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Sample records for vx2 liver tumor

  1. Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver Tumors

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    Ibarra, R.; Dazard, J-E.; Y. Sandlers; Rehman, F; Abbas, R.; Kombu, R.; Zhang, G-F; Brunengraber, H; Sanabria, J.

    2014-01-01

    Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+...

  2. MR diffusion-weighted imaging of rabbit liver VX-2 tumor

    Institute of Scientific and Technical Information of China (English)

    You-Hong Yuan; Quan-Liang Shang; Wei-Zhou Hu; Su-Wen Yuan; En-Hua Xiao; Jun Xiang; Ke-Li Tang; Ke Jin; Shi-Jian Yi; Qiang Yin; Rong-Hua Yan; Zhong He

    2005-01-01

    AIM: To investigate the implanting method of rabbit liver VX-2 tumor and its MR diffusion-weighted imaging (DWI) characteristics.METHODS: Thirty-five New Zealand rabbits were included in the study. VX-2 tumor was implanted subcutaneously in 14 rabbits and intrahepatically in 6 for pre-experiments. VX-2 tumor was implanted intrahepatically in 12 rabbits for experiment and three were used as the control group. DWI, T1- and T2-weighted of MR1 were performed periodically in 15 rabbits for experiment before and after implantation. The distinction of VX-2 tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values. The statistical significance was calculated byanalysis of variance (ANOVA) of the randomized block design using SPSS10.0 software. RESULTS: The successful rate of subcutaneous implantation of VX-2 tumor was 29% (4/14) while that of intrahepatic implantation of it was 33% (2/6) in the preexperiment. The successful rate of intrahepatic implantation of VX-2 tumor in the experiment was 83% (10/12) and 15 tumors grew in 10 successfully implanted rabbits. The DWT signal of VX-2 tumor was high and became lower when the b value increased step by step. The signal of VX-2 tumor on the map of ADC was low. When the b value was 100 or 300 s/mm2, the ADC value of normal group and VX-2 tumor group was respectively 2.57±0.26, 1.73±0.31, 1.87±0.25 and 1.57±0.23 mm2/s. Their distinction was significant (F= 43.26, P<0.01), the tumor ADC value between b values 100 and 300 s/mm2 wassignificant (Tukey HSP, P<0.05) and the ADC value between VX-2 tumor and normal liver was also significant (Tukey HSP, P<0.01). VX-2 tumor developed quickly and metastasized early to all body, especially to the lung, liver, lymph nodes of mediastinum, etc.CONCLUSION: The DWI signal of rabbit VX-2 tumor has its characteristics on MR DWI and DWI plays an important role in diagnosing and discovering VX-2 tumor.

  3. Gene expression and MR diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

    Institute of Scientific and Technical Information of China (English)

    You-Hong Yuan; En-Hua Xiao; Jian-Bin Liu; Zhong He; Ke Jin; Cong Ma; Jun Xiang; Jian-Hua Xiao; Wei-Jian Chen

    2008-01-01

    AIM: To investigate the dynamic characteristics and the correlation between PCNA, Bax, nm23, E-cadherin expression and apparent diffusion coefficient (ADC)on MR diffusion-weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model. METHODS: Forty New Zealand rabbit liver VX-2 tumor models were included in the study. DWI was carried out periodically after chemoembolization. All VX-2 tumor samples in each group were examined by histopathology and StTept Avidin-Biotin Complex (SABC)immunohistochemical staining. RESULTS" The PCNA expression index in VX-2 tumors was higher than in the normal parenchyma around the tumor (P<0. 001). Nm23, Bax or E-caderin expression index in VX-2 tumors were lower than in the normal parenchyma around the tumor (all P<0. 001). PCNA and nm23 expression in the VX-2 tumor periphery first increased and then decreased (P<0. 001 and P=0. 03, respectively), while the expression of Bax and E-cadherin before and after chemoembolization was insignificant. When b-value was 100 s/mm2, there was a linear correlation between PCNA expression and ADC in the area of VX-2 tumor periphery (P<0. 001), and PCNA expression in VX-2 tumor periphery influenced the ADC. CONCLUSION: The potential of VX-2 tumor infiltrating and metastasizing decreases, while its ability to proliferate increases for a short time after chemoembolization. To some degree, the ADC value indirectly reflects the proliferation of VX-2 tumor cells.

  4. Characteristics and pathological mechanism on magnetic resonance diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate dynamic characteristics and pathological mechanism of signal in rabbit VX-2 tumor model on diffusion-weighted imaging (DWI) after chemoembolization.METHODS: Forty New Zealand rabbits were included in the study and forty-seven rabbit VX-2 tumor models were raised by implanting directly and intrahepatically after abdominal cavity opened. Forty VX-2 tumor models from them were divided into four groups. DWI was performed periodically and respectively for each group after chemoembolization. All VX-2 tumor samples of each group were studied by pathology. The distinction of VX-2tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values. The statistical significance between different time groups, different area groups or different b-value groups was calculated by using SPSS12.0 software.RESULTS: Under b-value of 100 s/mm2, ADC values were lowest at 16 h after chemoembolization in area of VX-2 tumor periphery, central, and normal liver parenchyma around tumor, but turned to increase with further elongation of chemoembolization treatment. The distinction of ADC between different time groups was significant respectively (F = 7.325, P < 0.001; F = 2.496,P < 0.048; F = 6.856, P < 0.001). Cellular edema in the area of VX-2 tumor periphery or normal liver parenchyma around tumor, increased quickly in sixteen h after chemoembolization but, from the 16th h to the 48th h, cellular edema in the area of normal liver parenchyma around tumor decreased gradually and that in the area of VX-2 tumor periphery decreased lightly at, and then increased continually. After chemoembolization, Cellular necrosis in the area of VX-2 tumor periphery was more significantly high than that before chemoembolization. The areas of dead cells in VX-2 tumors manifested low signal and high ADC value, while the areas of viable cells manifested high signal and low ADC value.CONCLUSION: DWI is able to detect and differentiate tumor necrotic areas from viable

  5. Targeted hyperthermia after selective embolization with ferromagnetic nanoparticles in a VX2 rabbit liver tumor model

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    Sun HL

    2013-10-01

    Full Text Available Hongliang Sun,1 Linfeng Xu,1 Tianyuan Fan,2 Hongzhi Zhan,3 Xiaodong Wang,3 Yanfei Zhou,2 Ren-jie Yang3 1Department of Interventional Therapy, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 2Pharmacy School of Beijing University, Beijing, 3Department of Interventional Therapy, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China Background: The purpose of this study was to observe the effect and feasibility of hyperthermia and the influence of heat on surrounding organs in a VX2 rabbit liver model exposed to an alternating magnetic field after embolization with ferromagnetic nanoparticles. Methods: Forty rabbits containing implanted hepatic VX2 carcinomas were divided into four groups, each containing ten rabbits. Fourteen days after tumor transplantation, we opened the abdomen to observe the size and shape of the tumor. A transfemoral retrograde approach was then used for hepatic arterial catheterization in groups B, C, and D to perform angiography and embolization. The next day, three rabbits in group B and all rabbits in group D were exposed to an alternating magnetic field, and the temperature was recorded simultaneously in the center of the tumor, at the edge of the tumor, and in the normal liver parenchyma. On day 28, all animals was euthanized to observe changes in the implanted liver tumor and the condition of the abdomen. A pathologic examination was also done. Results: Before surgery, there was no significant difference in tumor volume between the four groups. Three different temperature points (center of the tumor, edge of the tumor, and in the normal liver parenchyma of group B under an alternating magnetic field were 37.2°C ± 1.1°C, 36.8°C ± 1.2°C, and 36.9°C ± 2.1°C, none of which were significantly different from pretreatment values. Three points basal temperature in group D showed no significant difference (F = 1.038, P = 0.413. Seven to 26

  6. Quantitative dual energy CT measurements in rabbit VX2 liver tumors: Comparison to perfusion CT measurements and histopathological findings

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    Zhang, Long Jiang, E-mail: kevinzhanglongjiang@yahoo.com.cn [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Wu, Shengyong, E-mail: cjr.wushengyong@vip.163.com [Institute of Tianjin Medical Imaging, Tianjin 300192 (China); Wang, Mei, E-mail: 281406196@qq.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Lu, Li, E-mail: xuzhoululi@163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Chen, Bo, E-mail: chenbo1985@yahoo.com.cn [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Jin, Lixin, E-mail: lixin.jin@siemens.com [Siemens Healthcare, MR Collaboration NE Asia, Shanghai (China); Wang, Jiandong, E-mail: jdwang1216@163.com [Department of Pathology, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 200012 (China); Larson, Andrew C., E-mail: a-larson@northwestern.edu [Department of Radiology, Northwestern University, Chicago, IL (United States); Lu, Guang Ming, E-mail: cjr.luguangming@vip.163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China)

    2012-08-15

    Purpose: To evaluate the correlation between quantitative dual energy CT and perfusion CT measurements in rabbit VX2 liver tumors. Materials and methods: This study was approved by the institutional animal care and use committee at our institution. Nine rabbits with VX2 liver tumors underwent contrast-enhanced dual energy CT and perfusion CT. CT attenuation for the tumors and normal liver parenchyma and tumor-to-liver ratio were obtained at the 140 kVp, 80 kVp, average weighted images and dual energy CT iodine maps. Quantitative parameters for the viable tumor and adjacent liver were measured with perfusion CT. The correlation between the enhancement values of the tumor in iodine maps and perfusion CT parameters of each tumor was analyzed. Radiation dose from dual energy CT and perfusion CT was measured. Results: Enhancement values for the tumor were higher than that for normal liver parenchyma at the hepatic arterial phase (P < 0.05). The highest tumor-to-liver ratio was obtained in hepatic arterial phase iodine map. Hepatic blood flow of the tumor was higher than that for adjacent liver (P < 0.05). Enhancement values of hepatic tumors in the iodine maps positively correlated with permeability of capillary vessel surface (r = 0.913, P < 0.001), hepatic blood flow (r = 0.512, P = 0.010), and hepatic blood volume (r = 0.464, P = 0.022) at the hepatic arterial phases. The effective radiation dose from perfusion CT was higher than that from DECT (P < 0.001). Conclusions: The enhancement values for viable tumor tissues measured in iodine maps were well correlated to perfusion CT measurements in rabbit VX2 liver tumors. Compared with perfusion CT, dual energy CT of the liver required a lower radiation dose.

  7. Characteristics of liver on magnetic resonance diffusion-weighted imaging: Dynamic and image pathological investigation in rabbit liver VX-2 tumor model

    Institute of Scientific and Technical Information of China (English)

    You-Hong Yuan; En-Hua Xiao; Jian-Bin Liu; Zhong He; Ke Jin; Cong Ma; Jun Xiang; Jian-Hun Xiao; Wei-Jian Chen

    2008-01-01

    AIM: To investigate dynamical and image pathological characteristics of the liver on magnetic resonance (MR) diffusion-weighted imaging (DWI) in the rabbit VX-2 tumor model.METHODS: Forty New Zealand rabbits were included in the study and VX-2 tumor piece was implanted intrahepatically. Fifteen animals received two intrahepatic implantations while 25 had one intrahepatical implantation. DWI, T1-and T2-weighted of magnetic resonance imaging (MRI) were carried out on the 7th and the 14th d after implantation and DWI was conducted, respectively on the 21th d. Ten VX-2 tumor samples were studied pathologically.RESULTS: The rate of lump detected by DWI, T1WI and T2WI was 78.7%,10.7% and 53.5% (χ2= 32.61, P<0.001) on the 7th d after implantation and 95.8%,54.3% and 82.9% (χ2= 21.50, P<0.001) on the 14th d. The signal of most VX-2 tumors on DWI was uniform and it was equal on the map of apparent diffusion coefficient (ADC). The signal of VX tumors did not decrease on the 7th d after implantation, most of them slowly growing during the week following implantation without significant cell dying within the tumor. VX-2 tumors grew increasingly within 14 d after implantation but the signal of most VX-2 tumors on DWI or on the map of ADC was uniform or uneven and ADC of VX tumors decreased obscurely or slightly because tumor necrosis was still not obvious. On the 21th d after implantation, the signal of most VX-2 tumors on DWI or on the map of ADC was uneven because tumor necrosis was evident and ADC of VX-2 tumor necrotic areas decreased. The areas of viable cells in VX-2 tumors manifested a high signal on DWI and a low signal on the map of ADC. The areas of dead cells or necrosis in VX-2 tumors manifested low signals on DWI and low, equal or high signals on the map of ADC but they manifested high signals on DWI and on the map of ADC at the same time when the areas of necrotic tumor became liquefied or cystic. The border of tumors on DWI appeared gradually distinct and

  8. [Effect of lipiodol emulsion and local hyperthermia on hepatic tissue blood flow in rabbits with VX-2 liver tumor].

    Science.gov (United States)

    Suzuki, K; Tada, I; Okada, K; Kim, Y I; Kobayashi, M

    1988-08-01

    The effect of intra-arterial infusion of lipiodol-emulsion and local hyperthermia on tissue blood flow was examined in experimental hepatic tumor and normal liver of rabbits. VX-2 tumor was implanted in liver of rabbit. The tissue blood flow was estimated by hydrogen gas clearance method when the tumor grew to about 2 cm. Tissue blood flow in tumor (64.5 ml/min/100 g) was significantly less than in normal liver (90.8 ml/min/100 g) (p less than 0.005). The intra-arterial infusion of lipiodol-emulsion did not alter the flow in either tissue. However, the addition of hyperthermia induced a substantial rise of tissue blood flow in normal liver (35% increase, from 93.8 to 127 ml/min/100 g) when compared with in VX-2 tumor (8.9% increase, from 65.1 to 71.8 ml/min/100 g). These were accompanied by a selective heating of liver tumor; the tumor temperature rose to 43 degrees C, although that of normal liver remained at 38 degrees C. Our results suggested that a specific temperature rise of liver tumor after infusion of lipiodol-emulsion and local heating might be related to a different response of microcirculation in tumor and normal liver to the hyperthermia.

  9. Irinotecan Loaded in Eluting Beads: Preclinical Assessment in a Rabbit VX2 Liver Tumor Model

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    Rao, Pramod P.; Pascale, Florentina [Institute Gustave Roussy, Department of Interventional Radiology (France); Seck, Atman [Institute Gustave Roussy, UPRES EA 3535, Pharmacologie et Nouveaux Traitements du Cancer (France); Auperin, Anne [Institute Gustave Roussy, Department of Biostatistics and Epidemiology (France); Drouard-Troalen, Laurence [Institute Gustave Roussy, Department of Biology and Pathology (France); Deschamps, Frederic; Teriitheau, Christophe [Institute Gustave Roussy, Department of Interventional Radiology (France); Paci, Angelo [Institute Gustave Roussy, UPRES EA 3535, Pharmacologie et Nouveaux Traitements du Cancer (France); Denys, Alban; Bize, Pierre [Centre Hospitalier Universitaire Vaudois, Department of Interventional Radiology (Switzerland); Baere, Thierry de, E-mail: debaere@igr.fr [Institute Gustave Roussy, Department of Interventional Radiology (France)

    2012-12-15

    Purpose: The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform. Material and Methods: Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver.ResultsTwelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03). Conclusion: Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.

  10. Radiofrequency ablation of liver VX2 tumor: experimental results with MR diffusion-weighted imaging at 3.0T.

    Directory of Open Access Journals (Sweden)

    Yubao Liu

    Full Text Available To evaluate the value of DWI in detecting the lesions of pre- and post-radiofrequency ablation (RFA of the rabbit liver VX2 tumors.Twenty-two New Zealand White rabbits were tested. The protocol was approved by the Committee on the Ethics of Animal Experiments. Twenty separate tumor fragments were implanted into the livers of 20 rabbits, the liver was exposed by performing midline laparotomy. 3.0T MR DWI (b = 0, 200, 400, 600, 800,1000 s/mm2 were performed 14-21 days after tumor implantation (mean, 17 days in the 18 tumor-bearing animals. Then RFA was performed in the 18 tumor-bearing animals and in the two healthy animals. 3.0T MR DWI was performed 7-10 days after RFA (mean, 8 days. Pathology exam was performed immediately after the completion of post- RFA MR imaging. Analyzing the features of MRI and ADC values in the pre- and post- RFA lesions of the VX2 tumors, and histopathologic results were compared with imaging findings.The difference of ADC value between viable tumor and normal liver parenchyma was significant (P<.001. After RFA, when b = 200, 400, 600, 800, 1000 s/mm2, the differences of ADC values of viable tumor, granulation tissue, necrosis, normal liver parenchyma were significant (P<.001. At the time the animals were sacrificed after RFA and MR imaging, histopathologic results of local viable tumors were found in 9 (50% of the 18 treated tumors. Macroscopic viable tumors were found at the RFA sites in 3 (17%, all 3 macroscopic viable tumors were visualized at the periphery of the RFA areas.3.0T MR DWI can be used to follow up the progress of the RFA lesion, it is useful in detecting different tissues after RFA, and it is valuable in the further clinical research.

  11. Arsenic trioxide treatment of rabbit liver VX-2 carcinoma via hepatic arterial cannulationinduced apoptosis and decreased levels of survivin in the tumor tissue

    OpenAIRE

    LI, HONG; Gong, Jian; Jiang, Xuyuan; Shao, Haibo

    2013-01-01

    Aim To investigate the role of tumor apoptosis-inhibitory protein survivin in arsenic trioxide-induced apoptosis in VX-2 carcinoma in the rabbit liver by means of transcatheter arterial chemoembolization. Methods Sixteen rabbits with 32 implanted hepatic VX-2 tumors were randomly divided into two groups. The experimental group received 2 mg of arsenic trioxide and 1 mL of ultra-fluid lipiodol co-injected via hepatic arterial cannulation and the control group received o...

  12. Effect of hepatic artery embolization on liver hypertrophy response in a rabbit liver VX2 tumor model

    Institute of Scientific and Technical Information of China (English)

    Krijn P van Lienden; Lisette T Hoekstra; Jessica D van Trigt; Joris J Roelofs

    2013-01-01

    BACKGROUND: Portal  vein  embolization  not  only  induces hypertrophy  of  the  non-embolized  liver,  but  also  enhances tumor growth. The latter could be prevented by embolizing the hepatic  arteries  supplying  the  tumor-bearing  liver  segments. This  study  aimed  to  determine  the  effects  of  transcatheter arterial  embolization  (TAE)  on  tumor  volume  and  liver regeneration in a rabbit VX2 tumor model. METHODS: Twenty-three  rabbits  underwent  subcapsular tumor  implantation  with  a  VX2tumor.  Two  weeks  after implantation,  18  rabbits  were  used  for  TAE  experiments,  5 were for sham controls. Tumor response and liver regeneration response of the  embolized  cranial  and  non-embolized caudal liver lobes were assessed by CT volumetry, liver to body weight index, and the amount of proliferating hepatocytes. RESULTS: All  super-selective  arterial  tumor  embolization procedures were performed successfully. Despite embolization, the  tumor  volume  increased  after  an  initial  steady  state.  The tumor volume after embolization was smaller than that of the sham  group,  but  this  difference  was  not  significant.  Massive necrosis  of  the  tumor,  however,  was  seen  after  embolization, without  damage  of  the  surrounding  liver  parenchyma.  There was a significant atrophy response of the tumor bearing cranial lobe  after  super-selective  arterial  embolization  of  the  tumor with a concomitant hypertrophy response of the non-embolized, caudal  lobe.  This  regeneration  response  was  confirmed histologically by a

  13. Ultrasonograpy of VX-2 Liver Tumor in Rabbit Treated by High Intensity Focused Ultrasound Combined with Microbubble Contrast Agent

    Science.gov (United States)

    Xiaojuan, Ji; Jinqing, Li; Zhibiao, Wang; Jianzhong, Zou; Wenzhi, Chen; Jin, Bai

    2007-05-01

    Objective: To assess the value of sonographic appearance and to investigate the sonographic character of VX-2 liver tumor in rabbit treated by high intensity focused ultrasound (HIFU) combined with microbubble contrast agent. Methods: Forty-five rabbits bearing VX-2 tumors were randomly averagely assigned into three groups. In group A irradiation was sustained until the target region became hyperechoic. In group B therapy was stopped as soon as hyperecho occurred, and in group C irradiation time was prolonged to ensure the occurrence of coagulation necrosis. Results: Exposure duration for tumors treated purely with HIFU was the longest, whilst the use of microbubble contrast agent combined with HIFU shortened the exposure duration significantly. The gross examination and ultrasonogram coagulation necrosis area measurements correlated strongly (r=0.986,P<0.05) in the microbubble-enhanced HIFU group. Conclusion: It was feasible to enhance HIFU therapy with microbubble contrast agent. The characteristic change in the ultrasound images made it possible to assess the enhanced HIFU therapeutic efficacy in order to adjust the treatment program.

  14. Arterial embolization hyperthermia using As2O3 nanoparticles in VX2 carcinoma-induced liver tumors.

    Directory of Open Access Journals (Sweden)

    Hui Yu

    Full Text Available BACKGROUND: Combination therapy for arterial embolization hyperthermia (AEH with arsenic trioxide (As(2O(3 nanoparticles (ATONs is a novel treatment for solid malignancies. This study was performed to evaluate the feasibility and therapeutic effect of AEH with As(2O(3 nanoparticles in a rabbit liver cancer model. The protocol was approved by our institutional animal use committee. METHODOLOGY/PRINCIPAL FINDINGS: In total, 60 VX(2 liver-tumor-bearing rabbits were randomly assigned to five groups (n = 12/group and received AEH with ATONs (Group 1, hepatic arterial embolization with ATONs (Group 2, lipiodol (Group 3, or saline (Group 4, on day 14 after tumor implantation. Twelve rabbits that received AEH with ATONs were prepared for temperature measurements, and were defined as Group 5. Computed tomography was used to measure the tumors' longest dimension, and evaluation was performed according to the Response Evaluation Criteria in Solid Tumors. Hepatic toxicity, tumor necrosis rate, vascular endothelial growth factor level, and microvessel density were determined. Survival rates were measured using the Kaplan-Meier method. The therapeutic temperature (42.5°C was obtained in Group 5. Hepatotoxicity reactions occurred but were transient in all groups. Tumor growth was delayed and survival was prolonged in Group 1 (treated with AEH and ATONs. Plasma and tumor vascular endothelial growth factor and microvessel density were significantly inhibited in Group 1, while tumor necrosis rates were markedly enhanced compared with those in the control groups. CONCLUSIONS: ATON-based AEH is a safe and effective treatment that can be targeted at liver tumors using the dual effects of hyperthermia and chemotherapy. This therapy can delay tumor growth and noticeably inhibit tumor angiogenesis.

  15. Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate: a biodistribution and survival study.

    Science.gov (United States)

    Vali, Mustafa; Vossen, Josephina A; Buijs, Manon; Engles, James M; Liapi, Eleni; Ventura, Veronica Prieto; Khwaja, Afsheen; Acha-Ngwodo, Obele; Ganapathy-Kanniappan, Shanmugasundaram; Shanmugasundaram, Ganapathy; Syed, Labiq; Wahl, Richard L; Geschwind, Jean-Francois H

    2008-10-01

    The aim of this study was to determine the biodistribution and tumor targeting ability of (14)C-labeled 3-bromopyruvate ([(14)C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [(14)C]3-BrPA on tumor and healthy tissue glucose metabolism by determining (18)F-deoxyglucose (FDG) uptake. Last, we determined the survival benefit of i.a. administered 3-BrPA. In total, 60 rabbits with VX2 liver tumor received either 1.75 mM [(14)C]3-BrPA i.a., 1.75 mM [(14)C]3-BrPA i.v., 20 mM [(14)C]3-BrPA i.v., or 25 ml of phosphate-buffered saline (PBS). All rabbits (with the exception of the 20 mM i.v. group) received FDG 1 h before sacrifice. Next, we compared survival of animals treated with i.a. administered 1.75 mM [(14)C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [(14)C]3-BrPA was 1.8 +/- 0.2% percentage of injected dose per gram of tissue (%ID/g), whereas other tissues showed minimal uptake. After i.v. infusion (1.75 mM), tumor uptake of [(14)C]3-BrPA was 0.03 +/- 0.01% ID/g. After i.a. administration of [(14)C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [(14)C]3-BrPA, there was no significant difference in tumor FDG uptake. Survival analysis showed that rabbits treated with 1.75 mM 3-BrPA survived longer (55 days) than controls (18.6 days). Intra-arterially delivered 3-BrPA has a favorable biodistribution profile, combining a high tumor uptake resulting in blockage of FDG uptake with no effects on healthy tissue. The local control of the liver tumor by 3-BrPA resulted in a significant survival benefit.

  16. Transcatheter arterial embolization combined with radiofrequency ablation activates CD8+ T-cell infiltration surrounding residual tumors in the rabbit VX2 liver tumors

    Directory of Open Access Journals (Sweden)

    Duan XH

    2016-05-01

    Full Text Available Xu-Hua Duan,1,2 Teng-Fei Li,2 Guo-Feng Zhou,1,* Xin-Wei Han,2,* Chuan-Sheng Zheng,1 Peng-fei Chen,2 Gan-Sheng Feng11Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Henan Province, Zhengzhou, People’s Republic of China*These authors contributed equally to this work Purpose: To evaluate the effect of transcatheter arterial embolization (TAE combined with radiofrequency ablation (RFA treatment (TAE + RFA on the expression of heat shock protein 70 (HSP70 in residual tumors and explore the relationship between the HSP70 and CD8+ T-cell infiltrate surrounding residual tumors in the rabbit VX2 liver tumor model.Materials and methods: Animals with VX2 liver tumors were randomized into four groups (control, TAE, RFA, and TAE + RFA with 15 rabbits in each group. Five rabbits in each group were sacrificed on days 1, 3, and 7 after treatment. HSP70 expression and infiltration of CD8+ T-cells in the liver and residual tumors surrounding the necrosis zone were detected by immunohistochemistry staining. The maximal diameters of tumor necrosis, numbers of metastases, and tumor growth rate were compared on day 7 after treatment.Results: TAE + RFA achieved larger maximal diameter of tumor necrosis, lower tumor growth rate, and fewer metastatic lesions, compared with other treatments on day 7. The number of CD8+ T-cells in the TAE + RFA group was significantly higher than in other groups on days 1, 3, and 7. There was a positive correlation between HSP70 expression level and infiltration of CD8+ T-cells surrounding the residual tumor on day 1 (r=0.9782, P=0.012, day 3 (r=0.93, P=0.021, and day 7 (r=0.8934, P=0.034.Conclusion: In the rabbit VX2 liver tumor model, TAE + RFA activated the highest number of CD8+ T-cells surrounding residual tumors. TAE + RFA appears to be a beneficial

  17. Arsenic trioxide treatment of rabbit liver VX-2 carcinoma via hepatic arterial cannulation-induced apoptosis and decreased levels of survivin in the tumor tissue.

    Science.gov (United States)

    Li, Hong; Gong, Jian; Jiang, Xuyuan; Shao, Haibo

    2013-02-01

    To investigate the role of tumor apoptosis-inhibitory protein survivin in arsenic trioxide-induced apoptosis in VX-2 carcinoma in the rabbit liver by means of transcatheter arterial chemoembolization. Sixteen rabbits with 32 implanted hepatic VX-2 tumors were randomly divided into two groups. The experimental group received 2 mg of arsenic trioxide and 1 mL of ultra-fluid lipiodol co-injected via hepatic arterial cannulation and the control group received only 1 mL of lipiodol. Animals were sacrificed 3 weeks after trans-catheterial arterial chemoembolization. Tumor tissue and tumor-peripheral tissue were collected for analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining was used to assess tumor cells apoptosis. Immunohistochemistry was used to assess the presence of survivin protein. Reverse transcription polymerase chain reaction was used to determine the expression of survivin gene. The number of apoptotic cells significantly increased in the tumor tissue (5.20 ± 0.60%) compared to tumor-peripheral tissue (1.29 ± 0.42%) of the arsenic trioxide-treated group. Survivin expression levels in the tumor tissue were significantly reduced in arsenic trioxide-treated group (7.68 ± 0.65) compared to the control group (35.30 ± 4.63). Transcatheter arterial chemoembolization with arsenic trioxide induced apoptosis of VX-2 carcinoma, in which tumor apoptosis-inhibitory protein survivin may have played a role.

