 ng/mL for AFP, 40 mAU/mL for PIVKA-II, and 5% for AFP-L3). The area under the receiver operating characteristic curve (AUROC) for HCC diagnosis was 0.765 (95% confidence interval [CI], 0.728-0.801) for AFP; 0.823 (95% CI, 0.791-0.854) for PIVKA-II; and 0.755 (95% CI, 0.718-0.792) for AFP-L3. The AUROC for early HCC diagnosis was 0.754 (95% CI, 0.691-0.816) for AFP, 0.701 (95% CI, 0.630-0.771) for PIVKA-II, and 0.670 (95% CI, 0.596-0.744) for AFP-L3. Combining the three tumor markers increased the AUROC to 0.877 (95% CI, 0.851-0.903) for HCC diagnosis, and 0.773 (95% CI, 0.704-0.841) for early HCC diagnosis. Diagnostic accuracy improved upon combining the AFP, PIVKA-II, and AFP-L3 tumor markers compared to each marker alone in detecting HCC and early HCC in cirrhotic patients.

  19. microRNA-122 abundance in hepatocellular carcinoma and non-tumor liver tissue from Japanese patients with persistent HCV versus HBV infection.

    Science.gov (United States)

    Spaniel, Carolyn; Honda, Masao; Selitsky, Sara R; Yamane, Daisuke; Shimakami, Tetsuro; Kaneko, Shuichi; Lanford, Robert E; Lemon, Stanley M

    2013-01-01

    Mechanisms of hepatic carcinogenesis in chronic hepatitis B and hepatitis C are incompletely defined but often assumed to be similar and related to immune-mediated inflammation. Despite this, several studies hint at differences in expression of miR-122, a liver-specific microRNA with tumor suppressor properties, in hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV) versus hepatitis C virus (HCV) infection. Differences in the expression of miR-122 in these cancers would be of interest, as miR-122 is an essential host factor for HCV but not HBV replication. To determine whether the abundance of miR-122 in cancer tissue is influenced by the nature of the underlying virus infection, we measured miR-122 by qRT-PCR in paired tumor and non-tumor tissues from cohorts of HBV- and HCV-infected Japanese patients. miR-122 abundance was significantly reduced from normal in HBV-associated HCC, but not in liver cancer associated with HCV infection. This difference was independent of the degree of differentiation of the liver cancer. Surprisingly, we also found significant differences in miR-122 expression in non-tumor tissue, with miR-122 abundance reduced from normal in HCV- but not HBV-infected liver. Similar differences were observed in HCV- vs. HBV-infected chimpanzees. Among HCV-infected Japanese subjects, reductions in miR-122 abundance in non-tumor tissue were associated with a single nucleotide polymorphism near the IL28B gene that predicts poor response to interferon-based therapy (TG vs. TT genotype at rs8099917), and correlated negatively with the abundance of multiple interferon-stimulated gene transcripts. Reduced levels of miR-122 in chronic hepatitis C thus appear to be associated with endogenous interferon responses to the virus, while differences in miR-122 expression in HCV- versus HBV-associated HCC likely reflect virus-specific mechanisms contributing to carcinogenesis. The continued expression of miR-122 in HCV-associated HCC may signify

  20. microRNA-122 abundance in hepatocellular carcinoma and non-tumor liver tissue from Japanese patients with persistent HCV versus HBV infection.

    Directory of Open Access Journals (Sweden)

    Carolyn Spaniel

    Full Text Available Mechanisms of hepatic carcinogenesis in chronic hepatitis B and hepatitis C are incompletely defined but often assumed to be similar and related to immune-mediated inflammation. Despite this, several studies hint at differences in expression of miR-122, a liver-specific microRNA with tumor suppressor properties, in hepatocellular carcinoma (HCC associated with hepatitis B virus (HBV versus hepatitis C virus (HCV infection. Differences in the expression of miR-122 in these cancers would be of interest, as miR-122 is an essential host factor for HCV but not HBV replication. To determine whether the abundance of miR-122 in cancer tissue is influenced by the nature of the underlying virus infection, we measured miR-122 by qRT-PCR in paired tumor and non-tumor tissues from cohorts of HBV- and HCV-infected Japanese patients. miR-122 abundance was significantly reduced from normal in HBV-associated HCC, but not in liver cancer associated with HCV infection. This difference was independent of the degree of differentiation of the liver cancer. Surprisingly, we also found significant differences in miR-122 expression in non-tumor tissue, with miR-122 abundance reduced from normal in HCV- but not HBV-infected liver. Similar differences were observed in HCV- vs. HBV-infected chimpanzees. Among HCV-infected Japanese subjects, reductions in miR-122 abundance in non-tumor tissue were associated with a single nucleotide polymorphism near the IL28B gene that predicts poor response to interferon-based therapy (TG vs. TT genotype at rs8099917, and correlated negatively with the abundance of multiple interferon-stimulated gene transcripts. Reduced levels of miR-122 in chronic hepatitis C thus appear to be associated with endogenous interferon responses to the virus, while differences in miR-122 expression in HCV- versus HBV-associated HCC likely reflect virus-specific mechanisms contributing to carcinogenesis. The continued expression of miR-122 in HCV

  1. Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: A multicenter study of 412 patients

    Science.gov (United States)

    Decaens, Thomas; Roudot-Thoraval, Françoise; Bresson-Hadni, Solange; Meyer, Carole; Gugenheim, Jean; Durand, Francois; Bernard, Pierre-Henri; Boillot, Olivier; Compagnon, Philippe; Calmus, Yvon; Hardwigsen, Jean; Ducerf, Christian; Pageaux, Georges Philippe; Dharancy, Sébastien; Chazouillères, Olivier; Cherqui, Daniel; Duvoux, Christophe

    2006-01-01

    AIM: To assess pre-orthotopic liver transplantation (OLT) factors that could be evaluated pre-operatively or controlled post-operatively associated with hepatocellular carcinoma (HCC) recurrence and disease-free survival after liver transplantation (LT). METHODS: Four hundred and twelve patients transplanted for HCC between 1988 and 1998 in 14 French centers, who survived the postoperative period were studied. Kaplan Meier estimates were calculated for 24 variables potentially associated with recurrence of HCC. Uni- and multivariate analyses were conducted to identify independent predictors of recurrence. RESULTS: Overall 5-year disease-free survival was 57.1%. By univariate analysis, variables associated with disease-free survival were: presence of cirrhosis (P = 0.001), etiology of liver disease (P = 0.03), α fetoprotein level ( 2000; P 2N; P = 0.02), the number of nodules (1, 2-3 or ≥ 4; P = 0.02), maximal diameter of the largest nodule ( 5 cm; P 10 cm; P < 0.0001), bi-lobar location (P = 0.01), preoperative portal thrombosis (P < 0.0001), peri-operative treatment of the tumor (P = 0.002) and chemoembolization (P = 0.03), tumor differentiation (P = 0.01), initial type of calcineurin inhibitor (P = 0.003), the use of antilymphocyte antibodies (P = 0.02), rejection episodes (P = 0.003) and period of LT (P < 0.0001). By multivariate analysis, 6 variables were independently associated with HCC recurrence: maximal diameter of the largest nodule (P < 0.0001), time of LT (P < 0.0001), tumor differentiation (P < 0.0001), use of anti-lymphocyte antibody (ATG) or anti-CD3 antibody (OKT3) (P = 0.005), preoperative portal thrombosis (P = 0.06) and the number of nodules (P = 0.06). CONCLUSION: This study identifies immunosuppression, through the use of ATG or OKT3, as a predictive factor of tumor recurrence, and confirms the prognostic value of tumor differentiation. PMID:17143948

  2. Alpha-Fetoprotein and Novel Tumor Biomarkers as Predictors of Hepatocellular Carcinoma Recurrence after Surgery: A Brilliant Star Raises Again

    Directory of Open Access Journals (Sweden)

    Quirino Lai

    2012-01-01

    Full Text Available Alpha-fetoprotein (AFP, des-γ-carboxy prothrombin (DCP, and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3 have been developed with the intent to detect hepatocellular carcinoma (HCC and for the surveillance of at-risk patients. However, at present, none of these tests can be recommended to survey cirrhotic patients at risk for HCC development because of their suboptimal ability for routine clinical practice in HCC diagnosis. Starting from these considerations, these markers have been therefore routinely and successfully used as predictors of survival and HCC recurrence in patients treated with curative intent. All these markers have been largely used as predictors in patients treated with hepatic resection or locoregional therapies, mainly in Eastern countries. In recent studies, AFP has been proposed as predictor of recurrence after liver transplantation and as selector of patients in the waiting list. Use of AFP modification during the waiting list for LT is still under investigation, potentially representing a very interesting tool for patient selection. The development of a new predictive model combining radiological and biological features based on biological markers is strongly required. New genetic markers are continuously discovered, but they are not already fully available in the clinical practice.

  3. Overexpression of the metastasis-associated gene MTA3 correlates with tumor progression and poor prognosis in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Chuanxi; Li, Guanzhen; Li, Jiamei; Li, Jie; Li, Tao; Yu, Jinyu; Qin, Chengyong

    2017-08-01

    Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers in the world. However, there remains a lack of effective diagnostic and treatment markers. We aimed to explore metastasis-associated protein 3 (MTA3) expression and function in HCC and its relationship with clinicopathological factors. We investigated the expression pattern and clinicopathological significance of MTA3 in 90 patients with HCC via immunohistochemistry and explored MTA3 function via gene knockdown of MTA3. MTA3 was overexpressed in HCC cell nuclei and downregulated in HCC cell cytoplasm. The former finding correlated with metastasis (P = 0.010) and poor prognosis (P = 0.018). In addition, deleting MTA3 inhibited HCC cell growth, invasion, and metastasis in vitro, as shown in the colony formation, migration, and wound-healing assays. These results indicate that MTA3 is an oncogene of HCC, predicts poor prognosis of HCC, and may be a future marker of HCC treatment. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  4. A mechanism for stroke complicating thrombus aspiration.

    Science.gov (United States)

    Brown, Eddie D; Blankenship, James C

    2017-01-01

    We propose a mechanism of how stroke may be caused by thrombus aspiration during primary percutaneous coronary intervention (PPCI), and how it may be technique-dependent. Two recent meta-analyses report increased risk of stroke in patients undergoing routine thrombus aspiration during STEMI and the value of this technique has been controversial. The mechanism of stroke has not been fully explained. This case demonstrates 2 mechanisms by which aspiration might cause thrombus embolization. We recommend that if thrombus aspiration is performed during PPCI for STEMI, it should be done selectively and carefully. It is prudent to make sure the guide catheter tip is not free in the aorta when the aspiration catheter is withdrawn, to maintain suction on the aspiration catheter as it is withdrawn (particularly if the aspiration port seems to be obstructed), and to aspirate the guide catheter after the aspiration catheter is removed to capture any fragments of thrombus that remain in the guide catheter. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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; Anders, Robert A; Xu, Yang

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. 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.

  7. 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

  8. The Human Homolog of Drosophila Headcase Acts as a Tumor Suppressor through Its Blocking Effect on the Cell Cycle in Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Jun Wang

    Full Text Available The molecular pathogenesis of hepatocellular carcinoma (HCC is heterogeneous and extremely complex. Thus, for individual molecular targeted therapy, novel molecular markers are needed. The abnormal expression of the human homolog of Drosophila headcase (HECA homo has been found in pancreatic, colorectal, and oral squamous cell carcinoma. Studies of oral squamous cell carcinoma have also demonstrated that the HECA homo protein can be negatively controlled by the Wnt-pathway and transcription factor 4 (TCF4 and can slow cell division by interacting with cyclins and CDKs. However, the role of HECA in HCC has not been reported elsewhere. Here, immunohistochemical analysis revealed that the downregulation of HECA homo protein occurred in 71.0% (66/93 of HCC cases and was positively correlated with a poorly differentiated grade, high serum AFP level, liver cirrhosis and large tumor size. The expression of HECA homo was detected in five live cell lines. In vitro, the overexpression of HECA homo in HepG2, Huh-7 and MHCC-97H cells could inhibit cell proliferation and colony formation and induce G1 phase arrest. In contrast, the downregulation of HECA homo could promote cell proliferation, colony formation and the cell cycle process. However, neither the overexpression nor downregulation of HECA homo in the three cell lines could affect cell migration or invasion. Collectively, HECA homo is regularly expressed in normal live cells, and the HECA homo protein level is heterogeneously altered in HCC, but the downregulation of HECA homo is more common and positively correlated with several malignant phenotypes. The HECA homo protein can slow cell proliferation to some extent primarily through its blocking effect on the cell cycle. Hence, the HECA homo protein may act as a tumor suppressor in HCC and might be a potential molecular marker for diagnostic classification and targeted therapy in HCC.

  9. Identification of microRNAs specific for epithelial cell adhesion molecule-positive tumor cells in hepatocellular carcinoma.

    Science.gov (United States)

    Ji, Junfang; Zheng, Xin; Forgues, Marshonna; Yamashita, Taro; Wauthier, Eliane L; Reid, Lola M; Wen, Xinyu; Song, Young; Wei, Jun S; Khan, Javed; Thorgeirsson, Snorri S; Wang, Xin Wei

    2015-09-01

    Therapies that target cancer stem cells (CSCs) hold promise in eliminating cancer burden. However, normal stem cells are likely to be targeted owing to their similarities to CSCs. It is established that epithelial cell adhesion molecule (EpCAM) is a biomarker for normal hepatic stem cells (HpSCs), and EpCAM(+) AFP(+) hepatocellular carcinoma (HCC) cells have enriched hepatic CSCs. We sought to determine whether specific microRNAs (miRNAs) exist in hepatic CSCs that are not expressed in normal HpSCs. We performed a pair-wise comparison of the miRNA transcriptome of EpCAM(+) and corresponding EpCAM(-) cells isolated from two primary HCC specimens, as well as from two fetal livers and three healthy adult liver donors by small RNA deep sequencing. We found that miR-150, miR-155, and miR-223 were preferentially highly expressed in EpCAM(+) HCC cells, which was further validated. Their gene surrogates, identified using miRNA and messenger RNA profiling in a cohort of 292 HCC patients, were associated with patient prognosis. We further demonstrated that miR-155 was highly expressed in EpCAM(+) HCC cells, compared to corresponding EpCAM(-) HCC cells, fetal livers with enriched normal hepatic progenitors, and normal adult livers with enriched mature hepatocytes. Suppressing miR-155 resulted in a decreased EpCAM(+) fraction in HCC cells and reduced HCC cell colony formation, migration, and invasion in vitro. The reduced levels of identified miR-155 targets predicted the shortened overall survival and time to recurrence of HCC patients. miR-155 is highly elevated in EpCAM(+) HCC cells and might serve as a molecular target to eradicate the EpCAM(+) CSC population in human HCCs. © 2015 by the American Association for the Study of Liver Diseases.

  10. Associating liver partition and portal vein ligation for bleeding hepatocellular carcinoma in HBV cirrhosis: a safety strategy.

    Science.gov (United States)

    Levi Sandri, Giovanni Battista; Vennarecci, Giovanni; Lepiane, Pasquale; Ettorre, Giuseppe Maria

    2017-01-01

    The incidence of hepatocellular carcinoma (HCC) spontaneous tumor rupture varies between 3% and 26%. For resectable HCC ruptures, emergency hepatectomy or staged hepatectomy after transcatheter arterial embolization (TAE) are life-saving procedures, and efficient therapeutic methods. We report a multimodal therapy including TAE, associating liver partition and portal vein ligation (ALPPS) and immunoglobuline infusion for a huge bleeding HCC with portal vein tumor thrombosis (PVTT) in hepatitis B virus (HBV) cirrhosis. ALPPS first step began with an abdominal toilette due to the massive hemoperitoneum and a portal vein incision at the bifurcation of the right and left portal veins was performed. A freely floating left part of the thrombus was extracted from the left portal vein in order to restore the left portal vein. The right portal vein with complete thrombosis was closed. Liver partition was then performed. The second step was performed without complications. A HCC Edmondson grade 4 (pT3b) and a cirrhotic liver parenchyma were described. Postoperative ascites decompensation was treated and patient was discharged in postoperative day 21. The reported triple strategy allowed us to prolong patient live. A multimodal therapy including TAE, ALPPS and immunoglobuline is a good option for a life treatment in case of huge bleeding hepatocellular carcinoma with PVTT in HBV cirrhosis.

  11. Sarcoidosis-associated hepatocellular carcinoma.

    Science.gov (United States)

    Ogata, Sho; Horio, Takuya; Sugiura, Yoshiaki; Shimazaki, Hideyuki; Saito, Hiroki; Aiko, Satoshi; Nakanishi, Kuniaki; Kawai, Toshiaki

    2010-12-01

    Sarcoidosis is a systemic granulomatous inflammation of unknown etiology, and seems to involve the liver parenchyma in most cases. However, sarcoidosis-associated hepatocellular carcinoma is rare. We report here a case in which a hepatocellular carcinoma occurred within the liver, which was probably involved as a result of systemic sarcoidosis. A 57-year-old Japanese man had been followed up for 2 years because of diabetic nephropathy and sarcoidosis. On admission for pneumonia, imaging studies revealed an unexpected hepatic tumor. Histology revealed a hepatocellular carcinoma accompanied by T-lymphocytic infiltration and marked granulomatous inflammation, which was surrounding some tumor nodules. The background liver parenchyma exhibited a moderate degree of fibrosis with granulomatous inflammation. The patient had no other apparent liver disease such as viral hepatitis, steatohepatitis, or primary biliary cirrhosis. Therefore, in the present case, sarcoidosis may be considered the probable background etiology for hepatocarcinogenesis.

  12. [A case of left atria subendocardial thrombus with 
sick sinus syndrome].

    Science.gov (United States)

    Liang, Xiongfei; Yang, Yifeng

    2016-09-28

    The clinical data for a patient with sick sinus syndrome was retrospectively analyzed. The patient was treated because of his heart palpitations and the increased chest pain. The patient admitted to the hospital under consideration for the left atrial tumor dependent on the echocardiography findings. After the CT scan and the dynamic ECG examination, the patient successfully underwent the left atrial tumor resection, atrial septal repair and cardiac pacing lead installation. The postoperative pathological diagnosis showed that the infective endocarditis and left atrial thrombus in left atrium was cured. The patient was discharged after postoperative anti-inflammatory therapy. By analyzing the reasons for misdignosis before or during surgery, the possible mechanisms for left atrial subendocardial thrombus have been found. This study suggests that it is necessary to combine imaging diagnosis and clinical observations to distinguish tumor from excrescence.

  13. 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

  14. Extrahepatic bile duct hepatocellular carcinoma due to recurrence of hematogenous metastasis 50 months after hepatectomy.

    Science.gov (United States)

    Kumata, Hiroyuki; Miyagi, Shigehito; Murakami, Keigo; Fujio, Atsushi; Hara, Yasuyuki; Nakanishi, Chikashi; Kawagishi, Naoki; Sasano, Hironobu; Kamei, Takashi; Ouchi, Noriaki

    2017-12-01

    Recurrent hepatocellular carcinoma (HCC) in the extrahepatic bile duct is rare with most cases diagnosed after manifesting sudden obstructive jaundice. Here, we report an extremely rare case of recurrent HCC in the common bile duct due to hematogenous metastasis. A 66-year-old man underwent an extended left hepatectomy for HCC in the medial segment of the liver. Fifty months later, he presented with sudden obstructive jaundice. Endoscopic retrograde cholangiography showed a space-occupying lesion in the common bile duct, which was suspected as cholangiocarcinoma. Therefore, he underwent extrahepatic bile duct resection and choledochojejunostomy with lymph node dissection. Macroscopically, a polypoid tumor and several nodular tumors were found in the common bile duct, which was obstructed by a tumor thrombus. Histopathologically, the tumors were diagnosed as metastases from the HCC resected 50 months before. Several distinct, nodular tumors were observed in the subepithelium of the common bile duct and had invaded some blood vessels. These findings support the conclusion that the HCC metastasized hematogenously to the extrahepatic bile duct. Recurrent HCC in the extrahepatic bile duct due to hematogenous metastasis is rare, and it is difficult to diagnose. Further similar cases should be accumulated for clarifying the pathological mechanism.

  15. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  16. Left ventricular mass: Myxoma or thrombus?

    Directory of Open Access Journals (Sweden)

    Monish S Raut

    2015-01-01

    Full Text Available Patient with embolic episode should always be evaluated for cardiac mass. Mass in left ventricular can be a myxoma or thrombus even in a normal functioning heart . In either case, mobile mass with embolic potential should be surgically resected.

  17. Submitral left ventricular aneurysm associated with thrombus ...

    African Journals Online (AJOL)

    Methods: In April 2017, a 25-year-old patient havingsubmitral left ventricular aneurysm with New York Heart Association (NYHA) class IV heart failure and mild left ventricular systolic dysfunctionreceived medical treatment at our institution. She had severe mitral regurgitation and aneurysmal thrombus. The diagnosis was ...

  18. Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: A multicenter study of 412 patients

    OpenAIRE

    Decaens, Thomas; Roudot-Thoraval, Françoise; Bresson-Hadni, Solange; Meyer, Carole; Gugenheim, Jean; Durand, Francois; Bernard, Pierre-Henri; Boillot, Olivier; Compagnon, Philippe; Calmus, Yvon; Hardwigsen, Jean; Ducerf, Christian; Pageaux, Georges Philippe; Dharancy, Sébastien; Chazouillères, Olivier

    2006-01-01

    AIM: To assess pre-orthotopic liver transplantation (OLT) factors that could be evaluated pre-operatively or controlled post-operatively associated with hepatocellular carcinoma (HCC) recurrence and disease-free survival after liver transplantation (LT).

  19. 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 calcification...

  20. Aflatoxin-induced TP53 R249S mutation in hepatocellular carcinoma in Thailand: association with tumors developing in the absence of liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Stephanie Villar

    Full Text Available Primary Liver Cancer (PLC is the leading cause of death by cancer among males in Thailand and the 3(rd among females. Most cases are hepatocellular carcinoma (HCC but cholangiocarcinomas represent between 4 and 80% of liver cancers depending upon geographic area. Most HCC are associated with chronic infection by Hepatitis B Virus while a G → T mutation at codon 249 of the TP53 gene, R249S, specific for exposure to aflatoxin, is detected in tumors for up to 30% of cases. We have used Short Oligonucleotide Mass Analysis (SOMA to quantify free circulating R249S-mutated DNA in plasma using blood specimens collected in a hospital case:control study. Plasma R249S-mutated DNA was detectable at low concentrations (≥ 67 copies/mL in 53 to 64% of patients with primary liver cancer or chronic liver disease and in 19% of controls. 44% of patients with HCC and no evidence of cirrhosis had plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL, compared to 21% in patients with both HCC and cirrhosis, 22% in patients with cholangiocarcinoma, 12% in patients with non-cancer chronic liver disease and 3% of subjects in the reference group. Thus, plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL tended to be more common in patients with HCC developing without pre-existing cirrhosis (p = 0.027. Overall, these results support the preferential occurrence of R249S-mutated DNA in HCC developing in the absence of cirrhosis in a context of HBV chronic infection.

  1. Imaging features of hepatocellular carcinoma compared to intrahepatic cholangiocarcinoma and combined tumor on MRI using liver imaging and data system (LI-RADS) version 2014.

    Science.gov (United States)

    Horvat, Natally; Nikolovski, Ines; Long, Niamh; Gerst, Scott; Zheng, Jian; Pak, Linda Ma; Simpson, Amber; Zheng, Junting; Capanu, Marinela; Jarnagin, William R; Mannelli, Lorenzo; Do, Richard Kinh Gian

    2018-01-01

    To evaluate the prevalence of major and ancillary imaging features from liver imaging reporting and data systems (LI-RADS) version 2014 and their interreader agreement when comparing hepatocellular carcinoma (HCC) to intrahepatic cholangiocarcinoma (ICC) and combined tumor (cHCC-CC). The Institutional Review Board approved this HIPAA-compliant retrospective study and waived the requirement for patients' informed consent. Patients with resected HCC (n = 51), ICC (n = 40), and cHCC-CC (n = 11) and available pre-operative contrast-enhanced MRI were included from 2000 to 2015. Imaging features and final LI-RADS category were evaluated by four radiologists. Imaging features were compared by Fisher's exact test and interreader agreements were assessed by κ statistics. None of the features were unique to either HCC or non-HCC. Imaging features that were significantly more common among HCC compared to ICC and cHCC-CC included washout (76%-78% vs. 10%-35%, p Features that were more common among ICC and cHCC-CC included peripheral arterial phase hyperenhancement (40%-64% vs. 10%-14%, p features (κ = 0.41-0.55). Moderate agreement was also achieved in the assignment of LR-M (κ = 0.53), with an overall sensitivity and specificity for non-HCC malignancy of 86.3% and 78.4%, respectively. HCC and non-HCC show significant differences in the prevalence of imaging features defined by LI-RADS, and are identified by radiologists with moderate interreader agreement. Using LI-RADS, radiologists also achieved moderate interreader agreement in the assignment of the LR-M category.

  2. Time of Dropout From the Liver Transplant List in Patients With Hepatocellular Carcinoma: Clinical Behavior According to Tumor Characteristics and Severity of Liver Disease.

    Science.gov (United States)

    Salvalaggio, P R; Felga, G E; Guardia, B D; Almeida, M D; Pandullo, F L; Matielo, C E; Evangelista, A; Curvelo, L; Rocco, R A; Alves, J A; Meirelles, R F; Filho, S P M; de Rezende, M B; Pedroso, P T; Diaz, L G; Rusi, M B; Viveiros, M M; Neves, D B

    2016-09-01

    Prolonged time on the waiting list affects post-transplant survival of patients with hepatocellular carcinoma (HCC). However, it is not yet known which patients will be at higher risk for early dropout from the list. We investigate specific risk factors for early waiting list dropout in patients with HCC. This was a single-center, intention-to-treat analysis of adults with HCC, within the Milan criteria, from July 2006 through September 2013. Patients were divided into groups according to waiting list time. The main end point was dropout from the list. The dropout rates of the study cohort at 3, 6, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Patients who dropped out from the list tended to be older, with blood types A and O, and with higher Child-Pugh and Model for End-Stage Liver Disease (MELD) scores. They also had larger nodules, responded poorly to trans-arterial chemo-embolization (TACE), and had a higher alpha-fetoprotein. Those with blood types B and AB appeared to be protected for dropout (odds ratio [OR] = 0.21, P = .02). Patients who responded to TACE were also protected (OR = 0.22, P < .001). When we looked into time to dropout, the only baseline characteristic that stood out was a higher MELD score (13 for those dropping out up to 90 days vs 10 for those dropping out after 180 days, P = .0025). We conclude that patients who drop out early from the list are primarily driven by the severity of liver disease. Patients who had progressive HCC had a high tumor load and poor response to loco-regional therapies, dropping out from the list after 180 days of inclusion. Copyright © 2016. Published by Elsevier Inc.

  3. Differential impact of risk factors for tumor recurrence in hepatitis B and hepatitis C virus-infected patients undergoing liver transplantation for hepatocellular carcinoma.

    Science.gov (United States)

    Krasnodębski, Maciej; Grąt, Michał; Masior, Łukasz; Patkowski, Waldemar; Krawczyk, Marek

    2015-02-02

    Hepatitis B (HBV) and C (HCV) virus infection are the 2 most important risk factors for the development of the hepatocellular carcinoma (HCC). The aim of this study was to assess the importance of the type of viral infection in evaluation of HCC recurrence risk after liver transplantation (LT). This retrospective study was based on 130 HCC patients undergoing LT. Patients were subdivided by HBV or HCV infection only or HBV and HCV co-infection (HBV-HCV). The primary outcome measure was recurrence-free survival (RFS) 5 years after transplantation. The 5-year RFS did not differ significantly according to HBV infection, HCV infection, or HBV-HCV co-infection in the entire study cohort (p=0.902) or among patients who fulfilled (p=0.454) or did not fulfill (p=0.999) the Milan criteria. Neither HCV (p=0.869) nor HBV (p=0.968) infection significantly affected 5-year RFS following adjustment for covariates. Higher lesion number (p=0.004), increased alpha-fetoprotein (p=0.017), microvascular invasion (p=0.004), and female donor sex (p=0.025) were significant risk factors for poor RFS in HBV patients; older recipient age (p=0.010) and increased total tumor volume (p=0.028) were significant risk factors in HCV patients. Although the viral infection type does not affect post-LT outcomes in HCC patients, the influence of other risk factors is markedly different in HBV- and HCV-related HCC.

  4. Role of DLC1 tumor suppressor gene and MYC oncogene in pathogenesis of human hepatocellular carcinoma: potential prospects for combined targeted therapeutics (review).

    Science.gov (United States)

    Zimonjic, Drazen B; Popescu, Nicholas C

    2012-08-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer death, and its incidence is increasing worldwide in an alarming manner. The development of curative therapy for advanced and metastatic HCC is a high clinical priority. The HCC genome is complex and heterogeneous; therefore, the identification of recurrent genomic and related gene alterations is critical for developing clinical applications for diagnosis, prognosis and targeted therapy of the disease. This article focuses on recent research progress and our contribution in identifying and deciphering the role of defined genetic alterations in the pathogenesis of HCC. A significant number of genes that promote or suppress HCC cell growth have been identified at the sites of genomic reorganization. Notwithstanding the accumulation of multiple genetic alterations, highly recurrent changes on a single chromosome can alter the expression of oncogenes and tumor suppressor genes (TSGs) whose deregulation may be sufficient to drive the progression of normal hepatocytes to malignancy. A distinct and highly recurrent pattern of genomic imbalances in HCC includes the loss of DNA copy number (associated with loss of heterozygosity) of TSG-containing chromosome 8p and gain of DNA copy number or regional amplification of protooncogenes on chromosome 8q. Even though 8p is relatively small, it carries an unusually large number of TSGs, while, on the other side, several oncogenes are dispersed along 8q. Compelling evidence demonstrates that DLC1, a potent TSG on 8p, and MYC oncogene on 8q play a critical role in the pathogenesis of human HCC. Direct evidence for their role in the genesis of HCC has been obtained in a mosaic mouse model. Knockdown of DLC1 helps MYC in the induction of hepatoblast transformation in vitro, and in the development of HCC in vivo. Therapeutic interventions, which would simultaneously target signaling pathways governing both DLC1 and MYC functions in hepatocarcinogenesis, could

  5. Automated Entire Thrombus Density Measurements for Robust and Comprehensive Thrombus Characterization in Patients with Acute Ischemic Stroke

    NARCIS (Netherlands)

    Santos, Emilie M M; Niessen, Wiro J; Yoo, Albert J; Berkhemer, Olvert A; Beenen, Ludo F; Majoie, Charles B; Marquering, Henk A; Vroomen, P.C.

    2016-01-01

    BACKGROUND AND PURPOSE: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to

  6. 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.

  7. Preclinical trials for prevention of tumor progression of hepatocellular carcinoma by LZ-8 targeting c-Met dependent and independent pathways.

    Directory of Open Access Journals (Sweden)

    Jia-Ru Wu

    Full Text Available Hepatocellular carcinoma (HCC is among the most lethal cancers. Mounting studies highlighted the essential role of the HGF/c-MET axis in driving HCC tumor progression. Therefore, c-Met is a potential therapeutic target for HCC. However, several concerns remain unresolved in c-Met targeting. First, the status of active c-Met in HCC must be screened to determine patients suitable for therapy. Second, resistance and side effects have been observed frequently when using conventional c-Met inhibitors. Thus, a preclinical system for screening the status of c-Met signaling and identifying efficient and safe anti-HCC agents is urgently required. In this study, immunohistochemical staining of phosphorylated c-Met (Tyr1234 on tissue sections indicated that HCCs with positive c-Met signaling accounted for approximately 46% in 26 cases. Second, many patient-derived HCC cell lines were established and characterized according to motility and c-Met signaling status. Moreover, LZ8, a medicinal peptide purified from the herb Lingzhi, featuring immunomodulatory and anticancer properties, was capable of suppressing cell migration and slightly reducing the survival rate of both c-Met positive and negative HCCs, HCC372, and HCC329, respectively. LZ8 also suppressed the intrahepatic metastasis of HCC329 in SCID mice. On the molecular level, LZ8 suppressed the expression of c-Met and phosphorylation of c-Met, ERK and AKT in HCC372, and suppressed the phosphorylation of JNK, ERK, and AKT in HCC329. According to receptor array screening, the major receptor tyrosine kinase activated in HCC329 was found to be the epidermal growth factor receptor (EGFR. Moreover, tyrosine-phosphorylated EGFR (the active EGFR was greatly suppressed in HCC329 by LZ8 treatment. In addition, LZ8 blocked HGF-induced cell migration and c-Met-dependent signaling in HepG2. In summary, we designed a preclinical trial using LZ8 to prevent the tumor progression of patient-derived HCCs with c

  8. 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 ...... 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....