  18. Monitoring of VX2 tumor growth in rabbit liver using T2-weighted and dynamic contrast-enhanced magnetic resonance imaging at 1.5T

    Science.gov (United States)

    Jao, Jo-Chi; Mac, Ka-Wai; Chang, Chiung-Yun; Wu, Yu-Chiuan; Hsiao, Chia-Chi; Chen, Po-Chou

    2017-03-01

    This study aimed to investigate the VX2 tumor growth in rabbit liver using T2-weighted imaging (T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Five New Zealand white (NZW) rabbits were implanted with VX2 cell suspension in liver. Afterwards, MRI was performed 7, 14, 21 and 28 days after tumor implantation. A 1.5T clinical MRI scanner was used to perform scans. After 3-plane localizer, T1 weighted imaging (T1WI), T2WI, and DCE-MRI using a three-dimensional gradient echo pulse sequence was performed. After 4 pre-contrast images were acquired, each rabbit was injected i.v. with 0.1 mmol/kg Dotarem. The total scan time after Dotarem administration was 30 minutes. All acquired images were analyzed using ImageJ software. Several regions of interest were selected from the rims of tumor, liver, and muscle. The enhancement ratio (ER) was calculated by dividing the MR signal after Dotarem injection to the MR signal before Dotarem injection. The maximum ER (ER_max) value of tumor for each rabbit was observed right after the Dotarem injection. The T2W MR signal intensities (T2W_SI) and the ER_max values obtained 7, 14, 21 and 28 days after tumor implantation were analyzed with a linear regression algorithm. Both T2W_SI and ER_max of tumors increased with time. The changes for T2W_SI and ER_max of tumors between 7 and 28 days after tumor implantation were 32.66% and 18.14%, respectively. T2W_SI is more sensitive than ER_max for monitoring the growth of VX2 tumor in a rabbit liver model.

  19. Non-thermal ablation of rabbit liver VX2 tumor by pulsed high intensity focused ultrasound with ultrasound contrast agent: Pathological characteristics

    Institute of Scientific and Technical Information of China (English)

    Cheng-Wen Zhou; Fa-Qi Li; Yan Qin; Chun-Mei Liu; Xiao-Lin Zheng; Zhi-Biao Wang

    2008-01-01

    AIM:To investigate the pathological characteristics of non-thermal damage induced by pulsed high intensity focused ultrasound (PHIFU) combined with ultrasound contrast agent (UCA),SonoVue (Bracco SpA,Milan,Italy) in rabbit liver VX2 tumor.METHODS:Liver VX2 tumor models were established in 20 rabbits,which were divided randomly into PHIFU combined with ultrasound contrast agent group (PHIFU + UCA group) and sham group.In the PHIFU + UCA group,0.2 mL of SonoVue was injected intravenously into the tumor,followed by ultrasound exposure of Isp 5900 W/cm2.The rabbits were sacrificed one day after ultrasound exposure.Specimens of the exposed tumor tissues were obtained and observed pathologically under light microscope and transmission electron microscope.The remaining tumor tissues were sent for 2,3,5-Triphenyltetrazolium chloride (TTC) staining.RESULTS:Before TTC staining,tumor tissues in both the sham and the PHIFU + UCA groups resembled gray fish meat.After TTC staining,the tumor tissues were uniformly stained red,with a clear boundary between tumor tissue and normal tissue.Histological examination showed signs of tumor cell injury in PHIFU + UCA group,with cytoplasmic vacuoles of various sizes,chromatin margination and karyopyknosis.Electron microscopic examination revealed tumor cell volume reduction,karyopyknosis,chromatin margination,intercellular space widening,the presence of high electron-density apoptotic bodies and vacuoles in cytoplasm.CONCLUSION:The non-thermal effects of PHIFU combined with UCA can be used to ablate rabbit liver VX2 tumors.

  20. FDG-PET for Evaluating the Antitumor Effect of Intraarterial 3-Bromopyruvate Administration in a Rabbit VX2 Liver Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Sun; Chung, Jin Wook; Jae, Hwan Jun [Seoul National University College of Medicine, Seoul (Korea, Republic of)] (and others)

    2007-06-15

    We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model. VX2 carcinoma was grown in the livers of ten rabbits. Two weeks later, liver CT was performed to confirm appropriate tumor growth for the experiment. After tumor volume-matched grouping of the rabbits, transcatheter intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five animals each, respectively). FDG-PET scan was performed the day before, immediately after and a week after 3-BrPA administration. FDG uptake was semiquantified by measuring the standardized uptake value (SUV). A week after treatment, the experimental animals were sacrificed and the necrosis rates of the tumors were calculated based on the histopathology. The SUV of the VX2 tumors before treatment (3.87{+-}1.51 [mean SD]) was significantly higher than that of nontumorous liver parenchyma (1.72{+-}0.34) (p < 0.0001, Mann-Whitney U test). The SUV was significantly decreased immediately after 3-BrPA administration (2.05{+-}1.21) (p = 0.002, Wilcoxon signed rank test). On the one-week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41{+-}0.73) than that before treatment (p 0.002), although three out of ten animals showed a slightly increasing tendency for the FDG uptake. The tumor necrosis rate ranged from 50.00% to 99.90% (85.48%{+-}15.87). There was no significant correlation between the SUV or the SUV decrease rate and the tumor necrosis rate in that range. Even though FDG-PET cannot exactly reflect the tumor necrosis rate, FDG-PET is a useful modality for the early assessment of the antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor.

  1. Tumor hepático experimental (VX-2 em coelho: implantação do modelo no Brasil Experimental liver tumor (VX-2 in rabbits: implantation of the model in Brazil

    Directory of Open Access Journals (Sweden)

    Rogério Saad Hossne

    2002-08-01

    Full Text Available Os estudos para a investigação de novas modalidades terapêuticas em biologia tumoral, deveriam passar por estudos experimentais prévios. Neste sentido dispõem-se hoje de uma grande variedade de modelos tumorais experimentais; em determinadas investigações faz-se necessária a adequação do modelo tumoral às necessidades biológicas, patológicas e experimentais dos estudos. Desta forma, em nosso serviço, buscávamos um modelo tumoral hepático para estudos experimentais que se adequasse às seguintes características: fácil manipulação, crescimento controlável, evolução e agressividade semelhantes aos seres humanos. Os dados da literatura nos levaram a busca do tumor hepático VX-2, em coelhos. Neste artigo discutimos as vantagens da utilização deste modelo experimental e a sua introdução em nosso país.Studies for investigation of new therapeutic modalities in tumoral biology should be based on previous experimental studies. Then, there are a great variety of tumoral experimental models today. Some investigations have been done necessary an adaptation of the tumoral model to the needing of the studies biological and pathological. So, in our laboratory, we looked for a tumoral hepatic model for experimental studies with the following characteristics: easy manipulation, control of growing, evolution and aggressiveness like to humans. Data of the literature took us the search of the hepatic tumor VX-2, in rabbits. In this article we discussed the advantages of use this experimental model and its introduction in our country. Experimental hepatic tumor (VX-2 in rabbit. Implantation of the model in Brazil.

  2. Treatment of (131)I-labeled anti-CD147 monoclonal antibody in VX2 carcinoma-induced liver tumors.

    Science.gov (United States)

    Niu, Huanzhang; Wang, Ruihua; Cheng, Jingliang; Gao, Shegan; Liu, Baoping

    2013-07-01

    Hepatocellular carcinoma (HCC) is a major health problem worldwide. CD147 has been reported to be overexpressed in HCC and blocking CD147 expression can decrease tumor growth. (131)I is often used in combination with other drugs to treat HCC and yields positive results. In this study, we combined the (131)I and CD147 monoclonal antibody to treat HCC in a rabbit VX2 animal model. In the (131)I-labeled CD147 antibody ((131)I-CD147-Ab) treatment group, the animals lived considerably longer than the animals in the other treatment groups. Metastasis and tumor growth in the (131)I-CD147-Ab treatment group were also inhibited. MMP2 and CD31 expression were significantly lower in the treatment group, whereas Tunel staining was overexpressed. These findings suggest that (131)I-CD147-Ab is a promising drug in the treatment of HCC, by inhibiting metastasis and growth and by decreasing the expression of MMP2 and CD31 or by inducing tumor necrosis. After testing the biochemical parameters, (131)I-CD147-Ab caused fewer side-effects in the animals.

  3. STUDY EXPERIENCE AND ESTABLISHMENT OF METASTATIC RABBIT MODEL WITH VX-2 CARCINOMA IN LIVER%兔肝VX2移植癌模型的建立

    Institute of Scientific and Technical Information of China (English)

    陈利平; 文天夫

    2011-01-01

    [目的]制作VX-2兔肝移植癌模型.[方法]新西兰白兔10只,采用VX-2瘤株动物自身接种传代.采用瘤组织块包埋法,均接种于肝左叶.[结果]2周后均顺利成瘤,该瘤在肝组织中呈浸润式生长.[结论]成功建立了兔VX-2移植性肝癌模型,为肝癌治疗的基础及临床研究提供了成熟的大型实验动物肝癌模型.%[Objective]To establish a metastatic rabbit VX-2 liver tumor model.[Methods]10 New-Zealand white rabbits were inoculated with VX-2 carcinoma in the left lobe of the liver by implantation.[Results]The tumor was successfully established two weeks later.The tumor grew in the liver tissue and infiltrated into the normal liver tissue.[Conclusion]It is successful to establish a modified metastatic rabbit VX-2 liver carcinma model, and it makes it possible to gain a reliable mature large animal model of tumor for the basic and clinical study of therapy of liver carcinoma.

  4. Dynamic contrast-enhanced MRI using a macromolecular MR contrast agent (P792): Evaluation of antivascular drug effect in a rabbit VX2 liver tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Sun [Dept. of Radiology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Han, Joon Koo; Lee, Jeong Min; Woo, Sung Min; Choi, Byung Ihn [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Young Il [Dept. of Radiology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah (United Arab Emirates); Choi, Jin Young [Dept. of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-10-15

    To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.

  5. Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kageyama, Ken, E-mail: kageyamaken0112@gmail.com; Yamamoto, Akira, E-mail: loveakirayamamoto@gmail.com; Okuma, Tomohisa, E-mail: o-kuma@msic.med.osaka-cu.ac.jp; Hamamoto, Shinichi, E-mail: hamashin_tigers1975@yahoo.co.jp; Takeshita, Toru, E-mail: takeshita3595@view.ocn.ne.jp; Sakai, Yukimasa, E-mail: sakaiy@trust.ocn.ne.jp; Nishida, Norifumi, E-mail: norifumin@med.osaka-cu.ac.jp; Matsuoka, Toshiyuki, E-mail: tmatsuoka@msic.med.osaka-cu.ac.jp; Miki, Yukio, E-mail: yukio.miki@med.osaka-cu.ac.jp [Osaka City University, Department of Radiology, Graduate School of Medicine (Japan)

    2013-10-15

    Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.

  6. Thermo-sensitive composite hydrogels based on poloxamer 407 and alginate and their therapeutic effect in embolization in rabbit VX2 liver tumors.

    Science.gov (United States)

    Huang, Lili; Shen, Ming; Li, Rongxin; Zhang, Xiangyu; Sun, Ying; Gao, Pei; Fu, Hao; Liu, Hongqiang; He, Yang; Du, Yuqing; Cao, Jun; Duan, Yourong

    2016-11-08

    Interventional embolization therapy is an effective, most widely used method for inoperable liver tumors. Blood-vessel-embolic agents were essential in transarterial embolization (TAE). In this work, thermo-sensitive composite hydrogels based on poloxamer 407, sodium alginate, hydroxymethyl cellulose and iodixanol (PSHI), together with Ca2+ (PSHI-Ca2+) were prepared as liquid embolic agents for TAE therapy to liver cancer. With increasing temperature, PSHI exhibited two phase states: a flowing sol and a shrunken gel. Rheology tests showed good fluidity and excellent viscoelastic behavior with a gelation temperature (GT) of 26.5°C. The studies of erosion indicated that PSHI had calcium ion-related erosion characteristics and showed a slow erosion rate in an aqueous environment. When incubated with L929 cells, the thermo-sensitive composite hydrogels had low cytotoxicity in vitro. The results of analyzing the digital subtraction angiography and computed tomography images obtained from in vitro and in vivo assays indicated a good embolic effect in the renal arteries of normal rabbits. Angiography and histological studies on VX2 tumor-bearing rabbits indicated that PSHI-Ca2+ successfully occluded the tumors, including the peripheral vessels. In conclusion, PSHI-Ca2+ was a promising embolic agent for transarterial embolization therapy.

  7. Thermo-sensitive composite hydrogels based on poloxamer 407 and alginate and their therapeutic effect in embolization in rabbit VX2 liver tumors

    Science.gov (United States)

    Huang, Lili; Shen, Ming; Li, Rongxin; Zhang, Xiangyu; Sun, Ying; Gao, Pei; Fu, Hao; Liu, Hongqiang; He, Yang; Du, Yuqing; Cao, Jun; Duan, Yourong

    2016-01-01

    Interventional embolization therapy is an effective, most widely used method for inoperable liver tumors. Blood-vessel-embolic agents were essential in transarterial embolization (TAE). In this work, thermo-sensitive composite hydrogels based on poloxamer 407, sodium alginate, hydroxymethyl cellulose and iodixanol (PSHI), together with Ca2+ (PSHI-Ca2+) were prepared as liquid embolic agents for TAE therapy to liver cancer. With increasing temperature, PSHI exhibited two phase states: a flowing sol and a shrunken gel. Rheology tests showed good fluidity and excellent viscoelastic behavior with a gelation temperature (GT) of 26.5°C. The studies of erosion indicated that PSHI had calcium ion-related erosion characteristics and showed a slow erosion rate in an aqueous environment. When incubated with L929 cells, the thermo-sensitive composite hydrogels had low cytotoxicity in vitro. The results of analyzing the digital subtraction angiography and computed tomography images obtained from in vitro and in vivo assays indicated a good embolic effect in the renal arteries of normal rabbits. Angiography and histological studies on VX2 tumor-bearing rabbits indicated that PSHI-Ca2+ successfully occluded the tumors, including the peripheral vessels. In conclusion, PSHI-Ca2+ was a promising embolic agent for transarterial embolization therapy. PMID:27602579

  8. Tumor Uptake of Hollow Gold Nanospheres after Intravenous and Intra-arterial Injection: PET/CT Study in a Rabbit VX2 Liver Cancer Model

    Science.gov (United States)

    Tian, Mei; Lu, Wei; Zhang, Rui; Xiong, Chiyi; Ensor, Joe; Nazario, Javier; Jackson, James; Shaw, Colette; Dixon, Katherine A.; Miller, Jennifer; Wright, Kenneth; Li, Chun; Gupta, Sanjay

    2014-01-01

    Purpose This study was designed to investigate the intratumoral uptake of hollow gold nanospheres (HAuNS) after hepatic intra-arterial (IA) and intravenous (IV) injection in a liver tumor model. Materials and Methods Fifteen VX2 tumor-bearing rabbits were randomized into five groups (N=3 in each group) that received either IV 64Cu-labeled PEG-HAuNS (IV-PEG-HAuNS), IA 64Cu-labeled PEG-HAuNS (IA-PEG-HAuNS), IV cyclic peptide (RGD)-conjugated 64Cu-labeled PEG-HAuNS (IV-RGD-PEG-HAuNS), IA RGD-conjugated 64Cu-labeled PEG-HAuNS (IA-RGD-PEG-HAuNS), or IA 64Cu-labeled PEG-HAuNS with lipiodol (IA-PEG-HAuNS-lipiodol). The animals underwent PET/CT 1 hour after injection, and uptake expressed as percentage of injected dose per gram of tissue (%ID/g) was measured in tumor and major organs. The animals were euthanized 24 hours after injection, and tissues were evaluated for radioactivity. Results At 1 hour after injection, animals in the IA-PEG-HAuNS-lipiodol group showed significantly higher tumor uptake (P < 0.001) and higher ratios of tumor-to-normal liver uptake (P < 0.001) than those in all other groups. The biodistribution of radioactivity 24 hours after injection showed that IA delivery of PEG-HAuNS with lipiodol resulted in the highest tumor uptake (0.33 %ID/g; P < 0.001) and tumor-to-normal liver ratio (P < 0.001) among all delivery methods. At 24 hours, the IA-RGD-PEG-HAuNS group showed higher tumor uptake than the IA-PEG-HAuNS group (0.20 %ID/g vs. 0.099 %ID/g; P < 0.001). Conclusion Adding iodized oil to IA-PEG-HAuNS maximizes nanoparticle delivery to hepatic tumors and therefore may be useful in targeted chemotherapy and photoablative therapy. PET/CT can be used to noninvasively monitor the biodistribution of radiolabeled HAuNS after IV or IA injection. PMID:23608932

  9. Assessment of hepatic VX2 tumors with combined percutaneous transhepatic lymphosonography and contrast-enhanced ultrasonographic imaging

    Institute of Scientific and Technical Information of China (English)

    Cun Liu; Ping Liang; Yang Wang; Pei Zhou; Xin Li; Zhi-Yu Han; Shao-Ping Liu

    2008-01-01

    AIM: To evaluate the feasibility and efficacy of percutaneous transhepatic lymphosonography (PTL) as a novel method for the detection of tumor lymphangiogenesis in hepatic VX2 of rabbits and to evaluate combined PTL and routine contrast-enhanced ultrasonographic imaging for the diagnosis of liver cancer.METHODS: Ten rabbits with VX2 tumor were included in this study.SonoVue (0.1 mL/kg) was injected into each rabbit v/a an ear vein for contrast-enhanced ultrasonographic imaging,and 0.5 mL SonoVue was injected into the normal liver parenchyma near the VX2 tumor for PTL.Images and/or movie clips were stored for further analysis.RESULTS: Ultrasonographic imaging showed VX2 tumors ranging 5-19 mm in the liver of rabbits.The VX2 tumor was hyperechoic and hypoechoic to liver parenchyma at the early and later phase,respectively.The hepatic lymph vessels were visualized immediately after injection of contrast medium and continuously visualized with SonoVue(R) during PTL.The boundaries of VX2 tumors were hyperechoic to liver parenchyma and the tumors.There was a significant difference in the values for the boundaries of VX2 tumors after injection compared with the liver normal parenchyma and the tumor parenchyma during PTL.CONCLUSION: PTL is a novel method for the detection of tumor lymphangiogenesis in hepatic VX2 of rabbits.Combined PTL and contrast-enhanced ultrasonographic imaging can improve the diagnosis of liver cancer.

  10. Photodynamic therapy for implanted VX2 tumor in rabbit brains

    Science.gov (United States)

    Li, Fei; Feng, Hua; Lin, Jiangkai; Zhu, Gang; Chen, Zhi; Li, Cong-yan

    2005-07-01

    To evaluate the therapeutic effect and the safety of single photodynamic therapy (PDT) with hematoporphyrin derivative produced in China, 60 New Zealand adult rabbits with VX2 tumor implanted into the brain were divided randomly into non-PDT-group and PDT-group. 36 rabbits of the PDT-group were performed photodynamic therapy. The survival time, neurological deteriorations, intracranial pressure (ICP), histology, pathology, tumor volume and brain water content were measured. Other 12 rabbits were received hematoporphyrin derivative and light irradiation of the normal brain. The ICP, histology, pathology, and brain water content were measured. The result indicated that Simple PDT may elongate the average survival time of the rabbits with VX2 tumors significantly; kill tumor cells; cause transient brain edema and increase ICP, but it is safe to be used in treating brain tumor.

  11. Effects of acetylsalicylic acid and acetic acid solutions on VX2 liver carcinoma in rabbits: in vivo analysis Efeitos das soluções de aspirina e de ácido acético em fígado de coelhos portadores de tumor hepático VX2: análise in vivo

    Directory of Open Access Journals (Sweden)

    Rogério Saad-Hossne

    2007-08-01

    Full Text Available PURPOSE: To analyze, in vitro, the effects of acetylsalicylic acid (aspirin and acetic acid solutions on VX2 carcinoma cells in the liver of rabbits with VX2 hepatic tumors; to determine the histolytic and anatomopathological characteristics of the solutions; and to evaluate the eventual biochemical and hepatic changes. METHODS: A total of 48 rabbits were evaluated. The animals were randomized into two groups, protocol 3 (study group and protocol 4 (controls, and each group was then subdivided into 3 subgroups. Four days after implantation of the tumor in the liver, median laparotomy was performed with a 0.4-ml injection of a solution of either aspirin (5.0%, acetic acid (5.0% or saline. The animals were sacrificed after 24 hours (protocol 3 or after 11 days (protocol 4. Body weight, clinical evolution and biochemical levels, as well as the abdominal and thoracic cavities, were evaluated, and liver microscopy was performed. RESULTS: No changes in clinical evolution, body weight or biochemical levels were reported. However, an increase in alkaline phosphatase was observed in protocol 4 (controls. The tumor was eliminated in both protocols. CONCLUSION: Acetylsalicylic acid and acetic acid solutions cause the destruction of experimental hepatic tumors.OBJETIVO: Analisar os efeitos das soluções de aspirina e de ácido acético, in vivo, em fígado de coelhos portadores de tumor hepático VX2, verificando o efeito histolítico e anatomo-patológico das soluções e eventuais alterações bioquímicas hepáticas. MÉTODOS: Utilizou-se 48 coelhos, divididos em 2 protocolos experimentais(3 e 4, subdivididos em 3 grupos cada. Após 4 dias da implantação do tumor no fígado, procedeu-se a laparotomia mediana, com injeção de 0,4 ml da solução de aspirina (5,0%, de ácido acético (5,0% e solução salina; o sacrifício ocorreu apos 24 horas (protocolo 3 e 11 dias (protocolo 4; avaliou-se o peso, evolução clinica, dosagens bioquímicas, cavidade

  12. Study on MRI DWIBS in the evaluation of effectivenesse of magnetic labeled dendritic cell vaccine in treatment of rabbit liver VX2 tumor%DWIBS评价SPIO标记树突状细胞治疗兔VX2肝癌的疗效

    Institute of Scientific and Technical Information of China (English)

    曹新山; 姜兴岳; 毛锡金; 王静; 秦东京

    2012-01-01

    目的 探讨磁共振背景信号抑制弥散加权成像( MR DWIBS)在评价磁标记负载肝癌抗原的树突状细胞疫苗活体内移植后对原发性肝癌的治疗作用.方法 用粒/巨细胞集落刺激因子(GM-CSF)和白细胞介素4(IL-4)诱导分化DC获得DC疫苗.并且用超顺磁性氧化铁标记.建立兔VX2肝癌模型,皮下注射磁标记的DC疫苗,观察DC疫苗的体内分布.运用DWIBS不同时间点活体检测肿瘤的大小、形态.结果 ①DC疫苗的体内分布.滏射树突状细胞疫苗后,兔肝细胞内可见较多蓝染铁颗粒沉着,而仅有少数Kupffer细胞内可见蓝染铁颗粒沉着;②肿瘤的DWIBS影像上,肝实质信号减低最显著,肿瘤边界清楚;③同时间点治疗组与对照组的凋亡指数(AI)情况:治疗后1周、2周治疗组分别与相应对照组凋亡指数差异有统计学意义(P<0.05);④不同时间点治疗组及对照组的ADC比值情况:治疗后1周、2周治疗组分别与相应对照组ADC比值差异有统计学意义(P<0.05).结论 磁标记负载肝癌抗原的Dc疫苗体内能诱导产生明显的抑瘤作用.而用DWIBS成像技术则为原发性肝癌的免疫基因治疗提供了重要的形态学信息.%Objective To investigate the MRI DWIBS imaging in the evaluation of effectivenesse of magnetic labeled dendritic cell vaccine in treatment of rabbit liver VX2 tumor. Methods In this work, GM-CSF and IL-4 were employed to induce the differentiation of dendritic cell (DC) to gain DV vaccine, which was further labeled with superparamagnetic iron oxides. The rabbit VX2 liver cancer model was then established and the magnetic labeled DC vaccine was injected into this model. The electrical microscopy was used to prove DC vaccine distribution in vivo. The changes in tumor volume and shape were observed by MRI DWIBS at different time points. Results ①Distribution of DC vaccine in vivo: after the administration of DC vaccine, many blue iron deposits were seen in

  13. The correlation of contrast-enhanced ultrasound and MRI perfusion quantitative analysis in rabbit VX2 liver cancer.

    Science.gov (United States)

    Xiang, Zhiming; Liang, Qianwen; Liang, Changhong; Zhong, Guimian

    2014-12-01

    Our objective is to explore the value of liver cancer contrast-enhanced ultrasound (CEUS) and MRI perfusion quantitative analysis in liver cancer and the correlation between these two analysis methods. Rabbit VX2 liver cancer model was established in this study. CEUS was applied. Sono Vue was applied in rabbits by ear vein to dynamically observe and record the blood perfusion and changes in the process of VX2 liver cancer and surrounding tissue. MRI perfusion quantitative analysis was used to analyze the mean enhancement time and change law of maximal slope increasing, which were further compared with the pathological examination results. Quantitative indicators of liver cancer CEUS and MRI perfusion quantitative analysis were compared, and the correlation between them was analyzed by correlation analysis. Rabbit VX2 liver cancer model was successfully established. CEUS showed that time-intensity curve of rabbit VX2 liver cancer showed "fast in, fast out" model while MRI perfusion quantitative analysis showed that quantitative parameter MTE of tumor tissue increased and MSI decreased: the difference was statistically significant (P 0.05). However, the quantitative parameter of them were significantly positively correlated (P liver cancer lesion and surrounding liver parenchyma, and the quantitative parameters of them are correlated. The combined application of both is of importance in early diagnosis of liver cancer.

  14. 平阳霉素混合碘油经动脉化疗栓塞抑制兔VX2肝癌生长的实验研究%Effects of transcatheter arterial chemoembolization with pingyangmycin-lipiodol emulsion on VX2 liver tumors in rabbits

    Institute of Scientific and Technical Information of China (English)

    刘曦; 罗小平; 曹闻挺; 邓昊

    2012-01-01

    栓塞治疗更加有效.%Objective To evaluate the changes induced in tumor tissue,the feeding artery,and neovascularization upon pingyangmycin-lipiodol emulsion treatment via transcatheter arterial chemoembolization (TACE) using the rabbit VX2 liver cancer model.Methods The VX2 liver tumor model was established in 28 rabbits,and baseline tumor volume (V1,in mm3) was measured by spiral scan computed tomography (CT).Then,the rabbits were randomly divided into four groups (n =7 each) and administered intraarterial therapies of:ultrafluid lipoidol embolization (group A); pingyangmycin (group B);pingyangmycin-lipiodol emulsion (group C); or saline (group D).All rabbits were sacrificed seven days later,and the response to therapy was determined by measuring the tumor volume (V2,in mm3),calculating the tumor growth rate,detecting expression of the vascular endothelial growth factor (VEGF) tumor biomarker,and performing histological analysis of the microvessel density (MVD) in the liver.Results Prior to therapy,the average V1 of the groups was statistically similar (A:389.8± 167.3,B:404.1 ± 184.9,C:355.1±158.3,D:378.1 ± 189.0; (F=0.257,P> 0.05).In contrast,after therapy the average V2 of the groups was significantly different (A:922.6±32.9,B:665.9±99.9,C:349.5± 177.8,D:1403.5±411.2; F=26.23,P<0.05),as was the tumor growth ratio (A:1.4,B:0.6,C:-0.02,D:2.7) and the mean positive ratio of VEGF (A:57.1%,B:42.9%,C:28.6%,D:100%;F=8.407,P<0.05).MVD was highest in group D and lowest in group C (all,P<0.05).Bivariate correlation analysis revealed a positive correlation between VEGF expression and MVD (r=0.743,P<0.01).Conclusion Pingyangmyein exerts anti-tumor effects in the rabbit VX2 liver cancer model but is more effective when adminis tered as the combination therapy ofpingyangmycin-lipiodol emulsion with TACE.

  15. Intrahepatic transneedle inoculation of VX2 particles for obtaining a solitary hepatic tumor in an animal model

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jin Han; Choi, Jong Cheol; Shin, Tae Beom; Park, Byeong Ho [Dong-A University, School of Medicine, Busan (Korea, Republic of)

    2005-07-15

    %) had tumor growth both in the liver and the peritoneal cavity, suggesting tumor leakage from the injection site into the peritoneal cavity. The remaining rabbits (n=17) had successful inoculation in the liver parenchyma as a solitary mass. Three of twenty rabbits (15%) showed tumor regression after successful inoculation. Tumor metastasis in extratumoral regions, including the liver and peritoneal seeding, increased beginning in the fourth week and more than 12x103 mm{sup 3} in volume after the initial inoculation of the VX2 tumors. This new technique using innoculated intrahepatic VX2 tumor particles seems to be a simple and effective method for obtaining a solitary hepatic tumor in animal models. Results of this study suggest that a solitary intrahepatic tumor model without metastasis can be maintained. However, the evaluation of any therapeutic effects or any planned intervention should not occur until the fourth week following innoculation or less than 12x103 mm{sup 3} in volume after the inoculation of the VX2 tumor. The second highlighted section dose not seem to fir with the rest of the sentence. Consider rephrasing the last part of the sentence.

  16. Distribution of Iron Oxide Core-Titanium Dioxide Shell Nanoparticles in VX2 Tumor Bearing Rabbits Introduced by Two Different Delivery Modalities

    Energy Technology Data Exchange (ETDEWEB)

    Refaat, Tamer; West, Derek; El Achy, Samar; Parimi, Vamsi; May, Jasmine; Xin, Lun; Harris, Kathleen; Liu, William; Wanzer, Michael; Finney, Lydia; Maxey, Evan; Vogt, Stefan; Omary, Reed; Procissi, Daniele; Larson, Andrew; Paunesku, Tatjana; Woloschak, Gayle

    2016-08-03

    This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests. Quantification of NPs in tissues was done both by bulk inductively coupled plasma mass spectrometry (ICP-MS) analysis and by hard X-ray fluorescence microscopy. Both IV and IC NPs injection are feasible modalities for delivering NPs to VX2 liver tumors with comparable tumor accumulation. It is possible that this is an outcome of the fact that VX2 tumors are highly vascularized and hemorrhagic, and therefore enhanced permeability and retention (EPR) plays the most significant role in accumulation of nanoparticles in tumor tissue. It is, however, interesting to note that IV delivery led to increased sequestration of NPs by spleen and normal liver tissue, while IC delivery lead to more NP positive Kupffer cells. This difference is most likely a direct outcome of blood flow dynamics. Armed with this knowledge about nanoparticle delivery, we plan to test them as radiosensitizers in the future.

  17. Distribution of Iron Oxide Core-Titanium Dioxide Shell Nanoparticles in VX2 Tumor Bearing Rabbits Introduced by Two Different Delivery Modalities

    Directory of Open Access Journals (Sweden)

    Tamer Refaat

    2016-08-01

    Full Text Available This work compares intravenous (IV versus fluoroscopy-guided transarterial intra-catheter (IC delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests. Quantification of NPs in tissues was done both by bulk inductively coupled plasma mass spectrometry (ICP-MS analysis and by hard X-ray fluorescence microscopy. Both IV and IC NPs injection are feasible modalities for delivering NPs to VX2 liver tumors with comparable tumor accumulation. It is possible that this is an outcome of the fact that VX2 tumors are highly vascularized and hemorrhagic, and therefore enhanced permeability and retention (EPR plays the most significant role in accumulation of nanoparticles in tumor tissue. It is, however, interesting to note that IV delivery led to increased sequestration of NPs by spleen and normal liver tissue, while IC delivery lead to more NP positive Kupffer cells. This difference is most likely a direct outcome of blood flow dynamics. Armed with this knowledge about nanoparticle delivery, we plan to test them as radiosensitizers in the future.

  18. Thermochemical ablation therapy of VX2 tumor using a permeable oil-packed liquid alkali metal.

    Directory of Open Access Journals (Sweden)

    Ziyi Guo

    Full Text Available Alkali metal appears to be a promising tool in thermochemical ablation, but, it requires additional data on safety is required. The objective of this study was to explore the effectiveness of permeable oil-packed liquid alkali metal in the thermochemical ablation of tumors.Permeable oil-packed sodium-potassium (NaK was prepared using ultrasonic mixing of different ratios of metal to oil. The thermal effect of the mixture during ablation of muscle tissue ex vivo was evaluated using the Fluke Ti400 Thermal Imager. The thermochemical effect of the NaK-oil mixture on VX2 tumors was evaluated by performing perfusion CT scans both before and after treatment in 10 VX2 rabbit model tumors. VX2 tumors were harvested from two rabbits immediately after treatment to assess their viability using trypan blue and hematoxylin and eosin (H.E. staining.The injection of the NaK-oil mixture resulted in significantly higher heat in the ablation areas. The permeable oil controlled the rate of heat released during the NaK reaction with water in the living tissue. Perfusion computed tomography and its parameter map confirmed that the NaK-oil mixture had curative effects on VX2 tumors. Both trypan blue and H.E. staining showed partial necrosis of the VX2 tumors.The NaK-oil mixture may be used successfully to ablate tumor tissue in vivo. With reference to the controlled thermal and chemical lethal injury to tumors, using a liquid alkali in ablation is potentially an effective and safe method to treat malignant tumors.

  19. Impact of microbubble enhanced, pulsed, focused ultrasound on tumor circulation of subcutaneous VX2 cancer

    Institute of Scientific and Technical Information of China (English)

    Li Peijing; Zhu Mei; Xu Yali; Zhao Yang; Gao Shunji; Liu Zheng; Gao Yun-hua

    2014-01-01

    Background Intravascular microbubble-enhanced acoustic cavitation is capable of disrupting the vascular walls of capillaries and small vessels.This study was designed to investigate the impact of microbubble-enhanced,pulsed and focused ultrasound (MEUS) on the blood perfusion of subcutaneous VX2 tumors in rabbits.Methods Subcutaneous VX2 cancers in twenty New Zealand rabbits were treated by combining high-pressure amplitude,pulsed and focused therapeutic ultrasound (TUS) and intravenous microbubble injections.The TUS transducer was operated with a peak negative pressure of 4.6 MPa and a duty cycle of 0.41%.Controls were subcutaneous VX2 cancers treated with TUS or microbubbles only.Contrast-enhanced ultrasound (CEUS) and intravenous Evans Blue (EB) perfusion were performed to assess the tumor circulation.The tumor microvascular disruption was assessed by histological examination.Results CEUS showed that the tumor circulation almost vanished after MEUS treatment.The average peak grayscale value (GSV) of tumor CEUS dropped significantly from 84.1±22.4 to 15.8±10.8 in the MEUS-treated tumors but no significant GSV changes were found in tumors in the two control groups.The mean tumor EB content of the MEUS-treated tumors was significantly lower than that of the controls.Histological examination found scattered tumor microvascular disruption with intercellular edema after MEUS treatment.Conclusion The tumor circulation of VX2 cancers can be arrested or significantly reduced by MEUS due to microvascular disruption.

  20. Autoradiographic and histopathological studies of boric acid-mediated BNCT in hepatic VX2 tumor-bearing rabbits: Specific boron retention and damage in tumor and tumor vessels.

    Science.gov (United States)

    Yang, C H; Lin, Y T; Hung, Y H; Liao, J W; Peir, J J; Liu, H M; Lin, Y L; Liu, Y M; Chen, Y W; Chuang, K S; Chou, F I

    2015-12-01

    Hepatoma is a malignant tumor that responds poorly to conventional therapies. Boron neutron capture therapy (BNCT) may provide a better way for hepatoma therapy. In this research, (10)B-enriched boric acid (BA, 99% (10)B) was used as the boron drug. A multifocal hepatic VX2 tumor-bearing rabbit model was used to study the mechanisms of BA-mediated BNCT. Autoradiography demonstrated that BA was selectively targeted to tumors and tumor vessels. Histopathological examination revealed the radiation damage to tumor-bearing liver was concentrated in the tumor regions during BNCT treatment. The selective killing of tumor cells and the destruction of the blood vessels in tumor masses may be responsible for the success of BA-mediated BNCT for liver tumors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Histotripsy and metastasis: Assessment in a renal VX-2 rabbit tumor model

    Science.gov (United States)

    Styn, Nicholas R.; Hall, Timothy L.; Fowlkes, J. Brian; Cain, Charles A.; Roberts, William W.

    2012-10-01

    Histotripsy is a non-invasive, pulsed ultrasound technology where controlled cavitation is used to homogenize targeted tissue. We sought to assess the possibility that histotripsy may increase metastatic spread of tumor by quantifying the number of lung metastasis apparent after histotripsy treatment of aggressive renal VX-2 tumor compared to nontreated controls. VX-2 tumor was implanted in the left kidneys of 28 New Zealand White rabbits. Twenty rabbits were treated with histotripsy (day 13 after implantation) while 8 served as controls. All rabbits underwent left nephrectomy (day 14) and then were euthanized (day 19). This study was powered to detect a doubling in metastatic rate. Homogenized tumor was seen in all treated nephrectomy specimens. Whole-mount, coronal lung sections were viewed to calculate number and density of metastases. Viable tumor was present in all 28 lungs examined. Histology confirmed fractionation of tumor in all treatment rabbits. There was not a statistical difference in total lung metastases (88.7 vs. 72.5; p=0.29) or metastatic density (8.9 vs. 7.0 mets/cm2; p=0.22) between treated and control rabbits. Further investigation is planned to validate these results in the VX-2 model and to assess metastatic rates in less aggressive tumors treated with histotripsy.

  2. Cellular Imaging Using Equivalent Cross-Relaxation Rate Technique in Rabbit VX-2 Tumor Model.

    Science.gov (United States)

    Nishiofuku, Hideyuki; Matsushima, Shigeru; Taguchi, Osamu; Inaba, Yoshitaka; Yamaura, Hidekazu; Sato, Yozo; Tanaka, Toshihiro; Kichikawa, Kimihiko

    2011-01-01

    Equivalent cross-relaxation rate (ECR) imaging (ECRI) is a measurement technique that can be used to quantitatively evaluate changes in structural organization and cellular density by MRI. The aim of this study was to evaluate the correlation between the ECR value and cellular density in the rabbit VX2 tumor model. Five rabbits implanted with 10 VX2 tumors in the femur muscles were included in this study. We adopted the off-resonance technique with a single saturation transfer pulse frequency of 7 ppm downfield from water resonance. The ECR value was defined as the percentage of signal loss between the unsaturated and saturated images. ECR images were constructed based on the percentage of the ECR value. Pathological specimens were divided into 34 areas and classified into two groups: the viable group and the necrotic group. ECR values were measured and compared between groups. The correlation between the ECR value and cellular density was then determined. The mean ECR value was significantly higher in the viable group than in the necrotic group (61.2% vs. 35.8%). The area under the curve that calculated by receiver operating characteristic curve was 0.991 at 7 ppm. The regression graph showed a linear relationship between the ECR value and cellular density; the correlation coefficient (r) was 0.858. There is a strong association between the ECR value and cellular density in VX2 tumors and so ECRI could be a potentially useful technique for accurately depicting viable and necrotic areas.

  3. The Characteristics of Vascular Growth in VX2 Tumor Measured by MRI and Micro-CT

    Directory of Open Access Journals (Sweden)

    X.-L. Qi

    2012-01-01

    Full Text Available Blood supply is crucial for rapid growth of a malignant tumor; medical imaging can play an important role in evaluating the vascular characterstics of tumors. Magnetic resonance imaging (MRI and micro-computed tomography (CT are able to detect tumors and measure blood volumes of microcirculation in tissue. In this study, we used MR imaging and micro-CT to assess the microcirculation in a VX2 tumor model in rabbits. MRI characterization was performed using the intravascular contrast agent Clariscan (NC100150-Injection; micro-CT with Microfil was used to directly depict blood vessels with diameters as low as 17 um in tissue. Relative blood volume fraction (rBVF in the tumor rim and blood vessel density (rBVD over the whole tumor was calculated using the two imaging methods. Our study indicates that rBVF is negatively related to the volume of the tumor measured by ultrasound (R=0.90. rBVF in the tissue of a VX2 tumor measured by MRI in vivo was qualitatively consistent with the rBVD demonstrated by micro-CT in vitro (R=0.97. The good correlation between the two methods indicates that MRI studies are potentially valuable for assessing characteristics or tumor vascularity and for assessing response to therapy noninvasively.

  4. Gal-BSA-SPIO制备及兔VX2肝癌模型与人肝脏ASG受体的MRI研究%Synthesis of Gal-BSA-SPIO and magnetic resonance imaging of ASG receptors in rabbits bearing liver VX2 tumor and human liver

    Institute of Scientific and Technical Information of China (English)

    贾飞鸽; 张晓东; 许乙凯; 孟卓

    2009-01-01

    目的 尝试合成肝脏靶向对比剂乳糖基白蛋白超顺磁氧化铁(Gal-BSA-SPIO),探讨Gal-BSA-SPIO对肝癌的检出及其诊断价值.材料和方法采用还原胺法合成Gal-BSA.Gal-BSA与SPIO混合后超声振荡.建立20只兔的、VX2肝癌模型,随机分为SPIO组和Gal-BSA-SPIO组,行MR平扫及增强.测定肝脏及肿瘤的T2值.对13例人肝脏标本(肝癌6例、肝硬化4例、正常肝组织3例)Gal-BSA-SPIO孵育后,Perl's染色,观察去唾液酸糖蛋白(ASG)受体分布.统计学方法:对增强前后各组的T2值进行t检验.结果 Gal-BSA-SPIO平均粒径34.4 nm.20只兔VX2肿瘤直径3~12 nm,T1WI肝实质呈中等信号,肿瘤呈低信号,T2WI肝实质低信号,病灶为略高信号;GRE T2*WI肝实质中等信号,肿瘤略高信号.增强扫描,SPIO组T2WI肝实质信号轻中度下降,与肿瘤对比提高;Gal-BSA-SPIO组T2WI肝实质信号显著下降,肿瘤呈明亮的"灯泡征".正常肝脏的SPIO组和Gal-BSA-SPIO组增强后T2值明显下降,与增强前有显著性差异.肿瘤的SPIO组和Gal-BSA-SPIO组增强后T2值无明显下降,与增强前无显著性差异.组织学检查SPIO组,Kupffer细胞内见蓝染的铁颗粒;Gal-BSA-SPIO组.肝细胞内见较多的蓝染的铁颗粒,两组的肿瘤内未见蓝染的铁颗粒.Gal-BSA-SPIO孵育后,正常肝组织可见大量蓝染色,肝硬化及癌旁肝硬化组织均可见蓝染色;肝细胞癌罕见蓝染色.结论 Gal-BSA-SPIO可以与肝细胞膜的ASG受体可特异性结合,通过受体介导的特异性对肝脏产生负向增强作用,明显提高肿瘤对比噪声比.

  5. A Novel Minimally Invasive Technique to Create a Rabbit VX2 Lung Tumor Model for Nano-Sized Image Contrast and Interventional Studies

    OpenAIRE

    Takashi Anayama; Takahiro Nakajima; Michael Dunne; Jinzi Zheng; Christine Allen; Brandon Driscoll; Douglass Vines; Shaf Keshavjee; David Jaffray; Kazuhiro Yasufuku

    2013-01-01

    BACKGROUND: The rabbit VX2 lung cancer model is a large animal model useful for preclinical lung cancer imaging and interventional studies. However, previously reported models had issues in terms of invasiveness of tumor inoculation, control of tumor aggressiveness and incidence of complications. PURPOSE: We aimed to develop a minimally invasive rabbit VX2 lung cancer model suitable for imaging and transbronchial interventional studies. METHODS: New Zealand white rabbits and VX2 tumors were u...

  6. Effects of the Silibinin-loaded Temperature Sensitive Liposome-microbubble Complex on the Rabbit Liver VX2 Tumor in the Sub-hyperthermia Field%亚高温场中载水飞蓟宾热敏脂质体——微泡复合体对兔肝VX2肿瘤的作用研究

    Institute of Scientific and Technical Information of China (English)

    韩璐; 罗文; 郭凯; 李轲; 刘海静; 慕喜喜; 周晓东

    2015-01-01

    目的 观察在亚高温场中载水飞蓟宾热敏脂质体——微泡复合体(STLMC)对兔肝VX2肿瘤的作用.方法 将40只VX2荷瘤兔的40个肝转移瘤随机分为4组,每组10只动物:微波亚高温辐照组(SHM)、水飞蓟宾载药微泡组(STLMC)、微波亚高温辐照联合水飞蓟宾载药微泡治疗组(SHM+STLMC)、空白对照组(BL).分别给予不同干预:微波热辐照、STLMC注射、微波热辐照联合STLMC注射、无辐照无注射.治疗后7d及21 d,采用二维灰阶超声、超声造影成像分别评价术后各组肿瘤体积和最大径的变化.透射电镜观察各组干预区超微结构变化.结果 SHM+STLMC组术后7d及21d肿瘤体积及最大径均明显小于同期其余各组(P<0.05);电镜下各组均出现染色质异常、细胞器受损的巨噬细胞,SHM+STLMC组受损巨噬细胞数目较其余各组明显增多(P<0.05).结论 在亚高温场中STLMC可造成肿瘤微环境中巨噬细胞形态破坏,抑制肿瘤生长.

  7. Enhancing tissue permeability with MRI guided preclinical focused ultrasound system in rabbit muscle: From normal tissue to VX2 tumor.

    Science.gov (United States)

    Sun, Yao; Xiong, Xiaobing; Pandya, Darpan; Jung, Youngkyoo; Mintz, Akiva; Hayasaka, Satoru; Wadas, Thaddeus J; Li, King C P

    2017-06-28

    High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing physical energy based modality to ablate solid tumors with high power, or increase local permeability in tissues/tumors in pulsed mode with relatively low power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU (pHIFU) is present in the majority of novel applications recently developed for enhancing the delivery of drugs and genes. Previous studies have demonstrated the capability of pHIFU to change tissue local permeability for enhanced drug delivery in both mouse tumors and mouse muscle. Further study based on bulk tissues in large animals and clinical HIFU system revealed correlation between therapeutic effect and thermal parameters, which was absent in the previous mouse studies. In this study, we further investigated the relation between the therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues based on a rabbit model and a preclinical HIFU system. Correlation between therapeutic effect and thermal parameters was confirmed in our study on the same bulk tissues although different HIFU systems were used. Following the study in bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors implanted on both hind limbs of rabbits and investigated the feasibility to enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU technique. A radiolabeled peptidomimetic integrin antagonist, (111)In-DOTA-IA, was used following pHIFU treatment in our study to target VX2 tumor and serve as the radiotracer for follow-up single-photon emission computed tomography (SPECT) scanning. The results have shown significantly elevated uptake of (111)In-DOTA-IA in the area of VX2 tumors pretreated by pHIFU compared with the control VX2 tumors not being pretreated by pHIFU, and statistical analysis revealed averaged 34.5% enhancement 24h after systematic delivery of (111)In-DOTA-IA in VX2 tumors pretreated by pHIFU compared

  8. Heated lipiodol as an embolization agent for transhepatic arterial embolization in VX2 rabbit liver cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Cao Wei [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China)], E-mail: zjfurong2008@126.com; Wan Yi [Department of Health Statistics, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); Liang Zhihui [Department of Radiology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province 050082 (China); Duan Yunyou; Liu Xi [Department of Ultrasonography, Tangdu Hospital, Fourth Military Medical University, No. 1 Xinshi Road, Xi' an 710038 (China); Wang Zhimin; Liu Yiyong; Zhu Jia; Liu Xiongtao [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China); Zhang Hongxin [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China)], E-mail: cawe-001@163.com

    2010-02-15

    Purpose: To evaluate the therapeutic effect of heated (60 deg. C) lipiodol via hepatic artery administration in a rabbit model of VX2 liver cancer. Materials and methods: Thirty male New Zealand white rabbits were randomly divided into three groups with 10 rabbits assigned to each group. VX2 carcinoma cells were surgically implanted into the left hepatic lobe. The tumors were allowed to grow for 2 weeks, and studies were performed until the diameter of the tumors detected by ultrasonograph reached 2-3 cm. Under anesthesia, trans-catheter hepatic arterial embolization was performed and doxorubicin-lipiodol (37 deg. C) (1 mL), lipiodol (60 deg. C) (1 mL) or control (physiological saline (37 deg. C) (1 mL)) solution was injected into the hepatic arteries of animals in the three groups. One week later, the volume of the tumor was measured by ultrasonograph again. The serum of all rabbits was collected before injection and at 4 and 7 days after injection, and the level of aspartate aminotransferase (AST) was checked. The survival period of the three groups of rabbits after treatment was also recorded. During the last course of their disease, the rabbits were given analgesics to relieve suffering. Results: The tumor growth rate in the lipiodol (60 deg. C) group (0.92 {+-} 0.21, tumor volume from 1811 {+-} 435 to 1670 {+-} 564 mm{sup 3}) was significantly lower than that in the control group (3.48 {+-} 1.17, tumor volume from 1808 {+-} 756 to 5747 {+-} 1341 mm{sup 3}) (P < 0.05) and in the doxorubicin-lipiodol (37 deg. C) group (1.69 {+-} 0.26, tumor volume from 1881 {+-} 641 to 2428 {+-} 752 mm{sup 3}) (P < 0.05). Consequently, the survival period of the animals in the lipiodol (60 deg. C) group (41.0 {+-} 3.0 days) was significantly greater than that in the doxorubicin-lipiodol (37 deg. C) group (38.0 {+-} 2.5 days) (P < 0.05). On the other hand, there was no statistically significant difference in serum AST levels between the lipiodol (60 deg. C) group (148.2 {+-} 11

  9. Effect of hydroxyapatite nanoparticles on the growth and p53/c-Myc protein expression of implanted hepatic VX2 tumor in rabbits by intravenous injection

    Institute of Scientific and Technical Information of China (English)

    Jun Hu; Zhi-Su Liu; Sheng-Li Tang; Yue-Ming He

    2007-01-01

    AIM:To evaluate the effect of hydroxyapatite nanoparticles (Nano HAP) by intravenous injection on the inhibition of implanted hepatic VX2 tumor growth in rabbits and cell p53/c-Myc protein expression.METHODS: 60 hepatic VX2 tumor-bearing rabbits was randomly divided into five groups. Nano HAP collosol 20 mg/kg, 40 mg/kg, 5-FU solutions 20 mg/mL, mixed liquor of 5-FU solution 20 mg/mL and Nano HAP collosol 20 mg/kg were infused by vein, normal saline conducted as the control. The general state, weight, liver function and gross tumor volume were detected dynamically.The expression of p53 and c-Myc gene protein in tumor tissue was detected by immunohistochemistry methods.RESULTS: The growth of implanted hepatic VX2 tumors was significantly inhibited in all therapy groups, 3 wk after the injection, the tumor control rates in Nano HAP collosol groups were 25.5% and 32.5% respectively,and the gross tumor volumes were obviously less than that of control group. (24.81 ± 5.17 and 22.73 ± 4.23vs 33.32 ± 5.26, P < 0.05). The tumor control rate of 5-FU group was 43.7% (18.74 ± 4.40 vs 33.32 ± 5.26,P < 0.05), but the general state of the animals after injection aggravated; and the adverse reaction in the drug combination group obviously decreased. Due to the effect of Nano HAP, the positive expression of tumor associated the mutated p53 and c-Myc in tumor tissue was decreased obviously compared with the control group.CONCLUSION: Nano HAP has evident inhibitory action on rabbit implanted hepatic VX2 tumor in vivo, which may be the result of decreasing the expression of the mutated p53 and c-myc, and drug combination can obviously decrease the adverse reaction of 5-FU.

  10. Experimental Study of Multi-slice Spiral CT Perfusion Imaging in VX2 Soft-tissue Tumor of Rabbits

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jingfeng; WANG Renfa; WANG Min; LI Yonggang; YANG Haitao

    2006-01-01

    An experimental animal model of malignant soft-tissue tumor was established to investigate the applied value of multi-slice spiral CT perfusion imaging preliminarily. Ten New Zealand white rabbits which were implanted with VX2 tumor in either proximal thigh were subjected to CT plain scan and perfusion scan two weeks later respectively, then the original perfusion images were transmitted to AW4.0 Workstation. The functional maps and perfusion parameters including blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface (PS) were computed and analyzed. All the values of BF, BV and PS in VX2 soft-tissue tumors were obviously higher while the MTT-values were lower than those in the normal muscular tissues significantly. It was suggested that multi-slice spiral CT perfusion imaging is an accurate, convenient and relatively safe functional imaging technique, and can give a quantitative assessment to angiogenesis and blood perfusion of soft-tissue tumors.

  11. MR DIFFUSION WEIGHTED IMAGING FOR EVALUATION OF RADIOTHERAPEUTIC EFFECTS ON RABBIT VX2 TUMOR MODEL

    Institute of Scientific and Technical Information of China (English)

    Shuo Li; Hua-dan Xue; Xin-hai Wang; Fei Sun; Bo Jiang; Dong Liu; Jing Lei; Zheng-yu Jin

    2008-01-01

    Objective To investigate the feasibility of magnetic resonance (MR) diffusion weighted imaging (DWI) for evaluation of radiotherapeutic effects on rabbit VX2 tumor model.Methods Sixteen New Zealand white rabbits received a subcutaneous implantation of VX2 tumor cdl suspension 0.5 mL (4× 107cells/mL) in their right thighs to set up tumor model. And 2 weeks later they were randomly divided into therapy group (Group T, n = 10) and control group (Group C, n = 6). Group T received radiotherapy at a single dose of 10 Gy. MR imaging (MRI) scan including short TI inversion recovery echo-planar imaging DWI, T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) sequences were performed 1 day prior to as well as 1 day, 2 days, 3 days and 7 days after radiotherapy. Group C received only MRI scan at the same time points without any treatment. MRI appearance on T2WI, T1WI, and DWI images was compared and tumor volume was calculated. Apparent diffusion coefficient (ADC) values of the tumor were evaluated in all cases. HE staining was used for pathological study.Results Necrosis (n = 8) and hemorrhage (n = 2) were seen gradually on T2WI and T1WI images of Group T after time point of day 2 after irradiation. In Group C, no obvious necrosis was found until day 7. There was no significant difference in tumor volume between the two groups before radiotherapy. After radiotherapy, tumors in Group T showed a gradual growth but not as obvious as Group C. There was a significant difference in tumor volume between the two groups from day 2 on (P < 0.05). ADC value changed dramatically right from the 1st day after radio-therapy in Group T [(0.99 ± 0.15) ×10-3 mm2/s for 1 day before radiotherapy, (1.23 ± 0.08) ×10-3 , (1.45 ± 0.07) ×10-3 , (1.63 ± 0.06) ×10-3 , and (2.02 ± 0.18) ×10-3 mm2/s for day 1, 2, 3, and 7]; and ADC value had no significant changes after radiotherapy in Group C except day 7 [(1.07 ± 0.08) ×10-3 mm2/s for 1 day before radiotherapy, (1.03 ± 0.04) ×10

  12. Bioevaluation study of 32P-CP-PLLA particle brachytherapy in a rabbit VX2 lung tumor model.

    Science.gov (United States)

    Xu, Yu ping; Yang, Min; Pan, Dong hui; Wang, Li zhen; Liu, Lu; Huang, Peilin; Shao, Guoqiang

    2012-04-01

    The purpose of this study was to investigate the therapy effects of intratumoral administration of (32)P-CP-PLLA particles in a rabbit VX2 lung tumor model. 16 rabbits with tumors were randomly divided into 4 groups. 4 rabbits served as untreated controls, and others received intratumoral administration of (32)P-CP-PLLA particles with CT guidance. The total radioactivities in treated groups were as follows: a low activity was 93 MBq (n=4) (group 1), a medium activity was 185 MBq (n=4) (group 2) and a high activity was 370 MBq (n=4) (group 3). Brachytherapy treated VX2 tumors underwent (18)F-FDG PET/CT at 0 day, 3 day, 7 day and 14 day postinjection. In control group, (18)F-FDG PET/CT images were acquired at the same time points but without any treatment. Bremsstrahlung SPECT images were performed at 14 days after intratumoral brachytherapy in treated groups. After Bremsstrahlung SPECT and last (18)F-FDG PET/CT imagings, the rabbits were euthanized and the tumors were removed for histological examination. Bremsstrahlung SPECT images study indicated that there was no leakage of (32)P out of the injection site at 14 days after treatment. Compared with the control, the tumor volumes in treated groups significantly decreased, and (32)P-CP-PLLA particle produced a reduction in maximum or mean SUV of VX2 tumor (pCP-PLLA particle localized on the injecting sites. This novel brachytherapy device efficiently suppressed the growth of the VX2 tumors implanted in the rabbit. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Evaluation of the therapeutic efficacy of sequential therapy involving percutaneous microwave ablation in combination with 131I-hypericin using the VX2 rabbit breast solid tumor model.