  9. Clinical significance of half-lives of tumor markers α-fetoprotein and des-γ-carboxy prothrombin after hepatectomy for hepatocellular carcinoma.

    Science.gov (United States)

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

    2017-08-10

    The prognostic significance of the half-lives (HLs) of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) is unclear. We evaluated the HLs of AFP and DCP in a cohort of such patients. This study included data on 202 patients with HCC who underwent curative hepatectomy and had preoperative AFP concentrations ≥100 ng/mL or DCP ≥200 mAU/mL. We calculated the HLs of AFP and DCP from their values just before and 1 month after hepatectomy. We identified three groups: a normalization group, tumor marker concentrations within normal range 1 month post-hepatectomy; a long group, HL of AFP ≥7 days or DCP ≥4 days; and a short group, remaining patients. We evaluated associations between HL and prognosis. Three-year recurrence-free survival (RFS) in the normalization (n = 70), short (n = 71), and long groups (n = 61) was 41.3%, 46.0%, and 16.8%, respectively (P = 0.002). Five-year overall survival (OS) of normalization, short, and long groups was 72.6, 70.6 and 43.8%, respectively (P = 0.002). Multivariate analysis revealed that long HL is an independent risk factor for poor RFS (hazard ratio [HR] 2.21, P = 0.0006) and poor OS (HR 2.70, P = 0.004). The extrahepatic recurrence rate was 21.3% (13/61) in the long group, which is higher than in the normalization group (8.6%, 6/70) (P = 0.04) and short group (9.9%, 7/71) (P = 0.07). Post-hepatectomy HLs of AFP and DCP are predictors of long-term outcome in patients with HCC. © 2017 The Japan Society of Hepatology.

  10. 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

  11. Cellular apoptosis susceptibility (CAS) is linked to integrin ?1 and required for tumor cell migration and invasion in hepatocellular carcinoma (HCC)

    OpenAIRE

    Winkler, Juliane; Roessler, Stephanie; Sticht, Carsten; DiGuilio, Amanda L.; Drucker, Elisabeth; Holzer, Kerstin; Eiteneuer, Eva; Herpel, Esther; Breuhahn, Kai; Gretz, Norbert; Schirmacher, Peter; Ori, Alessandro; Singer, Stephan

    2016-01-01

    Importins and exportins represent an integral part of the nucleocytoplasmic transport machinery with fundamental importance for eukaryotic cell function. A variety of malignancies including hepatocellular carcinoma (HCC) show de-regulation of nuclear transport factors such as overexpression of the exportin Cellular Apoptosis Susceptibility (CAS). The functional implications of CAS in hepatocarcinogenesis remain, however, poorly understood. Here we integrated proteomics, transcriptomics and fu...

  12. Initial robotic assistance in the surgical management of renal cell carcinoma with level 4 cavoatrial thrombus.

    Science.gov (United States)

    Palma-Zamora, Isaac; Dalela, Deepansh; Barod, Ravi; Hsu, Linda; Menon, Mani; Rogers, Craig G

    2017-12-04

    We report a case of left-sided renal cell carcinoma (RCC) with level 4 cavoatrial tumor thrombus where robotic assistance was used to achieve hemostasis around the kidney in order to minimize coagulopathic hemorrhage from the nephrectomy bed during subsequent open completion nephrectomy and cavoatrial thrombectomy under extracorporeal circulation and hypothermic circulatory arrest. Robotic assistance allowed for meticulous dissection and ligation of parasitic and arterial vessels to the kidney, release of renal attachments, and exposure of the inferior vena cava. The kidney was mobilized while leaving the renal vein attached and tumor thrombus undisturbed using a "minimal touch" technique. Open completion nephrectomy and cavoatrial thrombectomy was then performed. An experienced cardiac anesthesia team performed intraoperative cardiac monitoring, including trans-esophageal echocardiography. A cardiothoracic surgeon was immediately available throughout the case. Cardiopulmonary bypass was initiated within 60 min of open incision with a total duration a circulatory arrest time of 25 min. There was no bleeding from the nephrectomy bed during bypass despite heparinization and hypothermia. A left RCC with level 4 thrombus may be approached with initial robotic assistance to achieve hemostasis of the nephrectomy bed for subsequent open completion nephrectomy and cavoatrial thrombectomy under extracorporeal circulation and hypothermic circulatory arrest.

  13. Thrombus imaging in acute stroke: correlation of thrombus length on susceptibility-weighted imaging with endovascular reperfusion success

    Energy Technology Data Exchange (ETDEWEB)

    Weisstanner, Christian; Gratz, Pascal P.; Schroth, Gerhard; Verma, Rajeev K.; Koechl, Arnold; Gralla, Jan; Zubler, Christoph; Hsieh, Kety; Mordasini, Pasquale; El-Koussy, Marwan [Bern University Hospital and University of Bern, Department of Diagnostic and Interventional Neuroradiology, Inselspital, Bern (Switzerland); Jung, Simon [Bern University Hospital and University of Bern, Department of Diagnostic and Interventional Neuroradiology, Inselspital, Bern (Switzerland); Bern University Hospital and University of Bern, Department of Neurology, Inselspital, Bern (Switzerland); Arnold, Marcel [Bern University Hospital and University of Bern, Department of Neurology, Inselspital, Bern (Switzerland)

    2014-08-15

    Susceptibility-weighted imaging (SWI) enables visualization of thrombotic material in acute ischemic stroke. We aimed to validate the accuracy of thrombus depiction on SWI compared to time-of-flight MRA (TOF-MRA), first-pass gadolinium-enhanced MRA (GE-MRA) and digital subtraction angiography (DSA). Furthermore, we analysed the impact of thrombus length on reperfusion success with endovascular therapy. Consecutive patients with acute ischemic stroke due to middle cerebral artery (MCA) occlusions undergoing endovascular recanalization were screened. Only patients with a pretreatment SWI were included. Thrombus visibility and location on SWI were compared to those on TOF-MRA, GE-MRA and DSA. The association between thrombus length on SWI and reperfusion success was studied. Eighty-four of the 88 patients included (95.5 %) showed an MCA thrombus on SWI. Strong correlations between thrombus location on SWI and that on TOF-MRA (Pearson's correlation coefficient 0.918, P < 0.001), GE-MRA (0.887, P < 0.001) and DSA (0.841, P < 0.001) were observed. Successful reperfusion was not significantly related to thrombus length on SWI (P = 0.153; binary logistic regression). In MCA occlusion thrombus location as seen on SWI correlates well with angiographic findings. In contrast to intravenous thrombolysis, thrombus length appears to have no impact on reperfusion success of endovascular therapy. (orig.)

  14. 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

  15. Validation of the Concept of a Common Typical Time of Disease Duration for Hepatocellular Carcinoma Patients Using the Fisher Information Processing of Tumor Imaging Results Combined With Network Phenotyping Strategy Quantification of Individual Patient Clinical Profile Patterns.

    Science.gov (United States)

    Pančoška, Petr; Skála, Lubomír; Nešetřil, Jaroslav; Carr, Brian I

    2015-08-01

    A primary goal of current clinical cancer research is the identification of prognostic tumor subtypes. It is increasingly clear that tumor growth depends on both internal tumor factors, and factors that are external to the tumor, such as microenvironment. We recently showed that parameter values alone are less important than the patterns of all patient parameters together for the identification of prognostic subtypes and have identified a network phenotyping strategy method to quantitatively describe the dependency of the tumor on the environment, to characterize hepatocellular carcinoma (HCC) subtypes. We have also shown that information about tumor mass together with patterns of other prognostic factors is related to survival. We now use a different patient cohort to validate this prognostic approach. A main finding is our identification of a common time of total disease duration (TDD) for every HCC patient. Clinical prognosis at the time of baseline patient evaluation is then calculable as the difference between TDD and the time from disease onset to diagnosis (T(onset)). We show that the total pattern of all parameter values and the differences in the relationships between this pattern and a reference pattern that, together with the tumor mass, best reflects the patient's prognosis at baseline. Our approach led us to identify 15 different composite HCC subtypes. Our results highlight the nearly identical TDD in all patients, which must therefore be a characteristic of the HCC disease, as opposed to the variable quantity of T(onset), which is impacted by multiple macro- and micro-environmental factors. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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.

  17. 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.

  18. Hepatocellular carcinoma: epidemiology and risk factors

    Directory of Open Access Journals (Sweden)

    Kew MC

    2014-08-01

    Full Text Available Michael C Kew Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa Abstract: Hepatocellular carcinoma is one of the major malignant tumors in the world today. The number of new cases of the tumor increases year by year, and hepatocellular carcinoma almost always runs a fulminant course and carries an especially grave prognosis. It has a low resectability rate and a high recurrence rate after surgical intervention, and responds poorly to anticancer drugs and radiotherapy. Hepatocellular carcinoma does not have a uniform geographical distribution: rather, very high incidences occur in Eastern and Southeastern Asia and in sub-Saharan Black Africans. In these regions and populations, the tumor shows a distinct shift in age distribution toward the younger ages, seen to greatest extent in sub-Saharan Black Africans. In all populations, males are more commonly affected. The most common risk factors for hepatocellular carcinoma in resource-poor populations with a high incidence of the tumor are chronic hepatitis B virus infection and dietary exposure to the fungal hepatocarcinogen aflatoxin B1. These two causative agents act either singly or synergistically. Both the viral infection and exposure to the fungus occur from early childhood, and the tumor typically presents at an early age. Chronic hepatitis C virus infection is an important cause of hepatocellular carcinoma in resource-rich countries with a low incidence of the tumor. The infection is acquired in adulthood and hepatocellular carcinoma occurs later than it does with hepatitis B virus-induced tumors. In recent years, obesity and the metabolic syndrome have increased markedly in incidence and importance as a cause of hepatocellular carcinoma in some resource-rich regions. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. Excessive iron

  19. Echocardiographic Algorithm for Post-Myocardial Infarction LV Thrombus: A Gatekeeper for Thrombus Evaluation by Delayed Enhancement CMR.

    Science.gov (United States)

    Weinsaft, Jonathan W; Kim, Jiwon; Medicherla, Chaitanya B; Ma, Claudia L; Codella, Noel C F; Kukar, Nina; Alaref, Subhi; Kim, Raymond J; Devereux, Richard B

    2016-05-01

    The goal of this study was to determine the prevalence of post-myocardial infarction (MI) left ventricular (LV) thrombus in the current era and to develop an effective algorithm (predicated on echocardiography [echo]) to discern patients warranting further testing for thrombus via delayed enhancement (DE) cardiac magnetic resonance (CMR). LV thrombus affects post-MI management. DE-CMR provides thrombus tissue characterization and is a well-validated but an impractical screening modality for all patients after an MI. A same-day echo and CMR were performed according to a tailored protocol, which entailed uniform echo contrast (irrespective of image quality) and dedicated DE-CMR for thrombus tissue characterization. A total of 201 patients were studied; 8% had thrombus according to DE-CMR. All thrombi were apically located; 94% of thrombi occurred in the context of a left anterior descending (LAD) infarct-related artery. Although patients with thrombus had more prolonged chest pain and larger MI (p ≤ 0.01), only 18% had aneurysm on echo (cine-CMR 24%). Noncontrast (35%) and contrast (64%) echo yielded limited sensitivity for thrombus on DE-CMR. Thrombus was associated with stepwise increments in basal → apical contractile dysfunction on echo and quantitative cine-CMR; the echo-measured apical wall motion score was higher among patients with thrombus (p improved overall performance (area under the curve 0.89 ± 0.44) for thrombus compared with ejection fraction (area under the curve 0.80 ± 0.61; p = 0.01). Apical wall motion partitions would have enabled all patients with LV thrombus to be appropriately referred for DE-CMR testing (100% sensitivity and negative predictive value), while avoiding further testing in more than one-half (56% to 63%) of patients. LV thrombus remains common, especially after LAD MI, and can occur even in the absence of aneurysm. Although DE-CMR yielded improved overall thrombus detection, apical wall motion on a noncontrast

  20. Diagnosis, staging and treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    A.V.C. França

    2004-11-01

    Full Text Available Hepatocellular carcinomas are aggressive tumors with a high dissemination power. An early diagnosis of these tumors is of great importance in order to offer the possibility of curative treatment. For an early diagnosis, abdominal ultrasound and serum alpha-fetoprotein determinations at 6-month intervals are suggested for all patients with cirrhosis of the liver, since this disease is considered to be the main risk factor for the development of the neoplasia. Helicoidal computed tomography, magnetic resonance and/or hepatic arteriography are suggested for diagnostic confirmation and tumor staging. The need to obtain a fragment of the focal lesion for cytology and/or histology for a diagnosis of hepatocellular carcinoma depends on the inability of imaging methods to diagnose the lesion. Several classifications are currently available for tumor staging in order to determine patient prognosis. All take into consideration not only the stage of the tumor but also the degree of hepatocellular dysfunction, which is known to be the main factor related to patient survival. Classifications, however, fail to correlate treatment with prognosis and cannot suggest the ideal treatment for each tumor stage. The Barcelona Classification (BCLC attempts to correlate tumor stage with treatment but requires prospective studies for validation. For single tumors smaller than 5 cm or up to three nodules smaller than 3 cm, surgical resection, liver transplantation and percutaneous treatment may offer good anti-tumoral results, as well as improved patient survival. Embolization or chemoembolization are therapeutic alternatives for patients who do not benefit from curative therapies.

  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...... of intraluminal thrombus specimens to the appearance on magnetic resonance imaging....

  2. Detection of extracellular genomic DNA scaffold in human thrombus

    DEFF Research Database (Denmark)

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

    2012-01-01

    PURPOSE: Mechanisms underlying transition of a thrombus susceptible to tissue plasminogen activator (TPA) fibrinolysis to one that is resistant is unclear. Demonstration of a new possible thrombus scaffold may open new avenues of research in thrombolysis and may provide mechanistic insight into t...

  3. Two-photon intravital imaging of thrombus development

    Science.gov (United States)

    Kamocka, Malgorzata M.; Mu, Jian; Liu, Xiaomin; Chen, Nan; Zollman, Amy; Sturonas-Brown, Barbara; Dunn, Kenneth; Xu, Zhiliang; Chen, Danny Z.; Alber, Mark S.; Rosen, Elliot D.

    2010-01-01

    Thrombus development in mouse mesenteric vessels following laser-induced injury was monitored by high-resolution, near-real-time, two-photon, intravital microscopy. In addition to the use of fluorescently tagged fibrin(ogen) and platelets, plasma was labeled with fluorescently tagged dextran. Because blood cells exclude the dextran in the single plane, blood cells appear as black silhouettes. Thus, in addition to monitoring the accumulation of platelets and fibrin in the thrombus, the protocol detects the movement and incorporation of unlabeled cells in and around it. The developing thrombus perturbs the blood flow near the thrombus surface, which affects the incorporation of platelets and blood cells into the structure. The hemodynamic effects and incorporation of blood cells lead to the development of thrombi with heterogeneous domain structures. Additionally, image processing algorithms and simulations were used to quantify structural features of developing thrombi. This analysis suggests a novel mechanism to stop the growth of developing thrombus.

  4. Liver (Hepatocellular) Cancer Prevention

    Science.gov (United States)

    ... Treatment Liver Cancer Prevention Liver Cancer Screening Research Liver (Hepatocellular) Cancer Prevention (PDQ®)–Patient Version What is ... to keep cancer from starting. General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer is a ...

  5. 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 ...

  6. Radiotherapy for metastatic fibrolamellar hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Justin G. Peacock

    2013-07-01

    Full Text Available Fibrolamellar hepatocellular carcinoma (FLHCC is a rare variant of hepatocellular carcinoma (HCC that commonly affects young individuals without a prior history of liver disease. FLHCC commonly results in a better prognosis than HCC; however, the risk of recurrence and metastatic disease is high. FLHCC is typically treated by primary resection of the tumor with 50-75% cure rates. The use of radiation therapy in FLHCC has not been assessed on its own, and may show some success in a very few reported combination therapy cases. We report on the successful use of radiation therapy in a case of metastatic FLHCC to the lung following primary and secondary resections. Our treatment of the large, metastatic, pulmonary FLHCC tumor with 40 Gy in 10 fractions resulted in an 85.9% tumor volume decrease over six months. This suggests FLHCC may be a radiosensitive tumor and radiotherapy may be valuable in unresectable or metastatic tumors.

  7. Effects of Attenuation and Thrombus Age on the Success of Ultrasound and Microbubble Mediated Thrombus Dissolution

    Science.gov (United States)

    Xie, Feng; Everbach, Carr; Gao, Shunji; Drvol, Lucas K; Shi, William T; Vignon, Francois; Powers, Jeff E; Lof, John; Porter, Thomas R

    2010-01-01

    The purpose of this study was to examine the effects of applied mechanical index, incident angle, attenuation, and thrombus age on the ability of 2D versus 3D diagnostic ultrasound and microbubbles to dissolve thrombi. A total of 180 occlusive porcine arterial thrombi of varying age (3 or 6 hours) were examined in a flow system. A tissue-mimicking phantom of varying thickness (5–10 cm) was placed over the thrombosed vessel and the 2D or 3D diagnostic transducer aligned with the thrombosed vessel using a positioning system. Diluted lipid encapsulated microbubbles were infused during ultrasound application. Percent thrombus dissolution (%TD) was calculated by comparison of clot mass before and after treatment. Both 2D and 3D guided ultrasound increased % TD compared to microbubbles alone, but % TD achieved with six hour old thrombi was significantly less than three hour old thrombi. Thrombus dissolution was achieved at 10 cm tissue mimicking depths, even without inertial cavitation. In conclusion, diagnostic 2D or 3D ultrasound can dissolve thrombi with intravenous non-targeted MB even at tissue attenuation distances of up to 10 centimeters. This treatment modality is less effective, however, for older aged thrombi. PMID:21208727

  8. 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.

  9. Hepatocellular adenoma: Classification, variants and clinical relevance.

    Science.gov (United States)

    Bioulac-Sage, Paulette; Sempoux, Christine; Balabaud, Charles

    2017-03-01

    Hepatocellular adenomas are benign tumors with two major complications, bleeding and malignant transformation. The overall narrative of hepatocellular adenoma has evolved over time. Solitary or multiple hepatocellular developing in the normal liver of women of child bearing age exposed to oral contraceptives still represents the most frequent clinical context, however, new associations are being recognized. Hepatocellular adenoma is discovered on a background of liver diseases such as non-alcoholic steatohepatitis, vascular diseases, and alcoholic cirrhosis. Hepatocellular adenoma is also reported in men, young or older adults, and even in infants. On the morpho-molecular side, the great leap forward was the discovery that hepatocellular adenoma was not a single entity and that at least 3 different subtypes exist, with specific underlying gene mutations. These mutations affect the HNF1A gene, several genes leading to JAK/STAT3 pathway activation and the CTNNB1 gene. All of them are associated with more or less specific histopathological characteristics and can be recognized using immunohistochemistry either with specific antibodies or with surrogate markers. Liver pathologists and radiologists are the key actors in the identification of the different subtypes of hepatocellular adenoma by the recognition of their specific morphological features. The major impact of the classification of hepatocellular adenoma is to identify subjects who are at higher risk of malignant transformation. With the development of new molecular technologies, there is hope for a better understanding of the natural history of the different subtypes, and, particularly for their mechanisms of malignant transformation. Copyright © 2017. Published by Elsevier Inc.

  10. ANGIOSCOPIC VERSUS ANGIOGRAPHIC DETECTION OF INTIMAL DISSECTION AND INTRACORONARY THROMBUS

    NARCIS (Netherlands)

    DENHEIJER, P; FOLEY, DP; ESCANED, J; HILLEGE, HL; VANDIJK, RB; SERRUYS, PW; LIE, KI

    Objectives. This study was undertaken to compare coronary angioscopy with angiography for the detection of intimal dissection and intracoronary thrombus. Background. It has been demonstrated previously that coronary angioscopy provides more intravascular detail than cineangiography. Both imaging

  11. Angioscopic versus angiographic detection of intimal dissection and intracoronary thrombus

    NARCIS (Netherlands)

    J. Escaned (Javier); H.L. Hillege (Hans); R.B. van Dijk (René); P.W.J.C. Serruys (Patrick); K.I. Lie (Kong); D.P. Foley (David); P. den Heijer (Peter)

    1994-01-01

    textabstractOBJECTIVES: This study was undertaken to compare coronary angioscopy with angiography for the detection of intimal dissection and intracoronary thrombus. BACKGROUND. It has been demonstrated previously that coronary angioscopy provides more intravascular detail than cineangiography. Both

  12. Glutathione treatment of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Dalhoff, K; Ranek, L; Mantoni, M

    1992-01-01

    abnormal alfa-1-fetoprotein (AFP) returned to normal after GSH treatment. AFP remained normal throughout the treatment period in the other women. These observations indicate that GSH may have a sex-dependent effect on HCC. However, further studies involving more patients are required to pursue......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...... daily from the time of diagnosis. Two patients withdrew shortly after receiving GSH due to intolerable side-effects. Of the six eligible patients, two had mildly advanced tumors and four moderately advanced tumors. At 1-2-month intervals the liver was CT and ultra-sound scanned to assess the growth...

  13. Reduced expression of TANGO in colon and hepatocellular carcinomas.

    Science.gov (United States)

    Arndt, Stephanie; Bosserhoff, Anja K

    2007-10-01

    The TANGO gene was originally identified as a new family member of the MIA gene family. The gene codes for a 14-kDa protein of so far unknown function. Recently, we identified TANGO as a tumor suppressor in malignant melanoma. In this study we evaluated TANGO transcription in different colon and hepatocellular carcinoma cell lines and tissue samples, to analyze whether loss of TANGO expression is a more general process in tumor development. TANGO was down-regulated or lost in all hepatocellular and colon cell lines compared to primary human hepatocytes or normal colon epithelial cells, respectively, and in most of the tumor samples compared to non-tumorous tissue. These results were confirmed in situ by immunohistochemistry on paraffin-embedded sections of colon and hepatocellular tumors. Functional assays with exogenous TANGO treatment of colon and hepatoma cell lines revealed reduced motility and invasion capacity. Our studies present for the first time the down-regulation of TANGO in colon and hepatocellular carcinoma and provide the first indications for a tumor suppressor role of the TANGO gene in human colon and hepatocellular carcinoma. Thus, functional relevant loss of TANGO expression may contribute to general tumor development and progression, and may provide a new target for therapeutic strategies.

  14. HVJ-liposome-mediated transfection of HSVtk gene driven by AFP promoter inhibits hepatic tumor growth of hepatocellular carcinoma in SCID mice.

    Science.gov (United States)

    Hirano, T; Kaneko, S; Kaneda, Y; Saito, I; Tamaoki, T; Furuyama, J; Tamaoki, T; Kobayashi, K; Ueki, T; Fujimoto, J

    2001-01-01

    Suicide gene therapy using ganciclovir (GCV) with transfection of the herpes thymidine kinase (HSVtk) gene has been studied for cancer therapy. The present study demonstrates an efficient method of suicide gene therapy for multiple hepatic tumors, involving repetitive transfection of the HSVtk gene driven by the alpha-fetoprotein (AFP) promoter using hemagglutinating virus of Japan (HVJ)-liposomes. AFP-producing cells (HUH7) and AFP-nonproducing cells (LS180) were injected subcutaneously (s.c.) to establish tumors in nude mice. Two plasmid constructs, bacterial LacZ gene driven by the AFP promoter (AFPLacZ), and HSVtk gene driven by the AFP promoter (AFPTK1) were encapsulated into the HVJ-liposome and used. When AFPLacZ was injected into the s.c. tumors, expression of LacZ gene was confined to HUH7 tumors. Repeated transfection of AFPTK1 followed by GCV treatment markedly suppressed growth of HUH7 tumors, and apoptosis of HUH7 cells was recognized in the tumor. Next, HUH7 cells were injected into the portal vein in severe combined immunodeficiency mice to establish a hepatic tumor model. After inoculation with the tumor, HVJ-liposomes containing the AFPTK1 plasmid vector were injected into the portal vein via the splenic hilum, followed by GCV treatment. This gene therapy significantly inhibited the growth of tumors in the liver and markedly improved survival. Three injections of the AFPTK1 plasmid vector completely inhibited tumor growth. This procedure seems to have great potential for the treatment of multiple hepatic tumors.

  15. Modified transarterial chemoembolization with locoregional administration of sorafenib for treating hepatocellular carcinoma: feasibility, efficacy, and safety in the VX-2 rabbit liver tumor model.

    Science.gov (United States)

    Seidensticker, Max; Streit, Sebastian; Nass, Norbert; Wybranski, Christian; Jürgens, Julian; Brauner, Jan; Schulz, Nadine; Kalinski, Thomas; Seidensticker, Ricarda; Garlipp, Benjamin; Steffen, Ingo; Ricke, Jens; Dudeck, Oliver

    2016-01-01

    We aimed to assess the feasibility, efficacy and safety of a local application of sorafenib within a conventional transarterial chemoembolization in the VX-2 tumor-bearing rabbit model. VX-2 tumors were induced in the left liver lobe of 10 New Zealand White rabbits. After two weeks, growth was verified by contrast-enhanced computed tomography (CT). Five rabbits were treated by transarterial chemoembolization using an emulsion of sorafenib and ethiodized oil (referred to as SORATACE; n=5). Rabbits receiving oral sorafenib for two weeks (n=2) and untreated rabbits (n=3) served as controls. After two weeks, contrast-enhanced CT was performed, followed by animal necropsy. The change in tumor diameter between baseline and follow-up was significantly different in the SORATACE group compared with the other groups; tumor shrinkage was observed in the SORATACE group only (P = 0.016). In both control groups, preserved hypervascularity was seen in the follow-up CT in all but one tumor. All tumors in the SORATACE group were devascularized in the follow-up CT. Importantly, substantial parenchymal damage in nontargeted areas of the tumor-bearing liver lobe was seen in rabbits treated with SORATACE. SORATACE demonstrated high efficacy in the treatment of experimental VX-2 liver tumors but was also associated with substantial liver parenchymal toxicity.

  16. Effects of Attenuation and Thrombus Age on the Success of Ultrasound and Microbubble Mediated Thrombus Dissolution

    OpenAIRE

    Xie, Feng; Everbach, Carr; Gao, Shunji; Drvol, Lucas K; Shi, William T; Vignon, Francois; Powers, Jeff E; Lof, John; Porter, Thomas R

    2011-01-01

    The purpose of this study was to examine the effects of applied mechanical index, incident angle, attenuation, and thrombus age on the ability of 2D versus 3D diagnostic ultrasound and microbubbles to dissolve thrombi. A total of 180 occlusive porcine arterial thrombi of varying age (3 or 6 hours) were examined in a flow system. A tissue-mimicking phantom of varying thickness (5–10 cm) was placed over the thrombosed vessel and the 2D or 3D diagnostic transducer aligned with the thrombosed ves...

  17. Genetic alteration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Chul; Kang, Tae Woong; Lee, Jin Oh [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Seoul (Korea, Republic of)

    1994-12-01

    Cancer of stomach, colon and liver are a group of the most common cancer in Korea. However, results with current therapeutic modalities are still unsatisfactory. The intensive efforts have been made to understand basic pathogenesis and to find better therapeutic tools for the treatment of this miserable disease. We studied the alteration of tumor suppressor genes and oncogenes in hepatocellular carcinoma in Korea. We found that alteration of Rb gene, APC were 33 %, 13 % respectively. But alterations of oncogenes such as myc, ras and mdm2 were rarely found. Our results suggests that HBV may act as oncogenic role in hepatocarcinogenesis instead of oncogenes. 6 figs, 2 tabs. (Author).

  18. Incidence, histology and management of intraluminal thrombus at post-chemotherapy retroperitoneal lymph node dissection.

    Science.gov (United States)

    Johnston, Paul; Beck, Stephen D W; Cheng, Liang; Masterson, Timothy A; Bihrle, Richard; Kesler, Kenneth; Foster, Richard S

    2013-09-01

    We determined the incidence, histology and management of intraluminal thrombus in a large group of patients treated with post-chemotherapy retroperitoneal lymph node dissection. We queried the testicular cancer database at our institution from January 1990 to June 2010. Tumor resection en bloc with major vascular structures and/or thrombectomy at post-chemotherapy retroperitoneal lymph node dissection was done in 240 patients, of whom 89 had a total of 98 intraluminal thrombi involving major vasculature. The site of the 98 thrombi was the inferior vena cava (72), aorta (1) and renal vein (20). Management of the 72 vena caval thrombi included cavectomy (36), partial cavectomy (9) and thrombectomy (27). For the 20 renal vein thrombi management included nephrectomy (18) and thrombectomy (2). The single aortic thrombus was managed by aortic resection and replacement. Pathological evaluation revealed bland thrombi in 31 cases, necrosis in 23, teratoma in 28, active germ cell cancer in 12 and sarcoma in 4. In 40 patients a total of 71 additional procedures were required, including nephrectomy in 32, liver resection in 6, bowel resection in 7, thoracotomy in 6, vertebral resection in 3, orchiectomy in 11, and duodenal repair, ureteroureterotomy, stent removal, cholecystectomy, appendectomy and paraspinal tumor removal in 1 each. There were 17 Clavien III or worse complications in a total of 11 patients, including 2 deaths. Average estimated blood loss was 1,165 ml (range 200 to 7,000) and average hospital stay was 9.3 days (range 2 to 70). The incidence of intraluminal thrombus at post-chemotherapy retroperitoneal lymph node dissection is 5.8%. Cancer pathology was observed in 44.9% of cases. Surgeons who perform post-chemotherapy retroperitoneal lymph node dissection should be well versed in vascular techniques with respect to the major vasculature. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

  19. Preoperative maximal removal rate of technetium-99m-galactosyl-human serum albumin of the remnant liver is associated with postoperative tumor relapse in hepatitis C virus-related hepatocellular carcinoma.

    Science.gov (United States)

    Yano, Koichi; Kondo, Kazuhiro; Nanashima, Atsushi; Fujii, Yoshiro; Imamura, Naoya; Hiyoshi, Masahide; Hamada, Takeomi; Tsuchimochi, Yuki; Wada, Takashi; Mizutani, Yoichi; Hirai, Toshinori

    2017-11-02

    Prognosis in patients with hepatocellular carcinoma (HCC) is not only influenced by tumor-related factors but also by the background liver functions. The maximal removal rate of technetium-99m-galactosyl human serum albumin (GSA-Rmax) of the remnant liver (rGSA-Rmax) is a useful candidate for predicting the liver function and clarifying the relationship between the remnant liver functional reserve and tumor-free survival in patients who have undergone hepatectomy. One hundred and sixty-five patients with HCC who underwent curative hepatectomy were divided into three groups of hepatitis B virus (B-HCC; n=42), hepatitis C virus (C-HCC, n=58), and non-B, non-C (NBNC-HCC, n=65). The relationship between rGSA-Rmax and survival was examined by univariate and multivariate analyses. In the C-HCC group, the albumin, or LHL15, level was significantly lower, and alanine aminotransferase, ICGR15, and the prevalence of grade B liver damage were significantly higher than other two groups (P<0.05). GSA-Rmax or rGSA-Rmax was not different between the three groups. Lower GSA-Rmax and rGSA-Rmax were only significantly associated with lower tumor-free survival in the C-HCC group by the univariate analysis (P<0.05) but not significantly by the multivariate analysis. GSA-Rmax and rGSA-Rmax reflect the severity of liver dysfunction and furthermore, the lower rGSA-Rmax is useful as a complementary factor to predict the early HCC recurrence after hepatectomy.

  20. Radiotherapy for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tokuuye, Koichi; Sumi, Minako; Kagami, Yoshikazu; Murayama, Shigeyuki [National Cancer Center Hospital, Tokyo (Japan). Radiation Oncology Div.; Kawashima, Mitsuhiko; Ikeda, Hiroshi [National Cancer Center Hospital East, Chiba (Japan). Radiation Div.; Ueno, Hideki; Okusaka, Takuji; Okada, Shuichi [National Cancer Center Hospital, Tokyo (Japan). Internal Medicine Div.