    Directory of Open Access Journals (Sweden)

    Miao Zhu

    Full Text Available Combination of percutaneous microwave ablation (PMWA and intravenous injection of 131I-hypericin(IIIH may bear potential as a mini-invasive treatment for tumor. The objective of this study was to assess the effect of PMWA and IIIH in breast tumor growth.Ten New Zealand White rabbits bearing VX2 breast carcinomas were randomly divided into two groups (each 5 examples and processed using PMWA followed by IIIH and IIIH alone. The IIIH activity was evaluated using planar scintigraphy, autoradiography and biodistribution analysis. The maximum effective safe dose of IIIH was found through 48 rabbits with VX2 breast tumor, which were randomized into six groups (n=8 per group. Subsequently, a further 75 rabbits bearing VX2 breast solid tumors were randomly divided into five groups (each 15 examples and treated as follows: A, no treatment group; B, PMWA alone; C, IIIH alone; D, PMWA+IIIH×1 (at 8 h post-PMWA; and E, PMWA+IIIH×2 (at 8 h and at 8 days post-PMWA. The therapeutic effect was assessed by measurement of tumor size and performation of positron emission tomography/computed tomograph (PET/CT scans, liver and renal function tests and Kaplan-Meier survival analysis.The planar scintigraphy findings suggested a significant uptake of 131I in necrotic tumor tissue. The autoradiography gray scales indicated higher selective uptake of IIIH by necrotic tissue, with significant differences between the groups with and those without necrotic tumor tissue (P<0.05. The maximum effective safe dose of IIIH was 1 mCi/kg. The PET/CT scans and tumor size measurement suggested improvements in treatment groups at all time points (P<0.01. Significant differences were detected among Groups A, B, D and E (P<0.05. Lower levels of lung metastasis were detected in Groups D and E (P<0.05. There were no abnormalities in liver and renal functions tests or other reported side effects.IIIH exhibited selective uptake by necrotic tumor tissue. Sequential therapy involving PMWA

  14. Establishment of rabbit model with VX2 cell pyriformsinus grafting tumor%兔梨状隐窝VX2瘤模型的建立及解剖与影像学观察

    Institute of Scientific and Technical Information of China (English)

    韩秀丽; 陈万军; 王兆鹏

    2012-01-01

    Objective To establish a rabbit model with pyriformsinus carcinoma (PSC) grown from grafted VX2 tumor cells to serve as an animal research tool system for experimental study of hypolaryngeal carcinoma. Methods Grafting tumor was prepared with VX2 tumour cells among New Zealand rabbits for several generations at first, and then, grafting tumor was taken made into a suspension with the tissue pieces at a size of 1 mm3 or so. (in the cell density about 1~2× 106/ml cells). After that, the tissue suspension was injected into pyriformsinus mucosa of 17 rabbits under direct laryngoscope to grow PSC. Following tumor suspension injected, all these rabbits were given CT scanning regularly to detect the growing status, and tumor tissues were collected to do histological assays to identify if the grafting tumor model of VX2 cells established successfully based on the analysis of tumor growing rate and their behaviour characteristics. Results Two to four weeks late following the tumor tissue suspension injected, Grafting tumors were successfully grown in piriform recess among 16 rabbits, as confirmed by CT images and histological evidences meaning that the model was prepared successfully. The growing rate of grafting tumor was 94.1% (16/17), while 90% of the animals with PSC died in 4 weeks following tumour cells grafting. Conclusions It is suggested that the preparing procedures for PSC model are practicable by using tissue suspension, made from the grafting tumors of VX2 cells prepared among Zealand rabbits at first, injecting into the mucosa of piriform recess of rabbits under direct laryngoscope. This kind of animal model can be utilized in the research field of hypolaryngeal carcinoma.%目的 建立兔梨状隐窝VX2移植瘤模型.方法 先以VX2细胞在新西兰大白兔制备移植瘤并传代,再将兔移植瘤制备组织悬液(组织块约1mm3大小,约含1~2×106/ml个细胞),直达喉镜下接种于17只兔梨状隐窝,然后行影像学观察及瘤

  15. Therapeutic efficacy of novel microwave-sensitized mPEG-PLGA@ZrO2@(DOX + ILS) drug-loaded microspheres in rabbit VX2 liver tumours.

    Science.gov (United States)

    Mao, Jingsong; Tang, Shunsong; Hong, Duo; Zhao, Fan; Niu, Meng; Han, Xiangjun; Qi, Ji; Bao, Han; Jiang, Yutian; Fu, Changhui; Long, Dan; Meng, Xianwei; Su, Hongying

    2017-03-09

    The use of nanomaterials as drug delivery systems shows good effects in treating tumors. However, the effective dose of drugs targeted to tumor tissues is very low because of the effect of the reticuloendothelial system (RES) in removing such foreign substances. In order to eliminate the RES effect, we developed mPEG-PLGA@ZrO2@(DOX + ILS) (mPEG-PLGA@ZrO2@[DOX + ILS]) drug-loaded microspheres. These microwave (MW)-sensitized microspheres directly embolized the blood-supply vessels of tumors to induce tumor ischemia and hypoxia, as well as to aggregate drugs within tumor tissues in a long-lasting manner. Additionally, combination with MW ablation can triple the effects for the inhibition of tumor growth. The MW sensitive ionic liquid (ILS) in microspheres can rapidly produce a high temperature in a MW field on the basis of MW sensitization, thus accelerating the degradation of microspheres to release DOX-loaded ZrO2 into the lesions to kill tumors. Microspheres can also prolong the pharmacological time and effect of drugs through the enhanced permeability and retention (EPR) effect of nanocarriers, as well as the sustained release of nanomaterials. Studies performed in vivo revealed that mPEG-PLGA@ZrO2@(DOX + ILS) showed good biosafety. We undertook sensitized microsphere embolism therapy using novel mPEG-PLGA@ZrO2@(DOX + ILS) microspheres in a rabbit VX2 liver tumor model. Three, 6 and 9 d after treatment, computed tomography indicated no significant change in tumor size, and diffusion weighted imaging showed a marked decrease of residual tumor tissues. With the multiple functions of inducing embolisms, sensitization, and the sustained release of chemotherapeutics, novel mPEG-PLGA@ZrO2@(DOX + ILS) microspheres can achieve good therapeutic efficacy, in combination with MW ablation and chemotherapy, while embolizing the blood vessels of arterial tumors.

  16. Percutaneous radiofrequency thermal ablation of lung VX2 tumors in a rabbit model: evaluation with helical CT findings for the complete and partal ablation

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Gong Yong; Han, Young Min; Lim, Yeong Su; Jang, Kyu Yun; Lee, Sang Yong; Chung, Gyung Ho [School of Medicine, Chonbuk National Univ., Chonju (Korea, Republic of)

    2004-05-01

    To evaluate the radiologic findings for complete and partial ablation after percutaneous CT-guided transthoracic radiofrequency ablation (RFA) of lung VX2 tumor implanted in rabbits. Thirteen rabbits with successfully implanted lung VX2 were used. Three rabbits as controls did not receive RFA while the other ten rabbits underwent RFA; 5 complete and 5 partial. RFA was performed using an internally cooled, 17-gauge electrode (Radionics, Burlington, MA) with a 1-cm active tip under CT guidance. Postprocedural CT was performed within 3 days, and we analyzed the ablated size, enhancement pattern, shape, margin, and complications of the complete and partial ablation groups. Rabbits were sacrificed after postprocedural CT with an overdose of ketamine, and pathologic findings of the ablated groups were compared with those of the control group. The size of the ablated lesions and the enhancement pattern differed between the completely and partially ablated groups on chest CT. The size of the ablated lesions was increased by 47.1% in the completely ablated group and by 2.1% in the partially ablated group. In the completely ablated group, VX2 tumor showed absolutely no enhancement, whereas only ablated pulmonary parenchyma outside VX2 showed mild enhancement on enhanced CT. In the partial ablated group, a part of VX2 became strongly enhanced on enhanced CT. On microscopic examination, the completely ablated group demonstrated that a viable tumor cell was not visible. In the partially ablated group, however, a viable tumor cell within the surrounding fibrous capsule on the peripheral area of the VX2 was observed. The important CT findings for evaluation of complete and partial RFA are the ablated size and enhancement pattern of the ablated lesion.

  17. Establishing models of portal vein occlusion and evaluating value of multi-slice CT in hepatic VX2 tumor in rabbits

    Institute of Scientific and Technical Information of China (English)

    Yue-Yong Qi; Li-Guang Zou; Ping Liang; Dong Zhang

    2007-01-01

    AIM: To establish models of portal vein occlusion of hepatic VX2 tumor in rabbits and to evaluate the value of multi-slice CT.METHODS: Forty New Zealand rabbits were divided into 4 groups according to digital table: Immediate group (group A; transplantation of tumor immediately after the portal vein occlusion), 3-wk group (group B;transplantation of tumor at 3 wk after the portal vein occlusion), negative control group (group C) and positive control group (group D), 10 rabbits in each group.Hepatic VX2 tumor was transplanted with abdominal-embedding innoculation immediately after the portal vein occlusion and at 3 wk after the portal vein occlusion.Meanwhile, they were divided into negative control group (Left external branch of portal vein was occluded by sham-operation, and left exite was embedded and inoculated pseudoly) and positive control group (Transplanted tumor did not suffer from the portal vein occlusion). All rabbits were scanned with multi-slice CT.RESULTS: All 40 animals were employed in the final analysis without death. Tumor did not grow in both immediate group and 3-wk group. In 3-wk group, left endite was atrophied and growth of tumor was inhibited.The maximal diameter of tumor was significantly smaller than that in positive control group (2.55 ± 0.46 vs3.59 ± 0.37 cm, t = 5.57, P < 0.001). Incidences of metastasis in the liver and lung were lower in 3-wk group than those in positive control group (10% vs 40%, and 90% vs 100%, respectively). The expression intensities of the vascular endothelium growth factor (VEGF) in groups A, B, C and D were 0.10 ± 0.06, 0.66 ± 0.21, 0.28± 0.09 and 1.48 ± 0.32, respectively. VEGF expression level in the test group A was significantly lower than that in the negative control group C (t = 5.07; P < 0.001).In addition, VEGF expression in the test group B was significantly lower than that in the positive control group D (t = 6.38; P < 0.001). Scanning with multi-slice CT showed that displaying rate of

  18. Assessment of hepatic VX2 tumors of rabbits with second harmonic imaging under high and low acoustic pressures

    Institute of Scientific and Technical Information of China (English)

    Wen-Hua Du; Wei-Xiao Yang; Xiang Wang; Xiu-Qin Xiong; Yi Zhou; Tao Li

    2003-01-01

    AIM: To investigate the possible clinical application value of second harmonic imaging under low acoustic pressure.METHODS: Six New Zealand rabbits, averaging 2.7±0.4kg, were selected and operated upon to construct hepatic VX2 tumor carrier model. Hepatic VX2 tumors were imaged with B mode Ultrasonography (US), and second harmonic imaging (SHI) under high mechanic index (1.6) and low mechanic index (0.1). Echo agent was intravenously injected through ear vein at a dose of 0.01 mL/kg under B mode US and high MI SHI, and 0.05 mL/kg under low MI SHI, and then the venous channel was cleaned with sterilized saline.All the images were recorded by magnetic optics (MO),and they were analyzed further by at least two independent experienced sonographers.RESULTS: Totally 6 hypoechoic and 3 hyperechoic lesions were found in the six carrier rabbits with a mean size about 2.1±0.4 under B mode ultrasound, they were oval or round in shape with a clear outline or a hypoechoic halo at the margin of the lesions. Contrast agent could not change the echogenicity of the lesions under B mode US and SHI under high acoustic pressure. However, it could greatly increase the real time visualization sensitivity of the lesions with SHI under low acoustic pressure.CONCLUSION: Our results suggest that contrast enhanced SHI with low MI and a bubble non-destructive method would be much more helpful than conventional SHI in our future clinical applications.

  19. VX2脑瘤血管生成的灌注CT研究%Experimental study on angiogenesis in rabbit VX2 brain tumor using perfusion CT

    Institute of Scientific and Technical Information of China (English)

    康立清; 张云亭; 孙世梅

    2006-01-01

    Objective: To study the perfusion CT features of rabbit VX2 brain tumor with correlation to MVD and VEGF, and to validate perfusion CT for reflection of tumor angiogenesis. Methods: Rabbit VX2 brain tumor model was established by injection of 100 μL viable tumor cells (107/mL) through a 2 mm-hole 5 mm to the right of the sagittal suture and 5 mm posterior to the coronal suture bored by dental drill. MRI was performed every 2 days after seven days of implantation to evaluate the growth of the tumor. Twenty New Zealand White rabbits with tumor size over 3 mm in diameter were randomly divided into 2 groups according to the tumor growth time with those less than 3 weeks as group 1 and those more than 3 weeks as group 2, and perfusion CT were performed accordingly. CT measurements of BV, BF and PS from tumor, peritumor and contralateral normal tissue regions were obtained. After that the animals were sacrificed and 2% Evans blue (2 mL/kg) was given intravenously in 16 of these animals 1 h prior to sacrifice to detect breakdown of the blood brain barrier. VEGF and MVD were evaluated in immunohistochemical examination of the specimens. Results: Tumor had significantly higher BV, BF and PS (P=0.000) than peritumor and normal tissue region. Tumor BV, BF and MVD in group 2 were significantly higher than that in group 1 (P<0.01).Significant linear correlation was found between MVD and BV (t=0.915, P=0.000), MVD and BF (r=0.901, P=0.000), and MVD and PS (r=0.459, P=0.042). We also found a rank correlation between PS and blue stain of tumor (rs=0.861, P=0.000). Conclusion: Perfusion CT can distinguish tumor from peritumor and normal tissue clearly, reflect tumor angiogenesis accurately, and provide useful information for the evaluation of brain tumor.

  20. Evaluation of 70-150-μm doxorubicin-eluting beads for transcatheter arterial chemoembolization in the rabbit liver VX2 tumour model.

    Science.gov (United States)

    Gholamrezanezhad, Ali; Mirpour, Sahar; Geschwind, Jean-Francois H; Rao, Pramod; Loffroy, Romaric; Pellerin, Olivier; Liapi, Eleni A

    2016-10-01

    To evaluate the pharmacokinetic profile (PK) and embolization effect of 70-150-μm doxorubicin eluting beads (DEBs) following intra-arterial injection (i.a.) in the rabbit liver VX2 tumour model. In this ACUC-approved study, 25 white New Zealand rabbits were randomly assigned into a small DEB group (SDB, n = 7, 70-150-μm DEBs), large DEB group (LDB, n = 7, 100-300-μm DEBs), untreated controls (n = 7), and doxorubicin controls (n = 4, without tumour, received i.a. 12.5 mg doxorubicin). Plasma PK was assessed up to 180 min post-injection. Drug tissue and liver enzyme levels, radiologic tumor response and histopathologic tumour necrosis were assessed at 7 days. Mean tumour doxorubicin concentrations were 922.83 nM (SD = 722.05) and 361.48 nM (SD = 473.23) for the SDB and LDB, respectively (p = 0.005). There was no statistically significant difference in tumour doxorubicinol, plasma doxorubicin and doxorubicinol PK values. More beads were observed in the SDB tumours (p = 0.01). Liver enzymes increased and gradually declined over the observation period, with significantly higher values in the SDB. In this preclinical study, plasma PK of i.a.-injected 70-150-μm DEBs was not different than that of 100-300-μm DEBs. More beads and higher tissue doxorubicin levels were observed in the SDB tumours. • Small and large doxorubicin-eluting beads show similar plasma pharmacokinetic profiles. • Higher tissue doxorubicin levels were observed in the small bead group. • Liver enzymes were overall significantly higher in the small bead group.

  1. Contrast investigation of multi-slice spiral CT perfusion imaging and pathological findings in VX2 soft-tissue tumor of rabbits

    Institute of Scientific and Technical Information of China (English)

    Jingfeng Zhang; Renfa Wang; Min Wang; Jing Zhang; Jinmei Sang

    2005-01-01

    Objective: To perform a contrast investigation of multi-slice spiral CT (MSCT) perfusion imaging and pathological findings in VX2 soft-tissue tumor of rabbits, and discuss the applicative value of multi-slice spiral CT perfusion imaging in soft-tissue tumors. Methods: 8 Newzealand white rabbits were implanted with 0.1 ml VX2 tumor tissue suspension in bilateral proximal thighs. 14 days and 21 days later, CT plain scan and perfusion scan were performed on these rabbits respectively, then the images were transmitted to AW4.0 workstation, the functional maps and perfusion parameters including blood flow (BF), blood volume (BV), mean transit time(MTT) and permeability surface (PS) were computed and analyzed. Subsequently, the rabbits were sacrificed, the tumors of which were taken out for pathological examination. The correlation between MSCT functional parametric images and pathological findings was analyzed.Results: All the values of BF, BV and PS of VX2 soft-tissue tumors were obviously higher while the MTT-values were lower than those of the normal muscular tissues significantly ( P < 0.001). Conclusion: Multi-slice spiral CT perfusion imaging is an accurate, convenient and relatively safe functional imaging technique, which can give a quantitative assessment to blood perfusion and angiogenesis of soft-tissue tumors.

  2. Multiparametric Monitoring of Early Response to Antiangiogenic Therapy: A Sequential Perfusion CT and PET/CT Study in a Rabbit VX2 Tumor Model

    Directory of Open Access Journals (Sweden)

    Jung Im Kim

    2014-01-01

    Full Text Available Objectives. To perform dual analysis of tumor perfusion and glucose metabolism using perfusion CT and FDG-PET/CT for the purpose of monitoring the early response to bevacizumab therapy in rabbit VX2 tumor models and to assess added value of FDG-PET to perfusion CT. Methods. Twenty-four VX2 carcinoma tumors implanted in bilateral back muscles of 12 rabbits were evaluated. Serial concurrent perfusion CT and FDG-PET/CT were performed before and 3, 7, and 14 days after bevacizumab therapy (treatment group or saline infusion (control group. Perfusion CT was analyzed to calculate blood flow (BF, blood volume (BV, and permeability surface area product (PS; FDG-PET was analyzed to calculate SUVmax, SUVmean, total lesion glycolysis (TLG, entropy, and homogeneity. The flow-metabolic ratio (FMR was also calculated and immunohistochemical analysis of microvessel density (MVD was performed. Results. On day 14, BF and BV in the treatment group were significantly lower than in the control group. There were no significant differences in all FDG-PET-derived parameters between both groups. In the treatment group, FMR prominently decreased after therapy and was positively correlated with MVD. Conclusions. In VX2 tumors, FMR could provide further insight into the early antiangiogenic effect reflecting a mismatch in intratumor blood flow and metabolism.

  3. Thermochemical Ablation Therapy of VX2 Tumor Using a Permeable Oil-Packed Liquid Alkali Metal

    OpenAIRE

    2015-01-01

    Objective Alkali metal appears to be a promising tool in thermochemical ablation, but, it requires additional data on safety is required. The objective of this study was to explore the effectiveness of permeable oil-packed liquid alkali metal in the thermochemical ablation of tumors. Methods Permeable oil-packed sodium–potassium (NaK) was prepared using ultrasonic mixing of different ratios of metal to oil. The thermal effect of the mixture during ablation of muscle tissue ex vivo was evaluat...

  4. Percutaneous medical ozone injection for transplanted VX2 tumors: an experimental study in rabbits%经皮注射医用臭氧治疗兔VX2移植瘤的实验研究

    Institute of Scientific and Technical Information of China (English)

    韩世龙; 朱晓黎; 张猛; 郭永团; 徐云华

    2013-01-01

    目的 观察臭氧局部注射治疗实体肿瘤的安全性、对肝肾功能的影响及所致的组织病理学改变.方法 建立兔VX2移植瘤模型24只,分为三组,A、B组均为9只,C组6只(假手术组).向A、B组瘤内分别注入40 μg/ml和70 μg/ml浓度臭氧,并于术前1d、术后1、3d抽静脉血.术后3d处死动物,取病理标本.观察术后动物生命体征、并发症及大体标本的组织学变化.结果 实验动物术后24 h内均出现活动减少、纳差,对刺激反应差,精神萎靡,24 h后恢复正常.A、B组各有1只荷瘤兔于术中或术后1h内死亡.术前1d,术后1、3d各组血清丙氨酸转氨酶、天冬氨酸转氨酶及肌酐比较无明显差异.肉眼及光镜下见A、B组坏死区大体标本无明显差异.C组镜下可见部分肿瘤细胞突破肌层向深处生长,肿瘤细胞排列紊乱,大量癌巢形成,细胞核大深染,核分裂,异性核.结论 VX2肿瘤内注入浓度为40 μg/ml和70μg/ml的医用臭氧安全、有效.%Objective To evaluate the safety and effectiveness of percutaneous medical ozone injection in treating solid transplanted VX2 tumors in rabbits, and to discuss the histopathological changes cause by ozone injection. Methods Transplanted VX2 tumor model was established in 24 rabbits. The rabbits were randomly divided into three groups. Rabbits in group A (n = 9) received medical ozone (40 μg/ ml) injection of the tumor. Rabbits in group B (n = 9) received medical ozone (70 μg/ml) injection of the tumor. Rabbits in group C (n = 6, used as sham group) received no treatment. The serum AIT, AST and Cr levels were determined at one day before and one, three days after the treatment. All the animals were sacrificed at three days after the treatment. The specimens were collected and sent for pathological examination. After the procedure, careful observation of animal's vital signs, complications was executed, and the pathological findings were recorded. Results After the treatment

  5. Combination of vascular endothelial growth factor antisense oligonucleotide therapy and radiotherapy increases the curative effects against maxillofacial VX2 tumors in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Zheng Linfeng, E-mail: zhenglinfeng04@yahoo.com.cn [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Li Yujie, E-mail: yujieli01@yahoo.com.cn [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Wang Han, E-mail: bingowh@hotmail.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Zhao Jinglong, E-mail: jinglongz@yahoo.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Wang Xifu, E-mail: wangxiechen001@163.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Hu Yunsheng, E-mail: springmorninghu@163.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Zhang Guixiang, E-mail: guixiangzhang@sina.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China)

    2011-05-15

    Purpose: To study the effects of combination of vascular endothelial growth factor (VEGF) antisense oligonucleotide therapy and radiotherapy on maxillofacial VX2 tumors in rabbits. Methods: We used 24 New Zealand white rabbits as a model to induce maxillofacial VX2 tumor. The rabbits were randomly divided into the following 4 groups: radiotherapy group (group A), treated with 16 Gy of radiotherapy; VEGF antisense oligonucleotide treatment group (group B), treated with an injection of 150 {mu}g of VEGF antisense oligonucleotide into the local tumor; VEGF antisense oligonucleotide combined with radiotherapy group (group C), treated with an injection of 150 {mu}g of VEGF antisense oligonucleotide into the local tumor immediately after 16 Gy of radiotherapy; and control group (group D), treated with an injection of 300 {mu}l 5% aqueous glucose solution into the local tumor. On days 3 and 14 after treatment, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed to calculate maximal enhancement ratio (MER), slope of enhancement (SLE), and tumor volume change. Rabbits were killed on day 14 to obtain samples for pathological examination and immunohistochemical staining for VEGF. Results: In group C, tumor volume was significantly reduced on day 14 after treatment, and the difference was statistically different as compared to that before treatment, on day 3 after treatment and other groups (P < 0.01). Values of both MER and SLE after treatment were significantly lower than the values before treatment (P < 0.05). Pathological specimen revealed tumor cell edema, bleeding, necrosis, vascular wall thickening and occlusion, and decreased VEGF expression. The immunohistochemical score (IHS) of group C was significantly different from groups A and D respectively (P < 0.05). Conclusion: Injecting the tumor with VEGF antisense oligonucleotide immediately after radiotherapy can enhance the curative effect on rabbit maxillofacial VX2 tumor, and DCE-MRI can serve

  6. Quantitative Reproducibility Study of CT Perfusion Parameters in Rabbits with Implanted VX-2 Lung Tumors%兔VX-2肺种植肿瘤CT灌注成像定量检测可重复性的研究

    Institute of Scientific and Technical Information of China (English)

    崔磊; 龚沈初; 何书; 尹剑兵; 杨巨顺; 杨红

    2011-01-01

    Purpose To prospectively evaluate the reproducibility of CT perfusion parameters in rabbits with implanted VX2 lung tumors. Materials and Methods Perfusion CT was performed twice with 24-hour interval in 10 New Zealand White rabbits with implanted VX2 lung tumors. The volume, maximum diameter, blood volume (B V), Blood flow (BF), Time to peak (TTP), Permeability surface (PS), Patlak BV (PBV), Patlak R square (PatRsq) and Patlak Residual (PatRea) were measured, and reproducibility was evaluated using Bland-Altman statistics. Results CT perfusion parameters showed good agreement between two perfusion examinations. Intragroup correlation coefficients (ICCs) were all more than 0.6, within-subject coefficient of variation (WCV) was from 10.8% to 30.2%. The WCV of PS (10.8%) and PBV (12.3%) showed excellent agreement between studies comparable to the WCV of volume (8.5%) and maximum diameter (10.0%). Conclusion The trial confirms that lung tumor perfusion CT yields a good reproducibility and a range of reference values for CT perfusion parameters.%目的 前瞻性评估兔VX-2肺种植肿瘤CT灌注检查测量参数的可重复性.材料与方法 10只肺种植肿瘤的新西兰大白兔行2次CT灌注检查(间隔24h),分别测量肿瘤体积、最大径、血容量、血流量、达峰时间、表面通透性(PS)、Patlak血容量(PBV)、Patlak R方程(PatRsq)及Patlak残差(PatRes).使用Bland-Altman法分析2组CT测量数据的可重复性.结果 2次CT检查所有的CT灌注参数均显示较好的一致性,组内相关系数(ICC)均>0.6,个体间变异系数(WCV) 10.8%~30.2%.其中,PS和PBV的WCV分别为10.8%和12.3%,与CT形态学指标体积及最大径相仿(8.5%和10.0%).结论 通过动物实验验证了肺种植肿瘤CT灌注的可重复性,初步确定了CT灌注参数变化的参考值范围,为进一步研究提供了实验数据.

  7. Comparison of endoscopic submucosal implantation vs. surgical intramuscular implantation of VX2 fragments for establishing a rabbit esophageal tumor model for mimicking human esophageal squamous carcinoma.

    Directory of Open Access Journals (Sweden)

    Jin Huang

    Full Text Available PURPOSE: This study was undertaken to establish a rabbit esophageal tumor model for mimicking human esophageal squamous carcinoma (ESC by endoscopic and surgical implantation of VX2 tumors. METHODS: Fragments of a VX2 tumour were endoscopically implanted in the submucosal layer of the thoracic esophagus of 32 New Zealand white rabbits, while 34 animals received surgical implantation into the muscular layer. Then, the animals were studied endoscopically and pathologically. The safety and efficiency of the two methods and the pathological features of the animal models were analyzed. RESULTS: Both the endoscopic and the surgical method had a relatively high success rate of tumor implantation [93.7% (30/32 vs. 97.1% (33/34] and tumor growth [86.7% (26/30 vs. 81.8% (27/33], and the variation in the results was not statistically significant (P>0.05. Compared with those produced by the surgical method, the models produced by the endoscopic method had a higher rate of severe esophageal stricture [61.5% (16/26 vs. 29.6% (8/27] and of intra-luminal tumor growth [73.1% (19/26 vs. 37.0% (10/27], and had a lower rate of tumor invasion of adjacent organs [53.8% (14/26 vs. 81.5% (22/27]; all of these results were statistically significant (P0.05. CONCLUSION: The endoscopic and surgical methods are both safe and effective for establishment of VX2 tumors in the rabbit esophagus. The models produced by the two methods have different pathologic features mimicking that of human ESC. We recommend the models for studies on surgical procedures and minimally invasive treatments.