    2000-09-01

    Purpose: To retrospectively evaluate the effectiveness of radiotherapy with or without transarterial embolization (TAE) and/or percutaneous ethanol injection (PEI) in patients with hepatocellular carcinoma who were ineligible for surgery. Patients and Methods: From October 1984 to November 1997, 62 patients underwent radiotherapy receiving 50 to 70 Gy in 25 to 35 treatments with or without transarterial embolization and/or percutaneous ethanol injection and were followed for a median period of 8.6 months (1.5 to 92 months). Results: Overall median survival rates were 9.5 months. Significant prognostic factors were the extent of pretreatment liver function impairment, radiation field size and the existence of tumor thrombosis. Six-month and 1-year local control rates were 67 and 54%, respectively. Seven of the 8 patients who suffered from hepatic failure had poor pretreatment liver functions. Conclusion: Radiotherapy with or without transarterial embolization and/or percutaneous ethanol injection appears effective in controlling hepatocellular carcinoma and prolonged survival. Individualized treatment strategies are presented depending on the tumor presentation and the degree of liver function impairment. (orig.) [German] Hintergrund: Retrospektive Evaluierung der Wirksamkeit einer Bestrahlung mit oder ohne transarterielle Embolisation oder perkutaner Alkoholinjektion bei Patienten mit inoperablem hepatozellulaeren Karzinom. Patienten und Methodik: Von Oktober 1984 bis November 1997 wurden 62 Patienten mit einer Gesamtdosis von 50 bis 70 Gy in 25 bis 35 Fraktionen mit oder ohne transarterielle Embolisation oder perkutane Alkoholinjektion behandelt. Der mediane Follow-up betrug 8,6 Monate (1,5 bis 92 Monate). Ergebnisse: Das mediane Gesamtueberleben betrug 9,5 Monate. Signifikante prognostische Einflussfaktoren waren das Ausmass der praetherapeutischen Leberfunktionseinschraenkung, die Bestrahlungsfeldgroesse und das Vorhandensein von Tumorthrombosen. Nach sechs

  1. Transcriptomic characterization of fibrolamellar hepatocellular carcinoma

    Science.gov (United States)

    Simon, Elana P.; Freije, Catherine A.; Farber, Benjamin A.; Lalazar, Gadi; Darcy, David G.; Honeyman, Joshua N.; Chiaroni-Clarke, Rachel; Dill, Brian D.; Molina, Henrik; Bhanot, Umesh K.; La Quaglia, Michael P.; Rosenberg, Brad R.; Simon, Sanford M.

    2015-01-01

    Fibrolamellar hepatocellular carcinoma (FLHCC) tumors all carry a deletion of ∼400 kb in chromosome 19, resulting in a fusion of the genes for the heat shock protein, DNAJ (Hsp40) homolog, subfamily B, member 1, DNAJB1, and the catalytic subunit of protein kinase A, PRKACA. The resulting chimeric transcript produces a fusion protein that retains kinase activity. No other recurrent genomic alterations have been identified. Here we characterize the molecular pathogenesis of FLHCC with transcriptome sequencing (RNA sequencing). Differential expression (tumor vs. adjacent normal tissue) was detected for more than 3,500 genes (log2 fold change ≥1, false discovery rate ≤0.01), many of which were distinct from those found in hepatocellular carcinoma. Expression of several known oncogenes, such as ErbB2 and Aurora Kinase A, was increased in tumor samples. These and other dysregulated genes may serve as potential targets for therapeutic intervention. PMID:26489647

  2. 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.

  3. Thrombus age, clinical presentation, and reperfusion grade in myocardial infarction.

    Science.gov (United States)

    Carol, Antoni; Bernet, Mariana; Curós, Antoni; Rodríguez-Leor, Oriol; Serra, Jordi; Fernández-Nofrerías, Eduard; Mauri, Josepa; Bayes-Genís, Antoni

    2014-01-01

    Autopsy studies show that dynamic coronary thrombosis leads to infarction. We studied intracoronary thrombus age in ST-segment elevation myocardial infarction (STEMI) and its relationship with clinical presentation and epicardial reperfusion grade. Intracoronary thrombectomy was performed in 131 STEMI patients within 24 h after symptom onset, and material sufficient for pathological analysis was retrieved from 81 patients. Thrombus age was classified as fresh (5days). A fresh thrombus was found in 48 patients (60%), whereas the thrombus showed lytic or organized changes in 33 patients (40%). Both thrombus and plaque material were aspirated in 40% of cases. Lytic or organized thrombi were aspirated in one third of the cases early (thrombi were also aspirated in one third of STEMI of>12h evolution. In multivariable analysis, fresh thrombus was associated with both persistent ST-segment elevation (even after 12 h of onset) during percutaneous coronary intervention [odds ratio (OR) 4.23, 95% confidence interval (CI) 1.05-17.42, P=.042) and a previous history of ischemic heart disease (OR 4.54, 95% CI 1.41-14.64, P=.011). There were no associations between thrombus composition and epicardial reperfusion grade or the presence of the no-reflow phenomenon. Plaque components were found in all cases of distal embolization (5%). Intracoronary thrombi aspirated in STEMI frequently show more than one stage of maturation. Fresh thrombi predominate in patients with known ischemic heart disease or persistent ST-segment elevation. In STEMI, thromboaspiration revealed thrombi at different stages of maturation, supporting a dynamic process of rupture and repair of the atherosclerotic plaque. Fresh thrombi were present more frequently within 12 h of infarction onset but also in patients with symptoms beyond 12 h. When containing plaque material, thrombi were often associated with macroscopic distal embolization during angioplasty. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Effects of heat stress on the level of heat shock protein 70 on the surface of hepatocellular carcinoma Hep G2 cells: implications for the treatment of tumors.

    Science.gov (United States)

    Cui, Naizhong; Xu, Yongping; Cao, Zhenhui; Xu, Fanxing; Zhang, Peng; Jin, Liji

    2013-04-01

    The ability to distinguish tumor cells from normal cells is vital to allow the immune system to selectively destroy tumor cells. In order to find an effective marker, we used enzyme-linked immunosorbent assay, immunocytochemistry, immunofluorescence, and flow cytometry to investigate the effects of heat stress on the amount of heat shock protein 70 on the surface of tumor cells (Hep G2 cells). Heat shock protein 70 is the major stress-induced heat shock protein found on the surface of tumor cells. Our results indicate that the percentage of Hep G2 cells with a detectable level of heat shock protein 70 on their cell surface increased significantly (P heat stress at 42 °C for 2 h (up to 1.92 times the level before heat treatment). The detectable level of heat shock protein 70 on the surface of Hep G2 cells reached its peak 12 h after treatment. However, the fluorescent intensity of stressed and unstressed Hep G2 cells was not significantly different (P > 0.05). The increase in the level of heat shock protein 70 on the surface of tumor cells following heat stress could provide a basis for finding novel immunotoxins as targets for drug action and may have application to be used in conjunction with hyperthermia in the treatment of tumors.

  5. Tumor

    Science.gov (United States)

    ... peanut plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by or linked with viruses are: Cervical cancer (human papillomavirus) Most anal cancers (human papillomavirus) Some ...

  6. Regulator of Calcineurin 1 Gene Isoform 4, Down-regulated in Hepatocellular Carcinoma, Prevents Proliferation, Migration, and Invasive Activity of Cancer Cells and Metastasis of Orthotopic Tumors by Inhibiting Nuclear Translocation of NFAT1.

    Science.gov (United States)

    Jin, Haojie; Wang, Cun; Jin, Guangzhi; Ruan, Haoyu; Gu, Dishui; Wei, Lin; Wang, Hui; Wang, Ning; Arunachalam, Einthavy; Zhang, Yurong; Deng, Xuan; Yang, Chen; Xiong, Yi; Feng, Hugang; Yao, Ming; Fang, Jingyuan; Gu, Jianren; Cong, Wenming; Qin, Wenxin

    2017-09-01

    Individuals with Down syndrome have a low risk for many solid tumors, prompting the search for tumor suppressor genes on human chromosome 21 (HSA21). We aimed to identify and explore potential mechanisms of tumor suppressors on HSA21 in hepatocellular carcinoma (HCC). We compared expression of HSA21 genes in 14 pairs of primary HCC and adjacent noncancer liver tissues using the Affymetrix HG-U133 Plus 2.0 array (Affymetrix, Santa Clara, CA). HCC tissues and adjacent normal liver tissues were collected from 108 patients at a hospital in China for real-time polymerase chain reaction and immunohistochemical analyses; expression levels of regulator of calcineurin 1 (RCAN1) isoform 4 (RCAN1.4) were associated with clinical features. We overexpressed RCAN1.4 from lentiviral vectors in MHCC97H and HCCLM3 cells and knocked expression down using small interfering RNAs in SMMC7721 and Huh7 cells. Cells were analyzed in proliferation, migration, and invasion assays. HCC cells that overexpressed RCAN1.4 or with RCAN1.4 knockdown were injected into livers or tail veins of nude mice; tumor growth and numbers of lung metastases were quantified. We performed bisulfite pyrosequencing and methylation-specific polymerase chain reaction analyses to analyze CpG island methylation. We measured phosphatase activity of calcineurin in HCC cells. RCAN1.4 mRNA and protein levels were significantly decreased in primary HCC compared with adjacent noncancer liver tissues. Reduced levels of RCAN1.4 mRNA were significantly associated with advanced tumor stages, poor differentiation, larger tumor size, and vascular invasion. Kaplan-Meier survival analysis showed that patients with HCCs with lower levels of RCAN1.4 mRNA had shorter time of overall survival and time to recurrence than patients whose tumors had high levels of RCAN1.4 mRNA. In HCC cell lines, expression of RCAN1.4 significantly reduced proliferation, migration, and invasive activity. HCC cells that overexpressed RCAN1.4 formed smaller

  7. 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

  8. Cellular apoptosis susceptibility (CAS) is linked to integrin β1 and required for tumor cell migration and invasion in hepatocellular carcinoma (HCC)

    Science.gov (United States)

    Winkler, Juliane; Roessler, Stephanie; Sticht, Carsten; DiGuilio, Amanda L.; Drucker, Elisabeth; Holzer, Kerstin; Eiteneuer, Eva; Herpel, Esther; Breuhahn, Kai; Gretz, Norbert; Schirmacher, Peter; Ori, Alessandro; Singer, Stephan

    2016-01-01

    Importins and exportins represent an integral part of the nucleocytoplasmic transport machinery with fundamental importance for eukaryotic cell function. A variety of malignancies including hepatocellular carcinoma (HCC) show de-regulation of nuclear transport factors such as overexpression of the exportin Cellular Apoptosis Susceptibility (CAS). The functional implications of CAS in hepatocarcinogenesis remain, however, poorly understood. Here we integrated proteomics, transcriptomics and functional assays with patient data to further characterize the role of CAS in HCC. By analyzing ∼ 1700 proteins using quantitative mass spectrometry in HCC cells we found that CAS depletion by RNAi leads to de-regulation of integrins, particularly down-regulation of integrin β1. Consistent with this finding, CAS knockdown resulted in substantially reduced migration and invasion of HCC cell lines as analyzed by 2D ‘scratch’ and invasion chamber assays, respectively. Supporting the potential in vivo relevance, high expression levels of CAS in HCC tissue samples were associated with macroangioinvasion and poorer patient outcome. Our data suggest a previously unanticipated link between CAS and integrin signaling which correlates with an aggressive HCC phenotype. PMID:27015362

  9. Cardiac Tumors; Tumeurs cardiaques

    Energy Technology Data Exchange (ETDEWEB)

    Laissy, J.P.; Fernandez, P. [Centre Hospitalier Universitaire Bichat Claude Bernard, Service d' Imagerie, 76 - Rouen (France); Mousseaux, E. [Hopital Europeen Georges Pompidou (HEGP), Service de Radiologie Cardio Vasculaire et Interventionnelle, 75 - Paris (France); Dacher, J.N. [Centre Hospitalier Universitaire Charles Nicolle, 75 - Rouen (France); Crochet, D. [Centre Hospitalier Universitaire, Hopital Laennec, Centre Hemodynamique, Radiologie Thoracique et Vasculaire, 44 - Nantes (France)

    2004-04-01

    Metastases are the most frequent tumors of the heart even though they seldom are recognized. Most primary cardiac tumors are benign. The main role of imaging is to differentiate a cardiac tumor from thrombus and rare pseudo-tumors: tuberculoma, hydatid cyst. Echocardiography is the fist line imaging technique to detect cardiac tumors, but CT and MRl arc useful for further characterization and differential diagnosis. Myxoma of the left atrium is the most frequent benign cardiac tumor. It usually is pedunculated and sometimes calcified. Sarcoma is the most frequent primary malignant tumor and usually presents as a sessile infiltrative tumor. Lymphoma and metastases are usually recognized by the presence of known tumor elsewhere of by characteristic direct contiguous involvement. Diagnosing primary and secondary pericardial tumors often is difficult. Imaging is valuable for diagnosis, characterization, pre-surgical evaluation and follow-up. (author)

  10. Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2.

    Science.gov (United States)

    Huang, Bee-Piao; Lin, Chun-Shiang; Wang, Chau-Jong; Kao, Shao-Hsuan

    2017-01-01

    Tumor necrosis factor alpha (TNFα) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNFα on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNFα stimulus. We observed that HepG2 cell revealed a higher resistance to TNFα-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By using a label-free quantitative proteomic analysis, we found that 520 proteins were differentially expressed in the HepG2 cells exposed to TNFα, including 211 up-regulated and 309 down-regulated proteins. We further confirmed several proteins with significant expression change (TNFα/control ratio>2.0 or expressed proteins using Gene ontology and KEGG annotations, and the results implicated that TNFα might regulate ribosome, spliceosome, antigen processing and presentation, and energy metabolism in HepG2 cells. Moreover, we demonstrated that upregulation of heat shock protein 70 (HSP70) was involved in both the promoted migration and the inhibited apoptosis of HepG2 cells in response to TNFα. Collectively, these findings indicate that TNFα alters protein expression such as HSP70, which triggering specific molecular processes and signaling cascades that promote migration and inhibit apoptosis of HepG2 cells.

  11. Atrial Thrombus in a Neonate: A Diagnostic Challenge

    Directory of Open Access Journals (Sweden)

    Alicia Sheen

    2015-04-01

    Full Text Available Introduction - Left atrial thrombus is a rare finding in a neonate. In the previous literature, atrial thrombi have been associated with catheter placement or congenital heart disease in a preterm infant. Case - We report the case of a full-term neonate with no known risk factors found to have a left atrial thrombus. The neonate was born at 38 weeks' gestation to a 31-year-old female via cesarean section who was sent to the normal nursery. On postnatal day 5, the infant was noted to have low-to-medium level of oxygen saturations (∼90% and was transferred to the neonatal intensive care unit with an echocardiogram completed on postnatal day 6 demonstrating a mobile, pedunculated mass attached to the left atrial septum with an appearance concerning for atrial myxoma. The infant underwent surgical resection on postnatal day 8 and pathology revealed the mass to be a left atrial thrombus. Discussion - The rare finding of an atrial thrombus in a neonate has previously been associated with central venous catheter placement or congenital heart disease. This case is unusual in that the patient had neither condition. Although echocardiogram findings appeared more consistent with atrial myxoma, final pathology revealed a left atrial thrombus. Additionally, hypercoagulability work-up for this neonate was largely negative. This report underscores the importance of identification, search for etiology, and prompt therapy to prevent potential catastrophic outcomes.

  12. Cellular prognostic markers in hepatocellular carcinoma.

    Science.gov (United States)

    Buonaguro, Luigi; Tagliamonte, Maria; Petrizzo, Annacarmen; Damiano, Elvira; Tornesello, Maria Lina; Buonaguro, Franco M

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the five big killers worldwide and is frequently associated with chronic hepatitis B and C virus (HBV and HCV) infections. Tumor microenvironment consists of a complex network of cells and factors that plays a key role in the tumor progression and prognosis. This is true also for HCC. Several studies have shown strikingly strong correlation between HCC clinical prognosis and intratumoral infiltration of cells affecting tumor growth, invasion, angiogenesis and metastasis. None of such cells is yet validated for routine diagnostic and prognostic assessment. The present review aims at providing a state-of-the-art of such studies.

  13. Results of surgical treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Adriano Miziara Gonzalez

    2004-12-01

    Full Text Available Objective: To perform a retrospective review of 14 patientssubmitted to surgical treatment of hepatocellular carcinoma atthe Universidade Federal de Sao Paulo – UNIFESP. Methods:Review of data obtained from 14 patients with hepatocellularcarcinoma submitted to surgical resection in the Discipline ofSurgical Gastroenterology, at the Universidade Federal de SaoPaulo - Escola Paulista de Medicina, from June 1992 to September1998. Results: Three patients (21.4% were female and 11 (78.6%were male. Ten patients (71.4% had disease-related symptoms;76.8% were classified as Child-Pugh A. Alpha-fetoprotein levelswere analyzed in 13 patients and were elevated in 65.1%. Allpatients had abdominal ultrasound and computerized tomographyscans compatible with hepatocellular carcinoma. Surgicalresections varied from segmetectomy to trisegmentectomy.Bleeding was the most common intraoperative complication andcaused one death. The most frequent postoperative complicationwas ascitis, followed by pleural effusion, encephalopathy and biliaryfistula. Tumor recurrence rate was 61.5% at one year and wasrelated to tumors larger than 5 cm, tumor invasion and absence ofa capsule, suggesting late diagnosis. Mean disease-free survivalrate was 17 months and mean survival rate was 21 months.Conclusion: The patients with hepatocellular carcinoma submittedto surgical resection had a high recurrence rate in a one-yearfollow-up, probably due to large tumor size, vascular invasion andabsence of a capsule. The importance of an early diagnosis isemphasized.

  14. The miR-545/374a cluster encoded in the Ftx lncRNA is overexpressed in HBV-related hepatocellular carcinoma and promotes tumorigenesis and tumor progression.

    Directory of Open Access Journals (Sweden)

    Qi Zhao

    Full Text Available Hepatitis B virus (HBV infection is a major risk factor for hepatocellular carcinoma (HCC. Previous studies have shown several long noncoding RNAs (lncRNAs play various roles in HCC progression, but no research has focused on the expression pattern of microRNA clusters encoded in lncRNAs. The Ftx gene encodes a lncRNA which harbors 2 clusters of microRNAs in its introns, the miR-374b/421 cluster and the miR-545/374a cluster. To date, no research has focused on the role of the miR-545/374a and miR-374b/421 clusters in HBV-related HCC. In this study, 66 pairs of HBV-related HCC tissue and matched non-cancerous liver tissue specimens were analyzed for the expression of the Ftx microRNA clusters. Our results showed that the miR-545/374a cluster was upregulated in HBV-HCC tissue and significantly correlated with prognosis-related clinical features, including histological grade, metastasis and tumor capsule. Transfection studies with microRNA mimics and inhibitors revealed that miR-545/374a expression promoted in vitro cell proliferation, cell migration and invasion. The wild-type HBV-genome-containing plasmid or full-length HBx protein encoding plasmid was transfected into the Bel-7402 cell line and observed for their influence on miR-545/374a expression. We found that transfection of the HBV genome or HBx alone resulted in an increase in miR-545/374a expression. Next, by monitoring the expression of sera miR-545/374a before and after surgical tumor excision, we found serum miR-545/374a was tumor-derived and exhibited a sharp decrease 25 days after tumor excision. We also examined the gender-based difference in miR-545/374a expression among HCC patients and utilized microRNA target prediction software to find the targets of miR-545/374a. One of these targets, namely estrogen-related receptor gamma (ESRRG was inversely correlated with miR-545 expression. In conclusion, the overexpression of miR-545/374a cluster located in the Ftx lncRNA is partially

  15. 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

  16. Synthetic thrombus model for in vitro studies of laser thrombolysis

    Energy Technology Data Exchange (ETDEWEB)

    Hermes, R.E.; Trajkovska, K.

    1998-07-01

    Laser thrombolysis is the controlled ablation of a thrombus (blood clot) blockage in a living arterial system. Theoretical modeling of the interaction of laser light with thrombi relies on the ability to perform in vitro experiments with well characterized surrogate materials. A synthetic thrombus formulation may offer more accurate results when compared to in vivo clinical experiments. The authors describe the development of new surrogate materials based on formulations incorporating chick egg, guar gum, modified food starch, and a laser light absorbing dye. The sound speed and physical consistency of the materials were very close to porcine (arterial) and human (venous) thrombi. Photographic and videotape recordings of pulsed dye laser ablation experiments under various experimental conditions were used to evaluate the new material as compared to in vitro tests with human (venous) thrombus. The characteristics of ablation and mass removal were similar to that of real thrombi, and therefore provide a more realistic model for in vitro laser thrombolysis when compared to gelatin.

  17. 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.

  18. 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.

  19. Generic thrombus segmentation from pre- and post-operative CTA.

    Science.gov (United States)

    Lalys, Florent; Yan, Vincent; Kaladji, Adrien; Lucas, Antoine; Esneault, Simon

    2017-09-01

    Abdominal aortic aneurysm (AAA) is a localized, permanent and irreversible enlargement of the artery, with the formation of thrombus into the inner wall of the aneurysm. A precise patient-specific segmentation of the thrombus is useful for both the pre-operative planning to estimate the rupture risk, and for post-operative assessment to monitor the disease evolution. This paper presents a generic approach for 3D segmentation of thrombus from patients suffering from AAA using computed tomography angiography (CTA) scans. A fast and versatile thrombus segmentation approach has been developed. It is composed of initial centerline detection and aorta lumen segmentation, an optimized pre-processing stage and the use of a 3D deformable model. The approach has been designed to be very generic and requires minimal user interaction. The proposed method was tested on different datasets with 145 patients overall, including pre- and post-operative CTAs, abdominal aorta and iliac artery sections, different calcification degrees, aneurysm sizes and contrast enhancement qualities. The thrombus segmentation approach showed very accurate results with respect to manual delineations for all datasets ([Formula: see text] and [Formula: see text] for abdominal aorta sections on pre-operative CTA, iliac artery sections on pre-operative CTAs and aorta sections on post-operative CTA, respectively). Experiments on the different patient and image conditions showed that the method was highly versatile, with no significant differences in term of precision. Comparison with the level-set algorithm also demonstrated the superiority of the 3D deformable model. Average processing time was [Formula: see text]. We presented a near-automatic and generic thrombus segmentation algorithm applicable to a large variability of patient and imaging conditions. When integrated in an endovascular planning system, our segmentation algorithm shows its compatibility with clinical routine and could be used for pre

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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

    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 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. RESULTS: 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...

  2. CD4+CD25+CD127low regulatory T cells play predominant anti-tumor suppressive role in hepatitis B virus associated hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Shreya eSharma

    2015-02-01

    Full Text Available Background:Hepatocellular carcinoma (HCC is the second leading cause of cancer death worldwide and hepatitis B is one of the commonest causes. T regulatory cells (Tregs are strong immunomodulators and are likely to play a major role in HCC development. HBV infection is reported to induce expansion of Tregs. We investigated the CD4+CD25+CD127-veFoxP3+ Tregs in HBV related HCC as compared to non-HBV-HCC. Patients and Methods: Whole blood Immunophenotyping was analysed by multicolor flow cytometry in patients with HBV related HCC (HBV-HCC, n=17, non-HBV-HCC (n=22; NASH =16, alcohol related=6 and chronic hepatitis B infection (CHBV; n=10.T regulatory cells and functionality was checked by in vitro suppression assays using CD4+ CD25+ CD127low T regulatory cells. Levels of serum alpha fetoprotein(AFP,expression of FoxP3, IL-10, PD-1, TGF-β and Notch in Tregs and liver explants was analyzed by flow cytometry, immuno-histochemistry and quantitative RT-PCR.Results:CD4+CD25+hi and Foxp3 expression in CD4+CD25+hiCD127low was significantly increased (P=0.04, P=0.007 in HBVHCC compared to non-HBVHCC and CHBV patients. HBVHCC also showed high IL-10and TGF-β secreting CD4+CD25+hiTregs.The PD1 expression in CD4+CD25+hi was significantly decreased in the HBVHCC than non-HBVHCC. In HBVHCC, AFP levels were significantly high (median 941, range 2-727940 than non-HBVHCC (median 13.5, range 2-18,900. In HBVHCC,patients with high AFP (range;3982-727940 ng/ml showed positive correlation with Foxp3 expression in CD4+CD25+hi CD127low(r=0.857,p=0.014. Reduced PD1 expression in HBVHCC also had negative correlation with FOXP3 in CD4+CD25+hi CD127low(r=-0.78, p=0.04. However, AFP levels in non-HBVHCC showed negative correlation with (R=-0.67, p=0.005 with CD4+CD25+hi Tregs. Conclusions:Our results demonstrates that CD4+ CD25+hi Tregs from HBVHCC patients have decreased expression of PD-1, resulting in higher IL-10 and TGF-β secretion. Increased suppressive ability of

  3. Adverse genomic alterations and stemness features are induced by field cancerization in the microenvironment of hepatocellular carcinomas

    DEFF Research Database (Denmark)

    Castven, Darko; Fischer, Michael; Becker, Diana

    2017-01-01

    Hepatocellular Carcinoma (HCC) commonly develops in chronically damaged liver tissues. The resulting regenerative and inflammatory processes create an adverse milieu that promotes tumor-initiation and progression. A better understanding of the hepatic tumor-microenvironment interaction might infe...

  4. Therapeutic and scintigraphic applications of polymeric micelles: combination of chemotherapy and radiotherapy in hepatocellular carcinoma.

    Science.gov (United States)

    Shih, Ying-Hsia; Peng, Cheng-Liang; Chiang, Ping-Fang; Lin, Wuu-Jyh; Luo, Tsai-Yueh; Shieh, Ming-Jium

    2015-01-01

    This study evaluated a multifunctional micelle simultaneously loaded with doxorubicin (Dox) and labeled with radionuclide rhenium-188 ((188)Re) as a combined radiotherapy and chemotherapy treatment for hepatocellular carcinoma. We investigated the single photon emission computed tomography, biodistribution, antitumor efficacy, and pathology of (188)Re-Dox micelles in a murine orthotopic luciferase-transfected BNL tumor cells hepatocellular carcinoma model. The single photon emission computed tomography and computed tomography images showed high radioactivity in the liver and tumor, which was in agreement with the biodistribution measured by γ-counting. In vivo bioluminescence images showed the smallest size tumor (Pchemotherapy to maximize the effectiveness of treatment for hepatocellular carcinoma.

  5. Submitral Left Ventricular Aneurysm Associated with Thrombus

    African Journals Online (AJOL)

    2018-01-01

    Jan 1, 2018 ... ventricular wall adjacent to the posterior leaflet of the mitral valve is the commonly reportedpresentation (3).Other less frequently associated causes are: Takayasu's arteritis, rheumatic fever, tuberculosis, infective endocarditis, ischemic heart disease, and vascular tumors. There are also other reported ...

  6. Profibrillatory effects of intracoronary thrombus in acute regional ischemia of the in situ porcine heart

    NARCIS (Netherlands)

    Coronel, R.; Wilms-Schopman, F. J.; Janse, M. J.

    1997-01-01

    BACKGROUND: An intracoronary thrombus during regional ischemia is related to life-threatening arrhythmias. The electrophysiological consequences of a thrombus are unknown. METHODS AND RESULTS: In open chest pigs, regional ischemia was induced by intracoronary injection of a thrombus (protocol 1). In

  7. Benign hepatocellular nodules : What have we learned using the patho-molecular classification

    NARCIS (Netherlands)

    Sempoux, Christine; Chang, Charissa; Gouw, Annette; Chiche, Laurence; Zucman-Rossi, Jessica; Balabaud, Charles; Bioulac-Sage, Paulette

    Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are benign hepatocellular tumors that develop most frequently in females and in non-cirrhotic livers. HCA are prone to bleed and to transform into hepatocellutar carcinoma (HCC). Four major subgroups of HCA have been thus far

  8. Role of coagulation in the recruitment of colon adenocarcinoma cells to thrombus under shear.

    Science.gov (United States)

    Baker-Groberg, Sandra M; Itakura, Asako; Gruber, András; McCarty, Owen J T

    2013-11-01

    Colorectal cancer metastases can appear on the peritoneum and in lymph nodes, liver, and lungs, suggesting both hematogenous and lymphatic spreading of the primary tumor. While antithrombotic agents have been shown to reduce both long-term incidence and metastasis, the role of coagulation in facilitating metastasis is ill defined. We investigated the kinetics and molecular mechanisms of metastatic colon adenocarcinoma cell recruitment to thrombi under shear flow, ex vivo. Platelet aggregates were formed by perfusing citrated anticoagulated whole blood over immobilized fibrinogen or fibrillar collagen. Thrombi were formed by perfusing recalcified whole blood over fibrinogen or fibrillar collagen in the presence of coagulation. Cultured colon adenocarcinoma cells (SW620) were perfused either during or following platelet aggregate or thrombus formation. The degree of transient tumor cell interactions (recruitment, rolling, and release) and the number of firmly adhered tumor cells were quantified using fluorescence microscopy. Platelet aggregates and thrombi formed on either fibrinogen- or fibrillar-collagen supported SW620 cell interactions and adhesion under shear. Thrombi or fibrin supported a greater degree of SW620 cell interactions and adhesion compared with platelet aggregates or fibrinogen, respectively, demonstrating that coagulation promoted SW620 cell recruitment under shear. Interestingly, in the absence of anticoagulation, we observed SW620 preferentially binding to thrombus-bound polymorphonuclear leukocytes (PMNs). The addition of purified PMNs to thrombi resulted in a doubling of the number of interacting and bound SW620 cells. Since thrombi often accumulate and activate leukocytes, our findings suggest that leukocytes may play a role in localizing metastases to sites of thrombogenesis.

  9. 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. In princ......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....... In principle, three different approaches can be used in the treatment of tumors with superparamagnetic iron oxide nanoparticles: magnetically induced hyperthermia, drug targeting and selective suppression of tumor growth. This review focuses on the use of iron oxide nanoparticles for the diagnosis...

  10. Relationship between thrombus attenuation and different stroke subtypes

    NARCIS (Netherlands)

    Niesten, J.M.; Schaaf, I.C. van der; Biessels, G.J.; Otterloo, A.E. van; Seeters, T. van; Horsch, A.D.; Luitse, M.J.; Graaf, Y. van der; Kappelle, L.J.; Mali, W.P.Th.; Velthuis, B.K.; Meijer, A.; Dijk, E.J. van

    2013-01-01

    INTRODUCTION: More insights in the etiopathogenesis of thrombi could be helpful in the treatment of patients with acute ischemic stroke. The aim of our study was to determine the relationship between presence of a hyperdense vessel sign and thrombus density with different stroke subtypes. METHODS:

  11. Hepatocellular carcinoma and lifestyles.

    Science.gov (United States)

    Saran, Uttara; Humar, Bostjan; Kolly, Philippe; Dufour, Jean-François

    2016-01-01

    The majority of hepatocellular carcinoma occurs over pre-existing chronic liver diseases that share cirrhosis as an endpoint. In the last decade, a strong association between lifestyle and hepatocellular carcinoma has become evident. Abundance of energy-rich food and sedentary lifestyles have caused metabolic conditions such as obesity and diabetes mellitus to become global epidemics. Obesity and diabetes mellitus are both tightly linked to non-alcoholic fatty liver disease and also increase hepatocellular carcinoma risk independent of cirrhosis. Emerging data suggest that physical activity not only counteracts obesity, diabetes mellitus and non-alcoholic fatty liver disease, but also reduces cancer risk. Physical activity exerts significant anticancer effects in the absence of metabolic disorders. Here, we present a systematic review on lifestyles and hepatocellular carcinoma. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  12. 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

    ) 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 vein......, as observed in human FL-HCC. CONCLUSIONS: Using CRISPR/Cas9 technology, we found generation of the Dnajb1-Prkaca fusion gene in wild-type mice to be sufficient to initiate formation of tumors that have many features of human FL-HCC. Strategies to block DNAJB1-PRKACA might be developed as therapeutics...

  13. Serum protein biomarkers relevant to hepatocellular carcinoma and their detection.

    Science.gov (United States)

    Waidely, Eric; Al-Yuobi, Abdul-Rahman Obaid; Bashammakh, A S; El-Shahawi, Mohammad S; Leblanc, Roger M

    2016-01-07

    Hepatocellular carcinoma (HCC) is one of the most recurrent and lethal cancers worldwide. The low survival rate of this particular strain of carcinoma is largely due to the late stages at which it is diagnosed. Tumorigenesis of hepatocellular carcinoma is most frequently detected through ultrasonography, magnetic resonance imaging and computerized tomography scans, however, these methods are poor for detection of early tumor development. This review presents alternative hepatocellular carcinoma detection techniques through the use of protein and enzyme/isozyme biomarkers. The detection methods used to determine the serum levels of α-fetoprotein (AFP), glypican-3 (GPC3), Golgi protein 73 (GP73), α-L-fucosidase (AFU), des-γ-carboxyprothrombin (DCP), γ-glutamyl transferase (GGT) and squamous cell carcinoma antigen (SCCA) are presented and each marker's respective validity in the diagnosis of hepatocellular carcinoma is evaluated.