  8. Comparative Study of Images with Pathology:Superparamagnetic Iron Oxide-enhanced Magnetic Resonance Image(MRI)of Splenic VX2 Tumor in Rats

    Institute of Scientific and Technical Information of China (English)

    YANG Hong-yan; XU Yi-kai; WU Yuan-kui; LIU Wen-yuan; L(U) Guo-shi; CAO Guo-hong

    2008-01-01

    Objective:To establish a rodent model of VX2 tumor of the spleen,to analyze relationship between the change of the signal intensity on superparamagnetic iron oxide enhanced magnetic resonance image(MRI)and pathologic change to evaluate the ability of superparamagnetic iron oxide enhanced MRI for detection of splenic metastases.Methods:8 rodent models of VX2 tumor of spleen were established successfully.The images were obtained before and after administration of superparamagnetic iron oxide.T1-weighted spin-echo(SE)pulse sequence with a repetition time(TR)of 450 msec,and echo time(TE)of 12 msec(TR/TE=450/12)was used.The imaging parameters Of T2-weighted SE pulse sequence were as follows:TR/TE=4000/128. Results:On plain MR scanning T1-weighted splenic VX2 tumor showed hypointensity or isointensity which approximated to the SI of splenic parenchyma.Therefore all lesions were not displayed clearly.On superparamagnetic iron oxide enhancement T2WI sequence the SI of splenic parenchyma decreased obviously with percentage of signal intensity loss(PSIL)of 55.04%,But the SI of tumor was not evidently changed with PSIL of 0.87%. Nevertheless the SNR of normal splenic parenchyma around the lesions had obvious difference(P<0.001)comparatively.Therefore the contrast between tumor and spleen increased.and tumor displayed more clearly.Moreover the contrast-to-noise(CNR)between VX2 tumor and splenic parenchyma had an evident difference before and after admininstration of superparamagnetic iron oxide(P<0.001).Conclusion:On superparamagnetic iron oxide enhancement T1WI sequence the contrast of tumor-to-spleen is poor.Therefore it is not sensitive to characterize the lesions in spleen.On superparamagnetie iron oxide enhanced T2WI the contrast degree of lesions increases obviously.Consequently, superparamagnetic iron oxide-enhanced T2WI MRI scanning can improve the rate of detection and characterization for lesions of spleen.

  9. Effects of intra-arterial infusion of 3-bromopyruvate on metastases and survival benefit of hepatic VX2 tumor in rabbits%3-溴丙酮酸对兔VX2肝肿瘤转移及兔生存时间的影响

    Institute of Scientific and Technical Information of China (English)

    江雄鹰; 张小萍; 黄金华; 罗荣光; 苗碧建; 王琰

    2013-01-01

    目的 探讨3-溴丙酮酸(3-BrPA)经肝动脉灌注对兔VX2肝肿瘤转移及荷瘤兔生存时间的影响.方法 18只新西兰大白兔肝左叶种植VX2肿瘤,随机分成3组,每组6只.PBS灌注组:在肿瘤种植14 d后行肝动脉PBS溶液灌注.3-BrPA 7和14 d灌注组:在肿瘤种植7/14 d后行肝动脉3-BrPA溶液灌注.在肿瘤种植28 d后每组处死3只兔,解剖探查有无肝内转移、肾转移、肺转移及腹腔转移.每组剩余的3只兔观察其生存时间并进行比较.结果 肿瘤种植28 d后,PBS灌注组均发现肝内及腹腔转移(3/3),肾转移2只(2/3),肺转移2只(2/3).3-BrPA 7 d灌注组实验兔肝内和肺转移各有1只(1/3),未发现有腹腔和肾转移(0/3).3-BrPA14 d灌注组实验兔有2只发现肝内转移(2/3),肺和腹腔转移各有1只(1/3),未发现肾转移(0/3).生存时间比较显示3-BrPA 14 d灌注组实验兔生存时间[(27±5)d]显著长于PBS溶液灌注组[(17±3)d](P=0.041).而3-BrPA 7 d灌注组实验兔生存时间[(42±6)d]显著长于3-BrPA 14 d灌注组实验兔[(27±5)d](P=0.007).结论 经肝动脉灌3-BrPA能够有效减少兔VX2肝肿瘤的转移,并可延长移植VX2肝肿瘤兔的生存时间,且灌注时间越早,治疗效果越好.%Objective To evaluate the metastasis and survival of an intra-arterial infusion of 3-bromopyruvate (3-BrPA) on hepatic VX2 tumor in rabbits.Methods VX2 tumor was implanted in left lateral lobe of liver of 18 white New Zealand rabbits.The animals were randomized into 3 groups (n =6 each) and underwent an intra-arterial infusion of phosphate-buffered saline or 3-BrPA via hepatic artery at 14 days post-implantation.At 28 days post-implantation,3 rabbits in each group were sacrificed.The abdomen of these rabbits was opened and inspected for metastases.Then the survival of the remaining rabbits was observed.Results At 28 days post-implantation,in PBS group,there were intrahepatic metastasis and abdominal cavity dissemination (n =3),renal metastases (n =2

  10. CT spectral imaging for monitoring the therapeutic efficacy of VEGF receptor kinase inhibitor AG-013736 in rabbit VX2 liver tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peijie; Liu, Jie; Yan, Xiaopeng; Chai, Yaru; Chen, Yan; Gao, Jianbo; Pan, Yuanwei; Li, Shuai; Guo, Hua; Zhou, Yue [The First Affiliated Hospital of Zhengzhou University, The Department of Radiology, Zhengzhou, Henan Province (China)

    2017-03-15

    The aim of this study was to evaluate the value of computed tomography (CT) spectral imaging in assessing the therapeutic efficacy of a vascular endothelial growth factor (VEGF) receptor inhibitor AG-013736 in rabbit VX2 liver tumours. Twenty-three VX2 liver tumour-bearing rabbits were scanned with CT in spectral imaging mode during the arterial phase (AP) and portal phase (PP). The iodine concentrations(ICs)of tumours normalized to aorta (nICs) at different time points (baseline, 2, 4, 7, 10, and 14 days after treatment) were compared within the treated group (n = 17) as well as between the control (n = 6) and treated groups. Correlations between the tumour size, necrotic fraction (NF), microvessel density (MVD), and nICs were analysed. The change of nICs relative to baseline in the treated group was lower compared to the control group. A greater decrease in the nIC of a tumour at 2 days was positively correlated with a smaller increase in tumour size at 14 days (P < 0.05 for both). The tumour nIC values in AP and PP had correlations with MVD (r = 0.71 and 0.52) and NF (r = -0.54 and -0.51) (P < 0.05 for all). CT spectral imaging allows for the evaluation and early prediction of tumour response to AG-013736. (orig.)

  11. Assessment of tumor angiogenesis: dynamic contrast-enhanced MRI with paramagnetic nanoparticles compared with Gd-DTPA in a rabbit Vx-2 tumor model.

    Science.gov (United States)

    Kassner, Andrea; Thornhill, Rebecca E; Liu, Fang; Winter, Patrick M; Caruthers, Shelton D; Wickline, Samuel A; Lanza, Gregory M

    2010-01-01

    The purpose of this study was to evaluate the suitability of a macromolecular MRI contrast agent (paramagnetic nanoparticles, PNs) for the characterization of tumor angiogenesis. Our aim was to estimate the permeability of PNs in developing tumor vasculature and compare it with that of a low molecular weight contrast agent (Gd-DTPA) using dynamic contrast-enhanced MRI (DCE). Male New Zealand white rabbits (n = 5) underwent DCE MRI 12-14 days after Vx-2 tumor fragments were implanted into the left hind limb. Each contrast agent (PNs followed by Gd-DTPA) was evaluated using a DCE protocol and transendothelial transfer coefficient (K(i)) maps were calculated using a two-compartment model. Two regions of interest (ROIs) were located within the tumor core and hindlimb muscle and five ROIs were placed within the tumor rim. Comparisons were performed using repeated measures analysis of variance (ANOVA). The K(i) values estimated using PNs were significantly lower than those obtained for Gd-DTPA (p = 0.018). When PNs and Gd-DTPA data were analyzed separately, significant differences were identified among tumor rim ROIs for PNs (p < 0.0001), but not for Gd-DTPA data (p = 0.34). The mean K(i) for the tumor rim was significantly greater than that of either the core or the hindlimb muscle for both contrast agents (p < 0.05 for each comparison). In summary, the extravasation of Gd-DTPA was far greater than that of PNs, suggesting that PNs can reveal regional differences in tumor vascular permeability that are not otherwise apparent with clinical contrast agents such as Gd-DTPA. These results suggest that PNs show potential for the noninvasive delineation of tumor angiogenesis.

  12. Vascularity of hepatic VX2 tumors of rabbits: Assessment with conventional power Doppler US and contrast enhanced harmonic power Doppler US

    Institute of Scientific and Technical Information of China (English)

    Wen-Hua Du; Wei-Xiao Yang; Xiang Wang; Xiu-Qin Xiong; Yi Zhou; Tao Li

    2003-01-01

    AIM: To investigate the characteristics of the vascularity ofhepatic metastasis.METHODS: Six New Zealand rabbits, weighing averagely2.7±0.4 kg, were selected and operated to establish hepaticVX2 tumor carrier model. Hepatic VX2 tumors were thenimaged with conventional B mode US, second harmonicimaging (SHI), color Doppler flow imaging (CDFI), powerDoppler imaging (PDI) and harmonic PDI by a transducerS8 connected to HP-5 500 ultrasound system. A kind of selfmade echo contrast agent was intravenously injected at adose of 0.01 mL/kg through ear vein, and then the venouspassage was cleaned with sterilized saline.RESULTS: Totally, 6 hypoechoic lesions and 3 hyperechoiclesions were found in the six carrier rabbits with a mean sizeabout 2.1±0.4 cm under conventional B mode ultrasound, theywere oval or round in shape with a dear outline or a hypoechoichalo at the margin of the lesions. Contrast agent could notchange the echogenicity of the lesions under conventional Bmode and SHI, however, it could greatly increase the flowsensitivity of the lesions under PDI and harmonic PDI. Nutrientartery of these metastatic lesions might also be well depictedunder contrast enhanced PDI and harmonic PDI.CONCLUSION: Our result suggested that contrast enhancedPDI, especially harmonic PDI, was a promised method inthe detection of vascularity of hepatic tumor nodules.

  13. Experimental Study of CT Guided 32P-CP-PLLA Microparticle Implantation in the Treatment of Rabbit VX2 Lung Tumor

    Directory of Open Access Journals (Sweden)

    Donghui PAN

    2011-01-01

    Full Text Available Background and objective 32P-chromic phosphate-poly (L-lactic acid (32P-CP-PLLA microparticle is a novel potent brachytherapy implant, which has good biocompatibility and biodegradability. The aim of this study is to investigate the changes of pathology and PET/CT images in VX2 rabbit tumor after treatment with intratumorol administration of 32P-CP-PLLA microparticles, and to explore the effects and influence of tumor growth and apoptosis related proteins in VX2 lung tumor treatment with 32P-CP-PLLA microparticles. Methods Twenty-four tumor bearing rabbits were randomly divided into 4 groups (6 in each group. Group 1, 2 and 3 were treated groups; group 4 was the control. Under CT guidance, 32P-CPPLLA microparticles were implanted into tumors. Low, medium and high treatment doses were 93 MBq (group 1, 185 MBq (group 2 and 370 MBq (group 3, respectively. 18F-FDG PET/CT was performed at d0, d3, d7 and d14 after intratumoral administration. In the control group, 18F-FDG PET/CT images were acquired at the same time points but without treatment. The standardized uptake value (SUV of tumor regions were calculated. After last PET/CT imaging, the rabbits were euthanized and the tumors were removed for histological and immunohistochemical examination. The pathology and the expression of apoptosis related proteins (bcl-2, bax were compared. Results No significant difference of SUVmax was observed between the treatment groups and the control group at d0. At d14, the SUVmax values for group 1, 2 and 3 were 0.80±0.10, 1.1±0.19 and 2.85±0.15, respectively, and were significantly lower than that of the control group (5.61±0.50(P < 0.05. Significant dose-response relationship was observed in SUVmax between group 1 and group 2, and the SUV values gradually decreased from d7 to d14 after treatment. In group 3, SUVmax gradually increased and reached a peak at d7 then significantly decreased. The SUVmax values of group 3 were significantly lower than those of

  14. Interventional targeting administration of Ad-p53 combined with ultrasound irradiation in rabbit models of hepatic VX2 tumors%介入导入Ad-p53基因联合超声辐照治疗兔VX2肝癌

    Institute of Scientific and Technical Information of China (English)

    齐劲松; 杨瑞民; 赵鹏; 张铭秋; 崔红凯

    2013-01-01

    Objective To observe the effect of interventional targeting administration of Ad-p53 combined with ultrasound irradiation in rabbit models of hepatic VX2 tumors, as well as its impact on VEGF and MMP2. Methods Forty-two Chinchilla rabbits were collected and VX2 cancer cells were injected into the left lobe of liver on the observation in rabbits. The growth of cancer was monitored by ultrasound. Thirty rabbit models were successfully made and divided into 3 groups (each n=10) randomly. Fourteen days after transplantation of cancer cells, Ad-p53 was administrated through hepatic artery (in Ad-p53 group) or combined with ultrasound wave irradiation (in Ad-p53 + US group), while the same amount of saline was given for rabbits in control group. Three days later, the tumor size was observed with ultrasound, and then all rabbits were sacrificed, the serum VEGF level was measured by ELISA, the hepatic tissue expression of p53, MMP2 and VEGF were detected respectively by immunohistochemistry, and expression level of wild type p53 was measured using Western blot. Results No difference of tumor size was found between 3 groups before therapy. All tumor sizes increased, but the tumors in Ad-p53 + US group were relatively smaller. The efficiency of Ad-p53 transfection was improved in Ad-p53 group compared with control group, which was the highest in Ad-p53 + US group. Furthermore, the serum VEGF level decreased in Ad-p53 + US group, so did the expression of MMP2 and VEGF in Ad-p53 group and Ad-p53 + US group, more obviously in Ad-p53 + US group. Conclusion Ad-p53 can suppress the growth of hepatic VX2 tumors in rabbit models. The therapeutic efficacy of Ad-p53 can be improved by interventional targeting administration combining with ultrasound irradiation.%目的 探讨介入导向下联合超声辐照对兔VX2肝癌模型Ad-p53转染效率及该基因对VEGF、MMP2的影响.方法 青紫蓝兔42只,直视下手术,将VX2肿瘤细胞种植于肝左叶,以超声检测

  15. The evaluation of anti-angiogenic treatment effects for implanted rabbit VX2 breast tumors using functional multi-slice spiral computed tomography (f-MSCT)

    Energy Technology Data Exchange (ETDEWEB)

    Lei Zhen, E-mail: leizhen2004@163.com [Department of Anatomy, Chinese Medical University, No. 92, Beiermalu Road, Heping District, Shenyang, 110001 (China) and Department of Radiology, The First Hospital of Liaoning Medical College, No. 2, Wuduan, Renmin Street, Jinzhou, 121001 (China); Ma Heji, E-mail: maheji9831@sina.com [Department of Radiology, The First Hospital of Liaoning Medical College, No. 2, Wuduan, Renmin Street, Jinzhou, 121001 (China); Xu Na, E-mail: xuna821230@sohu.com [Department of Radiology, The First Hospital of Liaoning Medical College, No. 2, Wuduan, Renmin Street, Jinzhou, 121001 (China); Xi Huanjiu, E-mail: xihuanjiu2004@yahoo.cn [Anthropology Institute, Liaoning Medical College, No. 40, Sanduan, Songpo Rd, Jinzhou, 121001 (China)

    2011-05-15

    Objective: Investigate the benefit of functional multi-slice spiral computed tomography (f-MSCT) perfusion imaging in the non-invasive assessment of targeted anti-angiogenesis therapy on an implanted rabbit VX2 breast tumor model. Method: 69 female pure New Zealand white rabbits were randomly assigned to one of the 4 groups and received treatment accordingly: control (saline), Endostar, neoadjuvant chemotherapy (Cyclophosphamide, Epirubicin and 5-Fluorouracil, CEF), combination therapy (Endostar and CEF). After 2 weeks of treatment, f-MSCT perfusion scannings were performed for all rabbits and information about blood flow (BF), blood volume (BV), mean transit time (MTT) and surface permeability (SP) was collected. After perfusion imaging, tumor tissues were sampled for immunohistochemistry and the Western blot test of VEGF protein expression. Results: (1) The VEGF expression level, measured by immunohistochemistry and Western blot, decreased by treatment group (control > Endostar > CEF > combination therapy). The same was true for the mean BF, BV, MTT and PS, which decreased from the control group to the combination therapy group gradually. The mean MTT level increased in reverse order from the control to the combination therapy group. The difference between any 2 groups on these measures was statistically significant (P < 0.05). (2) There was moderate positive correlation between VEGF expression and BE, BV, or PS level (P < 0.05) and a negative correlation between VEGF expression and MTT level for all 4 groups (P < 0.05). Conclusion: Therefore, f-MSCT can be used as a non-invasive approach to evaluate the effect of anti-angiogenic therapy for implanted rabbit VX2 breast tumors.

  16. Experimental studies of rAd-p53 injection by interventional approach for the treatment of rabbit VX2 liver cancer%重组人p53腺病毒基因经介入途径治疗兔VX2肝癌的研究

    Institute of Scientific and Technical Information of China (English)

    罗仕华; 郑传胜; 冯敢生; 孙细梅; 周国锋; 梁惠民; 夏向文; 方建林

    2010-01-01

    Objective To evaluate the efficacy of recombinant human adenovirus p53 gene therapy (rAd-p53) in the rabbit VX2 liver cancer model using different interventional therapy approach. Methods Thirty New Zealand rabbits implanted with VX2 tumor in the liver were randomized into five groups with six of each. The tumor volumes (V1) were measured by MRI and CT scan 11 days after tumors implanted. The interventional therapy scheme performed as below: intraarterial 0.9% saline solution perfusion in group A, transcatheter arterial embolization with 0.5ml ultrafluid lipoidol in group B, intraarterial rAd-p53 gene perfusion in group C (1×106/VP); intraarterial rAd-p53 gene perfusion (1×107VP) in combination with transcatherter arterial etnbolization (ultrofluid lipiodol, 0.5 ml) in group D and intratumoral rAd-p53 gene (1 ×10/VP) injection in group E. The tumor volumes (V2) were measured by MRI and CT scan, and the tumor growth ratios were calculated 14 days after interventional procedures. Then all animals were sacrificed.The tumor tissues were explanted for irnrnunohistochemistry to observe the expressions of vascular endothelial cell growth factor (VEGF) and factor VIH. Microvessel density (MVD) of the tumor tissues was assessed by factor Ⅷ immunohistochemical analysis. In addition, apoptotic index was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Results The tumor volumes before therapy were (79.4 ±8.2), (75.3±7.8), (74.6±6.6), (78.7± 9.1), (75.8±8.4) mm3 respectively, without differences found among them (F = 12.248, P = 0.0636). But the tumor volumes after therapy were (564.7 ±96.7), (176.5 ±83.2), (239.6 ± 42.8), (159.8 ± 58.6), (334.7 ± 32.6) mm3 respectively (F= 24.537, P = 0.0218). The tumor growth ratios were 6.9, 2.6, 3.1,1.6 and 4.1 respectively. The mean apoptosis index were 12.0% ± 1.1%, 14.5%± 2.1%, 17.6% ± 2.3%, 18.6% ± 2.3% and 19.6% ± 2.5% respectively, with significant differences in group E in

  17. Benign Liver Tumors

    Science.gov (United States)

    ... A Life After Diagnosis Support for Chronic Illness Corporate Partnerships Interview with Kristen Hanks Liver Lowdown July ... Disease , Liver Transplant , Liver Cancer , Liver Tumor , Liver Failure Help Fight Liver Disease We rely upon donations ...

  18. An experiment study on the inhibition of rabbit VX2 soft-tissue tumor by low frequency ultrasound radiation and microbubbles%低频超声辐照联合微泡抑制兔VX2肿瘤生长的实验研究

    Institute of Scientific and Technical Information of China (English)

    王宇; 申锷; 胡兵

    2011-01-01

    Objective : To explore a noinvasive therapy of tumor by cavitation effect induced by microbuhbles mediated low frequency ultrasound radiation. Methods : VX2 tumor was implanted into the unilateral proximal thigh of 24 Newzealand white rabbits successfully. These rabbits were randomly divided into four groups, control group, simplicity microbubble group, simplicity ultrasound group, and ultrasound and microbubble group , when the tumors approached about 1. 0 centimeter in size, with 6 rabbits in each group. After treatment correspondently, measured the volume of gross tumor and observed the blood flow infusion by sonography for 2 weeks. Then, drew a growth curve and calculated the ratio of tumor growth,collected the tumor samples and histopathology damages were observed. Results: After treatment for two weeks , tumor volume and tumor growth ratio of ultrasound and microbubble group were significantly smaller than the other groups ( P < 0. 01 ) , the blood flow reduction was observed by contrast enhanced ultrasonography. Necrosis was observed by histopathology. No statistical difference among control group, simplicity microbubble group and simplicity ultrasound group. Conclusion: Low frequency ultrasound radiation of 20kHz with microbubble sonoVue in vascular can inhibit the growth of VX2 soft - tissue tumors in rabbits. It might be the mechanism of the VX2 tumor microcirculation being selectively destroyed by microbubbles mediated ultrasound cavitation.%目的:探索低频超声辐照联合静脉注射微泡抑制肿瘤生长的非创伤性治疗肿瘤的新方法.方法:24只新西兰大白兔后腿肌肉内接种VX2肿瘤,瘤体长至1cm左右随机分为对照组、单纯微泡组、单纯超声组和超声微泡组.各组经相应处理后,超声检测肿瘤大小、观察瘤体内血流灌注情况,绘制肿瘤生长曲线,计算肿瘤增长百分率.病理学观察治疗后各组瘤体组织的病理学损伤.结果:治疗后2周结果显示超声微泡组

  19. Noninvasive Measurement of Perfusion in Rabbit VX2 Tumors Using Flow sensitive Alternting Inversing Recovery with an Extra Radiofrequency Pulse

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Introduction:MR arterial spin-labeling technique is useful to measure tissue perfusion. The purpose of this study was to evaluate the feasibility of using a novel arterial spin-labeling technique to characterize regions of hyper and hypovascularity in experimental tumors in rabbits.

  20. Using the 64-slice Perfusion CT to Evaluate the Oxygen Tension(pO2) in the Rabbit VX2 Tumor Model: An Experimental Study%64层灌注CT评价兔VX2体部肿瘤模型氧分压的实验研究

    Institute of Scientific and Technical Information of China (English)

    孙昌进; 肖明勇; 阴俊; 于金明; 郞锦义; 王光辉; 李超; 李涛; 罗云秀; 吕海波; 张德康; 李彦; 黄建鸣

    2013-01-01

    Objective: To investigate the role of the 64-slice perfusion CT in the evaluation of the oxygen tension ( pO2 ) in the rabbit VX2 tumor model. Methods: Forty-five rabbit VX2 brain tumor model established successfully were examined with 64-detector row CT. Tumor specimens were assessed for the oxygen tension ( pO2 ) , perfusion, blood volume ( BV) , peak enhancement intensity ( PEI) and time to peak (TTP) , and Pearson correlation coefficients were conducted to represent the relationships between the perfusion parameters and pO2 of the tumor. pO2was measured by oxygen-sensitive electrodes guided by perfusion CT images. Results: Mean values for perfusion,BV,PEI, TTP and pO2 of the 45 tumors were 27. 102 ± 26. 723ml/min, 22. 1 96 ± 13. 680ml/100g,43. 456 ±28.73 HU, 38.823 ±14.759 sec,and 15.981 ± 14.815mmHg, respectively. BV,PEI, TTP were not significant correlated with pO2 (r =0.271, 0. 253 、- 0. 18 , P > 0. 05 ) , whereas positively correlation was found between perfusion with pO2 ( r = 0. 673, P = 0. 00 ). Conclusion: The perfusion value from 64-slice spiral CT perfusion imaging might to have ability to evaluate the tumor pO2%目的:利用64层灌注CT评价兔VX2肿瘤模型氧分压并与氧微电极法对照.方法:对45只成功建模兔VX2脑瘤模型行灌注CT检查.测量脑瘤兴趣区灌注值(perfusion)、血容量(blood volume,BV)、达峰时间(time to peak TTP)、最大峰值(peak enhancement intensity,PEI).结果与该兴趣区氧微电极法测得氧分压(PO2)对照.结果:45例成功建模兔VX2脑瘤兴趣区灌注值范围为1.3 ml/min~127.0 ml/min,平均为27.102 ml/min±26.723 ml/min;BV为1.2 ml/100g~53.1ml/100g,平均为22.196 ml/100g±13.680ml/100g,PEI为8.7 HU~124.6HU,平均为43.456 HU±28.73 HU; TTP为8.2 sec~62.5 sec,平均为38.823 sec±14.759 sec;对应区域PO2为0.14 mmHg~46.70mmHg,平均为15.981 mmHg±14.815mmHg.灌注值与对应区域PO2相关系数为0.673,有统计学意义(P=0.00).BV

  1. Feasibility of DCE-MRI for evaluation of anti-angiogenesis effect of Endostar in the model of rabbit VX2 bone tumor%DCE-MRI评价Endostar对兔VX2骨肿瘤模型抗血管生成的疗效

    Institute of Scientific and Technical Information of China (English)

    龚威; 查云飞; 闫力永; 邢栋; 王克军; 胡磊; 王娇; 刘昌盛

    2015-01-01

    Objective:To explore the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)based on the Reference-Region model for evaluating anti-tumor angiogenesis effect of endostar in rabbit VX2 bone tumor.Methods:20 rabbits with VX2 bone tumor (tumor size in soft tissue>1cm)were randomly divided into the control group (n= 10)and the experimental group (n= 10),and were accepted DCE-MRI examination before and 14 days after treatment (using saline in control group;using endostar with concentration of 1.5mg/8mL in experimental group).DCE-MRI parameters including microvascular permeability transfer constant (Ktrans )and microvascular permeability reflux con-stant (Kep )were acquired based on the Reference-Region model.All the rabbits were sacrificed after DCE-MRI scanning at the 14th day.MVD and VEGF expression were analyzed by immunohistochemical staining.Correlation analysis was per-formed between DCE-MRI parameters and immunohistochemistry results.Results:In the experimental group,the Ktrans , MVD and VEGF expression had statistical difference (P0.05)between the two regions.Before treatment,the Ktrans value of pe-ripheral region and central region of rabbit VX2 bone tumors in the control group were (32.58±3.10)and (28.5± 3.54)min-1 respectively;and were (27.7±4.75)and (23.9±4.40)min-1 in the experimental group;after treatment,they were (37.66±2.78)and (34.2±3.39)min-1 in control group,and were (22.2±4.29)and (18.3±4.23)min-1 in the ex-perimental group,respectively.In the experimental group,the Ktrans values of the peripheral region and central region of rab-bit VX2 bone tumors were correlated with the MVD and VEGF expression (r= 0.924,0.945,0.848 and 0.909,respective-ly;P0.01).Conclusion:The spatial distribution of blood perfusion in rabbit VX2 bone tumors has hetero-geneity.The Ktrans value in DCE-MRI based on the Reference-Region model can be applied to estimate the anti-tumor angio-genesis effect of endostar.%目的:

  2. 双源双能量CT评价兔VX2移植瘤介入术疗效的实验研究%The laboratory research of dual-source and dual-energy CT in evaluating the effect of rabbit VX2 tumor interventional therapy

    Institute of Scientific and Technical Information of China (English)