  14. 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...... national and topic-specific databases, bibliographies, conference abstracts, journals, and grey literature. Furthermore, we reviewed the reference lists and contacted the principal authors of the identified studies. SELECTION CRITERIA: Randomised clinical trials (irrespective of language or publication...

  15. Overview of Hepatocellular Adenoma in Japan

    Science.gov (United States)

    Sasaki, Motoko; Nakanuma, Yasuni

    2012-01-01

    Hepatocellular adenoma (HCA) is generally a benign hepatocellular tumor arising in a nonfibrotic/cirrhotic liver, and recently four major subgroups were identified based on genotype and phenotype classification from Europe. HCA is rare in Asian countries including Japan, and there have been few studies regarding the subgroups of HCA in Japan. We surveyed subgroups of HCA in 13 patients (7 women) in Japan, based on the phenotypic classification. As results, we identified 2 hepatocyte nuclear factor (HNF) 1α-inactivated HCAs (15%), two β-catenin-activated HCAs (15%), 5 inflammatory HCAs (39%), and 4 unclassified HCAs (29%). The use of oral contraceptives was found only in 2 unclassified HCAs (29%). Rather low percentage of female patients and use of oral contraceptives appear to be common clinicopathological features in Japan and also East Asian countries. Furthermore, a group of possible inflammatory HCAs characterized by strong immunoreactivity for serum amyloid A (SAA) was found in patients with alcoholic cirrhosis. The inflammatory HCA/SAA-positive hepatocellular neoplasm in alcoholic cirrhosis may be a new entity of HCA, which may have potential of malignant transformation. Further studies are needed to clarify genetic changes, monoclonality, and pathogenesis of this new type of hepatocellular neoplasm. PMID:22973519

  16. Overview of Hepatocellular Adenoma in Japan

    Directory of Open Access Journals (Sweden)

    Motoko Sasaki

    2012-01-01

    Full Text Available Hepatocellular adenoma (HCA is generally a benign hepatocellular tumor arising in a nonfibrotic/cirrhotic liver, and recently four major subgroups were identified based on genotype and phenotype classification from Europe. HCA is rare in Asian countries including Japan, and there have been few studies regarding the subgroups of HCA in Japan. We surveyed subgroups of HCA in 13 patients (7 women in Japan, based on the phenotypic classification. As results, we identified 2 hepatocyte nuclear factor (HNF 1α-inactivated HCAs (15%, two β-catenin-activated HCAs (15%, 5 inflammatory HCAs (39%, and 4 unclassified HCAs (29%. The use of oral contraceptives was found only in 2 unclassified HCAs (29%. Rather low percentage of female patients and use of oral contraceptives appear to be common clinicopathological features in Japan and also East Asian countries. Furthermore, a group of possible inflammatory HCAs characterized by strong immunoreactivity for serum amyloid A (SAA was found in patients with alcoholic cirrhosis. The inflammatory HCA/SAA-positive hepatocellular neoplasm in alcoholic cirrhosis may be a new entity of HCA, which may have potential of malignant transformation. Further studies are needed to clarify genetic changes, monoclonality, and pathogenesis of this new type of hepatocellular neoplasm.

  17. Catching a floating thrombus; a case report on the treatment of a large thrombus in the ascending aorta

    NARCIS (Netherlands)

    de Maat, Gijs Eduard; Vigano, Giorgio; Mariani, Massimo Alessandro; Natour, Ehsan

    2017-01-01

    Background: The ascending aorta is an uncommon site for non-infective thrombus. In non-aneurysmal and non-atherosclerotic vessels this condition becomes extremely rare, while it represents a source of potential cerebral and peripheral embolic events. Currently, there is no consensus in the

  18. 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.

  19. Salvage living-donor liver transplantation for liver failure following definitive radiation therapy for recurrent hepatocellular carcinoma: a case report.

    Science.gov (United States)

    Kitajima, T; Fujimoto, Y; Hatano, E; Nishida, H; Ogawa, K; Mori, A; Okajima, H; Kaido, T; Nakamura, A; Nagamatsu, H; Uemoto, S

    2015-04-01

    A 57-year-old man with a history of hepatitis B virus infection was referred to our hospital for living-donor liver transplantation (LDLT). Five years earlier, right lobectomy had been performed for solitary hepatocellular carcinoma (HCC) with bile duct tumor thrombus in segments 5 and 6 in the liver. Two years later, transarterial chemoembolization and radiofrequency ablation were performed for recurrent HCC. Two years after those local therapies, another recurrent HCC was treated with transhepatic arterial infusion chemotherapy with cisplatin and conventional radiation therapy (RT) with 60 Gy in 20 fractions, because the tumor was contiguous to the trunk of the portal vein. After the completion of RT, symptoms due to liver failure and severe infection caused by multiple liver abscesses developed despite the administration of antibiotics and percutaneous transhepatic cholangiodrainage. Therefore, LDLT was performed with the use of a right lobe graft donated by his wife. Vascular anastomosis was successfully performed with the use of normal procedures. The patient recovered uneventfully, and has since been doing well for 34 months, with no evidence of vascular complications. However, the degree of injury to the anastomotic vessels caused by definitive RT before LDLT remains unclear, whereas the safety and efficacy of some forms of RT as a bridge to deceased-donor LT have been reported. Salvage LDLT is effective for patients with liver failure after multidisciplinary treatment including radiation, while carefully taking radiation-induced vessel injury as a potential late complication into consideration, especially in LDLT cases. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Thrombus composition in sudden cardiac death from acute myocardial infarction.

    Science.gov (United States)

    Silvain, Johanne; Collet, Jean-Philippe; Guedeney, Paul; Varenne, Olivier; Nagaswami, Chandrasekaran; Maupain, Carole; Empana, Jean-Philippe; Boulanger, Chantal; Tafflet, Muriel; Manzo-Silberman, Stephane; Kerneis, Mathieu; Brugier, Delphine; Vignolles, Nicolas; Weisel, John W; Jouven, Xavier; Montalescot, Gilles; Spaulding, Christian

    2017-04-01

    It was hypothesized that the pattern of coronary occlusion (thrombus composition) might contribute to the onset of ventricular arrhythmia and sudden cardiac death (SCD) in myocardial infarction (MI). The TIDE (Thrombus and Inflammation in sudden DEath) study included patients with angiographically-proven acute coronary occlusion as the cause of a ST elevation MI (STEMI) complicated by Sudden Cardiac Death (SCD group) or not (STEMI group). Thrombi were obtained by thrombo-aspiration before primary percutaneous coronary stenting and analyzed with a quantitative method using scanning electron microscopy. We compared the composition of the thrombi responsible for the coronary occlusion between the two groups and evaluated factors influencing its composition. We included 121 patients and found that thrombus composition was not different between the SCD group (n=23) and the STEMI group (n=98) regarding content of fibrin fibers (60.3±18.4% vs. 62.4±18.4% respectively, p=0.68), platelets (16.3±19.2% vs. 15.616.7±%, p=0.76), erythrocytes (14.6±12.5% vs. 13±12.1%, p=0.73) and leukocytes (0.6±0.9% vs. 0.8±1.5%, p=0.93). Thrombus composition did not differ between patients receiving upstream-use of glycoprotein IIb/IIIa platelet receptor inhibitors (GPI) and patients free of GPI. The only factor found to influence thrombus composition was the ischemic time from symptom onset to primary PCI, with a decreased content in fibrin fibers (57.8±18.5% vs. 71.9±10.1%, p=0.0008) and a higher platelet content (19.2±19.1% vs. 7.9±5.7% p=0.014) in early presenters (6h of ischemic time). Composition of intracoronary thrombi in STEMI patients does not differ between those presenting with and without SCD. Time from symptom onset to coronary reperfusion seems to be the strongest factor influencing thrombus composition in MI. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Surgical treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Laca, L; Dedinska, I; Miklusica, J; Janik, J; Palkoci, B; Pindura, M

    2015-01-01

    The incidence of hepatocellular carcinoma (HCC) in Europe and throughout the world is currently increasing. This is caused by an increase in the number of patients with alcoholic liver damage, metabolic syndrome, and by increasing incidence of hepatitis B and C.From January 1, 2004 to December 31, 2013, resection or radiofrequency ablation of the liver was done in 360 patients with benign lesions or malignant tumors of the liver. In 28 patients HCC was diagnosed and histologically confirmed (7.8 %). Seven patients had HCC associated with liver cirrhosis (25 %), and 21 patients were without histologically confirmed cirrhosis (75 %). R0 resection was done in 18 (64 %) patients.Surgical complications occurred in 6 (21 %) patients and reoperation due to tumor relapse or progression was done eight times in 6 (21 %) patients. One-year and five-year patients' survivals were 64 % and 10 %, repectively, and did not statistically differ from the survival of the whole set of patients with tumor diseases in the given time period. In the future it will be possible to improve the long-term survival of patients with HCC by using screening methods for presymptomatic diagnosis of HCC, precise preoperative diagnosis and efforts for R0 resection (Tab. 1, Fig. 4, Ref. 11).

  2. A case of spontaneous regression of hepatocellular carcinoma after ultrasound guided liver biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Jeong Hyun [Dept. of Radiology, Dong A University Hospital, Dong A University College of Medicine, Busan (Korea, Republic of)

    2014-10-15

    Spontaneous regression of hepatocellular carcinoma after liver biopsy has not been reported in the English literature. Herein, we present a case of partial spontaneous regression of hepatocellular carcinoma after ultrasound guided liver biopsy in a 64-year-old female. During 28 months, the tumor, which had been shrinking, showed no interval change. However, after 28 months, tumor showed regrowth, which led to a segmentectomy.

  3. A RARE CASE OF HEPATOCELLULAR CARCINOMA IN THE ARABIAN SAND CAT (FELIS MARGARITA HARRISONI).

    Science.gov (United States)

    Chege, Stephen M; Vissiennon, Théophile; Cavero, Tatiana; Kinne, Joerg; Toosy, Arshad

    2015-12-01

    Primary liver cancer is uncommon and is generally classified as hepatocellular carcinoma (HCC), bile duct carcinoma, neuroendocrine (or carcinoid) tumor, and mesenchymal tumor (sarcoma). Here we describe the gross and histopathology characteristics of a rare HCC in a captive Arabian sand cat (Felis margarita harrisoni) held at Al Ain Zoo, United Arab Emirates. The description of this case in the Arabian sand cat adds to the current knowledge of hepatocellular carcinoma in captive nondomestic felids.

  4. HMGA1 Expression in Human Hepatocellular Carcinoma Correlates with Poor Prognosis and Promotes Tumor Growth and Migration in in vitro Models.

    Science.gov (United States)

    Andreozzi, Mariacarla; Quintavalle, Cristina; Benz, David; Quagliata, Luca; Matter, Matthias; Calabrese, Diego; Tosti, Nadia; Ruiz, Christian; Trapani, Francesca; Tornillo, Luigi; Fusco, Alfredo; Heim, Markus H; Ng, Charlotte Ky; Pallante, Pierlorenzo; Terracciano, Luigi M; Piscuoglio, Salvatore

    2016-12-01

    HMGA1 is a non-histone nuclear protein that regulates cellular proliferation, invasion and apoptosis and is overexpressed in many carcinomas. In this study we sought to explore the expression of HMGA1 in HCCs and cirrhotic tissues, and its effect in in vitro models. We evaluated HMGA1 expression using gene expression microarrays (59 HCCs, of which 37 were matched with their corresponding cirrhotic tissue and 5 normal liver donors) and tissue microarray (192 HCCs, 108 cirrhotic tissues and 79 normal liver samples). HMGA1 expression was correlated with clinicopathologic features and patient outcome. Four liver cancer cell lines with stable induced or knockdown expression of HMGA1 were characterized using in vitro assays, including proliferation, migration and anchorage-independent growth. HMGA1 expression increased monotonically from normal liver tissues to cirrhotic tissue to HCC (Pexpressed HMGA1, respectively. Patients with HMGA1-positive HCCs had earlier disease progression and worse overall survival. Forced expression of HMGA1 in liver cancer models resulted in increased cell growth and migration, and vice versa. Soft agar assay showed that forced expression of HMGA1 led to increased foci formation, suggesting an oncogenic role of HMGA1 in hepatocarcinogenesis. HMGA1 is frequently expressed in cirrhotic tissues and HCCs and its expression is associated with high Edmondson grade and worse prognosis in HCC. Our results suggest that HMGA1 may act as oncogenic driver of progression, implicating it in tumor growth and migration potential in liver carcinogenesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Pelvic skeletal metastasis of hepatocellular carcinoma with sarcomatous change: a case report

    Directory of Open Access Journals (Sweden)

    Lin Wei-Hsin

    2010-05-01

    Full Text Available Abstract Sarcomatoid hepatocellular carcinoma (HCC is a very rare histologic variant of HCC. The characteristic of skeletal metastatic sarcomatoid hepatocellular carcinoma has never been reported. We reported a patient with sarcomatoid hepatocellular carcinoma pelvic metastasis who presented with huge pelvic metastasis that had relatively small osteolytic lesion centrally located accompanied by huge bipeduncular invasive expansile lesions into surrounding soft tissue. The lesion showed almost non-isotope uptake in 99mTc-methylene diphosphonate bone scintigraphy study. He underwent radiotherapy and tumor excision but the tumor rapidly recurred. In addition, serum α-fetoprotein level was never elevated beyond normal limit (

  6. Role of Cellular Elements in Thrombus Formation and Dissolution

    OpenAIRE

    Wohner, N.

    2008-01-01

    Although fibrin forms the core matrix of thrombi, their structure depends also on the cellular elements embedded in its meshwork. Platelets are essential in the initial stages of thrombus formation, because they adhere and aggregate at sites of blood vessel wall injury and then serve as a surface for coagulation reactions, the overall rate of which determines the final structure of fibrin. In addition, platelets affect fibrinolysis through their proteins and phospholipids, which modulate plas...

  7. 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.

  8. Flow-mediated transport around a macroscopic arterial thrombus

    Science.gov (United States)

    Mukherjee, Debanjan; Garduno, Jocelyn; Shadden, Shawn

    2017-11-01

    Pathological blood clotting (thrombosis) is the acute cause of most major cardiovascular events including heart attack and stroke. Local blood and plasma transport in the neighborhood of a clot is thought to govern the thrombotic process (e.g. growth and consolidation), embolization, and the effectiveness of pharmacological treatments. To better understand the fluid mechanics near a clot it is necessary to resolve the dynamic interactions between a realistic thrombus with arbitrary shape and microstructure, and viscous, pulsatile flow. Here, we describe a computational technique to characterize flow-mediated transport phenomena in the vicinity of macro-scale arterial clots. The technique comprises (a) resolving unsteady flow around a thrombus model using a discrete particle fictitious domain finite element method; (b) identifying coherent transport features using finite time Lyapunov exponent fields, and (c) characterizing mixing using a particle-based approach. Numerical examples are discussed using realistic thrombus aggregates derived from experimental data, and pulsatile flow typical in human arteries. The results indicate the existence of local transport barriers and coherent regions in the vicinity of the clot with potential influence to local biochemical mechanics. National Science Foundation Award: 1354541; American Heart Association Award: 16POST27500023.

  9. Plasma fibronectin promotes thrombus growth and stability in injured arterioles

    Science.gov (United States)

    Ni, Heyu; Yuen, Peter S. T.; Papalia, Jessie M.; Trevithick, Jane E.; Sakai, Takao; Fässler, Reinhard; Hynes, Richard O.; Wagner, Denisa D.

    2003-01-01

    Mice lacking both of the best-known platelet ligands, von Willebrand factor and fibrinogen, can still form occlusive thrombi in injured arterioles. The platelets of these animals accumulate excessive amounts of fibronectin (FN). These observations led us to examine the contribution of plasma FN (pFN) to thrombus formation. Inactivation of the FN gene in FN conditional knockout mice reduced pFN levels to <2% and platelet FN to ≈20% of the levels in similarly treated control mice. The mice were then observed in a model of arterial injury to evaluate their capacity to form thrombi. The deficiency of pFN did not affect the initial platelet adhesion, but a delay of several minutes in thrombus formation was observed in the arterioles of pFN-deficient mice as compared with control mice. The thrombi that formed in the absence of pFN were stably anchored to the vessel wall but continuously shed platelets or small platelet clumps, thus slowing their growth significantly; the platelet/platelet cohesion was apparently diminished. Consequently the occlusion of pFN-deficient vessels was delayed, with the majority of vessels remaining patent at the end of the 40-min observation period. We conclude that, in addition to von Willebrand factor and fibrinogen, FN plays a significant role in thrombus initiation, growth, and stability at arterial shear rates and that deficiency in each of the three platelet ligands has its own specific impact on platelet plug formation. PMID:12606706

  10. Non-bleeding Spontaneous Rupture of Hepatocellular Carcinoma ...

    African Journals Online (AJOL)

    Rupture of hepatocellular carcinoma (HCC) is not uncommon and most ruptured HCC present with hemoperitoneum and hemorrhagic shock. Management of ruptured HCC is different than non.ruptured one. Short. and long.term mortality increases following rupture of HCC with increasing chances of tumor dissemination.

  11. Oncofetal gene SALL4 in aggressive hepatocellular carcinoma.

    Science.gov (United States)

    Yong, Kol Jia; Gao, Chong; Lim, Joline S J; Yan, Benedict; Yang, Henry; Dimitrov, Todor; Kawasaki, Akira; Ong, Chee Wee; Wong, Kwong-Fai; Lee, Sanghoon; Ravikumar, Sharada; Srivastava, Supriya; Tian, Xi; Poon, Ronnie T; Fan, Sheung Tat; Luk, John M; Dan, Yock Young; Salto-Tellez, Manuel; Chai, Li; Tenen, Daniel G

    2013-06-13

    Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment. We screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays. SALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult liver, but it is reexpressed in a subgroup of patients who have hepatocellular carcinoma and an unfavorable prognosis. Gene-expression analysis showed the enrichment of progenitor-like gene signatures with overexpression of proliferative and metastatic genes in SALL4-positive hepatocellular carcinomas. Loss-of-function studies confirmed the critical role of SALL4 in cell survival and tumorigenicity. Blocking SALL4-corepressor interactions released suppression of PTEN (the phosphatase and tensin homologue protein) and inhibited tumor formation in xenograft models in vivo. SALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype. The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma. (Funded by the Singapore National Medical Research Council and others.).

  12. Vibration assessment for thrombus formation in the centrifugal pump.

    Science.gov (United States)

    Nakazawa, T; Makinouchi, K; Takami, Y; Glueck, J; Tayama, E; Nosé, Y

    1997-04-01

    To clarify the correlation of vibration and thrombus formation inside a rotary blood pump, 40 preliminary vibration studies were performed on pivot bearing centrifugal pumps. No such studies were found in the literature. The primary data acquisition equipment included an accelerometer (Isotron PE accelerometer, ENDEVCO, San Juan Capistrano, CA, U.S.A.), digitizing oscilloscope (TDS 420, Tektronix Inc., Pittsfield, MA, U.S.A.), and pivot bearing centrifugal pumps. The pump impeller was coupled magnetically to the driver magnet. The accelerometer was mounted on the top of the pump casing to sense radial and axial accelerations. To simulate the 3 common areas of thrombus formation, a piece of silicone rubber was attached to each of the following 3 locations as described: a circular shape on the center bottom of the impeller (CI), an eccentric shape on the bottom of the impeller (EI), and a circular shape on the center bottom casing (CC). A fast Fourier transform (FFT) method at 5 L/min against 100 mm Hg, with a pump rotating speed of 1,600 rpm was used. The frequency response of the vibration sensors used spans of 40 Hz to 2 kHz. The frequency domain was already integrated into the oscilloscope, allowing for comparison of the vibration results. The area of frequency domain at a radial direction was 206 +/- 12.7 mVHz in CI, 239.5 +/- 12.1 mVHz in EI, 365 +/- 12.9 mVHz in CC, and 163 +/- 7.9 mVHz in the control (control vs. CI p = 0.07, control vs. EI p < 0.001, control vs. CC p < 0.001, EI vs. CC p < 0.001, CI vs. CC p < 0.001). Three types of imitation thrombus formations were roughly distinguishable. These results suggested the possibility of detecting thrombus formation using vibration signals, and these studies revealed the usefulness of vibration monitoring to detect thrombus formation in a centrifugal pump.

  13. Effects of attenuation and thrombus age on the success of ultrasound and microbubble-mediated thrombus dissolution.

    Science.gov (United States)

    Xie, Feng; Everbach, E Carr; Gao, Shunji; Drvol, Lucas K; Shi, William T; Vignon, Francois; Powers, Jeff E; Lof, John; Porter, Thomas R

    2011-02-01

    The purpose of this study was to examine the effects of applied mechanical index, incident angle, attenuation and thrombus age on the ability of 2-D vs. 3-D diagnostic ultrasound and microbubbles to dissolve thrombi. A total of 180 occlusive porcine arterial thrombi of varying age (3 or 6 h) were examined in a flow system. A tissue-mimicking phantom of varying thickness (5 to 10 cm) was placed over the thrombosed vessel and the 2-D or 3-D diagnostic transducer aligned with the thrombosed vessel using a positioning system. Diluted lipid-encapsulated microbubbles were infused during ultrasound application. Percent thrombus dissolution (%TD) was calculated by comparison of clot mass before and after treatment. Both 2-D and 3-D-guided ultrasound increased %TD compared with microbubbles alone, but %TD achieved with 6-h-old thrombi was significantly less than 3-h-old thrombi. Thrombus dissolution was achieved at 10 cm tissue-mimicking depths, even without inertial cavitation. In conclusion, diagnostic 2-D or 3-D ultrasound can dissolve thrombi with intravenous nontargeted microbubbles, even at tissue attenuation distances of up to 10 cm. This treatment modality is less effective, however, for older aged thrombi. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  14. Dissolution of large intracardiac thrombus, potential role of the emerging oral fibrinolytic agent

    Directory of Open Access Journals (Sweden)

    Rony M. Candrasatria

    2016-04-01

    Full Text Available Intracardiac thrombus may persist in some cases even after anticoagulant therapy. This opens a possibility to add a potent thrombolytic agent into therapeutic regimen without increasing bleeding risk any further. Increasing evidence showed a promising efficacy and safety of oral fibrin specific lumbrokinase as a thrombolytic agent. To the best of our knowledge, report of the use of lumbrokinase on intracardiac thrombus is limited. We reported two cases of intracardiac thrombi. In first patient, after two-month therapy with lumbrokinase, the previous 8 cm2 left atrial thrombus was completely disappeared. Second patient had left ventricular thrombus due to low left ventricular ejection fraction caused by coronary artery disease. A significant dissolution in thrombus size on repeated follow-up was found. Both patients did not experience any significant adverse effect. This case series aims to present the potential use of lumbrokinase as as oral antithrombotic therapy in intracardiac thrombus.

  15. Negative regulatory role of PI3-kinase in TNF-induced tumor necrosis.

    NARCIS (Netherlands)

    Matschurat, S.; Blum, S.; Mitnacht-Kraus, R.; Dijkman, H.B.P.M.; Kanal, L.; Waal, R.M.W. de; Clauss, M.

    2003-01-01

    Tissue factor is the prime initiator of blood coagulation. Expression of tissue factor in tumor endothelial cells leads to thrombus formation, occlusion of vessels and development of hemorrhagic infarctions in the tumor tissue, often followed by regression of the tumor. Tumor cells produce

  16. 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.

  17. 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.)

  18. Value of Thrombus CT Characteristics in Patients with Acute Ischemic Stroke.

    Science.gov (United States)

    Borst, J; Berkhemer, O A; Santos, E M M; Yoo, A J; den Blanken, M; Roos, Y B W E M; van Bavel, E; van Zwam, W H; van Oostenbrugge, R J; Lingsma, H F; van der Lugt, A; Dippel, D W J; Marquering, H A; Majoie, C B L M

    2017-09-01

    Thrombus CT characteristics might be useful for patient selection for intra-arterial treatment. Our objective was to study the association of thrombus CT characteristics with outcome and treatment effect in patients with acute ischemic stroke. We included 199 patients for whom thin-section NCCT and CTA within 30 minutes from each other were available in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) study. We assessed the following thrombus characteristics: location, distance from ICA terminus to thrombus, length, volume, absolute and relative density on NCCT, and perviousness. Associations of thrombus characteristics with outcome were estimated with univariable and multivariable ordinal logistic regression as an OR for a shift toward better outcome on the mRS. Interaction terms were used to investigate treatment-effect modification by thrombus characteristics. In univariate analysis, only the distance from the ICA terminus to the thrombus, length of >8 mm, and perviousness were associated with functional outcome. Relative thrombus density on CTA was independently associated with functional outcome with an adjusted common OR of 1.21 per 10% (95% CI, 1.02-1.43; P = .029). There was no treatment-effect modification by any of the thrombus CT characteristics. In our study on patients with large-vessel occlusion of the anterior circulation, CT thrombus characteristics appear useful for predicting functional outcome. However, in our study cohort, the effect of intra-arterial treatment was independent of the thrombus CT characteristics. Therefore, no arguments were provided to select patients for intra-arterial treatment using thrombus CT characteristics. © 2017 by American Journal of Neuroradiology.

  19. 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

  20. Diagnosis of left atrial thrombus by technetium-99m radionuclide angiography

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Toshiisa; Nishimura, Tsunehiko; Hayashida, Kohei; Takamiya, Makoto; Kozuka, Takahiro

    1988-06-01

    Detection of left atrial (LA) thrombus in the mitral valve disease is important in the decision of treatment course or indication for operation. The LA thrombus usually locates in the LA appendage. On the other hand, technetium-99m radionuclide angiography labeled by red blood cell (RNA) often shows LA appendage clearly in the mitral valve disease, but when the LA appendage is occupied by LA thrombus, LA appendage will not be demonstrated by RNA. On the basis of this hypothesis, the diagnostic accuracy of RNA to detect LA thrombus by the visualization of LA appendage was evaluated retrospectively in 60 patients of mitral valve disease who had undergone operation and whether the LA thrombus was present or not had been clarified. The sensitivity of first-pass and equilibrium RNA to detect LA thrombus was 83 % and 67 %, and the specificity 79 % and 54 %, and the accuracy 80 % and 57 % respectively. The first-pass RNA showed a good diagnostic accuracy to detect LA thrombus, but there were two cases of false negative those had LA thrombus not located in the LA appendage, and there were 10 cases of false positive those did not have dilated LA appendages. But negative predictive value was so high that the clearly observed LA appendage convinced us of the absence of LA thrombus. The diagnostic accuracy of equilibrium RNA was relatively low but it often demonstrated a characteristic shape of LA appendage, so it seemed useful as an assistant diagnostic method.

  1. 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.)

  2. Validation and ranking of seven staging systems of hepatocellular carcinoma.

    Science.gov (United States)

    Chen, Zhan-Hong; Hong, Ying-Fen; Lin, Jinxiang; Li, Xing; Wu, Dong-Hao; Wen, Jing-Yun; Chen, Jie; Ruan, Dan-Yun; Lin, Qu; Dong, Min; Wei, Li; Wang, Tian-Tian; Lin, Ze-Xiao; Ma, Xiao-Kun; Wu, Xiang-Yuan; Xu, Ruihua

    2017-07-01

    The aim of the present study was to evaluate the ability of seven staging systems to predict 3- and 6-month and cumulative survival rates of patients with advanced hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Data were collected from 220 patients with HBV-associated HCC who did not receive any standard anticancer treatment. Participants were patients at The Third Affiliated Hospital of Sun Yat-sen University from September 2008 to June 2010. The participants were classified according to the Chinese University Prognostic Index (CUPI), the Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), China Integrated Score (CIS) systems, Barcelona Clinic Liver Cancer (BCLC), Okuda and tumor-node-metastasis (TNM) staging systems at the time of diagnosis and during patient follow-up. The sensitivity and specificity of the predictive value of each staging system for 3- and 6-month mortality were analyzed by relative operating characteristic (ROC) curve analysis with a non-parametric test being used to compare the area under curve (AUC) of the ROC curves. In addition, log-rank tests and Kaplan-Meier estimator survival curves were applied to compare the overall survival rates of the patients with HCC defined as advanced using the various staging systems, and the Akaike information criterion (AIC) and likelihood ratio tests (LRTs) were used to evaluate the predictive value for overall survival in patients with advanced HCC. Using univariate and multivariate Cox's model analyses, the factors predictive of survival were also identified. A total of 220 patients with HBV-associated HCC were analyzed. Independent prognostic factors identified by multivariate analyses included tumor size, α-fetoprotein levels, blood urea nitrogen levels, the presence or absence of portal vein thrombus, Child-Pugh score and neutrophil count. When predicting 3-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.806, 0.772, 0.751, 0

  3. A new classification of inferior vena cava thrombus in renal cell carcinoma could define the need for cardiopulmonary or venovenous bypass

    Directory of Open Access Journals (Sweden)

    Anil Mandhani

    2015-01-01

    Conclusion: Renal vein thrombus should not be categorized as level I thrombus. Level II thrombus, irrespective of its relation to the diaphragm, could be managed without venovenous or cardiopulmonary bypass.

  4. Specific diagnosis of hepatocellular carcinoma by delayed hepatobiliary imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Y.; Nakano, S.; Ibuka, K.; Hashizume, T.; Noguchi, A.; Sasaki, Y.; Imaoka, S.; Fujita, M.; Kawamoto, S.; Kasugai, H.

    1986-01-15

    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.

  5. Therapeutic response of untreatable hepatocellular carcinoma after application of the immune modulators IL-2, BCG and melatonin.

    Science.gov (United States)

    Tomov, Bojidar; Popov, Dimitar; Tomova, Radosveta; Vladov, Nicola; Den Otter, Willem; Krastev, Zachary

    2013-10-01

    Application of immunotherapy to a patient with untreatable hepatocellular carcinoma. The patient had a tumor of 60 mm in the liver. The pathological anatomic diagnosis was adenoma. However, after surgery of the tumor seven new lesions arose, showing that the original tumor had been a hepatocellular carcinoma. In addition, when hepatocellular adenomas grow to a size of more than 6-8 cm, they are considered cancerous and thus become a risk for hepatocellular carcinoma. The patient was treated with interleukin-2, Bacillus Calmette Guerin, and melatonin. During treatment, the alpha-fetoprotein levels in blood fell from 5,000 IU/ml to zero, at which level it remained during the follow-up period of two years. No tumor was detectable on MRI and CT. Six years after the diagnosis of untreatable hepatocellular carcinoma, the patient remains in a good condition. In this case, combined immunomodulating therapy was effective. For patients with metastasized tumors of the liver who are not suitable for conventional therapy, immunomodulation may delay tumor progression, induce tumor regression, or even be curative in some patients. Immunotherapeutic approaches combined with conventional methods for hepatocellular carcinoma treatment may be able to improve therapeutic efficacy.

  6. 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.

  7. Left atrial thrombus formation and resolution during dabigatran therapy: A Japanese Heart Rhythm Society report

    Directory of Open Access Journals (Sweden)

    Hideo Mitamura, MD

    2015-08-01

    Conclusions: LA thrombus developed in 4% of patients with AF receiving Dabi. Older patients with a higher CHADS2 score receiving a lower Dabi dosage were more likely to develop LA thrombus, which was resolved with a prolonged or increased dosage. A higher Dabi dosage may be more beneficial before ECV but prospective randomized studies would be needed to confirm these results.

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

    NARCIS (Netherlands)

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

  9. 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

  10. Saphenous vein covered stenting for right coronary artery lesion containing thrombus.

    Science.gov (United States)

    Joseph, D; Bashi, V V; Guhathakurtha, S; Harilal, H; Jacob, A; George, T; Suguna, S

    1997-12-01

    Vein covered stenting to close coronary pseudoaneurysm and perforation and in the setting of acute myocardial infarction have been described. This case report describes saphenous vein covered stenting to exclude a large thrombus in a right coronary artery lesion. Vein covered stenting may be considered as an option when dealing with a thrombus containing lesion.

  11. Proteomic Analysis of Intraluminal Thrombus Highlights Complement Activation in Human Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Martinez-Pinna, Roxana; Madrigal-Matute, Julio; Tarin, Carlos

    2013-01-01

    To identify proteins related to intraluminal thrombus biological activities that could help to find novel pathological mechanisms and therapeutic targets for human abdominal aortic aneurysm (AAA).......To identify proteins related to intraluminal thrombus biological activities that could help to find novel pathological mechanisms and therapeutic targets for human abdominal aortic aneurysm (AAA)....

  12. [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.

  13. 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.

  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. 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)

  16. Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke.

    Science.gov (United States)

    Santos, Emilie M M; Marquering, Henk A; den Blanken, Mark D; Berkhemer, Olvert A; Boers, Anna M M; Yoo, Albert J; Beenen, Ludo F; Treurniet, Kilian M; Wismans, Carrie; van Noort, Kim; Lingsma, Hester F; Dippel, Diederik W J; van der Lugt, Aad; van Zwam, Wim H; Roos, Yvo B W E M; van Oostenbrugge, Robert J; Niessen, Wiro J; Majoie, Charles B

    2016-03-01

    Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may increase tissue oxygenation, improve thrombus dissolution, and augment intra-arterial treatment success. We hypothesize that the combination of computed tomographic angiography and noncontrast computed tomography imaging allows measurement of contrast agent penetrating a permeable thrombus, and it is associated with improved outcome. Thrombus and contralateral artery attenuations in noncontrast computed tomography and computed tomographic angiography images were measured in 184 Multicenter Randomized Clinical trial of Endovascular treatment of acute ischemic stroke in the Netherlands (MR CLEAN) patients with thin-slice images. Two quantitative estimators of the thrombus permeability were introduced: computed tomographic angiography attenuation increase (Δ) and thrombus void fraction (ε). Patients were dichotomized as having a pervious or impervious thrombus and associated with outcome, recanalization, and final infarct volume. Patients with Δ≥10.9 HU (n=81 [44%]) and ε≥6.5% (n=77 [42%]) were classified as having a pervious thrombus. These patients were 3.2 (95% confidence interval, 1.7-6.4) times more likely to have a favorable outcome, and 2.5 (95% confidence interval, 1.3-4.8) times more likely to recanalyze, for Δ based classification, and similarly for ε. These odds ratios were independent from intravenous or intra-arterial treatment. Final infarct volume was negatively correlated with both perviousness estimates (correlation coefficient, -0.39 for Δ and -0.40 for ε). This study shows that simultaneous measurement of thrombus attenuation in noncontrast computed tomography and computed tomographic angiography allows for quantification of thrombus perviousness. Thrombus perviousness is strongly associated with improved functional outcome, smaller final infarct

  17. Nanomedicines: a theranostic approach for hepatocellular carcinoma.

    Science.gov (United States)

    Usmani, Afreen; Mishra, Anuradha; Ahmad, Mohd

    2017-09-08

    The liver is an imperative organ of tremendous importance concerned with maintenance of metabolic functions and detoxification of exogenous and endogenous challenges like xenobiotics, viral infections and chronic alcoholism. Liver diseases particularly hepatitis B virus infections, liver cirrhosis and hepatocellular carcinoma continue to pose a significant health challenge worldwide due to the lack of therapeutic management options besides liver resection and transplantation. Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer mortality worldwide. HCC has a high mortality rate because of poor diagnosis. The majority of patients with liver cancer die within one year as a result of poor patient compliance. HCC is clinically treated by chemotherapy besides surgery. However, most anticancer drugs have high toxicity and low specificity, leading to systemic toxicity and severe side effects. To limit the severe side effects of cancer chemotherapy on normal tissues, tumor targeting drug delivery systems need to be explored, which provides the impetus to develop targeted therapies for achieving higher efficacy with minimal side effects. The nanostructures used as good drug carriers, possess advantages of good solubility including high drug encapsulation efficiency, high cellular uptake, further desirable pharmacokinetics and can preferentially accumulate at the tumor site through the enhanced permeability and retention (EPR) effect with the goal of minimizing toxic effects on healthy tissues while maintaining antitumor efficacy.

  18. Hepatocellular adenoma: when and how to treat? Update of current evidence

    NARCIS (Netherlands)

    Thomeer, Maarten G.; Broker, Mirelle; Verheij, Joanne; Doukas, Michael; Terkivatan, Turkan; Bijdevaate, Diederick; de Man, Robert A.; Moelker, Adriaan; Ijzermans, Jan N.

    2016-01-01

    Hepatocellular adenoma (HCA) is a rare, benign liver tumor. Discovery of this tumor is usually as an incidental finding, correlated with the use of oral contraceptives, or pregnancy. Treatment options have focused on conservative management for the straightforward, smaller lesions ( <5 cm), with

  19. An atypical age-specific pattern of hepatocellular carcinoma in Peru: a threat for Andean populations.

    Science.gov (United States)

    Bertani, Stéphane; Pineau, Pascal; Loli, Sebastian; Moura, Julien; Zimic, Mirko; Deharo, Eric; Ruiz, Eloy

    2013-01-01

    In South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country. A retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin. Surprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics. The analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population.

  20. Expression of Fra-1 in human hepatocellular carcinoma and its prognostic significance.

    Science.gov (United States)

    Gao, Xiao-Qiang; Ge, Yong-Sheng; Shu, Qing-Hua; Ma, Hua-Xing

    2017-06-01

    This study aimed to explore the clinical significance and prognostic value of Fra-1 in hepatocellular carcinoma patients after curative resection. Fra-1 expression was investigated using a combination of techniques: immunohistochemistry for 66 samples of hepatocellular carcinoma and quantitative real-time polymerase chain reaction and western blotting assays for 19 matched hepatocellular carcinoma specimens. Fra-1 was present in 38 of 66 (57.6%) tumor tissues, with intense staining in the nuclei. There was also positive staining in 14 of 66 (21.2%) adjacent peritumoral tissues, with weak staining in the cytoplasm. Quantitative real-time polymerase chain reaction and western blotting assays confirmed higher expression of Fra-1 messenger RNA and Fra-1 protein in tumor tissues than adjacent non-tumor tissues for 19 hepatocellular carcinoma samples (p expression of Fra-1 was significantly related to vascular invasion and serum alpha-fetoprotein. Kaplan-Meier survival analysis found that overexpressed Fra-1 was correlated with poor overall survival and disease-free survival. Multivariate analysis identified Fra-1 as an independent prognostic factor. Fra-1 may be involved in the progress of hepatocellular carcinoma and could be a promising molecular candidate in the diagnosis and treatment of hepatocellular carcinoma.

  1. D-Dimer and thrombus burden in acute pulmonary embolism.

    Science.gov (United States)

    Keller, Karsten; Beule, Johannes; Balzer, Jörn Oliver; Dippold, Wolfgang

    2018-01-17

    Thrombus burden in pulmonary embolism (PE) is associated with higher D-Dimer-levels and poorer prognosis. We aimed to investigate i) the influence of right ventricular dysfunction (RVD), deep venous thrombosis (DVT), and high-risk PE-status on D-Dimer-levels and ii) effectiveness of D-Dimer to predict RVD in normotensive PE patients. Overall, 161 PE patients were analyzed retrospectively, classified in 5 subgroups of thrombus burden according to clinical indications and compared regarding D-Dimer-levels. Linear regression models were computed to investigate the association between D-Dimer and the groups. In hemodynamically stable PE patients, a ROC curve was calculated to assess the effectiveness of D-Dimer for predicting RVD. Overall, 161 patients (60.9% females, 54.0% aged >70 years) were included in this analysis. The D-Dimer-level was associated with group-category in a univariate linear regression model (β 0.050 (95%CI 0.002-0.099), P = .043). After adjustment for age, sex, cancer, and pneumonia in a multivariate model we observed an association between D-Dimer and group-category with borderline significance (β 0.047 (95%CI 0.002-0.096), P = .058). The Kruskal-Wallis test demonstrated that D-Dimer increased significantly with higher group-category. In 129 normotensive patients, patients with RVD had significantly higher D-Dimer values compared to those without (1.73 (1.11/3.48) vs 1.17 (0.65/2.90) mg/l, P = .049). A ROC curve showed an AUC of 0.61, gender non-specific, with calculated optimal cut-off of 1.18 mg/l. Multi-variate logistic regression model confirmed an association between D-Dimer >1.18 mg/l and RVD (OR2.721 (95%CI 1.196-6.190), P = .017). Thrombus burden in PE is related to elevated D-Dimer levels, and D-Dimer values >1.18 mg/l were predictive for RVD in normotensive patients. D-Dimer levels were influenced by DVT, but not by cancer, pneumonia, age, or renal impairment. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Role of cellular elements in thrombus formation and dissolution.

    Science.gov (United States)

    Wohner, N

    2008-07-01

    Although fibrin forms the core matrix of thrombi, their structure depends also on the cellular elements embedded in its meshwork. Platelets are essential in the initial stages of thrombus formation, because they adhere and aggregate at sites of blood vessel wall injury and then serve as a surface for coagulation reactions, the overall rate of which determines the final structure of fibrin. In addition, platelets affect fibrinolysis through their proteins and phospholipids, which modulate plasmin activity. Leukocytes form mixed aggregates with platelets and thus influence the structure of thrombi. After activation they secrete different proteases (elastase, cathepsin G, matrix metalloproteinases) that enhance the von Willebrand factor-dependent platelet adhesion. Leukocyte-derived enzymes, first of all elastase, effect fibrinolysis by direct digestion of fibrin or indirectly modulate it by partial degradation of zymogens and inhibitors of coagulation and fibrinolytic proteases.

  3. Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation

    Science.gov (United States)

    Gorog, Diana A.

    2017-01-01

    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. PMID:28841147

  4. Detection of Left Ventricular Thrombus by Cardiac Magnetic Resonance in Embolic Stroke of Undetermined Source.

    Science.gov (United States)

    Takasugi, Junji; Yamagami, Hiroshi; Noguchi, Teruo; Morita, Yoshiaki; Tanaka, Tomotaka; Okuno, Yoshinori; Yasuda, Satoshi; Toyoda, Kazunori; Gon, Yasufumi; Todo, Kenichi; Sakaguchi, Manabu; Nagatsuka, Kazuyuki

    2017-09-01

    We aimed to use contrast-enhanced cardiac magnetic resonance (CE-CMR) imaging to elucidate the prevalence of left ventricular (LV) thrombus in patients suspected of embolic stroke of undetermined source (ESUS) with previous myocardial infarction or LV dysfunction (LV ejection fraction [LVEF] stroke between 2014 and 2015. Patients with myocardial infarction or LVEFstroke subtypes were as follows: small artery disease, 17% (10 of 60); large artery atherosclerosis, 5% (3 of 60); cardioembolic stroke, 49% (29 of 60); ESUS, 23% (14 of 60); and undetermined causes other than ESUS, 6% (4 of 60). Of 60 patients examined via CE-CMR, LV thrombus was confirmed in 12 patients, whereas only 1 had been detected on transthoracic echocardiography (P=0.04). Importantly, 29% (4 of 14) of patients with ESUS had LV thrombus. A prediction model based on CE-CMR findings showed higher performance in LV thrombus detection, permitting a net improvement of 0.46 (95% confidence interval, 0.08-0.82; P=0.016) in cardioembolic stroke reclassification. Compared with patients without LV thrombus, those with LV thrombus had lower LVEF (median: 26% versus 40%; P=0.003). Notably, 42% (5 of 12) of patients with LV thrombus had LVEF≥30%. When ESUS-suspected patients have myocardial infarction or LV dysfunction, CE-CMR may help improve detection of cardioembolic stroke and provide relevant information for anticoagulation therapy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02251665. © 2017 American Heart Association, Inc.

  5. Whole-Brain Susceptibility-Weighted Thrombus Imaging in Stroke: Fragmented Thrombi Predict Worse Outcome.

    Science.gov (United States)

    Gratz, P P; Schroth, G; Gralla, J; Mattle, H P; Fischer, U; Jung, S; Mordasini, P; Hsieh, K; Verma, R K; Weisstanner, C; El-Koussy, M

    2015-07-01

    The prevalence and clinical importance of primarily fragmented thrombi in patients with acute ischemic stroke remains elusive. Whole-brain SWI was used to detect multiple thrombus fragments, and their clinical significance was analyzed. Pretreatment SWI was analyzed for the presence of a single intracranial thrombus or multiple intracranial thrombi. Associations with baseline clinical characteristics, complications, and clinical outcome were studied. Single intracranial thrombi were detected in 300 (92.6%), and multiple thrombi, in 24 of 324 patients (7.4%). In 23 patients with multiple thrombi, all thrombus fragments were located in the vascular territory distal to the primary occluding thrombus; in 1 patient, thrombi were found both in the anterior and posterior circulation. Only a minority of thrombus fragments were detected on TOF-MRA, first-pass gadolinium-enhanced MRA, or DSA. Patients with multiple intracranial thrombi presented with more severe symptoms (median NIHSS scores, 15 versus 11; P = .014) and larger ischemic areas (median DWI ASPECTS, 5 versus 7; P = .006); good collaterals, rated on DSA, were fewer than those in patients with a single thrombus (21.1% versus 44.2%, P = .051). The presence of multiple thrombi was a predictor of unfavorable outcome at 3 months (P = .040; OR, 0.251; 95% CI, 0.067-0.939). Patients with multiple intracranial thrombus fragments constitute a small subgroup of patients with stroke with a worse outcome than patients with single thrombi. © 2015 by American Journal of Neuroradiology.

  6. 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.

  7. Left Ventricular Thrombus Formation After Repair of Anomalous Left Coronary Artery From the Pulmonary Artery

    Science.gov (United States)

    Freud, Lindsay R.; Koenig, Peter R.; Russell, Hyde M.; Patel, Angira

    2014-01-01

    Although thrombus formation following myocardial infarction in adults is well known, intracardiac thrombosis in children is uncommon. We report the case of a large left ventricular thrombus in an infant with ischemic cardiomyopathy secondary to anomalous origin of the left coronary artery from the pulmonary artery. Given its mobility and protrusion across the aortic valve, the patient underwent urgent thrombus removal through a transaortic approach. There were no embolic or neurologic complications. This case highlights that thrombectomy may be performed safely and successfully in critically ill pediatric patients. PMID:24668990

  8. Playing games with a thrombus: a dangerous match. Paradoxical embolism from a huge central venous cathether thrombus: a case report

    Directory of Open Access Journals (Sweden)

    Mariana Sylvie

    2010-03-01

    Full Text Available Abstract Thromboembolism is a major cause of death in cancer patients. The association between paraneoplastic hypercoagulability of oncological patients and long-term central venous catheters (CVC may result in CVC associated thrombosis. Patent Foramen Ovale (PFO, especially when associated with atrial septal aneurysm (ASA is a risk factor for paradoxical embolism. We report a case of paradoxical embolism with stroke in an oncological patient with a huge CVC thrombus playing "ping-pong" with an hypermobile ASA with a PFO. We review the management of hypercoagulability in oncologic patients and discuss the potential role of routine transthoracic echocardiography before the implantation of long term central venous catheters to identify predisposing conditions to paradoxical embolism and select patients for anticoagulant therapy.

  9. A jumping left atrial thrombus connected to a pulmonary vein thrombus using transthoracic echocardiography and 64-slice multi-detector computed tomography

    Directory of Open Access Journals (Sweden)

    Hidekazu Takeuchi

    2015-03-01

    Full Text Available Few studies have reported the differences between transthoracic echocardiography (TTE and 64-slice multidetector CT (64-MDCT in identifying left atrium (LA thrombi. I report the case of a 70 year old man with coronary artery disease and angina who was diagnosed with a thrombus in the left lower pulmonary vein extending to the LA using a non-invasive 64-MDCT scan and TTE. TTE was unable to clearly identify a thrombus in the pulmonary veins, whereas a 64-MDCT scan identified a thrombus in the pulmonary vein but was unable to detect a moving thrombus attached to the mitral valves. The 64-MDCT images of LA thrombi are smaller than those of TTE and the video created using TTE demonstrated a moving thrombus connected to the mitral valve, which was underdiagnosed by a 64-MDCT scan. This case illustrates the complementary role for both TTE and 64-MDCT in the noninvasive diagnosis of left atrial-pulmonary vein thrombi.

  10. CT assessment of liver hemodynamics in patients with hepatocellular carcinoma after argon-helium cryoablation.

    Science.gov (United States)

    Hao, Xue-Jia; Li, Jin-Ping; Jiang, Hui-Jie; Li, Da-Qing; Ling, Zai-Sheng; Xue, Li-Ming; Feng, Guang-Long

    2013-12-01

    Assessment of tumor response after argon-helium cryoablation is critical in guiding future therapy for unresectable hepatocellular carcinoma. This study aimed to evaluate liver hemodynamics in hepatocellular carcinoma after argon-helium cryoablation with computed tomography perfusion. The control group comprised 40 volunteers without liver disease. The experimental group was composed of 15 patients with hepatocellular carcinoma treated with argon-helium cryoablation. Computed tomography perfusion parameters were measured: hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion. After treatment, in the tumor foci, permeability of capillary vessel surface was higher, and hepatic blood flow, hepatic blood volume, hepatic arterial fraction, and hepatic arterial perfusion values were lower (P0.05). Computed tomography perfusion can evaluate tumor response after argon-helium cryoablation.

  11. Role of SERPINB3 in hepatocellular carcinoma.

    Science.gov (United States)

    Pontisso, Patrizia

    2014-01-01

    SERPINB3 (formerly known as squamous cell carcinoma antigen-1 or SCCA1) is a member of the family of serine-protease inhibitors. SERPINB3 protects cells from oxidative stress conditions, but in chronic liver damage this serpin may lead to hepatocellular carcinoma through different strategies, including inhibition of apoptosis, induction of epithelial to mesenchymal transition and decrease of desmosomal junctions, cell proliferation and invasiveness. SERPINB3 may also contribute to tumor cell resistance to anti-neoplastic drugs through its binding to the respiratory Complex I, protecting cells from the pro-oxidant action of chemotherapeutic agents. Mechanisms of tumor growth promotion induced by SERPINB3 include the inhibition of intratumor infiltration of natural killer cells, up-regulation of Myc oncogene and the recent identification of this serpin as a Ras-responsive factor. In the liver SERPINB3 and SERPINBB4 isoforms (known as squamous cell carcinoma antigen or SCCA) are undetectable in normal hepatocytes, but their expression progressively increases in chronic liver diseases, dysplastic nodules and hepatocellular carcinoma. High SERPINB3 levels have been recently detected in HCC tissue of patients with early tumor recurrence after surgical resection. In serum SERPINB3/4 isoforms (or SCCA) are detectable bound to IgMs (SCCA-IgM) in the majority of HCV infected patients with HCC and in patients with cirrhosis their levels and/or the progressive increase have been found correlated to the risk of HCC development. Preliminary findings in patients with HCC revealed that SCCA-IgM was predictive of HCC prognosis, since low levels of this biomarker were able to identify HCC patients with long overall and progression-free survival.

  12. 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

  13. A Peculiar Mutation Spectrum Emerging from Young Peruvian Patients with Hepatocellular Carcinoma

    Science.gov (United States)

    Marchio, Agnès; Bertani, Stéphane; Rojas Rojas, Teresa; Doimi, Franco; Terris, Benoît; Deharo, Eric; Dejean, Anne; Ruiz, Eloy; Pineau, Pascal

    2014-01-01

    Hepatocellular carcinoma usually afflicts individuals in their later years following longstanding liver disease. In Peru, hepatocellular carcinoma exists in a unique clinical presentation, which affects patients around age 25 with a normal, healthy liver. In order to deepen our understanding of the molecular processes ongoing in Peruvian liver tumors, mutation spectrum analysis was carried out on hepatocellular carcinomas from 80 Peruvian patients. Sequencing analysis focused on nine genes typically altered during liver carcinogenesis, i.e. ARID2, AXIN1, BRAF, CTNNB1, NFE2L2, H/K/N-RAS, and TP53. We also assessed the transcription level of factors involved in the control of the alpha-fetoprotein expression and the Hippo signaling pathway that controls contact inhibition in metazoans. The mutation spectrum of Peruvian patients was unique with a major class of alterations represented by Insertions/Deletions. There were no changes at hepatocellular carcinoma-associated mutation hotspots in more than half of the specimens analyzed. Furthermore, our findings support the theory of a consistent collapse in the Hippo axis, as well as an expression of the stemness factor NANOG in high alpha-fetoprotein-expressing hepatocellular carcinomas. These results confirm the specificity of Peruvian hepatocellular carcinoma at the molecular genetic level. The present study emphasizes the necessity to widen cancer research to include historically neglected patients from South America, and more broadly the Global South, where cancer genetics and tumor presentation are divergent from canonical neoplasms. PMID:25502816

  14. 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.

  15. Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke

    NARCIS (Netherlands)

    Santos, E.M.; Marquering, H.A.; Blanken, M.D. den; Berkhemer, O.A.; Boers, A.M.; Yoo, A.J.; Beenen, L.F.; Treurniet, K.M.; Wismans, C.; Noort, K. van; Lingsma, H.F.; Dippel, D.W.; Lugt, A. van der; Zwam, W.H. van; Roos, Y.B.; Oostenbrugge, R.J. van; Niessen, W.J.; Majoie, C.B.; Heijden, E.H.F.M. van der; Dijk, E.J. van; Vries, J. de; Jenniskens, S.F.M.

    2016-01-01

    BACKGROUND AND PURPOSE: Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may increase tissue oxygenation, improve thrombus dissolution, and augment

  16. Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke

    NARCIS (Netherlands)

    Santos, Emilie M. M.; Marquering, Henk A.; den Blanken, Mark D.; Berkhemer, Olvert A.; Boers, Anna M. M.; Yoo, Albert J.; Beenen, Ludo F.; Treurniet, Kilian M.; Wismans, Carrie; van Noort, Kim; Lingsma, Hester F.; Dippel, Diederik W. J.; van der Lugt, Aad; van Zwam, Wim H.; Roos, Yvo B. W. E. M.; van Oostenbrugge, Robert J.; Niessen, Wiro J.; Majoie, Charles B.; Vroomen, P.C.

    Background and Purpose- Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may increase tissue oxygenation, improve thrombus dissolution, and augment

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

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    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.

  18. Intense Microbubbles Mimicking Mobile Thrombus in a Patient with Prosthetic Mitral Valve

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    Fatma Yılmaz Coşkun

    2017-06-01

    Full Text Available Microbubbles have been presumed as gaseous emboli, which originate during mechanical heart valve closure, but are not seen in bioprosthetic valves. In this report, we presented a cluster of microbubbles mimicking mobile thrombus in a patient with mechanical mitral valve prosthesis. A 30-year-old female with a history of implanted mechanical valve at the mitral position underwent a routine examination. She was asymptomatic and her physical examination was unremarkable. Transthoracic echocardiography showed a mobile thrombus-like mass on the ventricular side of the prosthetic mitral valve moving into the left ventricular outflow tract. However, close examination of images indicated that the mass was in fact intense microbubbles mimicking thrombus. Intense mobile microbubbles can be misdiagnosed as a mobile thrombus. We recommend and underscore the importance of detailed echocardiographic examination in case of mobile mass to avoid misdiagnosis in patients with mechanical heart valves.

  19. 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

  20. Microbubble mediated thrombus dissolution with diagnostic ultrasound for the treatment of chronic venous thrombi.

    Science.gov (United States)

    Kutty, Shelby; Wu, Juefei; Hammel, James M; Xie, Feng; Gao, Shunji; Drvol, Lucas K; Lof, John; Radio, Stanley J; Therrien, Stacey L; Danford, David A; Porter, Thomas R

    2012-01-01

    Central venous catheter (CVC) thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo. A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments). Baseline intracardiac echocardiography (ICE, 10.5F, Siemens), fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. A thrombus was then allowed to form and age over 24 hours. The created thrombus was localized and measured by ICE, and transthoracic image guided high mechanical index (MI) two-dimensional US treatments (1.1-1.7 MI; iE33, Philips) applied intermittently whenever intravenously infused MBs (3% MRX-801; NuVox) were visualized near the thrombus (n = 10; Group A). Control pigs (n = 10; Group B) received US without MB. All treatments were randomized. Post-treatment thrombus area by ICE planimetry was compared with pre-treatment measurements. Thrombus area measurements before and after treatment were 0.22 and 0.10 cm(2) respectively in Group A; compared to 0.24 and 0.21 cm(2) in Group B (p  = 0.0003). Effectiveness of longer duration US and MB thrombolytic treatments were studied (n = 4), which suggested that near complete thrombus dissolution is possible. No pulmonary emboli, alterations in oxygen saturation, or hemodynamics occurred with either treatment. Guided high MI diagnostic US+systemic MB facilitates reduction of aged CVC associated thrombi in vivo. MB enhanced sonothrombolytic therapy may be a non-invasive safe alternative to thrombolytic agents in treating thrombotic CVC occlusions.

  1. Microbubble mediated thrombus dissolution with diagnostic ultrasound for the treatment of chronic venous thrombi.

    Directory of Open Access Journals (Sweden)

    Shelby Kutty

    Full Text Available Central venous catheter (CVC thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB enhanced sonothrombolysis for aged CVC associated thrombi in vivo.A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments. Baseline intracardiac echocardiography (ICE, 10.5F, Siemens, fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. A thrombus was then allowed to form and age over 24 hours. The created thrombus was localized and measured by ICE, and transthoracic image guided high mechanical index (MI two-dimensional US treatments (1.1-1.7 MI; iE33, Philips applied intermittently whenever intravenously infused MBs (3% MRX-801; NuVox were visualized near the thrombus (n = 10; Group A. Control pigs (n = 10; Group B received US without MB. All treatments were randomized. Post-treatment thrombus area by ICE planimetry was compared with pre-treatment measurements. Thrombus area measurements before and after treatment were 0.22 and 0.10 cm(2 respectively in Group A; compared to 0.24 and 0.21 cm(2 in Group B (p  = 0.0003. Effectiveness of longer duration US and MB thrombolytic treatments were studied (n = 4, which suggested that near complete thrombus dissolution is possible. No pulmonary emboli, alterations in oxygen saturation, or hemodynamics occurred with either treatment.Guided high MI diagnostic US+systemic MB facilitates reduction of aged CVC associated thrombi in vivo. MB enhanced sonothrombolytic therapy may be a non-invasive safe alternative to thrombolytic agents in treating thrombotic CVC occlusions.

  2. Endovascular Treatment of Thoracic Aortic Floating Thrombus in Patients Presenting with Acute Lower Limb Ischemia

    Directory of Open Access Journals (Sweden)

    Nano Giovanni

    2011-01-01

    Full Text Available We report two cases of descending thoracic aorta floating thrombus treated with Bolton Relay thoracic free-flow stent graft. The patients had symptoms of lower limb ischemia; they underwent preoperative angiography and CTscan, then we proceeded with endovascular exclusion of the thrombus from the systemic circulation. At 12 months, the graft was still patent in both patients, without any signs of endoleak.

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

    Science.gov (United States)

    Govindarajan, Vijay; Rakesh, Vineet; Reifman, Jaques; Mitrophanov, Alexander Y.

    2016-01-01

    A comprehensive 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 predict and control pathological states caused by a malfunctioning blood coagulation system. Despite numerous investigations, the spatial and temporal details of thrombus growth as a multicomponent process are not fully understood. Here, we used computational modeling to investigate the temporal changes in the spatial distributions of the key enzymatic (i.e., thrombin) and structural (i.e., platelets and fibrin) components within a growing thrombus. Moreover, we investigated the interplay between clot structure and its mechanical properties, such as hydraulic resistance to flow. Our model relied on the coupling of computational fluid dynamics and biochemical kinetics, and was validated using flow-chamber data from a previous experimental study. The model allowed us to identify the distinct patterns characterizing the spatial distributions of thrombin, platelets, and fibrin accumulating within a thrombus. Our modeling results suggested that under the simulated conditions, thrombin kinetics was determined predominantly by prothrombinase. Furthermore, our simulations showed that thrombus resistance imparted by fibrin was ∼30-fold higher than that imparted by platelets. Yet, thrombus-mediated bloodflow occlusion was driven primarily by the platelet deposition process, because the height of the platelet accumulation domain was approximately twice that of the fibrin accumulation domain. Fibrinogen supplementation in normal blood resulted in a nonlinear increase in thrombus resistance, and for a supplemented fibrinogen level of 48%, the thrombus resistance increased by ∼2.7-fold. Finally, our model predicted that restoring the normal levels of clotting factors II, IX, and X while simultaneously restoring fibrinogen (to 88% of its normal level) in diluted blood can restore fibrin generation to

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

    OpenAIRE

    Govindarajan, Vijay; Rakesh, Vineet; Reifman, Jaques; Mitrophanov, Alexander Y.

    2016-01-01

    A comprehensive 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 predict and control pathological states caused by a malfunctioning blood coagulation system. Despite numerous investigations, the spatial and temporal details of thrombus growth as a multicomponent process are not fully understood. Here, we used computational modeling to investigate the temporal changes in the spatial...

  5. 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.

  6. Successful Surgical Control of Peritoneal Dissemination of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Norio Yokoigawa

    2012-09-01

    Full Text Available Treatment for the peritoneal dissemination of hepatocellular carcinoma (HCC has not yet been established. We report a patient with HCC associated with disseminated intra-abdominal tumor. A 74-year-old man was admitted to our hospital. Computed tomography showed a 3 × 3 cm mass in the left hepatic lobe and a giant mass between the stomach and spleen. At laparotomy, the tumor was seen in the medial segment and evaginated to the diaphragm. There was a tumor between the stomach and spleen, confirmed as a 5 × 5 cm tumor evaginated from the left diaphragm, and a 7 × 7 cm tumor adhesive to the spleen. These two tumors were not continuous and were separated. Furthermore, we confirmed a 10 × 10 cm tumor in the pelvic cavity. We performed partial hepatectomy, resection of the tumor evaginated from the diaphragm, resection of the tumor of the spleen and tail of pancreas, and resection of the tumor in the pelvic cavity. Histopathologically, all resected tumors were confirmed to be well-differentiated HCC. HCC rarely disseminates intraperitoneally. It is considered that the peritoneal dissemination of HCC occurred from poorly differentiated or undifferentiated type. Then this report is a rare case. Although surgical treatment of peritoneal dissemination of HCC is not curative, surgery may improve survival and provide good quality of life in selected cases.

  7. Supporting roles of platelet thrombospondin-1 and CD36 in thrombus formation on collagen.

    Science.gov (United States)

    Kuijpers, Marijke J E; de Witt, Susanne; Nergiz-Unal, Reyhan; van Kruchten, Roger; Korporaal, Suzanne J A; Verhamme, Peter; Febbraio, Maria; Tjwa, Marc; Voshol, Peter J; Hoylaerts, Marc F; Cosemans, Judith M E M; Heemskerk, Johan W M

    2014-06-01

    Platelets abundantly express the membrane receptor CD36 and store its ligand thrombospondin-1 (TSP1) in the α-granules. We investigated whether released TSP1 can support platelet adhesion and thrombus formation via interaction with CD36. Mouse platelets deficient in CD36 showed reduced adhesion to TSP1 and subsequent phosphatidylserine expression. Deficiency in either CD36 or TSP1 resulted in markedly increased dissolution of thrombi formed on collagen, although thrombus buildup was unchanged. In mesenteric vessels in vivo, deficiency in CD36 prolonged the time to occlusion and enhanced embolization, which was in agreement with earlier observations in TSP1-deficient mice. Thrombi formed using wild-type blood stained positively for secreted TSP1. Releasate from wild-type but not from TSP1-deficient platelets enhanced platelet activation, phosphatidylserine expression, and thrombus formation on collagen. The enhancement was dependent on CD36 because it was without effect on thrombus formation by CD36-deficient platelets. These results demonstrate an anchoring role of platelet-released TSP1 via CD36 in platelet adhesion and collagen-dependent thrombus stabilization. Thus, the TSP1-CD36 tandem is another platelet ligand-receptor axis contributing to the maintenance of a stable thrombus. © 2014 American Heart Association, Inc.

  8. 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.