    祁克信; 劳群; 贾玉柱

    2013-01-01

    Objective To explore the diagnostic value of the dual-energy technique with dual-source in the evaluation of therapeutic effect of interventional therapy for hepatocarcinoma.Methods 8 rabbits with tumor growing well were treated with intervention operation,paralleled with double energy CT scan and focal area image,CT and color order change were measured by dual energy liver OVERLAY workstation.Meanwhile,The necrosis and survival of tumor were evaluated by dual energy CT after hepatocarcinoma intervention therapy.Results Taking pathologic diagnosis as gold standard,compared with imaging and pathological results in the order of black,red,orange and red,accuracies were 87.2%,72.3%,71.5% and 83.6% respectively.Sensitivities were 95.1%,37.4%,54.7% and 63.8% respectively.Specificities were 85.4%,86.3%,81.5% and 85.8% respectively.Positive predictives value were 61.4%,54.2%,62.4% and 55.6% respectively.Negative predictive values were 96.3%,76.2%,79.7% and 91.3 % respectively.According to the Spearman relevance analysis,there was strong positive correlation between survival of tumor cells and image color scale (r =12.35,P < 0.05).Conclusion The necrosis and survival of tumor cells in rabbit VX2 liver tumor model can be preliminarily reflected by dual source CT dual energy enhancement scanning.The results provide good reference to the application of dual-source and dual-energy in clinical diagnosis and treatment.%目的 探讨双源双能量CT评价肝癌介入治疗疗效的价值.方法 8只生长良好的荷瘤兔,行介入手术,并进行双源双能量CT扫描,利用双源工作站OVERLAY信息图像,测量病灶区CT值,并记录其色阶变化,探讨双能量CT在肝癌介入治疗后肿瘤存活与坏死情况.结果 以全部的病理诊断为金标准,经过病理和影像对照分析,按黑色、暗红色、红色、橘红色顺序,色阶准确度分别为87.2%、72.3%、71.5%、83.6%,敏感度分别为95.1

  3. 超顺磁性氧化铁粒子增强磁共振成像在大鼠脾脏荷VX2肿瘤模型的应用%Superparamagnetic iron oxide: Enhanced detection of splenic VX2 tumor with magnetic resonance imaging in rats

    Institute of Scientific and Technical Information of China (English)

    阳红艳; 许乙凯; 吴元魁; 刘文源; 吕国士

    2007-01-01

    的脾实质信号强度显著下降,脾VX2肿瘤的对比噪声比较增强前显著提高,差异有统计学意义(P<0.01).结论:超顺磁性氧化铁粒子增强T1加权像MR图像上正常脾实质与VX2肿瘤组织的对比差,病灶的检出率低,不利于描述病灶的特征.超顺磁性氧化铁粒子增强T2加权成像MR图像上脾脏-肿瘤的对比显著,提高了病灶的检出率,改善了病灶的影像学特征的描述.%BACKGROUND:Sensitivity of diagnoses differentiating smaller nodes of splenic metastasis (< 1 cm) from CT and MRI is poor. So whether superparamagnetic iron oxide can enhance magnetic resonance imaging (MRI) of splenic VX2 tumor in rats need to be further studied.OBJECTTVE: To establish splenic VX2 tumor models, investigate MRI scanning combining with superparamagnetic iron oxide of specific reticuloendothelial system, and study the diagnostic significance of superparamagnetic iron oxide-enhanced MR images on splenic metastases.DESIGN: Duplicated-measured animal study.SETTING: Medical Imaging Center, Nanfang Hospital of the Southern Medical University.MATERIALS: The experiment was carried out in the Medical Imaging Center (Military Key Laboratory), Nanfang Hospital of the Southern Medical University from May 2005 to March 2006. A total of 25 adult SD rats, of either gender, weighing 200-300 g, were selected in this study. The animal experiment had got confirmed consent from local ethic committee. All rats were randomly divided into tumor group (n =20) and blank control group (n =5).METHODS: Models of VX2 tumor in spleen were established successfully. The images obtained before and after administration of superparamagnetic iron oxide. T1-weighted image(T1WI) (450/12 ms) and T2-weighted image(T2WI)(4 000/128 ms) were used to scan sequences. The imaging parameters of various tissues were analyzed before and after superparamagnetic iron oxide-enhanced MRI scanning. Rats in the blank control group were not used to establish models

  4. The Value of Diagnosing Rabbit VX2 Peritoneal Implantation Metastasis Tumor by 256 Line CT JOG-H Perfusion Scan%256排CT JOG-H模式灌注扫描诊断兔VX2腹膜腔移植瘤的诊断价值评价

    Institute of Scientific and Technical Information of China (English)

    佟元涛

    2015-01-01

    Objective To evaluate the value of diagnosing rabbit VX2 peritoneal implantation metastasis tumor by 256 line CT JOG-H perfusion scan. Method The rabbits were induced into tumor models by injecting suspended particle, then CT perfusion scan were used to scan the abdomen of rabbit model. Pathological result was taken as gold standard to evaluate CT perfusion scan.Results CT perfusion scan was superior than CT enhanced scan in detecting the metastatic tumor less than 10mm,10-20 mm by CT enhanced scan.Conclusion CT perfusion scan was superior than CT enhanced scan in detecting the metastatic tumor less than 20 mm. In the focus greater than 20 mm, CT perfusion scan was equal to CT enhanced scan .%目的:评估CT灌注对腹腔内移植瘤的诊断价值。方法制作兔VX2腹膜腔移植瘤模型,对瘤兔腹部进行CT灌注扫描获得影像学结果,以病理结果为金标准评价CT增强加CT灌注的诊断价值。结果在对<10 mm及对10~20 mm的腹腔种植瘤进行扫描对于病灶检出能力CT增强加CT灌注扫描要优于单纯CT增强扫描。结论对于20 mm以下的病灶CT增强加CT灌注扫描检出能力在敏感度、特异度、准确度方面优于单纯CT增强,而对于>20 mm的病灶CT增强与CT增强加CT灌注检出结果相同均与病理结果一致。

  5. Blocking effect on microcirculation of rabbits VX2 tumors by low-intensity pulsed therapeutic ultrasound combined with microbubbles%低能量脉冲式超声联合微泡对兔VX2肿瘤微循环的阻断作用

    Institute of Scientific and Technical Information of China (English)

    朱梅; 李佩倞; 钟渝; 梁红敏; 何利平; 刘政

    2012-01-01

    To investigate the blocking effect on microcirculation of rabbits VX2 tumors by low-intensity pulsed ultrasound combined with intravenous microbubble injection. Methods Thirty-six rabbits bearing subcutaneous VX2 tumors were randomly divided into 3 groups. For ultrasound combined with microbubbles group, pulsed ultrasound was delivered to the tumor surface for 10 min following intravenous infusion with microbubbles as ultrasound and microbubbles. For microbubbles group, only microbubbles were injected, while for ultrasound group, only exposure under pulsed ultrasound was performed. The tumor perfusion areas in CEUS were measured at 0, 30 min, 60 min. After treatment, 6 rabbits in each group were taken randomly to sacrifice for pathological observation. Results The contrast perfusion of tumors immediately vanished after treatment in ultrasound combined with microbubbles group, then recovered gradually at 30 min and 60 min. Pathological examination showed significant swell and hemorrhage, damages in the endothelia, abundance intercellular fluid, and in situ thrombosis in ultrasound combined with microbubbles group. There was no obvious change in CEUS and pathology in microbubbles group, nor in ultrasound group. Conclusion The tumor microcirculation can be blocked by microbubble associated with low energy ultrasound. The mechanism may be related to vessel wall injury caused by ultrasound cavitation, and tissue edema increases the resistance to the blood circulation of tumor areas.%目的 探讨低能量脉冲式超声联合微泡对兔VX2肿瘤微循环的阻断作用及其病理机制.方法 将36只皮下VX2荷瘤兔随机平均分成3组:超声微泡组注入0.2 ml/kg体质量微泡5ml,并辅以超声辐照10 min;单纯超声组注入生理盐水5 ml,辐照10 min;单纯微泡组仅注入0.2 ml/kg体质量微泡5 ml,不进行超声辐照.CEUS观察各组治疗前、治疗后0.30 min、60 min时血流灌注情况,比较各时间点的灌注面积.治

  6. ~(18)F-FDG PET/CT for the evaluation of pathological changes of the VX2 rabbit tumors after treatment of Ar-He knife%兔VX2移植瘤氩氦刀治疗前后~(18)F-FDGPET/CT显像及病理学变化

    Institute of Scientific and Technical Information of China (English)

    易峰涛; 张永学; 王慧; 宋华志

    2010-01-01

    Objective To study the correlation of ~(18)F-fluorodeoxyglucose (FDG) PET/CT with pathological changes of the VX2 rabbit tumors after treatment of Ar-He knife,and to explore the evolution of the Ar-He knife curative effect for VX2 rabbit tumors.Methods Thirty-six Japanese white rabbits had successfully been implanted with VX2 tumors in thighs.Four weeks later,the rabbits with VX2 tumors were imaged with FDG PET/CT before they were treated with Ar-He cryoablation.The rabbits were evenly and randomly divided into 6 groups (6 rabbits in each group) and imaged with FDG PET/CT respectively on the first day,third day,seventh day,fourteenth day,thirtieth day and sixtieth day after cryoablation.The rabbits in each group were sacriftced after post-treatment FDG PET/CT imaging for pathology and immunohistochemistry studies.The standardized uptake value (SUV) of tumor regions were calculated and compared with pathology and immunohistochemistry findings in the cryoablative area in each group.Paired-samples t-test and bivariate correlation analysis were evaluated by statistical software SPSS 16.0.Results After ArHe cryoablation,pathological changes of "necrosis-inflammatory response→organization" were found.On CT imaging,the tumors enlarged during 3-14 d after treatment and then shrank gradually.On FDG PET imaging,the maximum SUV (SUV_(max)) dropped dramatically on the first day after the operation(from 2.54±1.12 to 0.67±0.12),and increased slightly on the third day (1.71±0.82),and then continually dropped to 0.51±0.32 (60 d afterthe operation).The differences of SUV_(max) between pre-and after cryoablationin each stage were significant,respectively (t=5.471,8.716,11.388,5.713,7.144 and 7.213,all P<0.05).The size and SUV_(max) of the targeting area did not correlate with each other(r=0.259,P=0.675).The change of the MVD closely correlated with SUV_(max)(r=0.865,P=0.032).Conclusion FDG PET/CT can reveal the pathological change of tumor tissue after Ar-He cryoablation

  7. Liver Tumors (For Parents)

    Science.gov (United States)

    ... Teaching Kids to Be Smart About Social Media Liver Tumors KidsHealth > For Parents > Liver Tumors Print A A A What's in this ... Malignant (Cancerous) Tumors Symptoms Diagnosis Treatment Coping The liver is the body's largest solid organ. Lying next ...

  8. CT导引下32P-磷酸铬-聚-L-乳酸粒子植入治疗兔VX2肺肿瘤的实验研究%Experimental Study of CT Guided32P-CP-PLLA Microparticle Implantation in the Treatment of Rabbit VX2 Lung Tumor

    Institute of Scientific and Technical Information of China (English)

    潘栋辉; 杨敏; 徐宇平; 王立振; 刘璐; 黄培林

    2011-01-01

    子可通过电离辐射诱导bcl-2和bax基因参与VX2移植瘤细胞凋亡过程的调控,从而抑制肿瘤生长.%Background and objective 32P-chromic phosphate-poly (L-lactic) acid (32P-CP-PLLA) microparticle is a novel potent brachytherapy implant, which has good biocompatibility and biodegradability. The aim of this study is to investigate the changes of pathology and PET/CT images in VX2 rabbit tumor after treatment with intratumorol administration of 32P-CP-PLLA microparticles, and to explore the effects and influence of tumor growth and apoptosis related proteins in VX2 lung tumor treatment with 32P-CP-PLLA microparticles. Methods Twenty-four tumor bearing rabbits were randomly divided into 4 groups (6 in each group). Group 1, 2 and 3 were treated groups; group 4 was the control. Under CT guidance, 32P-CP-PLLA microparticles were implanted into tumors. Low, medium and high treatment doses were 93 MBq (group 1), 185 MBq (group 2) and 370 MBq (group 3), respectively. 18F-FDG PET/CT was performed at d0, d3, d7 and d14 after intratumoral administration. In the control group, 18F-FDG PET/CT images were acquired at the same time points but without treatment. The standardized uptake value (SUV) of tumor regions were calculated. After last PET/CT imaging, the rabbits were euthanized and the tumors were removed for histological and immunohistochemical examination. The pathology and the expression of apoptosis related proteins (bcl-2, bax) were compared. Results No significant difference of SUVmax was observed between the treatment groups and the control group at do. Atd14, the SUVmax values for group 1, 2 and 3 were 0.80±0.10, 1.1 ±0.19 and 2.85 ±0.15, respectively, and were significantly lower than that of the control group (5.61±0.50) (P<0.05). Significant dose-response relationship was observed in SUVmax between group 1 and group 2, and the SUV values gradually decreased from d7 to d14 after treatment. In group 3, SUVmax gradually increased and reached a

  9. Intravoxel Incoherent Motion Diffusion Weighted MR Imaging for Monitoring the Instantly Therapeutic Efficacy of Radiofrequency Ablation in Rabbit VX2 Tumors without Evident Links between Conventional Perfusion Weighted Images.

    Directory of Open Access Journals (Sweden)

    Ziyi Guo

    Full Text Available To investigate the intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI as a potential valuable marker to monitor the therapy responses of VX2 to radiofrequency ablation (RF Ablation.The institutional animal care and use committee approved this study. In 10 VX2 tumor-bearing rabbits, IVIM-DWI examinations were performed with a 3.0T imaging unit by using 16 b values from 0 to 800 sec/mm2. The true diffusion coefficient (D, pseudodiffusion coefficient (D* and perfusion fraction (f of tumors were compared between before and instantly after RF Ablation treatment. The differences of D, D* and f and conventional perfusion parameters (from perfusion CT and dynamic enhanced magnetic resonance imaging, DCE-MRI in the coagulation necrosis area, residual unablated area, untreated area, and normal control had been calculated by compared t-test. The correlation between f or D* with perfusion weighted CT including blood flow, BF (milliliter per 100 mL/min, blood volume, BV (milliliter per 100 mL/min, and capillary permeability-surface area, PMB (as a fraction or from DCE-MRI: transfer constant (Ktrans, extra-vascular extra-cellular volume fraction (Ve and reflux constant (Kep values had been analyzed by region-of-interest (ROI methods to calculate Pearson's correlation coefficients.In the ablated necrosis areas, f and D* significantly decreased and D significantly increased, compared with residual unblazed areas or untreated control groups and normal control groups (P < 0.001. The IVIM-DWI derived f parameters showed significant increases in the residual unablated tumor area. There was no significant correlations between f or D* and conventional perfusion parameters.The IVIM-DW derived f, D and D* parameters have the potential to indicate therapy response immediately after RF Ablation treatment, while no significant correlations with classical tumor perfusion metrics were derived from DCE-MRI and perfusion-CT measurements.

  10. Vx2肝癌改良模型的建立及其DSA影像分析%Vx2 carcinoma model and its DSA imagining features in rabbits

    Institute of Scientific and Technical Information of China (English)

    曹玮; 王执民; 张洪新; 王义清; 郭卫平; 李文献; 倪代会; 梁志会; 齐连君

    2001-01-01

    AIM To establish suitable metastatic rabbit Vx2 liver tumor model for experimental study, probe into different tumor transplanted methods and analyze the DSA (digital substract angiography) imagining features of the liver tumor. METHODS 60 male New Zealand white rabbits were divided into 3 groups at random, 20 in each group. 5×107 Vx2 carcinoma cells were injected via hepatic artery, pecutaneous into liver by syringe needle in the different 2 groups (control groups); the 3rd group (retrofit group) were transplanted tumor tissue mass (about 106~108 carcinoma cells) into liver. Then we observed: ①the success rate of implanting tumor; ②the volume change of tumor by ultrasonograpy (the growth rate of tumor was calculated); ③the biological features of tumor (histopathology and electronic microscope photographs); ④the DSA imagining features of tumor. RESULTS The success rates of transplanting tumor of 3 groups were 7/20, 10/20, 19/20; the retrofit group was the highest of 3 groups (P<0.05). The tumor grew as exponential curve. Histopathology and electronic microscope photographs indicated that tumor grew in the liver tissue and infiltrated into the normal liver tissue, and that it had the similar biological features of squamous cell carcinoma transplanted in other sites of rabbits. The DSA imagining of tumor indicated that the carcinoma had liberal blood vessels. CONCLUSION A retrofit metastatic rabbit Vx2 liver carcinoma model has successfully been set up, The success rate of the method by which tumor tissue mass transplanted is obviously higher than the other two methods. This makes it possible to gain a reliable mature large tumor animal model for study.%目的 建立可供实验研究的稳定的兔Vx2移植性肝癌模型,探讨不同植瘤方式的成功率,并分析该肿瘤的DSA影像特征. 方法 新西兰白兔60只,随机分3组,每组20只. 将Vx2瘤细胞(5×107个)经肝动脉或经肝包膜分别接种于2组兔的肝

  11. Radioembolization of liver tumors

    NARCIS (Netherlands)

    van den Hoven, AF

    2016-01-01

    Radioembolization is a therapy during which radioactive microspheres are administered through a microcatheter placed in the hepatic arterial vasculature in order to irradiate liver tumors from within. In the past decennium, this treatment has evolved as a safe and effective treatment option for pati

  12. [Local treatment of liver tumors

    DEFF Research Database (Denmark)

    Pless, T.K.; Skjoldbye, Bjørn Ole

    2008-01-01

    Local treatment of non-resectable liver tumors is common. This brief review describes the local treatment techniques used in Denmark. The techniques are evaluated according to the evidence in literature. The primary local treatment is Radiofrequency Ablation of both primary liver tumors and liver...

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

    Science.gov (United States)

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

    2017-03-01

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

  14. Evaluation of multi-slice spiral CT perfusion on blood supply of rabbits model bearing VX2 hepatic carcinoma%多排螺旋CT灌注成像对兔VX2肝癌血供的评价

    Institute of Scientific and Technical Information of China (English)

    周悦; 高剑波; 杨学华; 张永高; 岳松伟; 曲艳红

    2011-01-01

    Aim:To assess the diagnostic value of Muhi-slice CT perfusion for blood supply evaluation of the rabbits VX2 hepatic tumors. Methods: VX2 hepatic carcinoma mass were implanted into the left lobe of liver of 30 rabbits via laparotomic route. Multi-slice CT enhancement and perfusion were performed in these rabbits at twenty-one day after implantation. The CT imaging features of the tumors were observed and the perfusion parameters were measured in the rim of the tumor, non-tumorous regions nearby the tumor and the normal liver tissues. Results: Twenty-five (83%) rabbits were sucessfully implanted with the tumor. The tumors which has smooth border were demostrated itself as the round-shaped tumors with hypodensity on plain CT scan,significantly tinge-enhancement on arterial phase, relatively hypodensity on portal phase and no enhanced in the zone of necrosis. Blood flow, blood volume, permeability surface, hepatic arterial fraction, hepatic arterial perfusion increased and mean transit time decreased in the rim of the tumor compared with those of the non-normorous regions nearby the tumor and the normal liver ( P < 0.05). Conclusion: Multi-slice CT perfusion could evaluate the blood supply station of hepatic tumors in vivo by perfusion parameters.%目的:探讨多排螺旋CT灌注成像对兔VX2肝癌血供的评价价值.方法:采用开腹瘤组织块直接包埋法将VX2肝癌移植瘤植入30只新西兰大白兔肝左叶,并于种植后第21天行多排螺旋CT增强及灌注扫描,观察其CT征象,并对比肿瘤边缘区、瘤旁肝组织以及对照肝组织的CT灌注参数(血流量、血容量、平均通过时间、表面通透性、肝动脉分数以及肝动脉灌注量).结果:25只(83%)大白兔种植成功.CT平扫肿瘤为类圆形低密度灶;增强动脉期病灶表现为边缘环状强化;门脉期呈相对低密度,中心见低密度坏死区,与周围组织界限较清.CT灌注成像结果:肿瘤边缘区、瘤旁肝组织及对照肝

  15. Interferometric phase-contrast X-ray CT imaging of VX2 rabbit cancer at 35keV X-ray energy

    Science.gov (United States)

    Takeda, Tohoru; Wu, Jin; Tsuchiya, Yoshinori; Yoneyama, Akio; Lwin, Thet-Thet; Hyodo, Kazuyuki; Itai, Yuji

    2004-05-01

    Imaging of large objects at 17.7-keV low x-ray energy causes huge x-ray exposure to the objects even using interferometric phase-contrast x-ray CT (PCCT). Thus, we tried to obtain PCCT images at high x-ray energy of 35keV and examined the image quality using a formalin-fixed VX2 rabbit cancer specimen with 15-mm in diameter. The PCCT system consisted of an asymmetrically cut silicon (220) crystal, a monolithic x-ray interferometer, a phase-shifter, an object cell and an x-ray CCD camera. The PCCT at 35 keV clearly visualized various inner structures of VX2 rabbit cancer such as necrosis, cancer, the surrounding tumor vessels, and normal liver tissue. Besides, image-contrast was not degraded significantly. These results suggest that the PCCT at 35 KeV is sufficient to clearly depict the histopathological morphology of VX2 rabbit cancer specimen.

  16. Uncommon liver tumors

    Science.gov (United States)

    Wu, Chia-Hung; Chiu, Nai-Chi; Yeh, Yi-Chen; Kuo, Yu; Yu, Sz-Shian; Weng, Ching-Yao; Liu, Chien-An; Chou, Yi-Hong; Chiou, Yi-You

    2016-01-01

    Abstract Background: Beside hepatocellular carcinoma, metastasis, and cholangiocarcinoma, the imaging findings of other relatively uncommon hepatic lesions are less discussed in the literature. Imaging diagnosis of these lesions is a daily challenge. In this article, we review the imaging characteristics of these neoplasms. Methods: From January 2003 to December 2014, 4746 patients underwent liver biopsy or hepatic surgical resection in our hospital. We reviewed the pathological database retrospectively. Imaging of these lesions was reviewed. Results: Imaging findings of uncommon hepatic lesions vary. We discuss the typical imaging characteristics with literature review. Clinical and pathological correlations are also described. Primary hepatic lymphoma consists only of 1% of the extranodal non-Hodgkin lymphoma, and is defined as the one involving only the liver and perihepatic lymph nodes within 6 months after diagnosis. Combined hepatocellular and cholangiocarcinoma (cHCC-CC) shares some overlapping imaging characteristics with both HCC and cholangiocarcinoma because of being an admixture of them. Angiosarcoma is the most common hepatic mesenchymal tumor and is hypervascular in nature. Inflammatory pseudotumor is often heterogeneous on ultrasonography and with enhanced septations and rims in the portovenous phase after contrast medium. Angiomyolipoma (AML) typically presents with macroscopic fat components with low signal on fat-saturated magnetic resonance imaging (MRI) and presence of drainage vessels. Intraductal papillary neoplasm of the bile duct (IPNB) is thought of as a counterpart to the pancreatic intraductal papillary mucinous neoplasm. Most of the IPNBs secrete mucin and cause disproportional dilatation of the bile ducts. Mucinous cystic neoplasm (MCN) contains proteinaceous and colloidal components without ductal communication and characterizes with hyperintensity on T1-weighted imaging. Other extremely rare lesions, including epithelioid

  17. Immunological treatment of liver tumors

    Institute of Scientific and Technical Information of China (English)

    Maurizio Chiriva-Internati; Fabio Grizzi; Cynthia A Jumper; Everardo Cobos; Paul L Hermonat; Eldo E Frezza

    2005-01-01

    Although multiple options for the treatment of liver tumors have often been described in the past, including liver resection, radiofrequency ablation with or without hepatic pump insertion, laparoscopic liver resection and the use of chemotherapy, the potential of immunotherapy and gene manipulation is still largely unexplored.Immunological therapy by gene manipulation is based on the interaction between virus-based gene delivery systems and dendritic cells. Using viruses as vectors, it is possible to transduce dendritic cells with genes encoding tumor-associated antigens, thus inducing strong humoral and cellular immunity against the antigens themselves.Both chemotherapy and radiation therapy have the disadvantage of destroying healthy cells, thus causing severe side-effects. We need more precisely targeted therapies capable of killing cancer cells while sparing healthy cells. Our goal is to establish a new treatment for solid liver tumors based on the concept of cytoreduction,and propose an innovative algorithm.

  18. High-intensity Focused Ultrasound Ablation of Soft-tissue Tumors and Assessment of Treatment Response with Multiparametric Magnetic Resonance Imaging: Preliminary Study Using Rabbit VX2 Tumor Model

    Directory of Open Access Journals (Sweden)

    Kyung Won Kim

    2014-06-01

    Conclusion: Extracorporeal HIFU treatment for soft-tissue tumor may be a feasible approach with adjustment of input energy level. For post-treatment assessment, functional MRI techniques including DCE-MRI and ADC map may be useful and complementary to conventional MRI.

  19. Pediatric liver tumors--a pictorial review.

    Science.gov (United States)

    Jha, Priyanka; Chawla, Soni C; Tavri, Sidhartha; Patel, Chirag; Gooding, Charles; Daldrup-Link, Heike

    2009-01-01

    Hepatic masses constitute about 5-6% of all intra-abdominal masses in children. The majority of liver tumors in children are malignant; these malignant liver tumors constitute the third most common intra-abdominal malignancy in the pediatric age group after Wilms' tumor and neuroblastoma. Only about one third of the liver tumors are benign. A differential diagnosis of liver tumors in children can be obtained based on the age of the child, clinical information (in particular AFP) and imaging characteristics. The purpose of this review is to report typical clinical and imaging characteristics of benign and malignant primary liver tumors in children.

  20. Pediatric liver tumors - a pictorial review

    Energy Technology Data Exchange (ETDEWEB)

    Jha, Priyanka; Tavri, Sidhartha; Patel, Chirag; Gooding, Charles; Daldrup-Link, Heike [University of California, San Francisco, Department of Radiology, San Francisco, CA (United States); Chawla, Soni C. [Department of Radiological Sciences 2D115, Olive View-UCLA Medical Center, Sylmar, CA (United States)

    2009-01-15

    Hepatic masses constitute about 5-6% of all intra-abdominal masses in children. The majority of liver tumors in children are malignant; these malignant liver tumors constitute the third most common intra-abdominal malignancy in the pediatric age group after Wilms' tumor and neuroblastoma. Only about one third of the liver tumors are benign. A differential diagnosis of liver tumors in children can be obtained based on the age of the child, clinical information (in particular AFP) and imaging characteristics. The purpose of this review is to report typical clinical and imaging characteristics of benign and malignant primary liver tumors in children. (orig.)

  1. Assessment of intratumor hypoxia by integrated 18F-FDG PET / perfusion CT in a liver tumor model

    Science.gov (United States)

    Wang, Yong; Stewart, Errol; Desjardins, Lise; Hadway, Jennifer; Morrison, Laura; Crukley, Cathie

    2017-01-01

    Objectives Hypoxia in solid tumors occurs when metabolic demands in tumor cells surpass the delivery of oxygenated blood. We hypothesize that the 18F-fluorodeoxyglucose (18F-FDG) metabolism and tumor blood flow mismatch would correlate with tumor hypoxia. Methods Liver perfusion computed tomography (CT) and 18F-FDG positron emission tomography (PET) imaging were performed in twelve rabbit livers implanted with VX2 carcinoma. Under CT guidance, a fiber optic probe was inserted into the tumor to measure the partial pressure of oxygen (pO2). Tumor blood flow (BF) and standardized uptake value (SUV) were measured to calculate flow-metabolism ratio (FMR). Tumor hypoxia was further identified using pimonidazole immunohistochemical staining. Pearson correlation analysis was performed to determine the correlation between the imaging parameters and pO2 and pimonidazole staining. Results Weak correlations were found between blood volume (BV) and pO2 level (r = 0.425, P = 0.004), SUV and pO2 (r = -0.394, P = 0.007), FMR and pimonidazole staining score (r = -0.388, P = 0.031). However, there was stronger correlation between tumor FMR and pO2 level (r = 0.557, P < 0.001). Conclusions FMR correlated with tumor oxygenation and pimonidazole staining suggesting it may be a potential hypoxic imaging marker in liver tumor. PMID:28264009

  2. Cyst and tumor of liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008313 Significance of Golgi glycoprotein 73,a new tumor marker in the diagnosis of hepatocellular carcinoma:a primary study.MAO Yilei(毛一雷),et al.Dept Liver Surgery,PUMC & CAMS,Beijing 100730.Natl Med J China 2008;88(14):945-948.Objective To evaluate the sensitivity and specificity of Golgi glycoprotein 73(GP73)for the diagnosis of hepatitis B related hepatocelluar carcinoma(HCC).