  9. Elevated core-fucosylated IgG is a new marker for hepatitis B virus-related hepatocellular carcinoma

    Science.gov (United States)

    Yi, Chang-Hong; Weng, Hong-Lei; Zhou, Fei-Guo; Fang, Meng; Ji, Jun; Cheng, Cheng; Wang, Hao; Liebe, Roman; Dooley, Steven; Gao, Chun-Fang

    2015-01-01

    Immunoglubulin G (IgG) and its abnormal glycosylations are associated with carcinogenesis. The present study investigates the relationship between cancer-derived IgG and clinicopathological characteristics in hepatocellular carcinoma (HCC) and assesses the value of serum N-glycosylated IgG in diagnosing and monitoring hepatitis B virus (HBV)-related HCC. Tissue microarray analysis of 90 HCC tissues showed that HCC patients with IgG immunopositivity had higher levels of core-fucosylated α fetoprotein (AFP-L3), larger tumors, and a higher incidence of portal vein tumor thrombus. HCC-derived IgG stimulated the growth of liver cancer cells in vitro. HCC patients presented a significantly increased fraction of Lens culinaris agglutinin binding IgG (core-fucosylated IgG, IgG-L3) among total serum IgG. The clinical diagnostic performance of serum IgG-L3% was evaluated in 3 case-control studies (1 training set and 2 validation cohorts), including 293 patients with HCC, 131 with liver cirrhosis, 132 HBV carriers, and 151 healthy controls. IgG-L3% had better general diagnostic performance than AFP in the training set and validation cohort 1 (accuracy: 81.33–85.11% versus 63.33–78.61%). In validation cohort 2, where we aimed to assess the efficiency of IgG-L3% in patients with AFP-negative HCC, the diagnostic accuracy of IgG-L3% was 72.54–73.60%. Finally, a longitudinal evaluation based on 31 HCC patients demonstrated that IgG-L3% decreased in 24 patients after curative surgery. The remaining 7 patients showed elevated IgG-L3% and post-operative recurrence. HCC patients with higher IgG-L3% had poor survival during a 3-year follow up. We conclude that HCC-derived IgG is correlated with progressive behavior of HCC. Therefore, elevated core-fucosylated IgG is a new diagnostic and prognostic marker in HBV-related HCC. PMID:26587313

  10. [De novo lipogenesis: role in hepatocellular carcinoma].

    Science.gov (United States)

    Calvisi, D F

    2011-11-01

    Hepatocellular carcinoma (HCC) is one of the most frequent and lethal tumors worldwide. Thus, there is an urgent need to elucidate its molecular pathogenesis in order to develop novel diagnostic, preventive and therapeutic strategies for this deadly disease. Mounting evidence implies a pivotal role of proteins involved in lipid biosynthesis in the development and progression of human HCC. This review summarizes the data available on the pathogenetic relevance of lipogenic proteins in the growth of liver cancer cells, the mechanisms responsible for unrestrained lipid biosynthesis in HCC and the possible clinical implications arising from these discoveries. Altogether the data implicate the AKT-mTORC1-RPS6 signaling pathway as the main inducer of aberrant lipid synthesis in HCC and are indicative of therapeutic strategies aimed at inhibiting de novo lipogenesis for the treatment of human liver cancer.

  11. 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.

  12. Expression of BTG1 in hepatocellular carcinoma and its correlation with cell cycles, cell apoptosis, and cell metastasis.

    Science.gov (United States)

    Sun, G G; Lu, Y F; Cheng, Y J; Yang, C R; Liu, Q; Jing, S W; Han, X C

    2014-12-01

    This study aimed to analyze the expression, clinical significance of B cell translocation gene 1 (BTG1) in hepatocellular carcinoma, and the biological effect in its cell line by BTG1 overexpression. Immunohistochemistry and Western blot were used to analyze BTG1 protein expression in 70 cases of hepatocellular cancer and 32 cases of normal tissues to study the relationship between BTG1 expression and clinical factors. Recombinant lentiviral vector was constructed to overexpress BTG1 and then infect hepatocellular cancer HepG2 cell line. The level of BTG1 protein expression was found to be significantly lower in hepatocellular cancer tissue than normal tissues (P expression of BTG1 was significantly correlated with tumor invasion, lymph node metastasis, clinic stage, and histological grade of patients with hepatocellular cancer (P expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (P protein expression compared with HepG2 cell-untransfected BTG1 (P expression decreased in hepatocellular cancer and correlated significantly with lymph node metastasis, clinic stage, histological grade, poor overall survival, proliferation, and metastasis in hepatocellular cancer cell by regulating CND1, Bcl-2, and MMP-9 protein expression, suggesting that BTG1 may play important roles as a negative regulator to hepatocellular cancer cell.

  13. Laser Ablation for Small Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Claudio Maurizio Pacella

    2011-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common malignancies worldwide and is increasingly detected at small size (<5 cm owing to surveillance programmes in high-risk patients. For these cases, curative therapies such as resection, liver transplantation, or percutaneous ablation have been proposed. When surgical options are precluded, image-guided tumor ablation is recommended as the most appropriate therapeutic choice in terms of tumor local control, safety, and improvement in survival. Laser ablation (LA represents one of currently available loco-ablative techniques: light is delivered via flexible quartz fibers of diameter from 300 to 600 μm inserted into tumor lesion through either fine needles (21g Chiba needles or large-bore catheters. The thermal destruction of tissue is achieved through conversion of absorbed light (usually infrared into heat. A range of different imaging modalities have been used to guide percutaneous laser ablation, but ultrasound and magnetic resonance imaging are most widely employed, according to local experience and resource availability. Available clinical data suggest that LA is highly effective in terms of tumoricidal capability with an excellent safety profile; the best results in terms of long-term survival are obtained in early HCC so that LA can be proposed not only in unresectable cases but, not differently from radiofrequency ablation, also as the first-line treatment.

  14. 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.

  15. A splicing variant of Merlin promotes metastasis in hepatocellular carcinoma.

    Science.gov (United States)

    Luo, Zai-Li; Cheng, Shu-Qun; Shi, Jie; Zhang, Hui-Lu; Zhang, Cun-Zhen; Chen, Hai-Yang; Qiu, Bi-Jun; Tang, Liang; Hu, Cong-Li; Wang, Hong-Yang; Li, Zhong

    2015-10-07

    Merlin, which is encoded by the tumour suppressor gene Nf2, plays a crucial role in tumorigenesis and metastasis. However, little is known about the functional importance of Merlin splicing forms. In this study, we show that Merlin is present at low levels in human hepatocellular carcinoma (HCC), particularly in metastatic tumours, where it is associated with a poor prognosis. Surprisingly, a splicing variant of Merlin that lacks exons 2, 3 and 4 ((Δ2-4)Merlin) is amplified in HCC and portal vein tumour thrombus (PVTT) specimens and in the CSQT2 cell line derived from PVTT. Our studies show that (Δ2-4)Merlin interferes with the capacity of wild-type Merlin to bind β-catenin and ERM, and it is expressed in the cytoplasm rather than at the cell surface. Furthermore, (Δ2-4)Merlin overexpression increases the expression levels of β-catenin and stemness-related genes, induces the epithelium-mesenchymal-transition phenotype promoting cell migration in vitro and the formation of lung metastasis in vivo. Our results indicate that the (Δ2-4)Merlin variant disrupts the normal function of Merlin and promotes tumour metastasis.

  16. Viral pathogenesis of hepatocellular carcinoma in the United States.

    Science.gov (United States)

    Liang, T J; Jeffers, L J; Reddy, K R; De Medina, M; Parker, I T; Cheinquer, H; Idrovo, V; Rabassa, A; Schiff, E R

    1993-12-01

    Chronic hepatitis B virus infection is closely associated with the development of hepatocellular carcinoma, which is a major cause of cancer death worldwide. Recent studies have implicated hepatitis C virus infection as a major pathogenic agent of HBsAg-negative hepatocellular carcinoma. The significance of hepatitis C virus and hepatitis B virus infections in the occurrence of HBsAg-negative hepatocellular carcinoma has not been well established in the United States. We studied 91 HBsAg-negative American patients with hepatocellular carcinoma for evidence of hepatitis C virus or hepatitis B virus infection. These patients had no other predisposing factors to hepatocellular carcinoma. A sensitive polymerase chain reaction was employed to detect hepatitis C virus RNA and hepatitis B virus DNA in serum and liver. Three sets of hepatitis C virus and hepatitis B virus primers were used to optimize the detection of viral genomes. Hepatitis C virus antibodies were measured with second-generation immunoassays. Twenty-six (29%) of these patients carried low levels of hepatitis B virus DNA in either serum, liver/tumor tissue or both. On the basis of the results from serological and polymerase chain reaction analyses of serum and liver, we found that 53 of 91 patients (58%) exhibited evidence of hepatitis C virus infection. When data were combined, 14 patients (15%) had evidence of hepatitis B virus/hepatitis C virus coinfection, whereas 12 (13%) were infected with hepatitis B virus alone and 39 (43%) had hepatitis C virus only. Twenty-six (29%) had no markers of hepatitis B virus or hepatitis C virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Detection of thrombus size and protein content by ex vivo magnetization transfer and diffusion weighted MRI

    Directory of Open Access Journals (Sweden)

    Phinikaridou Alkystis

    2012-06-01

    Full Text Available Abstract Background To utilize a rabbit model of plaque disruption to assess the accuracy of different magnetic resonance sequences [T1-weighted (T1W, T2-weighted (T2W, magnetization transfer (MT and diffusion weighting (DW] at 11.7 T for the ex vivo detection of size and composition of thrombus associated with disrupted plaques. Methods Atherosclerosis was induced in the aorta of male New Zealand White rabbits (n = 17 by endothelial denudation and high-cholesterol diet. Subsequently, plaque disruption was induced by pharmacological triggering. Segments of infra-renal aorta were excised fixed in formalin and examined by ex vivo magnetic resonance imaging (MRI at 11.7 T and histology. Results MRI at 11.7 T showed that: (i magnetization transfer contrast (MTC and diffusion weighted images (DWI detected thrombus with higher sensitivity compared to T1W and T2W images [sensitivity: MTC = 88.2%, DWI = 76.5%, T1W = 66.6% and T2W = 43.7%, P P (ii MTC and DWI provided a more accurate detection of thrombus area with histology as the gold-standard [underestimation of 6% (MTC and 17.6% (DWI compared to an overestimation of thrombus area of 53.7% and 46.4% on T1W and T2W images, respectively]; (iii the percent magnetization transfer rate (MTR correlated with the fibrin (r = 0.73, P = 0.003 and collagen (r = 0.9, P = 0.004 content of the thrombus. Conclusions The conspicuity of the thrombus was increased on MTC and DW compared to T1W and T2W images. Changes in the %MTR and apparent diffusion coefficient can be used to identify the organization stage of the thrombus.

  18. Thrombus Aspiration in Patients With ST-Segment Elevation Myocardial Infarction Presenting Late After Symptom Onset.

    Science.gov (United States)

    Desch, Steffen; Stiermaier, Thomas; de Waha, Suzanne; Lurz, Philipp; Gutberlet, Matthias; Sandri, Marcus; Mangner, Norman; Boudriot, Enno; Woinke, Michael; Erbs, Sandra; Schuler, Gerhard; Fuernau, Georg; Eitel, Ingo; Thiele, Holger

    2016-01-25

    The aim of this study was to examine whether manual thrombus aspiration reduces microvascular obstruction assessed by cardiac magnetic resonance imaging in patients with ST-segment elevation myocardial infarction (STEMI) presenting late after symptom onset. Thrombus aspiration is an established treatment option in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). However, there are only limited data on the efficacy of thrombus aspiration in patients with STEMI presenting ≥12 h after symptom onset. Patients with subacute STEMI presenting ≥12 and ≤48 h after symptom onset were randomized to primary PCI with or without manual thrombus aspiration in a 1:1 ratio. Patients underwent cardiac magnetic resonance imaging 1 to 4 days after randomization. The primary endpoint was the extent of microvascular obstruction. A total of 152 patients underwent randomization. The mean time between symptom onset and PCI was 28 ± 12 h. Baseline characteristics were comparable between groups. The majority of patients (60%) showed at least a moderate amount of viable myocardium in the affected region. Extent of microvascular obstruction was not significantly different between patients assigned to thrombus aspiration and the control group (2.5 ± 4.0% vs. 3.1 ± 4.4% of left ventricular mass, p = 0.47). There were also no significant differences in infarct size, myocardial salvage, left ventricular ejection fraction, and angiographic and clinical endpoints between groups. In this first randomized trial of thrombectomy in patients with STEMI presenting late after symptom onset, routine thrombus aspiration before PCI failed to show a benefit for markers of reperfusion success. (Effect of Thrombus Aspiration in Patients With Myocardial Infarction Presenting Late After Symptom Onset; NCT01379248). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. PATHOPHYSIOLOGY STROKE NON-HEMORRHAGIC ET CAUSA THROMBUS

    Directory of Open Access Journals (Sweden)

    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;}

  20. 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

  1. Review of Mechanical Testing and Modelling of Thrombus Material for Vascular Implant and Device Design.

    Science.gov (United States)

    Johnson, S; Duffy, S; Gunning, G; Gilvarry, M; McGarry, J P; McHugh, P E

    2017-08-28

    A thrombus or blood clot is a solid mass, made up of a network of fibrin, platelets and other blood components. Blood clots can form through various pathways, for example as a result of exposed tissue factor from vascular injury, as a result of low flow/stasis, or in very high shear flow conditions. Embolization of cardiac or vascular originating blood clots, causing an occlusion of the neurovasculature, is the major cause of stroke and accounts for 85% of all stroke. With mechanical thrombectomy emerging as the new standard of care in the treatment of acute ischemic stroke (AIS), the need to generate a better understanding of the biomechanical properties and material behaviour of thrombus material has never been greater, as it could have many potential benefits for the analysis and performance of these treatment devices. Defining the material properties of a thrombus has obvious implications for the development of these treatment devices. However, to-date this definition has not been adequately established. While some experimentation has been performed, model development has been extremely limited. This paper reviews the previous literature on mechanical testing of thrombus material. It also explores the use of various constitutive and computational models to model thrombus formation and material behaviour.

  2. Local complement activation triggers neutrophil recruitment to the site of thrombus formation in acute myocardial infarction.

    Science.gov (United States)

    Distelmaier, Klaus; Adlbrecht, Christopher; Jakowitsch, Johannes; Winkler, Susanne; Dunkler, Daniela; Gerner, Christopher; Wagner, Oswald; Lang, Irene M; Kubicek, Markus

    2009-09-01

    Atherosclerotic plaque rupture with subsequent mural thrombus formation is considered the main event compromising epicardial flow in acute myocardial infarction (AMI). However, the precise mechanisms underlying acute coronary occlusion are unknown. We compared the proteomic profiles of systemic plasma and plasma derived from the site of thrombus formation of patients with AMI by two-dimensional gel electrophoresis and ELISA. We identified a local activation of the complement system, with selective accumulation of the complement activator C-reactive protein (CRP) and the downstream complement effectors C3a and C5a. CRP in coronary thrombus co-localised with C1q and C3 immunoreactivities, suggesting classical complement activation. In vitro, coronary thrombus derived plasma enhanced neutrophil chemotaxis in a C5a dependent fashion. In vivo, neutrophil accumulation at the site of thrombus formation paralleled the time delay from symptom onset to first balloon inflation or aspiration, and was correlated with C5a and enzymatic infarct size. We present the first direct evidence for localised complement activation in acute coronary thrombi. Our data indicate that local complement effectors amplify the vascular occlusion process in AMI by enhanced neutrophil recruitment.

  3. Evaluation of DNA aptamers directed to thrombin as potential thrombus imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Dougan, Hayes E-mail: dougan@triumf.ca; Weitz, Jeffrey I.; Stafford, Alan R.; Gillespie, Kris D.; Klement, Petr; Hobbs, John B.; Lyster, Donald M

    2003-01-01

    Two DNA aptamers directed against two separate exosites on human {alpha}-thrombin were evaluated for thrombus-imaging potential. Aptamer ODN 1 is directed to the thrombin substrate binding site (exosite 1). Our finding that ODN 1 competes with fibrin for binding to exosite 1 on thrombin suggests that ODN 1 will not be useful for thrombus imaging. Aptamer ODN 2 is directed against the thrombin heparin binding site (exosite 2). ODN 2 bound to model thrombi that were formed either by clotting purified fibrinogen with thrombin, or by recalcifying citrated plasma. As the thrombin content of thrombi was increased the rate of ODN 2 uptake into preformed thrombi increased, whereas the rate of release of ODN 2 out of preformed thrombi decreased. This in vitro data suggested that ODN 2 might be useful for thrombus imaging because it can bind to exosite 2 on fibrin-bound thrombin. However, in a rabbit jugular vein model using thrombus supplemented with human thrombin, ODN 2 uptake was equal to the ovalbumin control, and did not reflect thrombin content. While the in vitro results with ODN 2 were consistent with thrombus imaging, the rapid clearance of ODN 2 from circulation, combined with slow mass transfer in the clot, seem to work against in vivo thrombin-dependent imaging or washout analysis.

  4. Propranolol Hydrochloride in Treating Patients With Locally Recurrent or Metastatic Solid Tumors That Cannot Be Removed By Surgery

    Science.gov (United States)

    2017-11-27

    Male Breast Cancer; Recurrent Melanoma; Stage IV Breast Cancer; Stage IV Melanoma; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Hepatocellular Carcinoma

  5. FATE-NK100 as Monotherapy and in Combination With Monoclonal Antibody in Subjects With Advanced Solid Tumors

    Science.gov (United States)

    2017-10-23

    HER2 Positive Gastric Cancer; Colorectal Cancer; Head and Neck Squamous Cell Carcinoma; EGFR Positive Solid Tumor; Advanced Solid Tumors; HER2-positive Breast Cancer; Hepatocellular Carcinoma; Small Cell Lung Cancer; Renal Cell Carcinoma; Pancreas Cancer

  6. Notch Inhibitor PF-03084014 Inhibits Hepatocellular Carcinoma Growth and Metastasis via Suppression of Cancer Stemness due to Reduced Activation of Notch1-Stat3.

    Science.gov (United States)

    Wu, Chuan Xing; Xu, Aimin; Zhang, Cathy C; Olson, Peter; Chen, Lin; Lee, Terence K; Cheung, Tan To; Lo, Chung Mau; Wang, Xiao Qi

    2017-08-01

    Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma, indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084014 in hepatocellular carcinoma. Hepatocellular carcinoma spherical cells (stem-like cancer cells), a sphere-derived orthotopic tumor model and one patient-derived xenograft (PDX) model were used in our experiment. We demonstrated that PF-03084014 inhibited the self-renewal and proliferation of cancer stem cells. PF-03084014 reduced the hepatocellular carcinoma sphere-derived orthotopic tumor and blocked the hepatocellular carcinoma tumor liver to lung metastasis. We further tested the PF-03084014 in PDX models and confirmed the inhibition tumor growth effect. In addition, a low dose of PF-03084014 induced hepatocellular carcinoma sphere differentiation, resulting in chemosensitization. Antitumor activity was associated with PF-03084014-induced suppression of Notch1 activity, decreased Stat3 activation and phosphorylation of the Akt signaling pathway, and reduced epithelial-mesenchymal transition. These are the key contributors to the maintenance of cancer stemness and the promotion of cancer metastasis. Moreover, the Notch-Stat3 association was implicated in the clinical hepatocellular carcinoma prognosis. Collectively, PF-03084014 revealed antitumor and antimetastatic effects in hepatocellular carcinoma, providing evidence for the potential use of gamma-secretase inhibitors as a therapeutic option for the treatment of hepatocellular carcinoma. Mol Cancer Ther; 16(8); 1531-43. ©2017 AACR. ©2017 American Association for Cancer Research.

  7. 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

  8. 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.)

  9. Minimally invasive image-guided therapy for inoperable hepatocellular carcinoma: What is the evidence today?

    NARCIS (Netherlands)

    Seinstra, Beatrijs A.; van Delden, Otto M.; van Erpecum, Karel J.; van Hillegersberg, Richard; Mali, Willem P. Th M.; van den Bosch, Maurice A. A. J.

    2010-01-01

    Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10-15% of HCC patients are suitable candidates for hepatic resection and liver transplantation due to the advanced stage of the disease at time of diagnosis and

  10. Irradiation of hepatocellular carcinoma: Impact of breathing on motions and variations of volume of the tumor, liver and upper abdominal organs; L'irradiation des carcinomes hepatocellulaires: impact de la respiration sur les mouvements et variations de volume de la tumeur, du foie et des organes intra-abdominaux

    Energy Technology Data Exchange (ETDEWEB)

    Kubas, A.; Mornex, F.; D' Hombres, A.; Lorchel, F.; Chapet, O. [Centre hospitalier Lyon-Sud, Service de Radiotherapie-oncologie Rhone-Alpes, 69 - Pierre-Benite (France); Merle, P. [Hopital de l' Hotel-Dieu, Service d' Hepatogastroenterologie, 69 - Lyon (France)

    2008-12-15

    Purpose: To evaluate the amplitude of motion and the variations of volume of the tumor, the liver and upper abdominal organs induced by breathing during the irradiation of hepatocellular carcinoma (H.C.C.). Material and methods: Two scanners were performed in inhale and in exhale not forced in 20 patients with a H.C.C.. The liver (left/right lobes), the tumor, the duodenum, the two kidneys and the pancreas were delineated on each acquisition. The superposition of the two spirals made it possible to measure the displacements and variations of volume of these structures in the cranio caudal (C.C.), lateral (Lat), and anteroposterior (A.P.) directions. Results:The mean displacement of the tumour in C.C., Lat and A.P. was of 19.7 {+-} 8.3 mm, 4.5 {+-} 2.3 mm, and 8.9 {+-} 6.5 mm. The greatest amplitude of movement was obtained in C.C. for the right and left hepatic lobes (19 {+-} 6.5 mm, 10 {+-} 5.6 mm), the duodenum(12.6 {+-} 6.4 mm), the kidneys right and left (15.5 {+-} 6.1 mm, 16.2 {+-} 10 mm) and the pancreas (13.2 {+-} 6 mm). No significant variation of volume was observed for these organs. Conclusion: The movements of the tumour, the liver and the abdominal organs, induced by breathing are significant. The respiratory gating appears essential in particular with the development of new techniques of irradiation such as the intensity-modulated radiotherapy (I.M.R.T.) or the stereotactic body radiation therapy (S.B.R.T.). (authors)

  11. Immunosupression in liver transplant for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Juan Carlos Restrepo Restrepo

    2007-02-01

    Full Text Available

    The hepatocellular carcinoma (HCC has turned into a frequent indication for liver transplant. The reports of different series indicate that it represents at least 12% of all liver transplants in Europe. But what kind of inmunosuppression is better in these patients is an unanswered question. Our intension with this review is to give basic information to define which would be the best immunosuppression alternative. There is enough information on the relationship between immunosuppression and cancer, as it is seen in states of primary immunodeficiency or infection with the Human Immunodeficiency virus (HIV. The immune system offers a state of permanent guard to avoid the arousal of neoplasic diseases in immunocompetent patients and from this point of view it has been seen that in immunosuppressed patients there is an association with this condition and the development of lymphoproliferative disorders, which can range from reversible diseases (polyclonal proliferation of B type lymphocytes to the development of a lymphoma and other types of tumors, like the ones observed in skin, genital region or oropharynx. Colon tumors and breast tumors have not been associated with immunosuppression. Immunosuppressive medication takes part in a different manner in the development of tumors, it has been said that steroids that are associated with some tumors, especially those regarding skin, paradoxically have a protective role in the development of lymph tissue tumors.

    It has been said about Azathioprine and Mycophenolate mofetil (MMF that its immunosuppressive effect is an antiproliferative type of immunosuppression, inhibiting the synthesis of purinic nucleotides, especially in lymphocytes. Azathioprine has been involved in the development of hepatic tumors, especially in the era previous

  12. Epidemiology of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Mimi C Yu

    2000-01-01

    Full Text Available Although rare in Canada and the United States, hepatocellular carcinoma (HCC ranks as the eighth most common cancer in the world. High-risk regions are East and Southeast Asia, and sub-Saharan Africa. Independent of race and geography, rates in men are at least two to three times those in women; this sex ratio is more pronounced in high-risk regions. Rates of HCC in the United States have increased by 70% over the past two decades. Registry data in Canada and Western Europe show similar trends. In contrast, the incidence of HCC in Singapore and Shanghai, China, both high-risk regions, has declined steadily over the past two decades. Among white and black Americans, there is an inverse relationship between social class status and HCC incidence. Chronic infection by the hepatitis B virus (HBV is by far the most important risk factor for HCC in humans. It is estimated that 80% of HCC worldwide is etiologically associated with HBV. In the United States, although the infection rate in the general population is low, HBV is estimated to account for one in four cases of HCC among non-Asians. Chronic infection by the hepatitis C virus is another important risk factor for HCC in the United States; however, this virus is believed to play a relatively minor role in the development of HCC in Africa and Asia. Dietary aflatoxin exposure is an important codeterminant of HCC risk in Africa and parts of Asia. In Canada and the United States, excessive alcohol intake, cigarette smoking and oral contraceptive use in women also are risk factors for HCC.

  13. Handheld Echocardiography Saves the Brain: A Serendipitously Found Left Ventricular Thrombus.

    Science.gov (United States)

    Narichania, Aalap D; Shamoun, Fadi E

    2015-01-01

    Handheld echocardiography (HHE) is an emerging technology with potential to alter routine clinical practice. Our institution has adopted the use of HHE devices for both teaching and patient care. However, the appropriate clinical scope of HHE continues to be controversial, and the literature is largely devoid of prognosis-altering applications. We report the diagnosis of left ventricular (LV) thrombus with HHE. A 75-year-old man presented with a large anteroapical ST-elevation myocardial infarction (MI). Initial transthoracic echocardiography (TTE) after percutaneous intervention showed no LV thrombus. Before his hospital discharge, HHE was performed and showed LV thrombus. The finding substantially changed the patient's treatment and prognosis; he was discharged with warfarin. This observation will help guide further inquiry into the proper clinical role of HHE.

  14. Synthetic thrombus model for in-vitro studies of laser thrombolysis

    Science.gov (United States)

    Hermes, Robert E.; Trajkovska, Keti

    1998-05-01

    Laser thrombolysis is the controlled ablation of a thrombus (blood clot) blockage in a living arterial system. Theoretical modeling of the interaction of laser light with thrombi relies on the ability to perform in vitro experiments with well characterized surrogate materials. A synthetic thrombus formulation may offer more accurate results when compared to in vivo clinical experiments. We describe here the development of new surrogate materials based on formulations incorporating chicken egg, guar gum, modified food starch, and a laser light absorbing dye. The sound speed and physical consistency of the materials were very close to porcine (arterial) and human (venous) thrombi. Photographic and videotape recordings of pulsed dye laser ablation experiments under various experimental conditions were used to evaluate the new material as compared to in vitro tests with human (venous) thrombus. The characteristics of ablation and mass removal were similar to that of real thrombi, and therefore provide a more realistic model for in vitro laser thrombolysis when compared to gelatin.

  15. Pediatric hepatocellular carcinoma: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Schmid I

    2017-01-01

    Full Text Available Irene Schmid,1 Dietrich von Schweinitz,2 1Department of Pediatric Hematology and Oncology, 2Department of Pediatric Surgery, Dr. von Hauner Children`s Hospital, Ludwig-Maximilians-University, Munich, Germany Abstract: Hepatocellular carcinoma (HCC is a very rare entity in children, making it nearly impossible to orchestrate Phase II/III studies even as multinational cooperative trials. In contrast to adults, nearly 50% of the children have a response (α-fetoprotein decline and/or tumor shrinkage to chemotherapeutic agents such as cisplatin and doxorubicin (PLADO, demonstrating that HCC in childhood can be chemotherapy sensitive. As a result, the main treatment options in pediatric HCC focus on systemic drug therapies and resection as the central therapy. In nonmetastatic patients with complete resection upfront, the 5-year event-free survival and overall survival has reached 80%–90%. In almost all reported studies, children received adjuvant chemotherapy (mostly PLADO, but it has never been proven that postoperative chemotherapy is superior to observation. No data are available for the effects of sorafenib. The 3-year survival is <20% in children with unresectable HCC independent of the chemotherapy given preoperatively. Currently, PLADO in combination with sorafenib is recommended with the goal of achieving operability status. Alternatively, data are promising for the combination of sorafenib with gemcitabine and oxaliplatin. For children with nonresectable and nonmetastastic liver tumors, it has been shown that the Milan criteria regarding liver transplantation are not applicable – individual decisions have to be made. Transarterial chemoembolization could be offered to patients with chemotherapy-resistant liver tumors for palliative care or potentially to achieve surgical resectability, and therefore cure. Information about the feasibility or effects of new agents or approaches as discussed in adult HCC patients is not available for

  16. Gd-EOB-DTPA-enhanced MR imaging findings of hepatocellular adenoma: correlation with pathological findings.

    Science.gov (United States)

    Takara, Kenichi; Saito, Kazuhiro; Kusama, Hiroshi; Tsuchida, Akihiko; Aoki, Tatsuya; Nagao, Toshitaka; Imai, Yasuharu; Taira, Junichi; Moriyasu, Fuminori; Tokuuye, Koichi

    2011-01-01

    We report a case of a 28-year-old woman with hepatocellular adenoma and correlate findings of pathology and magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) enhancement. In the hepatobiliary phase, the peripheral region of the tumor that corresponded with proliferating hepatocytes with steatosis showed slight hypointensity compared with the surrounding liver parenchyma, and the central region of the tumor that corresponded with cellular areas showed isointensity.

  17. Distinct Claudin Expression Profiles of Hepatocellular Carcinoma and Metastatic Colorectal and Pancreatic Carcinomas

    OpenAIRE

    Holczbauer, Ágnes; Gyöngyösi, Benedek; Lotz, Gábor; Szijártó, Attila; Kupcsulik, Péter; Schaff, Zsuzsa; Kiss, András

    2013-01-01

    Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 col...

  18. Subcellular Localization of APE1/Ref-1 in Human Hepatocellular Carcinoma: Possible Prognostic Significance

    OpenAIRE

    Di Maso, Vittorio; Avellini, Claudio; Crocè, Lory Saveria; Rosso, Natalia; Quadrifoglio, Franco; Cesaratto, Laura; Codarin, Erika; Bedogni, Giorgio; Beltrami, Carlo Alberto; Tell, Gianluca; Tiribelli, Claudio

    2007-01-01

    APE1/Ref-1, normally localized in the nucleus, is a regulator of the cellular response to oxidative stress. Cytoplasmic localization has been observed in several tumors and correlates with a poor prognosis. Because no data are available on liver tumors, we investigated APE1/Ref-1 subcellular localization and its correlation with survival in 47 consecutive patients undergoing hepatocellular carcinoma (HCC) resection. APE1/Ref-1 expression was determined by immunohistochemistry in HCC and surro...

  19. Combined thrombus aspiration and recanalization in treating Budd-Chiari syndrome with inferior vena cava thrombosis.

    Science.gov (United States)

    Fu, Yu-Fei; Xu, Hao; Wu, Qian; Zhang, Qing-Qiao; Cui, Yan-Feng; Wei, Ning

    2015-12-01

    To investigate the feasibility, safety, and effectiveness of combined thrombus aspiration and inferior vena cava (IVC) recanalization for Budd-Chiari syndrome (BCS) patients with IVC thrombosis. From March 2011 to October 2014, 17 consecutive BCS patients with IVC thrombosis [male 13, female 4 (mean age 52.6 ± 8.4 years, range 43-72 years)] treated by combined thrombus aspiration and IVC recanalization were enrolled in this retrospective study. An 8F guiding catheter was used as the aspiration catheter. During the treatment, the aspiration catheter was placed from the right femoral vein to the IVC thrombi, and a 20-ml syringe was connected with the aspiration catheter for thrombus aspiration. IVC recanalization was performed after thrombus aspiration. Data on technical success, clinical success, and follow-up were analyzed. Technical success was achieved in all patients. After thrombus aspiration, 12 patients had no visible thrombi on IVC venography, while 5 patients were shown to have the IVC mural thrombi. Afterwards, 13 patients were treated by IVC balloon dilation, and 4 patients were treated by IVC stent insertion. No patient experienced dyspnea after treatment. The average IVC pressure decreased from 29.8 ± 3.4 cmH2O to 8.6 ± 2.1 cmH2O (P < 0.001). Clinical success was achieved in all patients. The average follow-up period was 15.3 ± 11.6 months (range 2-44 months). Long-term IVC patency was achieved in 15 of 17 patients. Combined thrombus aspiration and IVC recanalization can be a safe and effective method for BCS patients with IVC thrombosis.

  20. 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...

  1. New Insights in Hepatocellular Carcinoma

    NARCIS (Netherlands)

    C.D.M. Witjes (Carlijn)

    2012-01-01

    textabstractHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer mortality. HCC is one of the few cancers with well-defined major risk factors. Worldwide, in 80% of the cases HCC develops in cirrhotic livers, and cirrhosis is the

  2. An atypical age-specific pattern of hepatocellular carcinoma in Peru: a threat for Andean populations.

    Directory of Open Access Journals (Sweden)

    Stéphane Bertani

    Full Text Available BACKGROUND: In South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country. METHODS: A retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin. RESULTS: Surprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics. CONCLUSIONS: The analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population.

  3. 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.

  4. 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.

  5. Severe reversible dilated cardiomyopathy associated with a large left ventricular thrombus in a young child with middle aortic syndrome.

    Science.gov (United States)

    Ponniah, U; Overholt, E

    2014-01-01

    We report 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.

  6. Solitary skull metastasis as initial manifestation of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Cho Jun

    2008-06-01

    Full Text Available Abstract Background A solitary skull metastasis from hepatocellular carcinoma (HCC prior to diagnosis of the primary tumor without liver dysfunction is a very rare event. Case presentation A 71-year-old male, without known liver disease, presented to our institution with a palpable occipital scalp mass. On brain magnetic resonance imaging (MRI, a highly enhanced and osteolytic skull tumor was observed. The histological diagnosis obtained from the percutaneous needle biopsy was a cranial metastasis from HCC. The metastatic tumor was removed via occipital craniectomy, and the two primary liver mass lesions were subsequently treated by transarterial chemoembolization. Conclusion An isolated skull metastasis may be the sole initial presentation of HCC. Early diagnosis is essential in order to treat the primary disease. A skull metastasis from HCC should be considered in the differential diagnosis in patients with subcutaneous scalp mass and osteolytic defects on X-ray.

  7. Application of local ablative therapies for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHU Xiaoli

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a common malignant tumor in the world, and surgical resection and liver transplantation are two radical treatment modalities, but only 10%-20% of all patients can receive such treatments. In recent years, local therapies including radiofrequency ablation, microwave ablation, cryoablation, and the irreversible electroporation ablation which appeared recently have gradually become the alternative therapies for the patients who are unable to undergo surgery. In addition to local tumor growth control and improvement in survival outcomes, the ablation technology also helps to downgrade tumor for secondary resection. This article focuses on the research progress in radiofrequency ablation alone and in combination with other therapies in the treatment of HCC, compares radiofrequency ablation with other local ablative therapies, and briefly introduces the application of intelligent navigation technology in adjuvant ablation. With the development of medical imaging and progress in related fields, the ablation technology will be widely applied in clinical practice in the future.

  8. 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

  9. Rectal cancer presenting tumor thrombosis in the inferior vena cava and common iliac vein: case report

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, Sun Jung; Park, Seong Jin; Lee, Hae Kyung; Yi, Boem Ha; Park, Sung Il; Hong, Soo Jin; Kim, Hee Kyung; Park, Jeong Mi [Soonchunhyang University Hospital, Bucheon (Korea, Republic of)

    2008-10-15

    We report the radiologic findings of a rectal carcinoma case with tumor thrombus in the inferior vana cava and left common iliac vein of a 48-year-old woman. The patient complained of swelling in the left leg and consequently underwent a lymphoscintigraphy, CT venography, abdominal CT, PET-CT, pelvis MRI, and ultrasound doppler. The rectal cancer was determined via a colonoscopy. The tissue biopsy of tumor thrombus in the IVC was done during insertion of IVC filter and poorly differentiated adenocarcinoma was revealed by pathology.

  10. Hericium erinaceus enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Lee, Jong Seok; Hong, Eock Kee

    2010-11-28

    It has been demonstrated that the Hericium erinaceus (HE) mushroom, which primarily consists of polysaccharides, possesses anti-tumor activities. However, the mechanisms by which HE inhibits human hepatocellular carcinoma growth remain unknown. Our study demonstrates that HE acts as an enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling, and this sensitization can be achieved by reducing c-FLIP expression via JNK activation and enhancing intracellular Dox accumulation via the inhibition of NF-κB activity. These findings suggest that HE in combination with Dox serves as an effective tool for treating drug-resistant human hepatocellular carcinoma. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Hepatocellular Carcinoma Masquerading as a Large Renal Mass with Hepatic Invasion

    Directory of Open Access Journals (Sweden)

    Joseph R. N. Zabell

    2010-01-01

    Full Text Available Large masses are evaluated with imaging to assess primary origin and tumor spread. We present the unusual case of a 53-year-old male with a 17-cm right upper quadrant mass suspected to be renal or adrenal in origin based on radiographic findings. After surgical excision, the mass was subsequently discovered to be primary hepatocellular carcinoma with direct extension to the kidney and adrenal gland. A diagnosis of chronic hepatitis B was made postoperatively. Primary hepatocellular carcinoma with direct renal extension is an exceedingly rare occurrence based on our experience and review of the published literature.

  12. Radiofrequency thermal ablation of hepatocellular carcinoma: using contrast-enhanced harmonic power doppler sonography to assess treatment outcome.

    Science.gov (United States)

    Cioni, D; Lencioni, R; Rossi, S; Garbagnati, F; Donati, F; Crocetti, L; Bartolozzi, C

    2001-10-01

    We evaluated the accuracy of contrast-enhanced harmonic power Doppler sonography in assessing the outcome of radiofrequency thermal ablation of hepatocellular carcinoma. Fifty patients with 65 hepatocellular carcinoma nodules (1-5 cm in diameter; mean diameter, 2.5 cm) were studied using unenhanced and contrast-enhanced harmonic power Doppler sonography before and after IV administration of a microbubble contrast agent. The examinations were repeated after treatment of the tumors with radiofrequency ablation. Findings of the Doppler studies were compared with those of dual-phase helical CT, which were used as points of reference for assessing treatment outcome. Before radiofrequency treatment, intratumoral blood flow was revealed by unenhanced power Doppler sonography in 48 (74%) of 65 hepatocellular carcinoma nodules. After injection of the contrast agent, intratumoral enhancement was observed in 61 (94%) of 65 hepatocellular carcinomas (p enhancement on power Doppler sonograms. In nine of the 10 lesions that showed a residual viable tumor on helical CT scans, persistent intratumoral enhancement-matching the enhancing areas on helical CT images-was revealed by power Doppler sonography. These nine hepatocellular carcinomas were subjected to repeated radiofrequency thermal ablation with the guidance of contrast-enhanced power Doppler sonography. Complete necrosis was seen after the second treatment session in six of the nine lesions. Contrast-enhanced harmonic power Doppler sonography is an accurate technique for assessing the outcome of radiofrequency thermal ablation of hepatocellular carcinoma and may be useful in guiding additional treatment in patients with incomplete response to initial efforts.

  13. 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.

  14. 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.

  15. Hepatocellular Carcinoma: Novel Molecular Targets in Carcinogenesis for Future Therapies

    Directory of Open Access Journals (Sweden)

    Gaetano Bertino

    2014-01-01

    Full Text Available Background. Hepatocellular carcinoma is one of the most common and lethal malignant tumors worldwide. Over the past 15 years, the incidence of HCC has more than doubled. Due to late diagnosis and/or advanced underlying liver cirrhosis, only limited treatment options with marginal clinical benefit are available in up to 70% of patients. During the last decades, no effective conventional cytotoxic systemic therapy was available contributing to the dismal prognosis in patients with HCC. A better knowledge of molecular hepatocarcinogenesis provides today the opportunity for targeted therapy. Materials and Methods. A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS database for the following keywords: “hepatocellular carcinoma,” “molecular hepatocarcinogenesis,” “targeted therapy,” and “immunotherapy.” Discussion and Conclusion. Treatment decisions are complex and dependent upon tumor staging, presence of portal hypertension, and the underlying degree of liver dysfunction. The knowledge of molecular hepatocarcinogenesis broadened the horizon for patients with advanced HCC. During the last years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways.

  16. 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.

  17. Research advances in Hedgehog signaling pathway in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  18. What's New in Transarterial Therapies for Hepatocellular Carcinoma?

    Science.gov (United States)

    May, Benjamin J; Murthy, Ravi; Madoff, David C

    2012-05-01

    Transarterial therapies play an important role in the treatment of hepatocellular carcinoma, both in a palliative setting and as an adjunct to surgery. These therapies exploit the dual blood supply of the liver to selectively target tumors via the hepatic artery, while sparing nontumorous liver. Currently available therapies include transarterial embolization; chemoembolization, with or without drug-eluting beads; and radioembolization. Transarterial techniques are also being used in the development of novel therapies. This article provides an outline of the technical and clinical applications of intraarterial therapies in the treatment of HCC and highlights pertinent future directions.

  19. 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.

  20. Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.

    Science.gov (United States)

    Yildiz, Gokhan; Arslan-Ergul, Ayca; Bagislar, Sevgi; Konu, Ozlen; Yuzugullu, Haluk; Gursoy-Yuzugullu, Ozge; Ozturk, Nuri; Ozen, Cigdem; Ozdag, Hilal; Erdal, Esra; Karademir, Sedat; Sagol, Ozgul; Mizrak, Dilsa; Bozkaya, Hakan; Ilk, Hakki Gokhan; Ilk, Ozlem; Bilen, Biter; Cetin-Atalay, Rengul; Akar, Nejat; Ozturk, Mehmet

    2013-01-01

    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-gene

  1. Cellular and stromal characteristics in the scirrhous hepatocellular carcinoma: comparison with hepatocellular carcinomas and intrahepatic cholangiocarcinomas.

    Science.gov (United States)

    Okamura, Nobuyoshi; Yoshida, Muneki; Shibuya, Akitaka; Sugiura, Hitoshi; Okayasu, Isao; Ohbu, Makoto

    2005-11-01

    Scirrhous hepatocellular carcinoma (SHCC) is a rare variation of HCC, for which characteristics of tumor cells and the fibrotic stroma have not been clarified in detail. The present study was therefore carried out to elucidate cytological features of tumor and stromal cells and components of the stromal extracellular matrix in 15 SHCC patients undergoing hepatectomy without preoperative transarterial embolization. Diagnosis was on the basis of a scirrhous histological pattern exceeding 50% of the tumor area. Expression of cytoplasmic and extracellular matrix proteins was compared among SHCC, HCC and intrahepatic cholangiocarcinoma (ICC) cases with immunohistochemical staining. The lesions could be histologically divided into radiating and sinusoidal types. Common stromal components of SHCC and ICC were collagen types I and III. There was no expression of laminin-5 in the stroma of SHCC, but it was present in almost all ICC cases. Tenascin-C expression was significantly lower in the SHCC cases and its distribution differed between SHCC and ICC. Matrix metalloproteinase-7 (MMP-7) expression was significantly higher in SHCC compared with HCC. Almost all stromal cells were alpha-smooth muscle actin-positive both in SHCC and ICC, whereas glial fibrillary acid protein (GFAP)-positive stromal cells were significantly more increased in ICC than in SHCC. SHCC clearly differed from HCC with respect to collagen types I, III and MMP-7 expression, and from ICC with regard to stromal components including laminin-5, tenascin-C and GFAP(+) stromal cells.

  2. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    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

  3. Hepatocellular carcinoma in the adult Fontan patient.

    Science.gov (United States)

    Conroy, Michael R; Moe, Tabitha G

    2017-03-01

    In this study, we describe the case of a 36-year-old woman who was diagnosed with hepatocellular carcinoma on a background of Fontan procedure for tricuspid atresia. She had worsening heart failure in the months before presentation, and early investigations noted derangement in liver enzymes and hepatomegaly. Liver biopsy confirmed a hepatocellular carcinoma. Hepatocellular carcinoma is a rare but recognised consequence of cardiac cirrhosis in Fontan patients.

  4. A Thrombus Generation Model Applied to Aneurysms Treated with Shape Memory Polymer Foam and Metal Coils

    Science.gov (United States)

    Horn, John; Ortega, Jason; Hartman, Jonathan; Maitland, Duncan

    2015-11-01

    To prevent their rupture, intracranial aneurysms are often treated with endovascular metal coils which fill the aneurysm sac and isolate it from the arterial flow. Despite its widespread use, this method can result in suboptimal outcomes leading to aneurysm recurrence. Recently, shape memory polymer foam has been proposed as an alternative aneurysm filler. In this work, a computational model has been developed to predict thrombus formation in blood in response to such cardiovascular implantable devices. The model couples biofluid and biochemical phenomena present as the blood interacts with a device and stimulates thrombus formation. This model is applied to simulations of both metal coil and shape memory polymer foam treatments within an idealized 2D aneurysm geometry. Using the predicted thrombus responses, the performance of these treatments is evaluated and compared. The results suggest that foam-treated aneurysms may fill more quickly and more completely with thrombus than coil-filled aneurysms, potentially leading to improved long-term aneurysm healing. This work was performed in part under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  5. Fluid Characteristics in Abdominal Aortic Aneurysms (AAAs) and Its Correlation to Thrombus Formation

    Science.gov (United States)

    Tang, Rubing; Bar-Yoseph, Pinhas Z.; Lasheras, Juan

    2008-11-01

    It has been observed that most large Abdominal Aortic Aneurysms (AAAs) develop an intraluminal thrombus as they progressively enlarge. Previous studies have suggested that the build up of the thrombus may be associated with the altered hemodynamic patterns that arise inside the AAA. We have performed a parametrical computational study of the flow patterns inside enlarging AAA to investigate the possible mechanism controlling the thrombus formation. Pulsatile blood flows were simulated in idealized models of fusiform aneurysms with different dilatation ratios and the effects of shear-activated platelet accumulation and platelet/wall interaction were evaluated based on the calculated flow fields. The platelet activation level (PAL) was determined by computing the integral over time of flow shear stresses exerted over the platelets as they are transported throughout the aneurysm. Our results have shown that the values of PAL in AAAs are in fact smaller than the maximum value obtained in a healthy abdominal aorta. However, we show that the transportation of blood cells towards the wall and the formation of stagnation points on the aneurysm's wall play more significant roles in thrombus formation than PAL.

  6. 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.

  7. Coronary thrombus in patients undergoing primary PCI for STEMI: Prognostic significance and management

    OpenAIRE

    Vecchio, Sabine; Varani, Elisabetta; Chechi, Tania; Balducelli, Marco; Vecchi, Giuseppe; Aquilina, Matteo; Ricci Lucchi, Giulia; Dal Monte, Alessandro; Margheri, Massimo

    2014-01-01

    Acute ST-elevation myocardial infarction (STEMI) usually results from coronary atherosclerotic plaque disruption with superimposed thrombus formation. Detection of coronary thrombi is a poor prognostic indicator, which is mostly proportional to their size and composition. Particularly, intracoronary thrombi impair both epicardial blood flow and myocardial perfusion, by occluding major coronary arteries and causing distal embolization, respectively. Thus, although primary percutaneous coronary...

  8. 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.

  9. An Experimental Model of Large Pulmonary Embolism Employing Controlled Release of Subacute Caval Thrombus in Swine

    Science.gov (United States)

    Barbash, Israel M.; Schenke, William H.; Halabi, Majdi; Ratnayaka, Kanishka; Faranesh, Anthony Z.; Kocaturk, Ozgur; Lederman, Robert J.

    2011-01-01

    Purpose We aimed to develop a catheter based model of large pulmonary embolism in swine based on in situ venous thrombus formation. Materials and Methods Ten Yorkshire swine underwent transjugular implantation of a retrievable inferior vena cava (IVC) filter. A thrombin and collagen mixture was injected into a confined space created by two inflated balloons proximal and distal to the IVC filter. Animals were survived for 7±3 days to allow the thrombus to organize in situ. The caval thrombus was released upon transcatheter retrieval of the IVC filter and embolized into the main and branch pulmonary arteries. The severity of pulmonary embolism was scored by digital subtraction angiography (Miller index). At necropsy thrombi were recovered and analyzed by histopathology. Results Large pulmonary embolism was induced in all animals (average Miller index score of 15±5). Two animals developed saddle embolus with bilateral pulmonary artery occlusion and five developed proximal occlusion of either the left or right pulmonary arteries. Nevertheless no animal exhibited significant hemodynamic compromise. Large tubular thrombi were explanted in the size range of 5–10 cm long and .5–1 cm wide. Histology indicated an organized thrombus with infiltration of white blood cells and fibrin deposition. Conclusions Large caval thrombi can be formed in vivo and released at a predetermined time to induce large pulmonary embolism in a large animal model. This may help developing and testing new therapeutic approaches for pulmonary embolism. PMID:21802315

  10. Frequency and Relevance of Acute Peritraumatic Pulmonary Thrombus Diagnosed by Computed Tomographic Imaging in Combat Casualties

    Science.gov (United States)

    2013-08-01

    extremity traumatic amputation. Additional study is needed to characterize the natural history of peritraumatic pulmonary thrombus and the indications for...following trauma is typicallydiagnosed after a cardiopulmonary deterioration and may result in hypoxia, myocardial strain, and potentially death...of admission unless patients received resuscitative surgery (14.3%; n = 101) before imaging. Although some patients received treat- ment at a Role II

  11. Left atrial ball thrombus with acute mesenteric ischemia: Anesthetic management and role of transesophageal echocardiography

    Directory of Open Access Journals (Sweden)

    Neeti Makhija

    2014-01-01

    Full Text Available A 62 year old female with severe mitral stenosis, large left atrial ball thrombus and acute mesenteric ischemia emergently underwent mitral valve replacement, left atrial clot removal and emergency laparotomy for mesenteric ischemia. Peri-operative management issues, particularly, the anesthetic challenges and the role of transesophageal echocardiography are discussed.

  12. Shear-sensitive nanocapsule drug release for site-specific inhibition of occlusive thrombus formation

    NARCIS (Netherlands)

    Molloy, C. P.; Yao, Y.; Kammoun, H.; Bonnard, T.; Hoefer, T.; Alt, K.; Tovar-Lopez, F.; Rosengarten, G.; Ramsland, P. A.; van der Meer, A. D.; van den Berg, A.; Murphy, A. J.; Hagemeyer, C. E.; Peter, K.; Westein, E.

    2017-01-01

    Essentials Vessel stenosis due to large thrombus formation increases local shear 1-2 orders of magnitude. High shear at stenotic sites was exploited to trigger eptifibatide release from nanocapsules. Local delivery of eptifibatide prevented vessel occlusion without increased tail bleeding times.

  13. 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.

  14. A systems approach to hemostasis: 3. Thrombus consolidation regulates intrathrombus solute transport and local thrombin activity

    Science.gov (United States)

    Welsh, John D.; Tomaiuolo, Maurizio; Wu, Jie; Colace, Thomas V.; Diamond, Scott L.

    2014-01-01

    Hemostatic thrombi formed after a penetrating injury have a distinctive structure in which a core of highly activated, closely packed platelets is covered by a shell of less-activated, loosely packed platelets. We have shown that differences in intrathrombus molecular transport emerge in parallel with regional differences in platelet packing density and predicted that these differences affect thrombus growth and stability. Here we test that prediction in a mouse vascular injury model. The studies use a novel method for measuring thrombus contraction in vivo and a previously characterized mouse line with a defect in integrin αIIbβ3 outside-in signaling that affects clot retraction ex vivo. The results show that the mutant mice have a defect in thrombus consolidation following vascular injury, resulting in an increase in intrathrombus transport rates and, as predicted by computational modeling, a decrease in thrombin activity and platelet activation in the thrombus core. Collectively, these data (1) demonstrate that in addition to the activation state of individual platelets, the physical properties of the accumulated mass of adherent platelets is critical in determining intrathrombus agonist distribution and platelet activation and (2) define a novel role for integrin signaling in the regulation of intrathrombus transport rates and localization of thrombin activity. PMID:24951426

  15. Patterns of antigen expression in hepatoblastoma and hepatocellular carcinoma in childhood.

    Science.gov (United States)

    O'Brien, W J; Finlay, J L; Gilbert-Barness, E F

    1989-01-01

    Two hepatocellular carcinomas and six hepatoblastomas were examined for the presence of 13 antigens using immunoperoxidase, avidin-biotin, staining techniques. Primary antibodies were directed against alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), lysozyme (LYS), carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE), epithelial membrane antigen (EMA), hepatitis B surface antigen (HbSA), lactoferrin (LF), desmin (DES), vimentin (VIM), and keratin (KER). Except for HbSA, the antigen staining pattern was unable to differentiate between hepatoblastoma and hepatocellular carcinoma. Both neoplasms where positive for AFP, AAT, CEA, EMA, and KER; however, neither stained for GFAP, NSE, LYS, LF, HCG, or DES. Vimentin was weakly positive in those hepatoblastomas where mesenchymal tissue was present in the tumor. Only the tissue adjacent to hepatocellular carcinomas stained positively for HbSA and correlated with the elevated serum levels of HbSA.

  16. An overview of loco-regional treatments in patients and mouse models for hepatocellular carcinoma.

    Science.gov (United States)

    Bimonte, Sabrina; Barbieri, Antonio; Palaia, Raffaele; Leongito, Maddalena; Albino, Vittorio; Piccirillo, Mauro; Arra, Claudio; Izzo, Francesco

    2015-01-01

    Hepatocellular carcinoma is a highly aggressive malignancy and is the third leading cause of cancer-related deaths worldwide. Although surgery is currently considered the most effective curative treatment for this type of cancer, it is note that most of patients have a poor prognosis due to chemioresistence and tumor recurrence. Loco-regional therapies, including radiofrequency ablation, surgical resection and transcatheter arterial chemoembolization play a major role in the clinical management of hepatocellular carcinoma. In order to improve the treatment outcome of patients diagnosed with this disease, several in vivo studies by using different techniques on cancer mouse models have been performed. This review will focus on the latest papers on the efficacy of loco-regional therapy and combined treatments in patients and mouse models of hepatocellular carcinoma.

  17. From the palliative concept to R0 resection. SIRT in the individual tumor therapy; Vom Palliativkonzept zur R0-Resektion. Die SIRT in der individuellen Tumortherapie

    Energy Technology Data Exchange (ETDEWEB)

    Wetter, Axel [Universitaetsklinik Essen (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Theysohn, Jens; Schotten, Clemens; Schulze, Maren; Mueller, Stefan

    2017-02-15

    The selective internal radiotherapy (SIRT) with Y-90 charged microspheres is predominantly used for palliative therapy of hepatocellular tumors. In connection with additional medication SIRT can also trigger a volume reduction of the tumor for possible surgery.

  18. Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma as a Bridge to Liver Transplantation: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Antoine Bouchard-Fortier

    2011-01-01

    Full Text Available Background. Transcatheter arterial lipiodol chemoembolization (TACE can be used in cirrhotic patients with hepatocellular carcinoma to avoid tumor progression before transplantation. Objective. To evaluate the efficacy and safety of TACE used as a bridge to liver transplantation. Methods. TACE was performed in 30 cirrhotic patients with hepatocellular carcinoma. Milan criteria were used to select patients for transplant. Patients had a good or moderately impaired liver function, no arterioportal fistulae, and a good portal perfusion. Results. 48 TACE were performed in 30 patients. Before transplantation, 4 patients were dropped off the list due to tumor extension or liver failure. Complete necrosis of the tumor was observed in 11 patients and partial necrosis in 15 patients. After transplantation, 6 patients died and tumor recurrence was observed in 5 patients with a tumor beyond Milan criteria or no response to TACE. Conclusion. TACE is useful as a bridge to liver transplantation in a selected group of cirrhotic patients with hepatocellular carcinoma. A combined therapeutic approach before surgery might improve the prognosis in these patients.

  19. New advances in hepatocellular carcinoma

    OpenAIRE

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a conditi...

  20. Gene mutations in hepatocellular adenomas

    DEFF Research Database (Denmark)

    Raft, Marie B; Jørgensen, Ernö N; Vainer, Ben

    2015-01-01

    is associated with bi-allelic mutations in the TCF1 gene and morphologically has marked steatosis. β-catenin activating HCA has increased activity of the Wnt/β-catenin pathway and is associated with possible malignant transformation. Inflammatory HCA is characterized by an oncogene-induced inflammation due....... This review offers an overview of the reported gene mutations associated with hepatocellular adenomas together with a discussion of the diagnostic and prognostic value....

  1. Molecular genetics of hepatocellular neoplasia

    OpenAIRE

    Jain, Shilpa; Singhal, Shashideep; Lee, Peng; Xu, Ruliang

    2010-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer deaths worldwide. Proper classification and early identification of HCC and precursor lesions is essential to the successful treatment and survival of HCC patients. Recent molecular genetic, pathologic, and clinical data have led to the stratification of hepatic adenomas into three subgroups: those with mutant TCF1/HNF1 α gene, those with mutant β-catenin, and those without mutations in ei...

  2. Finding the origin of pulmonary emboli with a total-body magnetic resonance direct thrombus imaging technique

    Science.gov (United States)

    van Langevelde, Kirsten; Šrámek, Alexandr; Vincken, Patrice W.J.; van Rooden, Jan-Kees; Rosendaal, Frits R.; Cannegieter, Suzanne C.

    2013-01-01

    Pulmonary embolism is considered to originate from embolization of a deep-vein thrombosis, resulting in two manifestations of one disease: venous thrombosis. However, in up to 50% of patients with pulmonary embolism no deep-vein thrombosis is found with ultrasonography. An explanation for this low proportion is currently lacking. Other imaging modalities may increase the yield of detection of deep-vein thrombosis in the calf or in the abdominal region. Alternatively, not all pulmonary emboli may originate from deep-vein thromboses in the extremities. We searched for the origin of pulmonary emboli, by performing total-body magnetic resonance imaging-scans to visualize thrombi. Ninety-nine patients with a first pulmonary embolism confirmed by computed tomography underwent a magnetic resonance direct thrombus imaging-scan, a validated technique using endogenous contrast. Additionally, acquired and genetic risk factors were assessed. No thrombus was found in 55 patients, whereas a thrombus was identified in 44 patients. The commonest thrombus location was the lower leg; 12 patients had isolated calf vein thrombosis and five had isolated superficial vein thrombosis. A peripheral thrombus was found by magnetic resonance imaging in less than half of patients with pulmonary embolism. We propose several hypotheses to explain the absence of thrombi, such as a cardiac thrombus origin or embolization of the whole deep-vein thrombus. The possibility that pulmonary embolism arises de novo in the lungs, due to local inflammation-driven coagulation, needs to be considered. PMID:22801962

  3. Pre-infarction angina predicts thrombus burden in patients admitted for ST-segment elevation myocardial infarction.

    Science.gov (United States)

    Ahmed, Tarek A N; Sorgdrager, Bastiaan J; Cannegieter, Suzanne C; van der Laarse, Arnoud; Schalij, Martin J; Jukema, Wouter

    2012-04-01

    In patients with ST-elevation myocardial infarction (STEMI), high thrombotic burden, subsequent distal embolisation and myocardial no-reflow remain a large obstacle that may negate the benefits of urgent coronary revascularisation. We aimed at assessing the predictors of: 1) thrombus grade in patients undergoing primary percutaneous coronary intervention (PPCI) and 2) infarct size, in order to optimise therapy to reduce thrombus burden. One-hundred and fifty-three consecutive patients presenting with STEMI and undergoing PPCI were included. Thrombus was evaluated by angiography and scored according to the TIMI study group score. Next, patients were categorised into two groups that had either high thrombus grade (HTG; score 4-5) or low thrombus grade (LTG; score 1-3). We evaluated predictors of angiographic thrombus grade among a number of clinical, angiographic and laboratory data. We also assessed infarct size and scintigraphic left ventricular ejection fraction (LVEF) at three months in both patient groups. Ninety-four patients (58±11 years; 75% males) presented with HTG, whereas 59 patients (58±12 years; 78% males) presented with LTG. Pre-infarction angina (PIA) was more frequently encountered in the LTG group than in the HTG group (25% vs. 10%, p=0.009). Pre-procedural TIMI flow was significantly lower in the HTG group (pHTG group (pHTG. HTG proved an independent predictor of higher peak levels of creatine kinase (CK) (p<0.001) and troponin T (p<0.001), as well as lower LVEF (p=0.05) along with male gender and absence of prior statin therapy. Absence of PIA and proximal culprit lesions are associated with higher thrombus grade. Higher thrombus grade is associated with larger infarct size and slightly worse LV function. This may have clinical implications in planning strategies, particularly regarding pharmacotherapy, that aim to decrease thrombus burden prior to stent implantation.

  4. Left ventricular thrombus development during ventricular fibrillation and resolution during resuscitation in a swine model of sudden cardiac arrest.

    Science.gov (United States)

    Budhram, Gavin R; Mader, Timothy J; Lutfy, Lucienne; Murman, David; Almulhim, Abdullah

    2014-05-01

    Intracardiac thrombus is a well-known complication of low-flow cardiac states including acute myocardial infarction and atrial fibrillation. Little is known, however, about the formation of intracardiac (left ventricular [LV]) thrombus during the extreme low-flow state of cardiac arrest. Using a swine model of sudden cardiac arrest, we examined the sonographic development of LV thrombus over time after induction of ventricular fibrillation (VF) and resolution of thrombus with cardiopulmonary resuscitation (CPR). This observational study was IACUC approved. Forty-five Yorkshire swine were sedated, intubated, and instrumented under general anesthesia before VF was electrically induced. Sonographic data was collected immediately after VF induction and at 2-min intervals thereafter. Following 12min of untreated VF, resuscitation was initiated with closed chest compressions using an oxygen-powered mechanical resuscitation device. Observations were continued during attempted resuscitation. At the end of the experiment, the animals were euthanized while still at a surgical depth of anesthesia. The data was analyzed descriptively. Sonographic evidence of LV thrombus was observed in 43/45 animals (95.6% [95%CI: 85.2%, 98.8%]). Thrombus was detected within 6min in 39/45 (86.7% [95%CI: 73.8%, 93.8%]) animals that developed thrombus. Thrombus resolved within 2min after initiation of chest compressions in 31/43 (72.1% [95%CI: 57.3%, 83.3%]) animals. Similar to other low-flow cardiac states, LV thrombus develops early in the natural history of VF arrest and resolves quickly once forward flow is re-established by chest compressions. Institutional protocol number: 154600-8. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Optical Dynamic Analysis of Thrombus Inside a Centrifugal Blood Pump During Extracorporeal Mechanical Circulatory Support in a Porcine Model.

    Science.gov (United States)

    Fujiwara, Tatsuki; Sakota, Daisuke; Ohuchi, Katsuhiro; Endo, Shu; Tahara, Tomoki; Murashige, Tomotaka; Kosaka, Ryo; Oi, Keiji; Mizuno, Tomohiro; Maruyama, Osamu; Arai, Hirokuni

    2017-10-01

    Complications due to pump thrombus remain the weak point of mechanical circulatory support (MCS), such as the use of a left ventricular assist device (LVAD) or extracorporeal membrane oxygenation, leading to poor outcomes. Hyperspectral imaging (HSI) is an effective imaging method using a hyperspectral (HS) camera, which comprises a spectrophotometer and a charge-coupled device camera to discriminate thrombus from whole blood. Animal experiments were conducted to analyze dynamic imaging of thrombus inside a prototype of a hydrodynamically levitated centrifugal blood pump using an HSI system. Six pigs were divided into a venous circulation group (n = 3) and an arterial circulation group (n = 3). Inflow and outflow cannulae were inserted into the jugular veins in the venous circulation group. The latter simulated an LVAD application. To create thrombogenic conditions, pump flow was maintained at 1 L/min without anticoagulation. An image of the bottom surface of the pump was captured by the HS camera every 4 nm over the wavelength range of 608-752 nm. Real-time dynamic images of the inside of the pump were displayed on the monitor. Appearance of an area displaying thrombus was detected within 24 h after the start of the circulation in every experiment. This imaging system also succeeded in determining the origins of pump thrombus: from inside the pump in two cases, and from outside in four cases. Two main possible sources of pump thrombus originating outside the pump were identified on autopsy: wedge thrombus around the inflow cannula; and string-like thrombus at the junction between the pump inlet and circuit tube. The results of this study from close observation of the changing appearance of pump thrombus may contribute to improvements in the safety of extracorporeal MCS. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  6. Twist expression promotes migration and invasion in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Kobayashi Yoshiyuki

    2009-07-01

    Full Text Available Abstract Background Twist, a transcription factor of the basic helix-loop-helix class, is reported to regulate cancer metastasis. It is known to induce epithelial-mesenchymal transition (EMT. In this study, we evaluated the expression of twist and its effect on cell migration in hepatocellular carcinoma (HCC. Methods We examined twist expression using immunohistochemistry in 20 tissue samples of hepatocellular carcinoma, and assessed twist expression in HCC cell lines by RT-PCR and Western blot analysis. Ectopic twist expression was created by introducing a twist construct in the twist-negative HCC cell lines. Endogenous twist expression was blocked by twist siRNA in the twist-positive HCC cell lines. We studied EMT related markers, E-cadherin, Vimentin, and N-cadherin by Western blot analysis. Cell proliferation was measured by MTT assay, and cell migration was measured by in vitro wound healing assay. We used immunofluorescent vinculin staining to visualize focal adhesion. Results We detected strong and intermediate twist expression in 7 of 20 tumor samples, and no significant twist expression was found in the tumor-free resection margins. In addition, we detected twist expression in HLE, HLF, and SK-Hep1 cells, but not in PLC/RPF/5, HepG2, and Huh7 cells. Ectopic twist-expressing cells demonstrated enhanced cell motility, but twist expression did not affect cell proliferation. Twist expression induced epithelial-mesenchymal transition together with related morphologic changes. Focal adhesion contact was reduced significantly in ectopic twist-expressing cells. Twist-siRNA-treated HLE, HLF, and SK-Hep1 cells demonstrated a reduction in cell migration by 50, 40 and 18%, respectively. Conclusion Twist induces migratory effect on hepatocellular carcinoma by causing epithelial-mesenchymal transition.