  3. Quantiifcation of angiogenesis by CT perfusion imaging in liver tumor of rabbit

    Institute of Scientific and Technical Information of China (English)

    Hui-Jie Jiang; Zai-Ren Zhang; Bao-Zhong Shen; Yong Wan; Hong Guo; Jin-Ping Li

    2009-01-01

    BACKGROUND: Tumor angiogenesis is essential for primary and metastatic tumor growth. Computed tomography perfusion (CTP) is a new imaging method, made possible by the recent development of fast CT scanners and improved data analysis techniques, which allows measurement of the physiologic and hemodynamic properties of tissue vasculature. This study aimed to evaluate CTP in the quantiifcation of angiogenesis and to assess the relationship between tissue perfusion parameters and microvascular density (MVD) and vascular endothelial growth factor (VEGF), attempting to detect the physiologic properties of angiogenesis. METHODS: Sixteen rabbits with VX2 liver tumors underwent multi-slice CT perfusion (MSCTP) on day 14 after tumor inoculation. CTP parameters included hepatic blood lfow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic artery index (HAI), hepatic artery perfusion (HAP), and hepatic portal perfusion (HPP). The border of the tumor was stained with CD34 and VEGF immunohistochemical stains, and MVD was measured by anti-CD34. Then, CTP parameters were determined whether they were correlated with MVD and VEGF using Pearson’s correlation coefifcient. RESULTS: The positive expression of MVD was different in the center and border of the tumor (P0.05). CONCLUSIONS: Signiifcant correlations were found between perfusion parameters and MVD and VEGF. Therefore, MSCTP can be used to evaluate tumor angiogenesisin vivo.

  4. The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

    Energy Technology Data Exchange (ETDEWEB)

    Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo Cheol; Yoon, Jung Hwan; Park, Jae Hyung [Seoul National University Hospital, Seoul (Korea, Republic of); Chung, He Son [Korea Institute of Science and Technology, Seoul (Korea, Republic of)

    2009-12-15

    The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3- BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. The tumor necrosis rate was significantly higher in the high dose group (93% +- 7.6 [mean +- SD]) than that in the control group (48% +- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method

  5. Transcatheter Arterial Embolization of Renal VX-2 Carcinoma: Ethiodol-Ethanol Capillary Embolization Combined with Carboplatin

    Energy Technology Data Exchange (ETDEWEB)

    Konya, Andras; Pelt, Carolyn S. Van; Wright, Kenneth C. [The University of Texas MD Anderson Cancer Center, Hoston (United States); Choi, Byung Gil [The Catholic University of Korea, Seoul (Korea, Republic of)

    2007-04-15

    We wanted to determine whether transcatheter Ethiodol-based capillary embolization in combination with carboplatin could improve the efficiency of a 1:1 Ethiodol-ethanol mixture (EEM) to ablate kidneys that been inoculated with VX-2 carcinoma. The right kidney in 34 New Zealand white rabbits were inoculated with fresh VX-2 tumor fragments. One week later, the kidneys were subjected to transarterial treatment (4-5 rabbits/group): Saline infusion (Group 1); carboplatin infusion (5 or 10 mg, Groups 2A and 2B); carboplatin- Ethiodol (CE) alone (Group 3) and followed by main renal artery occlusion with ethanol (RAO) (Group 4); carboplatin-EEM (C-EEM) followed by RAO (Group 5); carboplatin infusion followed by EEM plus RAO (Group 6); and EEM followed by RAO (Group 7). The animals were followed for up to 3-weeks. The treated kidneys were evaluated angiographically and macroscopically. The kidneys that showed successful embolization macroscopically were entirely cut into serial sections, and these were examined microscopically. Histologically, the kidneys were evaluated on the basis of the residual tumor found in the serial sections. The results obtained with carboplatin infusion alone (Groups 2A and 2B) and CE without RAO (Group 3) were similar to those of the control animals (Group 1). Kidneys from Groups 4-7 demonstrated macroscopically successful embolization with histologically proven complete renal parenchyma infarction; however, some residual tumor was evident in all but one animal. None of the Ethiodol-based modalities combined with locoregional carboplatin were more efficacious for tumor ablation than EEM alone.

  6. Cyst and tumor of liver

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950340 Radioimmunoassay of acid isoferritin in pa-tients with primary liver cancer.LI Liren(李立人),etal.Dept Nucl Med,Guangdong Prov People’s Hosp,Guangzhou,Chin J Clin Oncol 1995;22(1):24-26.In order to measure the levels of serum acid isofer-ritin(AIF) in healthy subjects and patients with pri-mary liver caner (PLC).AIF were titrated with ra-dioimmunoassay technic in 128 cases of PLC,37 casesof liver cirrhosis (LC),as well as 60 healthy subjects.The AIF values in serum of healthy subjects were 112

  7. The cooperative effect of p53 and Rb in local nanotherapy in a rabbit VX2 model of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Dong S

    2013-10-01

    Full Text Available Shengli Dong,1 Qibin Tang,2 Miaoyun Long,3 Jian Guan,4 Lu Ye,5 Gaopeng Li6 1Department of General Surgery, The Second Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, Shanxi Province, 2Department of Hepatobiliopancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 3Department of Thyroid and Vascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 4Department of Radiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 5Infection Department, Guangzhou No 8 Hospital, Guangzhou, Guangdong Province, 6Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China Background/aim: A local nanotherapy (LNT combining the therapeutic efficacy of trans-arterial embolization, nanoparticles, and p53 gene therapy has been previously presented. The study presented here aimed to further improve the incomplete tumor eradication and limited survival enhancement and to elucidate the molecular mechanism of the LNT. Methods: In a tumor-targeting manner, recombinant expressing plasmids harboring wild-type p53 and Rb were either co-transferred or transferred separately to rabbit hepatic VX2 tumors in a poly-L-lysine-modified hydroxyapatite nanoparticle nanoplex and Lipiodol® (Guerbet, Villepinte, France emulsion via the hepatic artery. Subsequent co-expression of p53 and Rb proteins within the treated tumors was investigated by Western blotting and in situ analysis by laser-scanning confocal microscopy. The therapeutic effect was evaluated by the tumor growth velocity, apoptosis and necrosis rates, their sensitivity to Adriamycin® (ADM, mitomycin C, and fluorouracil, the microvessel density of tumor tissue, and the survival time of animals. Eventually, real-time polymerase chain reaction and enhanced chemiluminescence Western blotting

  8. Malignant tumors of the liver in children.

    Science.gov (United States)

    Aronson, Daniel C; Meyers, Rebecka L

    2016-10-01

    This article aims to give an overview of pediatric liver tumors; in particular of the two most frequently occurring groups of hepatoblastomas and hepatocellular carcinomas. Focus lays on achievements gained through worldwide collaboration. We present recent advances in insight, treatment results, and future questions to be asked. Increasing international collaboration between the four major Pediatric Liver Tumor Study Groups (SIOPEL/GPOH, COG, and JPLT) may serve as a paradigm to approach rare tumors. This international effort has been catalyzed by the Children's Hepatic tumor International Collaboration (CHIC) formation of a large collaborative database. Interrogation of this database has led to a new universal risk stratification system for hepatoblastoma using PRETEXT/POSTTEXT staging as a backbone. Pathologists in this international collaboration have established a new histopathological consensus classification for pediatric liver tumors. Concomitantly there have been advances in chemotherapy options, an increased role of liver transplantation for unresectable tumors, and a web portal system developed at www.siopel.org for international education, consultation, and collaboration. These achievements will be further tested and validated in the upcoming Paediatric Hepatic International Tumour Trial (PHITT). Copyright © 2016 Elsevier Inc. All rights reserved.

  9. [Epithelioid hemangioendothelioma: an uncommon liver tumor].

    Science.gov (United States)

    Pareja, Eugenia; Cortés, Miriam; Rayon, Miguel; Moya, Angel; Mir, Jose

    2010-01-01

    We report the case of a female patient who was referred to our unit because of a solid liver tumor, suggestive of metastasis. After biopsy, the patient was diagnosed with epithelioid hemangioendothelioma of the liver. Epithelioid hemangioendothelioma is a rare entity with an unpredictable, potentially fatal, clinical course and outcome. Due to its rarity, this entity should be considered when a solitary hepatic lesion is detected and should be included in the differential diagnosis with liver metastases. We highlight the infrequency of this tumor, its presentation as a solitary hepatic lesion and the indication of surgical treatment. We describe the clinical and pathological characteristics of epithelioid hemangioendothelioma of the liver and report a new case of this entity. The distinct therapeutic options are discussed. Copyright 2010 Elsevier España, S.L. All rights reserved.

  10. Aggressive surgery for metastatic liver neuroendocrine tumors.

    Science.gov (United States)

    Norton, Jeffrey A; Warren, Robert S; Kelly, Mary G; Zuraek, Marlene B; Jensen, Robert T

    2003-12-01

    Neuroendocrine tumors of the gastrointestinal tract (carcinoids, pancreatic endocrine tumors) have low malignant potential but can decrease survival rates if they spread to the liver (LNET). The records of 16 patients with LNET primarily from gastrointestinal carcinoids treated surgically were retrospectively reviewed. There were 12 women and 4 men. Median age was 56 years (range 25 to 75). Thirteen (81%) had a carcinoid tumor and 5 had gastrinoma. Two patients with multiple endocrine neoplasia type 1 had both a gastric carcinoid and a jejunal gastrinoma. Eight patients (50%) had the carcinoid syndrome. Each patient had all identifiable LNET either resected or ablated. Ten patients had liver wedge resections, 1 right trisegmentectomy, 5 left hepatic lobectomies, and 2 radiofrequency ablations. Thirteen (81%) patients had concomitant bowel resections. Two patients had concomitant total gastrectomies to remove stomach primaries. The final patient had an extraintestinal pelvic primary or a liver primary. There were no operative deaths, and all 8 (100%) patients with the carcinoid syndrome had amelioration of symptoms. The 5-year actuarial survival rate was 82% with a median follow-up of 32 months. This study demonstrates that liver and concomitant extrahepatic surgery can be performed safely in patients with liver metastases because of carcinoids or pancreatic endocrine tumors. It results in excellent long-term survival and amelioration of symptoms. Surgery should be the first-line therapy for patients with LNET.

  11. Radiofrequency ablation in the treatment of liver tumors in children

    NARCIS (Netherlands)

    van Laarhoven, Stijn; van Baren, Robertine; Tamminga, Rienk Yde Johan; de Jong, Koert Pieter

    Hepatoblastoma and liver metastasis of Wilms' tumors are rare hepatic tumors in children. Treatment of both tumors consists of a combination of chemotherapy and liver surgery. Radiofrequency ablation (RFA) is frequently used for the treatment of adult liver tumors but is rarely mentioned as a

  12. Cyst and tumor of liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930145 Incidence of human hepatitis B virus(HBV)DNA sequence present in duck hepaticcancer collected from Qidong.JIANG Huiqiu(蒋惠秋),GU Jianren(顾建人).Nation Onco-gene & Relate Gene Lab.,Shanghai Cancer In-stir.Tumor 1992;12(5):206-207.Previous reports have described the identifica-tion and molecular cloning of human HBV DNAsequence in duck hepatoma collected from Qi-Dong.The human HBV-like DNA was se-quenced and it had been demonstrated that theHBV DNA present in duck hepatoma was nothomologous to DHBV,but highly homologous

  13. Primary malignant liver mesenchymal tumor: A case report

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Primary malignant liver mesenchymal tumor is a rare condition defined as a tumor with vascular, fibrous, adi-pose, and other mesenchymal tissue differentiation. We report a case of primary malignant liver mesenchymal tumor in a 51-year-old male with anemia, weight loss and hepatomegaly. Finally unconventional liver biopsy and histological manifestation led to the definitive diag-nosis.

  14. Segmentation of liver and liver tumor for the Liver-Workbench

    Science.gov (United States)

    Zhou, Jiayin; Ding, Feng; Xiong, Wei; Huang, Weimin; Tian, Qi; Wang, Zhimin; Venkatesh, Sudhakar K.; Leow, Wee Kheng

    2011-03-01

    Robust and efficient segmentation tools are important for the quantification of 3D liver and liver tumor volumes which can greatly help clinicians in clinical decision-making and treatment planning. A two-module image analysis procedure which integrates two novel semi-automatic algorithms has been developed to segment 3D liver and liver tumors from multi-detector computed tomography (MDCT) images. The first module is to segment the liver volume using a flippingfree mesh deformation model. In each iteration, before mesh deformation, the algorithm detects and avoids possible flippings which will cause the self-intersection of the mesh and then the undesired segmentation results. After flipping avoidance, Laplacian mesh deformation is performed with various constraints in geometry and shape smoothness. In the second module, the segmented liver volume is used as the ROI and liver tumors are segmented by using support vector machines (SVMs)-based voxel classification and propagational learning. First a SVM classifier was trained to extract tumor region from one single 2D slice in the intermediate part of a tumor by voxel classification. Then the extracted tumor contour, after some morphological operations, was projected to its neighboring slices for automated sampling, learning and further voxel classification in neighboring slices. This propagation procedure continued till all tumorcontaining slices were processed. The performance of the whole procedure was tested using 20 MDCT data sets and the results were promising: Nineteen liver volumes were successfully segmented out, with the mean relative absolute volume difference (RAVD), volume overlap error (VOE) and average symmetric surface distance (ASSD) to reference segmentation of 7.1%, 12.3% and 2.5 mm, respectively. For live tumors segmentation, the median RAVD, VOE and ASSD were 7.3%, 18.4%, 1.7 mm, respectively.

  15. [Histopathological differential diagnosis of primary liver tumors].

    Science.gov (United States)

    Honsová, E

    2014-03-01

    The most common primary hepatic malignancy is hepatocellular carcinoma, which constitutes 80-85% of all malignant epithelial neoplasms originating in the liver. The second most common primary hepatic malignancy is cholangiocellular carcinoma. In recent years, remarkable progress has been made in elucidating the molecular pathology of hepatic tumors. Advances in our understanding of molecular subtypes have led to a creation of a new classification system of hepatocellular adenomas, with important genotype-phenotype correlations and easy application to routine diagnostic practice. In the field of early hepatic neoplasia, a consensus on the definition of dysplastic nodules and early hepatocellular carcinoma has been reached. Immunohistochemical detection of glypican-3 and stromal invasion are used for the differential diagnosis. A lot of problems still exist in the category of mixed hepatocellular and cholangiocellular carcinoma. Although this category is recognized in the WHO classification, confusing terminology has been generated to describe tumors with morphological features of both HCC and CC. We further specify problems and pitfalls of the differential histopathological diagnosis of liver malignant tumors.

  16. Localized fibrous tumor of the liver: imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Lecesne, R.; Drouillard, J.; Laurent, F. [Service d`Imagerie Medicale-Radiologie Diagnostique et Therapeutique, Hopital du Haut-Leveque, CHU Bordeaux, Pessac (France); Le Bail, B. [Department d`Anatomie et Cytologie Pathologiques, Groupe Hospitalier Pellegrin, CHU Bordeaux, Place Amelie Raba-Leon, Bordeaux (France); Saric, J. [Service de Chirurgie Digestive, Groupe Saint-Andre, CHU Bordeaux (France); Balabaud, C. [Service des Maladies de L`Appareil Digestif, Groupe Saint-Andre, CHU Bordeaux (France)

    1998-02-01

    We report the imaging of a localized fibrous tumor of the liver, focusing on color Doppler US, CT, MR imaging, and angiographic findings. We discuss the differential diagnosis of such a rare, benign lesion of the liver. Detailed imaging of this tumor has not been reported in the literature previously. (orig.) With 6 figs., 10 refs.

  17. Dietary sugar intake increases liver tumor incidence in female mice

    OpenAIRE

    Marin E. Healy; Sujoy Lahiri; Hargett, Stefan R.; Chow, Jenny D.Y.; Byrne, Frances L.; Breen, David S.; Kenwood, Brandon M.; Taddeo, Evan P.; Carolin Lackner; Caldwell, Stephen H.; Hoehn, Kyle L.

    2016-01-01

    Overnutrition can promote liver cancer in mice and humans that have liver damage caused by alcohol, viruses, or carcinogens. However, the mechanism linking diet to increased liver tumorigenesis remains unclear in the context of whether tumorigenesis is secondary to obesity, or whether nutrients like sugar or fat drive tumorigenesis independent of obesity. In male mice, liver tumor burden was recently found to correlate with sugar intake, independent of dietary fat intake and obesity. However,...

  18. In vivo magnetic resonance spectroscopy of liver tumors and metastases

    Institute of Scientific and Technical Information of China (English)

    EGW ter Voert; L Heijmen; HWM van Laarhoven; A Heerschap

    2011-01-01

    Primary liver cancer is the fifth most common malignancy in men and the eighth in women worldwide. The liver is also the second most common site for metastatic spread of cancer. To assist in the diagnosis of these liver lesions non-invasive advanced imaging techniques are desirable. Magnetic resonance (MR) is commonly used to identify anatomical lesions, but it is a very versatile technique and also can provide specific information on tumor pathophysiology and metabolism,in particular with the application of MR spectroscopy (MRS). This may include data on the type, grade and stage of tumors, and thus assist in further management of the disease. The purpose of this review is to summarize and discuss the available literature on proton, phosphorus and carbon-13-MRS as performed on primary liver tumors and metastases, with human applications as the main perspective. Upcoming MRS approaches with potential applications to liver tumors are also included. Since knowledge of some technical background is indispensable to understand the results, a basic introduction of MRS and some technical issues of MRS as applied to tumors and metastases in the liver are described as well. In vivo MR spectroscopy of tumors in a metabolically active organ such as the liver has been demonstrated to provide important information on tumor metabolism, but it also is challenging as compared to applications on some other tissues, in particular in humans, mostly because of its abdominal location where movement may be a disturbing factor.

  19. Pancreatic neuroendocrine tumor accompanied with multiple liver metastases

    Institute of Scientific and Technical Information of China (English)

    Tomohide; Hori; Kyoichi; Takaori; Shinji; Uemoto

    2014-01-01

    Pancreatic neuroendocrine tumor(P-NET) is rare and slow-growing. Current classifications predict its progno-sis and postoperative recurrence. Curative resection is ideal, although often difficult, because over 80% of pa-tients have unresectable multiple liver metastases and extrahepatic metastasis. Aggressive surgery for liver metastases is important to improve survival. Aggressive or cytoreductive surgery for liver metastases is indi-cated to reduce hormone levels and improve symptoms and prognosis. Liver transplantation was originally con-ceived as an ideal therapy for unresectable liver metas-tases. Unfortunately, there is no clear consensus on the role and timing of surgery for primary tumor and liver metastases. Surgeons still face questions in deciding the best surgical scenario in patients with P-NET with unresectable liver metastases.

  20. Dietary sugar intake increases liver tumor incidence in female mice.

    Science.gov (United States)

    Healy, Marin E; Lahiri, Sujoy; Hargett, Stefan R; Chow, Jenny D Y; Byrne, Frances L; Breen, David S; Kenwood, Brandon M; Taddeo, Evan P; Lackner, Carolin; Caldwell, Stephen H; Hoehn, Kyle L

    2016-02-29

    Overnutrition can promote liver cancer in mice and humans that have liver damage caused by alcohol, viruses, or carcinogens. However, the mechanism linking diet to increased liver tumorigenesis remains unclear in the context of whether tumorigenesis is secondary to obesity, or whether nutrients like sugar or fat drive tumorigenesis independent of obesity. In male mice, liver tumor burden was recently found to correlate with sugar intake, independent of dietary fat intake and obesity. However, females are less susceptible to developing liver cancer than males, and it remains unclear how nutrition affects tumorigenesis in females. Herein, female mice were exposed to the liver carcinogen diethylnitrosamine (DEN) and fed diets with well-defined sugar and fat content. Mice fed diets with high sugar content had the greatest liver tumor incidence while dietary fat intake was not associated with tumorigenesis. Diet-induced postprandial hyperglycemia and fasting hyperinsulinemia significantly correlated with tumor incidence, while tumor incidence was not associated with obesity and obesity-related disorders including liver steatosis, glucose intolerance, or elevated serum levels of estrogen, ALT, and lipids. These results simplify the pathophysiology of diet-induced liver tumorigenesis by focusing attention on the role of sugar metabolism and reducing emphasis on the complex milieu associated with obesity.

  1. Primitive neuroectodermal tumor of the liver: a case report.

    Science.gov (United States)

    Mani, Siddhartha; Dutta, Deep; De, Binay K

    2010-03-01

    Ewing sarcoma/primitive neuroectodermal tumor is a rare tumor of soft tissues of thoraco-pulmonary regions, pelvis and lower extremities. Involvement of visceral organs by primitive neuroectodermal tumor is even rarer, with the kidney being the most commonly involved organ. Involvement of the liver has been reported in the form of metastasis from other primary sources presenting as liver abscess. We report a 20-year-old lady presenting with massive hepatomegaly, with computed tomography scan evidence of diffuse hepatomegaly and a normal porta and intrahepatic biliary radicles. She subsequently underwent ultrasonography-guided true-cut needle biopsy of the liver. Histopathology of the liver revealed nests of small round blue tumor cells in the background of hepatocytes infiltrating the liver, which expressed Mic-2 and Fli-1, and were negative for cytokeratin, desmin, hepatocyte-specific antigen (OCHIE5), synaptophysin, chromogranin A and CD-20. Immunohistochemistry revealed CD-99-positive. Extensive search regarding any possible different site of involvement by the tumor was negative. The patient responded to a combination therapy of vincristine, adriamycin and cyclophosphamide alternating with ifosfamide and etoposide 3 weekly over 43 weeks and has been doing well even after 1 year of diagnosis. The clinical presentation, the macroscopic aspect, together with the histological pattern, the cytological characteristic and the cellular immunophenotype lead to the diagnosis of primary primitive neuroectodermal tumor of the liver which responded well to combination chemotherapy.

  2. Localization of liver tumors in freehand 3D laparoscopic ultrasound

    Science.gov (United States)

    Shahin, O.; Martens, V.; Besirevic, A.; Kleemann, M.; Schlaefer, A.

    2012-02-01

    The aim of minimally invasive laparoscopic liver interventions is to completely resect or ablate tumors while minimizing the trauma caused by the operation. However, restrictions such as limited field of view and reduced depth perception can hinder the surgeon's capabilities to precisely localize the tumor. Typically, preoperative data is acquired to find the tumor(s) and plan the surgery. Nevertheless, determining the precise position of the tumor is required, not only before but also during the operation. The standard use of ultrasound in hepatic surgery is to explore the liver and identify tumors. Meanwhile, the surgeon mentally builds a 3D context to localize tumors. This work aims to upgrade the use of ultrasound in laparoscopic liver surgery. We propose an approach to segment and localize tumors intra-operatively in 3D ultrasound. We reconstruct a 3D laparoscopic ultrasound volume containing a tumor. The 3D image is then preprocessed and semi-automatically segmented using a level set algorithm. During the surgery, for each subsequent reconstructed volume, a fast update of the tumor position is accomplished via registration using the previously segmented and localized tumor as a prior knowledge. The approach was tested on a liver phantom with artificial tumors. The tumors were localized in approximately two seconds with a mean error of less than 0.5 mm. The strengths of this technique are that it can be performed intra-operatively, it helps the surgeon to accurately determine the location, shape and volume of the tumor, and it is repeatable throughout the operation.

  3. Intra-Arterial Treatment of Primary and Metastatic Liver Tumors

    NARCIS (Netherlands)

    Buijs, M.A.M.; Vossen, J.A.

    2009-01-01

    The aims of this thesis were, first, to investigate the toxicities associated with trans-arterial chemoembolization (TACE) of liver tumors and to evaluate the use of MR imaging in characterizing tumor response after this locoregional therapy, second, to further develop intra-arterial therapy of live

  4. Biopsy of solid liver tumors:adverse consequences

    Institute of Scientific and Technical Information of China (English)

    Dhya Al-Leswas; Derek A O'Reilly; Graeme J Poston

    2008-01-01

    BACKGROUND:Percutaneous radiologically-guided liver biopsy is used routinely worldwide in all secondary-level hospital centers. While it has an undoubted role in the investigation and management of acute and chronic inlfammatory conditions of the liver, its role in hepatic oncology is doubtful and probably dangerous. METHOD:We report on two patients who underwent preoperative biopsy of potentially resectable liver tumors. RESULTS:At the time of surgery, there was evidence of seeding at the biopsy site in both cases. In case 1, potentially curative liver resection was rendered incurable because of gross peritoneal carcinomatosis lying adjacent to the site of liver biopsy. In case 2, the patient underwent curative liver resection, but there was histopathological evidence of peritoneal disease beyond the liver capsule along the falciform ligament at the site of the previous biopsy. CONCLUSIONS:No patient with a suspicious liver tumor which is thought to be malignant and has any possibility of being a potential candidate for liver surgery, should be subjected to pre-operative diagnostic biopsy in a non-specialist center.

  5. An Organotypic Liver System for Tumor Progression

    Science.gov (United States)

    2007-04-01

    parenchymal cells from the GFP- transgenic rats establish channel-filled organoid cultures in the bioreactor similar to non-GFP- transgenic animal ...Task 3. Seed bioreactors with cells. This task has been fully established. We have generated liver bioreactors with transgenic hepatocytes and...novel technology, liver, bioreactor 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE

  6. Sentinel Node Mapping of VX2 Carcinoma in Rabbit Thigh with CT Lymphography Using Ethiodized Oil

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yoon Jin; Kim, Young Hoon; Lee, Kyoung Ho; Park, Ji Hoon [Department of Radiology, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of); Lee, Hye Seung [Department of Pathology, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of); Jung, Seung Chai [Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Joo, Seung-Moon [Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 135-720 (Korea, Republic of)

    2014-07-01

    To assess the feasibility of computed tomography (CT) lymphography using ethiodized oil for sentinel node mapping in experimentally induced VX2 carcinoma in the rabbit thigh. This experiment received approval from the institutional animal use and care administrative advisory committee. Twenty-three rabbits with VX2 carcinoma in the thigh underwent CT before and after (1 hour, 2 hour) peritumoral injection of 2 mL ethiodized oil. After the CT examination, sentinel nodes were identified by peritumoral injection of methylene blue and subsequently removed. The retrieved sentinel and non-sentinel lymph nodes were investigated with radiographic and pathologic examinations. Based on the comparison of CT findings with those of radiographic and pathologic examinations, the diagnostic performance of CT for sentinel node identification was assessed. All 23 rabbits showed 53 ethiodized oil retention nodes on post-injection CT and specimen radiography, and 52 methylene blue-stained nodes at the right femoroiliac area. Of the 52 blue-stained sentinel nodes, 50 nodes demonstrated ethiodized oil retention. Thus, the sentinel node detection rate of CT was 96% (50 of 52). On pathologic examination, 28 sentinel nodes in 17 rabbits (nodes/rabbit, mean ± standard deviation, 1.7 ± 0.6) harbored metastasis. Twenty seven of the 28 metastatic sentinel nodes were found to have ethiodized oil retention. Computed tomography lymphography using ethiodized oil may be feasible for sentinel node mapping in experimentally induced VX2 carcinoma in the rabbit thigh.