  7. Reduced levels of histones H1o and H1b, and unaltered content of methylated DNA in rainbow trout hepatocellular carcinoma chromatin.

    Science.gov (United States)

    Davie, J R; Delcuve, G P; Nickel, B E; Moirier, R; Bailey, G

    1987-10-15

    The levels of histone subtypes and DNA methylation of aflatoxin-induced rainbow trout hepatocellular carcinoma and adult liver nuclei were compared. The hepatocellular carcinoma nuclei were enriched in the ubiquitinated species of histone H2A and depleted in histones H1o and H1b. The 5-methylcytosine content and methylation patterns of the vitellogenin genes and the transcriptionally inactive TPG-3 protamine gene were not altered in the trout hepatocellular carcinoma DNA. Thus, undermethylation of DNA is not a general feature of chemically induced tumors in vivo.

  8. Inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma.

    Science.gov (United States)

    Han, Ke-Qi; He, Xue-Qun; Ma, Meng-Yu; Guo, Xiao-Dong; Zhang, Xue-Min; Chen, Jie; Han, Hui; Zhang, Wei-Wei; Zhu, Quan-Gang; Nian, Hua; Ma, Li-Jun

    2015-04-28

    To study the inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma (HCC) in nude mice. CBRH-7919 HCC cells were injected into the subcutaneous region of nude mice. Beginning two weeks after the challenge, tumor growth was measured every week for six weeks. The stromal microenvironment and inflammatory cell infiltration was assessed by immunohistochemistry in paired tumor and adjacent peritumoral samples, and macrophage phenotype was assessed using double-stain immunohistochemistry incorporating expression of an intracellular enzyme. A chemokine PCR array, comprised of 98 genes, was used to screen differential gene expressions, which were validated by Western blotting. Additionally, expression of identified chemokines was knocked-down by RNA interference, and the effect on tumor growth was assessed. Inflammatory cell infiltrates are a key feature of adjacent peritumoral tissues with increased macrophage, neutrophil, and T cell (specifically helper and activated subsets) infiltration. Macrophages within adjacent peritumoral tissues express inducible nitric oxide synthase, suggestive of a proinflammatory phenotype. Fifty-one genes were identified in tumor tissues during the progression period, including 50 that were overexpressed (including CXCL1, CXCL2 and CXCL3) and three that were underexpressed (CXCR1, Ifg and Actb). RNA interference of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice and inhibited expression of CXCL2, CXCL3 and interleukin-1β protein. These findings suggest that CXCL1 plays a critical role in tumor growth and may serve as a potential molecular target for use in HCC therapy.

  9. Senescence and immortality in hepatocellular carcinoma.

    Science.gov (United States)

    Ozturk, Mehmet; Arslan-Ergul, Ayca; Bagislar, Sevgi; Senturk, Serif; Yuzugullu, Haluk

    2009-12-01

    Cellular senescence is a process leading to terminal growth arrest with characteristic morphological features. This process is mediated by telomere-dependent, oncogene-induced and ROS-induced pathways, but persistent DNA damage is the most common cause. Senescence arrest is mediated by p16(INK4a)- and p21(Cip1)-dependent pathways both leading to retinoblastoma protein (pRb) activation. p53 plays a relay role between DNA damage sensing and p21(Cip1) activation. pRb arrests the cell cycle by recruiting proliferation genes to facultative heterochromatin for permanent silencing. Replicative senescence that occurs in hepatocytes in culture and in liver cirrhosis is associated with lack of telomerase activity and results in telomere shortening. Hepatocellular carcinoma (HCC) cells display inactivating mutations of p53 and epigenetic silencing of p16(INK4a). Moreover, they re-express telomerase reverse transcriptase required for telomere maintenance. Thus, senescence bypass and cellular immortality is likely to contribute significantly to HCC development. Oncogene-induced senescence in premalignant lesions and reversible immortality of cancer cells including HCC offer new potentials for tumor prevention and treatment.

  10. Rare Gingival Metastasis by Hepatocellular Carcinoma

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    Li-Jun Xue

    2017-01-01

    Full Text Available Hepatocellular carcinoma (HCC uncommonly metastasizes to the gingiva, which always means a poor outcome. We reported a rare HCC case with multiple metastases to gingiva, lungs, and brain. A 60-year-old man was initially diagnosed as HCC with metastases to double lungs. He was subjected to a transarterial chemoembolization (TACE (5-fluorouracil, 750 mg and two cycles of intravenous chemotherapy (gemcitabine 1.8 g at days 1 and 8, oxaliplatin 200 mg at day 2, every 4 weeks. However, the volume of liver tumor still increased. A bean-size gingival nodule growing with occasional bleeding was also found. TACE (5-fluorouracil 750 mg, perarubicin 40 mg, cisplatin 20 mg was performed again and an oral sorafenib therapy (400 mg, twice per day was adopted. The disease maintained relatively stable for about 6 months until a second obvious progress. The gingival nodule was then palliatively excised and identified as a poorly differentiated metastatic HCC by histopathological examination. Best supportive treatments were made since the performance score was too bad. Finally, cerebral metastases occurred and the patient died of systemic failure. Upon review of previous reports, we discussed risk factors, clinical and pathological characteristics, treatments, and prognosis of gingival metastasis by HCC.

  11. Role of NuSAP in Prostate Tumor Progression

    Science.gov (United States)

    2012-06-01

    Proteomic approach to ETV5 during endometrial carcinoma invasion reveals a link to oxidative stress . Carcinogenesis 2009; 30: 1288 - 1297. 26 Murphy...overexpression in hepatocellular carcinoma correlates with early age onset, shorter patients survival and chemoresistance. Int J Cancer 2009; 124: 644...tumor recurrence, and poor prognosis of hepatocellular carcinoma . Clin Cancer Res 2007; 13 (Pt 1): 5368 - 5376. 33 Bogunovic D, O’Neill DW

  12. Angiogenesis: From Chronic Liver Inflammation to Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Paloma Sanz-Cameno

    2010-01-01

    Full Text Available Recently, new information relating to the potential relevance of chronic hepatic inflammation to the development and progression of hepatocellular carcinoma (HCC has been generated. Persistent hepatocellular injury alters the homeostatic balance within the liver; deregulation of the expression of factors involved in wound healing may lead to the evolution of dysplastic lesions into transformed nodules. Progression of such nodules depends directly on the development and organization of a vascular network, which provides the nutritional and oxygen requirements to an expanding nodular mass. Angiogenic stimulation promotes intense structural and functional changes in liver architecture and physiology, in particular, it facilitates transformation of dysplasia to nodular lesions with carcinogenic potential. HCC depends on the growth and spreading of vessels throughout the tumor. Because these vascular phenomena correlate with disease progression and prognosis, therapeutic strategies are being developed that focus on precluding vascular expansion in these tumors. Accordingly, an in-depth study of factors that promote and support pathological angiogenesis in chronic hepatic diseases may provide insights into methods of preventing the development of HCC and/or stimulating the regression of established HCC.

  13. Liver transplantation for Hepatocellular carcinoma: Predictors of ...

    African Journals Online (AJOL)

    DOWNLOAD FULL TEXT Open Access DOWNLOAD FULL TEXT Subscription or Fee Access. Liver transplantation for Hepatocellular carcinoma: Predictors of recurrence in our study. HD Smith. Abstract. Hepatocellular carcinoma (HCC) is an aggressive malignancy mostly complicating some underlying liver pathology that ...

  14. 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.

  15. Hepatocellular Carcinoma with Sarcomatoid Change without Anticancer Therapies

    Directory of Open Access Journals (Sweden)

    Naoki Yoshida

    2013-03-01

    Full Text Available Hepatocellular carcinoma (HCC with sarcomatoid change is a rare neoplasm of the liver, and recurrent therapies for HCC such as transcatheter arterial chemoembolization and percutaneous ablation therapy are presumed to promote sarcomatoid change. A 73-year-old man was admitted to our hospital diagnosed as having liver cancer originating from hepatitis C-related cirrhosis without any previous treatment for HCC. Ultrasonography showed that the tumor was hypoechoic, 3 cm in diameter, with unclear margins. Computed tomography demonstrated a low-density lesion with ring enhancement on delayed phase. Under a diagnosis of poorly differentiated HCC the patient underwent liver resection. Histologically, the tumor consisted of proliferation of spindle-shaped sarcomatoid carcinoma cells with unclear trabecular and pseudoglandular structures including a nodule of typical moderately differentiated HCC, which was observed to shift mutually in one region. Here, we report a case of sarcomatoid HCC with a review of the literature.

  16. Functional Roles and Therapeutic Applications of Exosomes in Hepatocellular Carcinoma

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    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.

  17. 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.

  18. Small Bowel Metastasis of Hepatocellular Carcinoma Detected by Capsule Endoscopy

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    A. Igawa

    2013-11-01

    Full Text Available We report a rare case of metastasis of hepatocellular carcinoma (HCC to the small bowel that presented as a pedunculated epithelial polyp. A 60-year-old man with liver cirrhosis type B was treated for HCC (stage IVb at our hospital. He had been admitted for melena and anemia. Capsule endoscopy was performed in this patient with obscure gastrointestinal bleeding. It showed a polypoid lesion with bleeding in the ileum. Double-balloon endoscopy was performed. The lesion was determined to be a pedunculated polyp in the ileum. Histological examination of biopsy specimens showed tumor cells resembling HCC. We performed endoscopic mucosal resection for the lesion by double-balloon endoscopy to prevent bleeding from the tumor. The patient had no melena or anemia and his condition improved after endoscopic mucosal resection. However, he died of liver failure 2 months later.

  19. Bone marrow metastasis presenting as bicytopenia originating from hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Young Mi Hong

    2016-06-01

    Full Text Available The bone is a common site for metastasis in hepatocellular carcinoma (HCC. However, bone marrow metastasis from HCC is rarely reported, and its frequency is unclear. Here we report a rare case of bone marrow metastasis that presented as bicytopenia originating from HCC without bone metastasis. A 58-year-old man was admitted for investigation of a liver mass with extensive lymph node enlargement that was detected when examining his general weakness and weight loss. Laboratory findings revealed anemia, thrombocytopenia, mild elevated liver enzymes, normal prothrombin time percentage and high levels of tumor markers (α-fetoprotein and des-γ-carboxyprothrombin. Abdominal computed tomography showed multiple enhanced masses in the liver and multiple enlarged lymph nodes in the abdomen. A bone marrow biopsy revealed only a few normal hematopoietic cells and abundant tumor cells. Despite its rarity, bone marrow metastasis should always be suspected in HCC patients even if accompanied by cirrhosis.

  20. The Role of Bridging Therapy in Hepatocellular Carcinoma

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    Roberto Galuppo

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the most common primary malignancy of the liver accounting for 7% of all cancers worldwide. Most cases of HCC develop within an established background of chronic liver disease. For that reason, liver resection is only possible in selected patients. Liver transplantation has become the treatment of choice in patients with HCC, end-stage liver disease, and significant portal hypertension. Shortage of organ donors has resulted in overall increase of waiting list time with increased risk of dropout due to tumor progression. Neoadjuvant therapies have emerged as an alternative to control tumor growth in patients while waiting. The aim of this study is to review the literature on the role of bridging therapy and downstaging prior to liver transplantation in patients with HCC. We are also presenting our single-center experience of 96 patients undergoing transplantation for HCC with and without bridging therapy.

  1. 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.

  2. Thalidomide induces complete remission of advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Cheng-Hung Chien

    2014-06-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most prevalent human cancers in the world, but its prognosis is extremely poor. HCC is considered a hypervascular tumor. Thalidomide, which has been known to inhibit growth factor-induced neovascularization, is a convenient alternative to target therapy such as sorafenib. We report a 65-year-old male patient with alcoholic liver cirrhosis that was diagnosed having multiple HCCs during surveillance. The patient was assessed as inoperable and unsuited for transhepatic arterial chemoembolization or systemic chemotherapy. After discussing the therapeutic alternatives, he decided to receive low-dose thalidomide (100 mg daily therapy. Fortunately, follow-up liver biochemical tests, serum α-fetoprotein level, and dynamic computed tomography showed complete remission of the HCCs 4.5 months after thalidomide treatment and this was documented for more than 22 months without evidence of tumor recurrence.

  3. Myofibroblasts are responsible for collagen synthesis in the stroma of human hepatocellular carcinoma: an in vivo and in vitro study.

    Science.gov (United States)

    Faouzi, S; Le Bail, B; Neaud, V; Boussarie, L; Saric, J; Bioulac-Sage, P; Balabaud, C; Rosenbaum, J

    1999-02-01

    Marked changes in extracellular matrix occur in the stroma of hepatocellular carcinoma, as compared to normal or cirrhotic liver. The cell types responsible for extracellular matrix synthesis within hepatocellular carcinoma have not been clearly identified. In vivo collagen synthesis was studied by in situ hybridization and immunohistochemistry for types I, IV, V and VI collagen, together with immunolabeling of alpha-smooth muscle actin, a myofibroblast marker, and CD34, an endothelial cell marker. In vitro, extracellular matrix deposition by cultured myofibroblasts was studied by reticulin staining, immunocytochemistry and RNase protection. All collagens studied were expressed in the stroma of the tumor, with a higher level of type VI and IV collagens than of type I and V. The majority of the cells expressing collagen transcripts in human hepatocellular carcinoma stroma were alpha-actin positive and CD 34 negative. In vitro experiments demonstrated that the hepatocellular carcinoma cell lines HepG2, HuH7 and Hep3B markedly increased extracellular matrix deposition by human liver myofibroblasts. This increase was mediated by a soluble mediator present in tumor cell conditioned medium. It was not explained by an increase in mRNA levels of extracellular matrix components, nor by a decrease in the secretion of matrix-degrading proteinases by myofibroblasts. Myofibroblasts are the main source of collagens in the stroma of hepatocellular carcinoma. Our data also indicate that tumoral hepatocytes increase extracellular matrix deposition by cultured myofibroblasts, probably by post-transcriptional mechanisms. The generation of hepatocellular carcinoma stroma by myofibroblasts could thus be under control of tumoral cells.

  4. Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice.

    Science.gov (United States)

    Wu, Tao; Heuillard, Emilie; Lindner, Véronique; Bou About, Ghina; Ignat, Mihaela; Dillenseger, Jean-Philippe; Anton, Nicolas; Dalimier, Eugénie; Gossé, Francine; Fouré, Gael; Blindauer, Franck; Giraudeau, Céline; El-Saghire, Hussein; Bouhadjar, Mourad; Calligaro, Cynthia; Sorg, Tania; Choquet, Philippe; Vandamme, Thierry; Ferrand, Christophe; Marescaux, Jacques; Baumert, Thomas F; Diana, Michele; Pessaux, Patrick; Robinet, Eric

    2016-10-14

    The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cells in immunodeficient mice. Luciferase allows for an easy repeated monitoring of tumor growth by in vivo bioluminescence. The intrahepatic injection was more efficient than intrasplenic or intraportal injection in terms of survival, rate of orthotopic engraftment, and easiness. A positive correlation between luciferase activity and tumor size, evaluated by Magnetic Resonance Imaging, allowed to define the endpoint value for animal experimentation with this model. Response to standard of care, sorafenib or doxorubicin, were similar to those previously reported in the literature, with however a strong toxicity of doxorubicin. Tumor vascularization was visible by histology seven days after Huh-7-Luc transplantation and robustly developed at day 14 and day 21. The model was used to explore different imaging modalities, including microtomography, probe-based confocal laser endomicroscopy, full-field optical coherence tomography, and ultrasound imaging. Tumor engraftment was similar after echo-guided intrahepatic injection as after laparotomy. Collectively, this orthotopic hepatocellular carcinoma model enables the in vivo evaluation of chemotherapeutic and surgical approaches using multimodal imaging.

  5. Placement and retrieval of a Guenther tulip filter in patients with a free floating thrombus in inferior vena cava

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Min Hyun; Kim, Young Hwan; Lee, Sang Kwon; Choi, Jin Soo; Kim, Mi Jeong; Koo, Ja Hyun; Kim, Hyoung Tae; Cho, Won Hyun [Keimyung University College of Medicine, Daegu (Korea, Republic of); Seong, Nak Kwan [Daegu Catholic School of Medicine, Daegu (Korea, Republic of)

    2005-07-15

    We wanted to assess the technical feasibility and clinical efficacy of the placement and retrieval of a Guenther Tulip filter for the prevention of fatal pulmonary embolism during the management of patients with a free floating thrombus in their inferior vena ca va (IVC). Six patients having a free floating thrombus in their IVC (three patients with an isolated free floating thrombus in the IVC that resulted from immobilization due to traumatic liver injury or cerebral infarction, two patients with coexisting deep vein thrombosis in the left lower extremity that was caused by May-Thurner syndrome, and one patient with coexisting deep vein thrombosis in the right lower extremity that was due to nephrotic syndrome and immobilization after hip joint replacement) underwent placement and retrieval of a Guenther Tulip filter. The placement of the filter was performed through the right internal jugular vein to prevent the risk of detachment of the thrombus during the procedure. Retrieval of filter was performed after the free floating thrombus of the IVC had disappeared on follow-up CT because of anticoagulation therapy, aspiration thrombectomy or catheter directed Urokinase thrombolysis. The Guenther Tulip filter was successfully placed in the IVC in all six patients and it was retrieved after the management of the free floating thrombus. The mean duration of the placement of the filter was 11 days (range:7-25 days). Two patients underwent placement of an iliac vein stent for the management of May-Thurner syndrome. Detachment of the free floating thrombus in the IVC and the subsequent thrombus entrapment in the filter were documented during aspiration thrombectomy or Urokinase thrombolysis in four patients. Recurrent thrombus didn't occur during the follow-up period (range:3-20 months) in five of the six patients. In one patient, a recurrent thrombus due to the discontinuance of anticoagulation therapy was identified at the filter detachment site of the IVC on the

  6. 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

  7. The prevention of circulatory collapse in left atrial myxoma or left atrail thrombus patients.

    Science.gov (United States)

    Sun, Jie; Ding, Zhengnian

    2016-05-01

    Some patients with myxoma or thrombus may develop to severe hypotension or sudden death. In this article, we hypothesize a clinical scenario that when the myxoma or thrombus blocks in the mitral valve and causes significant hypotension during anesthesia or surgery. Increasing cardiac preload will be an effective preventive method to increasing the mitral valve annulus and decreasing the severity of stenosis, as a result it will prevent circulatory collapse. Our hypothesis will decrease the possibility of lethal mitral valve stenosis induced by left atrial mass blocking the mitral valve area. In addition, we should also maintain a relative slow heart rate and a relative high systemic vascular resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. In vivo thrombus formation induced by complement activation on polymer surfaces.

    Science.gov (United States)

    Hayashi, K; Fukumura, H; Yamamoto, N

    1990-10-01

    To clarify involvement of complement activation in thrombus formation on polymer surfaces, in vitro complement activation was evaluated for polyethylene (PE) tubes radiation-graft copolymerized with acrylamide (AAm), acrylic acid (AC), 2-hydroxyethyl methacrylate (HEMA), N-vinylpyrrolidone (NVP), and vinyl alcohol (VOH), and compared to their in vivo antithrombogenicity and cell adherence in canine peripheral veins. The complement-activating surfaces (NVP and VOH) cause preferential adhesion of leukocytes and were more thrombogenic than the low complement-activating surfaces (AAm, PE, and HEMA). Infusion of naja haje cobra venom factor depressed leukocyte adhesion, followed by a marked decrease in thrombogenesis, for the strong classical-pathway-activating surface (NVP). Although estimation of in vitro activation for AC was inconclusive because of a large effect of adsorption, AC behaved like VOH in vivo. These results suggest that C5a(des Arg) mediated activation of leukocytes may play a role in thrombus formation by complement activation on polymer surfaces.

  9. Granulocytes in coronary thrombus evolution after myocardial infarction--time-dependent changes in expression of matrix metalloproteinases.

    Science.gov (United States)

    Li, Xiaofei; de Boer, Onno J; Ploegmaker, Hanneke; Teeling, Peter; Daemen, Mat Jap; de Winter, Robbert J; van der Wal, Allard C

    2016-01-01

    Remodeling of extracellular matrix is a key process during wound healing, which is strictly regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors [tissue inhibitors of metalloproteinases (TIMPs)]. In this study, we evaluated intrathrombotic MMPs and TIMPs and their cellular origin during thrombus evolution after disruption of coronary atherosclerotic plaque. Thrombectomy materials (N=120) obtained from patients with acute myocardial infarction were histologically classified in three groups based on thrombus age: fresh (5days) thrombi; materials showing a heterogeneous composition were classified according to oldest part. Presence and cellular origin of MMPs (MMP-1, MMP-2, MMP-8, MMP-9, and MMP-14) and TIMPs (TIMP-1, TIMP-2, and TIMP-3) was evaluated with immunostains (double) and with polymerase chain reaction. MMPs and TIMPs were present in all the thrombectomy samples. A distinct temporal change in extent and cellular origin of MMPs and TIMPs during thrombus evolution was observed. In the early (fresh and lytic) stages of thrombus, high numbers of neutrophilic granulocytes occupy the thrombus mass and produce large amounts of MMPs and TIMPs. However, with progression of thrombus evolution (organizing stage) and diminishment of neutrophil granulocytes, there is disappearance of MMP-8 and MMP-9, steep decline of MMP-1 and TIMP-2, and progressive decrease of TIMP-3. In contrast, intrathrombotic MMP-2 and MMP-14 are present at a constant high level during the entire process of thrombus evolution. These temporal changes indicate a complex time-dependent function of MMPs, which are largely granulocyte derived, in the healing process of thrombus after plaque disruption. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. 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.

  11. The Multifaceted Role of Podoplanin Expression in Hepatocellular Carcinoma

    Science.gov (United States)

    Cioca, Andreea; Ceausu, Amalia R.; Marin, Irina; Raica, Marius; Cimpean, Anca Maria

    2017-01-01

    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. PMID:28348421

  12. Genome-wide identification of RNA editing in hepatocellular carcinoma.

    Science.gov (United States)

    Kang, Lin; Liu, Xiaoqiao; Gong, Zhoulin; Zheng, Hancheng; Wang, Jun; Li, Yingrui; Yang, Huanming; Hardwick, James; Dai, Hongyue; Poon, Ronnie T P; Lee, Nikki P; Mao, Mao; Peng, Zhiyu; Chen, Ronghua

    2015-02-01

    We did whole-transcriptome sequencing and whole-genome sequencing on nine pairs of Hepatocellular carcinoma (HCC) tumors and matched adjacent tissues to identify RNA editing events. We identified mean 26,982 editing sites with mean 89.5% canonical A→G edits in each sample using an improved bioinformatics pipeline. The editing rate was significantly higher in tumors than adjacent normal tissues. Comparing the difference between tumor and normal tissues of each patient, we found 7 non-synonymous tissue specific editing events including 4 tumor-specific edits and 3 normal-specific edits in the coding region, as well as 292 edits varying in editing degree. The significant expression changes of 150 genes associated with RNA editing were found in tumors, with 3 of the 4 most significant genes being cancer related. Our results show that editing might be related to higher gene expression. These findings indicate that RNA editing modification may play an important role in the development of HCC. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. 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

  14. [Systemic treatment for hepatocellular carcinoma].

    Science.gov (United States)

    Spangenberg, H C; Zuber-Jerger, I; Thimme, R; Blum, H E; Von Weizsäcker, F

    2003-11-01

    Hepatocellular carcinoma (HCC) is one of the most frequent malignancies worldwide. A variety of pharmacological strategies has been evaluated in the treatment of HCC: classical chemotherapy, tamoxifen, octreotide, thymostimulin, pravastatin, (131)I-lipiodol as well as transarterial chemoperfusion (TAC) and chemoembolisation (TACE). TACE monotherapy or TACE combined with pravastatin resulted in a survival benefit of selected HCC patients. New strategies such as immunotherapy, antiangiogenic agents or cyclooxygenase inhibitors are under clinical investigation and might play a role in future therapies for HCC. Efficient strategies for the primary prevention of HCC are available and promising concepts in the secondary prevention have been reported.

  15. Microbubble Mediated Thrombus Dissolution with Diagnostic Ultrasound for the Treatment of Chronic Venous Thrombi

    OpenAIRE

    Shelby Kutty; Juefei Wu; Hammel, James M; Feng Xie; Shunji Gao; Drvol, Lucas K; John Lof; Radio, Stanley J.; Stacey L Therrien; Danford, David A.; Porter, Thomas R

    2012-01-01

    BACKGROUND: Central venous catheter (CVC) thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo. METHODS AND RESULTS: A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently appl...

  16. Superselective transcather arterial embolization for hepatocellular carcinoma with a mixture of ethanol and lipiodol

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jae Hyung; Han, Joon Koon; Choi, Byung Ihn; Han, Man Chung [Seoul National University, College of Medicine, Seoul (Korea, Republic of)

    1992-05-15

    To evaluate the effectiveness of superselective transcatheter arterial embolization (STAE) for hepatocellular carcinoma (HCC) with a mixture of ethanol and Lipiodol, STAE was done in 12 male patients with HCC. There were diagnosed clinically with angiographic findings and elevated alphafetprotein levels and three were recurrent tumors after surgery. Sono-guided aspiration biopsy proved the diagnosis of hepatocellular carcinoma in another six patients. The tumor was a small single nodule (2-5cm in diameter) in 11 patients. In one patient, two nodules were found. Superselective catheterization was done using 3F Tracker catheter (Target Therapeutics USA) coaxially through 6F catheter into the feeding hepatic artery, usually the third order branch. One to four cc of 75% ethanol mixed with Lipiodol was infused under fluoroscopy immediately after injection of 2% lidocaine. Immediate angiography and CT after 2 weeks were undertaken. Complete segmental or subsegmental devascularization including feeding arteries and tumor vascularities occurred in all patients. Follow-up angiography after 6 to 15 months revealed the tumor opacified by Lipiodol. The tumor decreased in 5 cases and recurrence was found in three patients. CT taken 2 weeks after STAE showed low density halo around the tumor in 5 cases. Subsequent segmentectomy in four patients revealed total or near total necrosis of the tumor and no evidence of damage in surrounding parenchyma. STAE for HCC with a mixture of ethanol and Lipiodol is an effective and safe measure for small HCC.

  17. SIRT1 prevents pulmonary thrombus formation induced by arachidonic acid via downregulation of PAF receptor expression in platelets.

    Science.gov (United States)

    Kim, Yun Hak; Bae, Jin Ung; Kim, In Suk; Chang, Chulhun L; Oh, Sae Ock; Kim, Chi Dae

    2016-12-01

    SIRT1, a class III histone deacetylase, is critically involved in cellular response to stress and modulates cardiovascular risk factors. However, its role in thrombus formation is largely unknown. Thus, this study investigated the effect of SIRT1 on pulmonary thrombus formation, and then identified its role in the modulation of platelet aggregation. In isolated human platelets, cell aggregation was increased by various platelet activators, such as platelet activating factor (PAF), arachidonic acid (AA), ADP, and thrombin. AA- and PAF-mediated platelet aggregations were suppressed by WEB2086, a PAF receptor (PAFR) antagonist. Pulmonary thrombus formation induced by PAF or AA was also attenuated by WEB2086, suggesting that PAFR plays a key role in AA-induced platelet aggregation. In platelets isolated from SIRT1-TG mice as well as in platelets treated with resveratrol or reSIRT1, PAFR expression was decreased, whereas this expressional downregulation by SIRT1 activators was inhibited in platelets treated with MG132 (a proteasome inhibitor) or NH 4 Cl (a lysosome inhibitor). Furthermore, platelet aggregation induced by AA was markedly attenuated by resveratrol and reSIRT1. Likewise, the increased pulmonary thrombus formation in mice treated with AA was also attenuated by SIRT1 activators. In line with these results, pulmonary thrombus formation was markedly attenuated in SIRT1-TG mice. Taken together, this study showed that SIRT1 downregulates PAFR expression on platelets via proteasomal and lysosomal pathways, and that this downregulation inhibits platelet aggregation in vitro and pulmonary thrombus formation in vivo.

  18. [Surgical treatment of hepatocellular carcinoma. Long term results].

    Science.gov (United States)

    Figueras, Juan; Ramos, Emilio; Ibáñez, Luis; Valls, Carles; Serrano, Teresa; Rafecas, Antonio; Casanovas, Teresa; Fabregat, Juan; Xiol, Xavier; Torras, Jaume; Baliellas, Carmen; Jaurrieta, Eduardo; Casais, Luis

    2002-03-30

    Surgical treatment for hepatocellular carcinoma remains controversial due to a lack of prospective randomized studies. Between January 1990 and December 2000, 121 liver transplantations (group 1) and 52 hepatectomies (group 2) were performed for hepatocellular carcinoma. Each surgical treatment was carried out depending on patients' and tumor's characteristics. Patients from group 1 had a more advanced tumoral grade, with higher involvement of two lobes (19 vs 4%; p = 0.015) and higher number of nodules (1.9 DE [2] vs 1.2 [0.6]; p = 0.001); yet the mean tumor size was lower (3 cm [1.5] vs 4.2 [3.2]; p = 0.006). Operative mortality (4% vs 2%; p = 0.66) and 5- and 10-years survival (68% and 42% vs 63% and 45%; p = 0.23) were similar between both groups. Nevertheless, 5- and 10-years recurrence rates (10.6% and 10.6% vs 50% and 65.5%; p < 0.0001) were more favourable in group 1. Prognostic factors of recurrence included microscopic vascular invasion (RR = 12.12; CI, 2.02-75.52) and alpha-fetoprotein levels higher than 300 ng/mL (RR = 7.12; 95% CI, 1.08-47.02) in group 1, and the pT3-4 stage (RR = 3.86; 95% CI, 1.06-14.03) in group 2. Mean time on waiting lists for liver transplantation was 3.06 (2.66) months and it has increased significantly in last years, especially among blood group 0 patients. However, this fact has not been associated with a worsening of survival rates (p = 0.98). After a good patient selection, either liver transplantation or hepatectomy achieve excellent long term survival rates in patients with hepatocellular carcinoma, though the former allows a better control of the tumoral disease. The increase of mean time on waiting lists for liver transplantation during the last years has not led to a worsening of survival results.

  19. Cardiac tumors: echo assessment

    Directory of Open Access Journals (Sweden)

    Rekha Mankad MD

    2016-12-01

    Full Text Available Cardiac tumors are exceedingly rare (0.001–0.03% in most autopsy series. They can be present anywhere within the heart and can be attached to any surface or be embedded in the myocardium or pericardial space. Signs and symptoms are nonspecific and highly variable related to the localization, size and composition of the cardiac mass. Echocardiography, typically performed for another indication, may be the first imaging modality alerting the clinician to the presence of a cardiac mass. Although echocardiography cannot give the histopathology, certain imaging features and adjunctive tools such as contrast imaging may aid in the differential diagnosis as do the adjunctive clinical data and the following principles: (1 thrombus or vegetations are the most likely etiology, (2 cardiac tumors are mostly secondary and (3 primary cardiac tumors are mostly benign. Although the finding of a cardiac mass on echocardiography may generate confusion, a stepwise approach may serve well practically. Herein, we will review such an approach and the role of echocardiography in the assessment of cardiac masses.

  20. A Computational Model for Thrombus Formation in Response to Cardiovascular Implantable Devices

    Science.gov (United States)

    Horn, John; Ortega, Jason; Maitland, Duncan

    2014-11-01

    Cardiovascular implantable devices elicit complex physiological responses within blood. Notably, alterations in blood flow dynamics and interactions between blood proteins and biomaterial surface chemistry may lead to the formation of thrombus. For some devices, such as stents and heart valves, this is an adverse outcome. For other devices, such as embolic aneurysm treatments, efficient blood clot formation is desired. Thus a method to study how biomedical devices induce thrombosis is paramount to device development and optimization. A multiscale, multiphysics computational model is developed to predict thrombus formation within the vasculature. The model consists of a set of convection-diffusion-reaction partial differential equations for blood protein constituents involved in the progression of the clotting cascades. This model is used to study thrombus production from endovascular devices with the goal of optimizing the device design to generate the desired clotting response. This work