  7. File list: Oth.Liv.05.AllAg.Liver_tumor [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  14. File list: InP.Liv.50.AllAg.Liver_tumor [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: ALL.Liv.10.AllAg.Liver_tumor [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  18. Application of neutron capture autoradiography to Boron Delivery seeking techniques for selective accumulation of boron compounds to tumor with intra-arterial administration of boron entrapped water-in-oil-in-water emulsion

    Energy Technology Data Exchange (ETDEWEB)

    Mikado, S. [Physical Science Laboratories, College of Industrial Technology, Nihon University, Chiba (Japan)], E-mail: mikado@cit.nihon-u.ac.jp; Yanagie, H. [Department of Nuclear Engineering and Management, University of Tokyo, Tokyo (Japan); Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Yasuda, N. [Fundamental Technology Center, National Institute of Radiological Sciences, Chiba (Japan); Higashi, S.; Ikushima, I. [Miyakonojyo Metropolitan Hospital, Miyazaki (Japan); Mizumachi, R.; Murata, Y. [Department of Pharmacology, Kumamoto Institute Branch, Mitsubishi Chemical Safety Institute Ltd., Kumamoto (Japan); Morishita, Y. [Department of Human and Molecular Pathology, University of Tokyo, Tokyo (Japan); Nishimura, R. [Faculty of Agriculture, Laboratory of Veterinary Surgery, University of Tokyo (Japan); Shinohara, A. [Department of Humanities, The Graduate School of Seisen University, Tokyo (Japan); Ogura, K. [Physical Science Laboratories, College of Industrial Technology, Nihon University, Chiba (Japan); Sugiyama, H. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Iikura, H.; Ando, H. [Japan Atomic Energy Agency, Ibaraki (Japan); Ishimoto, M. [Department of Nuclear Professional School, University of Tokyo (Japan); Takamoto, S. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Department of Cardiac Surgery, University of Tokyo Hospital, Tokyo (Japan); Eriguchi, M. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Department of Microbiology, Syowa University School of Pharmaceutical Sciences, Tokyo (Japan); Takahashi, H. [Department of Nuclear Engineering and Management, University of Tokyo, Tokyo (Japan); Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Kimura, M. [Department of Physics, Toho University, Chiba (Japan)

    2009-06-21

    It is necessary to accumulate the {sup 10}B atoms selectively to the tumor cells for effective Boron Neutron Capture Therapy (BNCT). In order to achieve an accurate measurement of {sup 10}B accumulations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of sliced samples of tumor tissues using CR-39 plastic track detectors. The CR-39 track detectors attached with the biological samples were exposed to thermal neutrons in the thermal column of the JRR3 of Japan Atomic Energy Agency (JAEA). We obtained quantitative NCAR images of the samples for VX-2 tumor in rabbit liver after injection of {sup 10}BSH entrapped water-in-oil-in-water (WOW) emulsion by intra-arterial injection via proper hepatic artery. The {sup 10}B accumulations and distributions in VX-2 tumor and normal liver of rabbit were investigated by means of alpha-track density measurements. In this study, we showed the selective accumulation of {sup 10}B atoms in the VX-2 tumor by intra-arterial injection of {sup 10}B entrapped WOW emulsion until 3 days after injection by using digitized NCAR images (i.e. alpha-track mapping)

  19. Cutaneous Metastases from Primary Hepatobiliary Tumors as the First Sign of Tumor Recurrence following Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Adam T. Hauch

    2014-01-01

    Full Text Available Cutaneous metastasis from hepatobiliary tumors is a rare event, especially following liver transplantation. We report our experience with two cases of cutaneous metastases from both hepatocellular carcinoma and mixed hepatocellular/cholangiocarcinoma following liver transplantation, along with a review of the literature.

  20. Impaired Preneoplastic Changes and Liver Tumor Formation in Tumor Necrosis Factor Receptor Type 1 Knockout Mice

    OpenAIRE

    Knight, Belinda; Yeoh, George C.T.; Husk, Kirsten L.; Ly, Tina; Abraham, Lawrence J; Yu, Changpu; Rhim, Jonathan A.; Fausto, Nelson

    2000-01-01

    Hepatic stem cells (oval cells) proliferate within the liver after exposure to a variety of hepatic carcinogens and can generate both hepatocytes and bile duct cells. Oval cell proliferation is commonly seen in the preneoplastic stages of liver carcinogenesis, often accompanied by an inflammatory response. Tumor necrosis factor (TNF), an inflammatory cytokine, is also important in liver regeneration and hepatocellular growth. The experiments reported here explore the relationship among the TN...

  1. Therapeutic efifcacy and bone marrow protection of the mdr1 gene and over-dose chemotherapy with doxorubicin for rabbits with VX2 hepatocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Yi Wang; Xian-Qing Jin; Shan Wang; Qiao Wang; Qing Luo; Xiao-Ji Luo

    2006-01-01

    BACKGROUND: Malignant tumors are common diseases threatening to the health and life of human being. Clinically, the multidrug resistance of tumor cells and bone marrow depression caused by chemotherapeutic agents are the main obstacles to the treatment of tumors, and both are related to the mdr1 gene. The over expression of the mdr1 gene in tumor cells contributes to the multidrug resistance of malignant tumor cells. With little expression of the mdr1 gene, bone marrow cells particularly susceptible to multidrug resistance-sensitive agents, which cause serious toxicity in bone marrow. This study was undertaken to assess therapeutic efifcacy of transplantation of bone marrow mononuclear cells transferred with the mdr1 gene and over-dose chemotherapy with doxorubicin for VX2 hepatocarcinoma of rabbits. METHODS: The mdr1 gene was transferred into the bone marrow mononuclear cells of rabbits, which was co-cultured with retroviral vector-containing supernatant, and the cells were autotransplanted into a rabbit model with VX2 hepatocarcinoma. After chemotherapy with doxorubicin, the protective effects of the mdr1 gene and therapeutic efifcacy of over-dose chemotherapy were observed. RESULTS:The mdr1 gene was transferred successfully into the bone marrow mononuclear cells, with a transduction efifciency of 35%. After autotransplantation, the mdr1 gene was expressed functionally in bone marrow with a positive rate of 8%, indicating that the gene played an important role in bone marrow protection. The rabbits with VX2 hepatocarcinoma, which had received the mdr1 gene-transduced cells, survived after chemotherapy with a 3-fold dose of adriamycin, and their white blood cell counts were (4.26±1.03)×104/L. Since hepatocarcinoma cells were eradicated, the survival time (97.00±46.75 d) of the rabbits was extended (P CONCLUSIONS:The transferring of the mdr1 gene into bone marrow mononuclear cells could confer chemoprotection to bone marrow, and over-dose chemotherapy could be

  2. Transarterial chemoembolization for primary and metastatic liver tumors

    Directory of Open Access Journals (Sweden)

    Popov M.V.

    2016-12-01

    Full Text Available The literature review presents the methodology of transarterial chemoembolization (TACE — widely used method of treatment of primary and secondary liver tumors. The TACE role as a neoadjuvant therapy and the role in the management of unresectable primary and secondary liver tumors are shown. The morphofunctional basis of TACE, benefits of superselective intra-arterial administration of cytostatic agents especially in combination with ischemic impact on a tumor are described. The subject of the choice of the chemotherapeutic agent is also touched; modern drug-loaded microspheres which allow the use of higher doses of the chemotherapeutic drug without increasing systemic effect and prolong its effect on tumor are described. Lack of correlation of presence and severity of a post-embolization syndrome with success of the procedure is noted.

  3. Differential diagnosis and management of liver tumors in infants

    Institute of Scientific and Technical Information of China (English)

    Israel; Fernez-Pineda; Rosa; Cabello-Laureano

    2014-01-01

    During the first year of life, most of the liver neoplasms are benign in origin, but some of these histologically benign lesions may be challenging in their management. Although most hepatic hemangiomas can be safely observed until involution is documented, some patients will need treatment due to progressive hepatomegaly, hypothyroidism and/or cardiac failure. Large mesenchymal hamartomas may require extensive hepatic resection and an appropriate surgical plan is critical to obtain good results. For malignant neoplasms such as hepatoblastoma, complete surgical resection is the mainstay of curative therapy. The decision about whether to perform an upfront or delayed resection of a primary liver malignant tumor is based on many considerations, including the ease of resection, surgical expertise, tumor histology and stage, and the likely chemosensitivity of the tumor. This article reviews the initial management of the more common hepatic tumors of infancy, focusing on the differential diagnosis and treatment options.

  4. Accurate Targeting of Liver Tumors in Stereotactic Radiation Therapy

    NARCIS (Netherlands)

    W. Wunderink (Wouter)

    2011-01-01

    textabstractThis doctoral thesis concerns the treatment of liver cancer patients using external beam radiotherapy. The quality of this treatment greatly depends on delivering a high radiation dose to the tumor while keeping the dose as low as possible to surrounding healthy tissues. One of the major

  5. Ablation techniques for primary and metastatic liver tumors

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Ablative treatment methods have emerged as safe and effective therapies for patients with primary andsecondary liver tumors who are not surgical candidatesat the time of diagnosis. This article reviews the currentliterature and describes the techniques, complicationsand results for radiofrequency ablation, microwaveablation, cryoablation, and irreversible electroporation.

  6. Imaging infrared spectroscopy for fixation-free liver tumor detection

    Science.gov (United States)

    Coe, James V.; Chen, Zhaomin; Li, Ran; Butke, Ryan; Miller, Barrie; Hitchcock, Charles L.; Allen, Heather C.; Povoski, Stephen P.; Martin, Edward W.

    2014-03-01

    Infrared (IR) imaging spectroscopy of human liver tissue slices has been used to identify and characterize a liver metastasis of breast origin (mucinous carcinoma) which was surgically removed from a consenting patient and frozen without formalin fixation or dehydration procedures, so that lipids and water remain in the tissues. Previously, a set of IR metrics was determined for tumors in fixation-free liver tissues facilitating a k-means cluster analysis differentiating tumor from nontumor. Different and more in depth aspects of these results are examined in this work including three metric color imaging, differencing for lipid identification, and a new technique to simultaneously fit band lineshapes and their 2nd derivatives in order to better characterize protein changes.

  7. Different imaging findings of inflammatory myofibroblastic tumor of the liver

    Institute of Scientific and Technical Information of China (English)

    Xiao-Fei Liu; Bao-Ming He; Xiao-Hui Ou-Yang; Zhi-Zhong Wang; Jia-Gui Su

    2012-01-01

    Inflammatory myofibroblastic tumor (IMT) in the liver is an uncommon lesion of uncertain pathogenesis.In most cases,symptomatological imaging and clinical studies suggest malignancy.We report a case of liver IMT with imaging findings from positron emission tomography/computed tomography (PET/CT),contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasonography (CEUS).This report was the first to depict a PET/CT scan of a liver IMT that revealed an inhomogeneous,intense (fluorine 18)-fluoro-2-deoxy-D-glucose uptake.The CECT and CEUS images showed a hepatic artery supplying blood to the mass and necrosis.The characteristic histopathological features and the presence of spindle cells expressing smooth muscle actin,collagen fibers and lymphocytes allowed for the diagnosis of liver IMT.Recognizing such findings will help to achieve a correct diagnosis and may prevent inappropriate treatment.

  8. Effects of acetylsalicylic acid and acetic acid solutions in VX2 carcinoma cells: In vitro analysis Efeito da solução de ácido acetilsalicílico e de ácido acético sobre o carcinoma vx-2: Análise in vitro

    Directory of Open Access Journals (Sweden)

    Rogério Saad-Hossne

    2006-06-01

    Full Text Available PURPOSE: To analyze, in vitro, the effects of acetylsalicylic acid (aspirin and acetic acid solutions on VX2 carcinoma cells in suspension and to examine the correlation between these effects and neoplastic cell death. METHODS: The VX2 tumor cells (10(7 cells/ml were incubated in solutions containing differing concentrations (2.5% and 5% of either acetylsalicylic acid or acetic acid, or in saline solution (controls. Every five minutes, cell viability was tested (using the trypan blue test and analyzed under light microscopy. RESULTS: Tumor cell viability (in % decreased progressively and, by 30 minutes, neoplastic cell death had occurred in all solutions. CONCLUSION: Based on this experimental model and the methodology employed, we conclude that these solutions cause neoplastic cell death in vitro.OBJETIVO: Analisar os efeitos das soluções de ácido acetil salicílico (aspirina e de ácido acético, in vitro, sobre células em suspensão do carcinoma VX-2, verificando-se as mesmas causam a morte das células neoplásicas. MÉTODOS: Procedeu-se a incubação das células tumorais VX-2 (10(7 células/ml com diferentes concentrações do ácido acetil salicílico (2,5% e 5% e de ácido acético (2,5% e 5%, sendo estudada a viabilidade celular pelo teste do azul tripian a cada 5 minutos; procedeu-se à análise à microscopia ótica. RESULTADOS: Observou-se que o percentual de viabilidade das células tumorais foi progressivamente diminuindo, sendo que ao final de 30 minutos todas as células neoplásicas estavam inviáveis em todas as soluções e concentrações utilizadas. CONCLUSÃO: Com base neste modelo experimental e com a metodologia empregada, concluiu-se que in vitro, estas soluções causam a morte (inviabilidade das células neoplásicas.

  9. Inflammatory angiomyolipoma of the liver: a rare hepatic tumor

    Directory of Open Access Journals (Sweden)

    Liu Yang

    2012-09-01

    Full Text Available Abstract Angiomyolipoma (AML is a rare mesenchymal neoplasm of the tumor, composed of a varying heterogeneous mixture of three tissue components: blood vessels, smooth muscle and adipose cells. Hepatic AML may demonstrate a marked histological diversity. We herein present one case of hepatic AML exhibiting prominent inflammatory cells in the background, which happened in a 61-year-old Chinese female patient, without signs of tuberous sclerosis. Histologically, the striking feature was the infiltration of numerous inflammatory cells in the background, including small lymphocytes, plasma cells, and eosnophils. The tumor cells were spindled and histiocytoid in shape, with slightly eosinophilic cytoplasm, and arranged along the vessels or scattered among the inflammatory background. Sinusoid structure was obviously seen in the tumor. Mature adipocytes and thick-walled blood vessels were focally observed at the boundaries between the tumor and surrounding liver tissues. The tumor cells were positive immunostaining for HMB-45, Melan-A, and smooth muscle actin. The inflammatory AML should be distinguished from other tumors with inflammatory background such as inflammatory myofibroblastic tumor and follicular dendritic cell tumor and deserves wider recognition for its occurrence as a primary hepatic tumor. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1828633072762370

  10. Primitive Neuroectodermal Tumor of the Liver: A Case Report

    Directory of Open Access Journals (Sweden)

    Eduardo Cambruzzi

    2011-01-01

    Full Text Available Primary liver sarcomas represent a rare group of neoplasias, with angiosarcoma being the most common histological type. Primitive neuroectodermal tumor (PNET represents a high malignant neoplasia that usually affects the central nervous system and soft tissues. An 18-year-old male patient was admitted with clinical complains of pain in the right upper abdominal quadrant. The clinical evaluation revealed a solid mass in the right hepatic lobe. On the gross examination of the resected liver specimen, the right lobe of the liver was replaced by a yellow-red solid mass measuring 21 cm in its largest dimension. On the histopathology, a tumor composed of small round blue cells with little cytoplasm and round nuclei was identified. The lesion revealed positive immunoexpression for vimentin and CD99 and negative immunostaining for desmin, CD45, cytokeratin, and neuroblastoma protein, suggesting, then, the diagnosis of PNET. Although it is an unusual tumor, it should be considered in the differential diagnosis of liver masses, especially in young patients.

  11. Cystic tumors of the liver: A practical approach

    Institute of Scientific and Technical Information of China (English)

    Paolo Del Poggio; Marco Buonocore

    2008-01-01

    Biliary cyst tumors (cystadenoma and cystadenocarcinoma) are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver, but differential diagnosis with multiloculated or complicated biliary cysts, atypical hemangiomas, hamartomas and lymphangiomas may be difficult. The most frequent challenge is to differentiate biliary cyst tumors from hemorrhagic cysts. Computerized tomography (CT) and magnetic resonance imaging (MRI) are often not diagnostic and in these cases fine needle aspiration (FNA) is used to confirm the presence of atypical biliary cells. FNA, however, lacks adequate sensitivity and specificity and should always be used in conjunction with imaging. Pre-operative differentiation of cystadenoma from cystadenocarcinoma is impossible and surgery must be performed if a biliary cyst tumor is suspected. When multiple cystic lesions are observed throughout the liver parenchyma, it is important to exclude liver metastasis, of which colonic cancer is the most common primary site. Multiple biliary hamartomas (von Meyenburg complex) can appear as a mixture of solid and cystic lesions and can be confused with cystic metastasis. Strong and uniform T2 hyperintensity on MRI is usually diagnostic, but occasionally a percutaneous biopsy may be required.

  12. Mechanistic Investigation of Toxaphene Induced Mouse Liver Tumors.

    Science.gov (United States)

    Wang, Zemin; Neal, Barbara H; Lamb, James C; Klaunig, James E

    2015-10-01

    Chronic exposure to toxaphene resulted in an increase in liver tumors in B6C3F1 mice. This study was performed to investigate the mode of action of toxaphene induced mouse liver tumors. Following an initial 14 day dietary dose range-finding study in male mice, a mechanistic study (0, 3, 32, and 320 ppm toxaphene in diet for 7, 14, and 28 days of treatment) was performed to examine the potential mechanisms of toxaphene induced mouse liver tumors. Toxaphene induced a significant increase in expression of constitutive androstane receptor (CAR) target genes (Cyp2b10, Cyp3a11) at 32 and 320 ppm toxaphene. aryl hydrocarbon receptor (AhR) target genes (Cyp1a1 and Cyp1a2) were slightly increased in expression at the highest toxaphene dose (320 ppm). No increase in peroxisome proliferator-activated receptor alpha activity or related genes was seen following toxaphene treatment. Lipid peroxidation was seen following treatment with 320 ppm toxaphene. These changes correlated with increases in hepatic DNA synthesis. To confirm the role of CAR in this mode of action, CAR knockout mice (CAR(-/-)) treated with toxaphene confirmed that the induction of CAR responsive genes seen in wild-type mice was abolished following treatment with toxaphene for 14 days. These findings, taken together with previously reported studies, support the mode of action of toxaphene induced mouse liver tumors is through a nongenotoxic mechanism involving primarily a CAR-mediated processes that results in an increase in cell proliferation in the liver, promotes the clonal expansion of preneoplastic lesions leading to adenoma formation.

  13. Is Diaphragm Motion a Good Surrogate for Liver Tumor Motion?

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Juan [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); School of Information Science and Engineering, Shandong University, Jinan, Shandong (China); Cai, Jing [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Wang, Hongjun [School of Information Science and Engineering, Shandong University, Jinan, Shandong (China); Chang, Zheng; Czito, Brian G. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Bashir, Mustafa R. [Department of Radiology, Duke University Medical Center, Durham, North Carolina (United States); Palta, Manisha [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Yin, Fang-Fang, E-mail: fangfang.yin@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2014-11-15

    Purpose: To evaluate the relationship between liver tumor motion and diaphragm motion. Methods and Materials: Fourteen patients with hepatocellular carcinoma (10 of 14) or liver metastases (4 of 14) undergoing radiation therapy were included in this study. All patients underwent single-slice cine–magnetic resonance imaging simulations across the center of the tumor in 3 orthogonal planes. Tumor and diaphragm motion trajectories in the superior–inferior (SI), anterior–posterior (AP), and medial–lateral (ML) directions were obtained using an in-house-developed normalized cross-correlation–based tracking technique. Agreement between the tumor and diaphragm motion was assessed by calculating phase difference percentage, intraclass correlation coefficient, and Bland-Altman analysis (Diff). The distance between the tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between the 2 motions. Results: Of all patients, the mean (±standard deviation) phase difference percentage values were 7.1% ± 1.1%, 4.5% ± 0.5%, and 17.5% ± 4.5% in the SI, AP, and ML directions, respectively. The mean intraclass correlation coefficient values were 0.98 ± 0.02, 0.97 ± 0.02, and 0.08 ± 0.06 in the SI, AP, and ML directions, respectively. The mean Diff values were 2.8 ± 1.4 mm, 2.4 ± 1.1 mm, and 2.2 ± 0.5 mm in the SI, AP, and ML directions, respectively. Tumor and diaphragm motions had high concordance when the distance between the tumor and tracked diaphragm area was small. Conclusions: This study showed that liver tumor motion had good correlation with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be used as a reliable surrogate for liver tumor motion.

  14. Combination of aspartic acid and glutamic acid inhibits tumor cell proliferation.

    Science.gov (United States)

    Yamaguchi, Yoshie; Yamamoto, Katsunori; Sato, Yoshinori; Inoue, Shinjiro; Morinaga, Tetsuo; Hirano, Eiichi

    2016-01-01

    Placental extract contains several biologically active compounds, and pharmacological induction of placental extract has therapeutic effects, such as improving liver function in patients with hepatitis or cirrhosis. Here, we searched for novel molecules with an anti-tumor activity in placental extracts. Active molecules were separated by chromatographic analysis, and their antiproliferative activities were determined by a colorimetric assay. We identified aspartic acid and glutamic acid to possess the antiproliferative activity against human hepatoma cells. Furthermore, we showed that the combination of aspartic acid and glutamic acid exhibited enhanced antiproliferative activity, and inhibited Akt phosphorylation. We also examined in vivo tumor inhibition activity using the rabbit VX2 liver tumor model. The treatment mixture (emulsion of the amino acids with Lipiodol) administered by hepatic artery injection inhibited tumor cell growth of the rabbit VX2 liver. These results suggest that the combination of aspartic acid and glutamic acid may be useful for induction of tumor cell death, and has the potential for clinical use as a cancer therapeutic agent.

  15. Tumor angiogenesis and its clinical significance in pediatric malignant liver tumor

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yi Sun; Zai-De Wu; Xiao-Feng Liao; Ji-Yan Yuan

    2005-01-01

    AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and microvascular density (MVD) count in pediatric malignant liver tumor and their dinical significances.METHODS: Fourteen children with malignant liver tumors including seven hepatocellular carcinomas (HCCs), five hepatoblastomas, one malignant mesenchymoma and one rhabdomyosarcoma were studied. Twelve adult HCC samples served as control group. All samples were examined with streptavidin-biotin peroxidase (SP) immunohistochemical staining for VEGF expression and MVD count.RESULTS: VEGF positive expression in all pediatric malignant liver tumors was significantly higher than that in adult HCC(0.4971±0.14 vs 0.4027±0.03, P<0.05). VEGF expression in pediatric HCC group was also markedly higher than that in adult HCC group (0.5665±0.10 vs 0.4027±0.03,P<0.01) and pediatric non-HCC group (0.5665±0.10 vs0.4276±0.15, P<0.05). The mean value of MVD in pediatric malignant liver tumors was significantly higher than that in adult HCC (33.66±12.24 vs 26.52±4.38, P<0.05).Furthermore, MVD in pediatric HCC group was significantly higher compared to that in adult HCC group (36.94±9.28 vs26.52±4.38, P<0.05), but there was no significant difference compared to the pediatric non-HCC group (36.94±9.28 vs30.37±14.61, P>0.05). All 7 children in HCC group died within2 years, whereas the prognosis in pediatric non-HCC group was better, in which two patients survived more than 5 years.CONCLUSION: Children with malignant liver tumors,especially with HCC, may have extensive angiogenesis that induces a rapid tumor growth and leads to a poor prognosis.

  16. Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post Radioembolization 90Y PET

    Directory of Open Access Journals (Sweden)

    Shyam Mohan Srinivas

    2014-10-01

    Full Text Available Background: Radioembolization with Yttrium-90 (90Y microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC. Using post-treatment 90Y PET/CT scans,the distribution of microspheres within the liver can be determined and quantitatively assessesed . We studied the radiation dose of 90Y delivered to liver and treated tumors.Methods: This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres® to the frequency of complications with mRECIST. 90Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL to an absorbed dose (Gy.Results: The 98 studied tumors received a mean dose of 169 Gy (mode 90-120 Gy;range 0-570 Gy. Tumor response by mRECIST criteria was performed for 48 tumors that had follow up scans. There were 21 responders (mean dose 215 Gy and 27 nonresponders (mean dose 167 Gy. The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p=0.099. Normal liver tissue received a mean dose of 67 Gy (mode 60-70 Gy; range 10-120 Gy. There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p=0.036.Conclusion: Our cohort of patients showed a possible dose response trend for the tumors. Collateral dose to normal liver is nontrivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the dose which the tumor or normal liver received.

  17. Human liver tumors in relation to steroidal usage.

    Science.gov (United States)

    Barrows, G H; Christopherson, W M

    1983-01-01

    Since 1973 a number of investigators have reported an association between liver neoplasia and steroid usage. Through referral material we have examined the histology of over 250 cases of hepatic neoplasia, most in patients receiving steroid medications. The majority have been benign, predominantly focal nodular hyperplasia (55%) and hepatocellular adenoma (39%). The average age was 31.4 years; 83% had significant steroid exposure with an average duration of 71 months for focal nodular hyperplasia and 79.6 months for hepatocellular adenoma. The type of estrogenic agent was predominantly mestranol; however, during the period mestranol was the most frequently used synthetic steroid. A distinct clinical entity of life threatening hemorrhage from the lesion occurred in 31% of patients with hepatocellular adenoma and 9% of patients with focal nodular hyperplasia. Recurrence of benign tumors has occurred in some patients who continued using steroids and regression has been observed in patients who had incomplete tumor removal but discontinued steroid medication. Medial and intimal vascular changes have been present in a large number of the benign tumors. The relationship of these vascular changes to oncogenesis is unclear, but similar lesions have been described in the peripheral vasculature associated with steroid administration. A number of hepatocellular carcinomas have also been seen. Of significance is the young age of these patients and lack of abnormal histology in adjacent nonneoplastic liver. A striking number of the malignant hepatocellular tumors have been of the uncommon type described as "eosinophilic hepatocellular carcinoma with lamellar fibrosis." The epidemiology of liver lesions within this series is difficult to assess, since the material has been referred from very diverse locations. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. PMID:6307679

  18. Gestational trophoblastic tumor with liver metastasis after misoprostol abortion.

    Science.gov (United States)

    Mousavi, S A; Behnamfar, F

    2009-04-01

    Early elective medical abortion is performed frequently in different countries of the world. Serious complications like gestational trophoblastic neoplasia (GTN) are uncommon and mostly nonmetastatic. High risk metastatic GTN following medical abortion is a rare event which may occur coincidentally. A 26 year-old-woman, gravida 2 para 1, 6 weeks after misoprostol abortion presented with sever nausea, vomiting, and right upper abdominal pain. Human chorionic gonadotropin (hCG) level was 2,500,000 mIU/ml and metastatic work up revealed multiple liver metastases. She totally received nine cycles of EMA-CO (ethoposide- methotrexate- actinomycin- cyclophosphamide, vincristine) regimen for treatment and consolidation. Six months after treatment she is in complete remission. Follow up of patients after medical abortion by means of single serum hCG measurement is highly recommended for early diagnosis of complications including gestational trophoblastic tumor. EMA-CO regimen seems to be an effective and safe treatment for liver metastatic gestational trophoblastic neoplasia.

  19. Initiation of liver growth by tumor necrosis factor: Deficient liver regeneration in mice lacking type I tumor necrosis factor receptor

    OpenAIRE

    Yamada, Yasuhiro; Kirillova, Irina; Peschon, Jacques J.; Fausto, Nelson

    1997-01-01

    The mechanisms that initiate liver regeneration after resection of liver tissue are not known. To determine whether cytokines are involved in the initiation of liver growth, we studied the regeneration of the liver after partial hepatectomy (PH) in mice lacking type I tumor necrosis factor receptor (TNFR-I). DNA synthesis after PH was severely impaired in these animals, and the expected increases in the binding of the NF-κB and STAT3 transcription factors shortly after...

  20. Liver tumor promoting effects of fenbendazole in rats.

    Science.gov (United States)

    Shoda, T; Onodera, H; Takeda, M; Uneyama, C; Imazawa, T; Takegawa, K; Yasuhara, K; Watanabe, T; Hirose, M; Mitsumori, K

    1999-01-01

    In order to examine whether fenbendazole has tumor-promoting activity, a total of 70 male Fischer 344 rats were initiated with a single intraperitoneal injection of 100 mg/kg of diethylnitrosamine (DEN) or were given the saline vehicle alone; beginning 1 wk later, rats were given a diet containing 3,600; 1,800; 600; 200; 70; or 0 ppm of fenbendazole for 8 wk. Subgroups of 5 rats each from the DEN+ 1,800; DEN+0; 1,800; and 0 ppm groups were euthanatized after 1 wk of fenbendazole treatment, and the remaining animals were euthanatized at 8 wk. After 1 wk, relative liver weights (ratios to body weights) were significantly increased in the DEN+ 1,800 and 1,800 ppm groups, and based on light microscopy, periportal hepatocellular hypertrophy was evident in these groups. After 8 wk, relative liver weights were significantly increased in the groups given > or =600 ppm with or without DEN initiation. Periportal hepatocellular hypertrophy, characterized by a marked increase in smooth endoplasmic reticulum, was observed in the groups given > or =600 ppm with or without DEN initiation. Induction of cytochrome P-450 (CYP) 1A2, 2B1, or 4A1 was noted in the fenbendazole-treated groups with or without DEN initiation; that associated with CYP 1A2 was most marked. Positive immunostaining for anti-CYP 1A1/2 or CYP 2B1/2 was observed diffusely in the livers of animals in the DEN+1,800 and DEN+3,600 ppm groups. The numbers and areas of connexin 32 (Cx32)-positive spots per square centimeter in centrilobular hepatocytes were significantly decreased in an almost dose-dependent manner with fenbendazole treatment after DEN initiation. In situ hybridization for Cx32 mRNA revealed a remarkable decrease in its expression in the centrilobular hepatocytes in the DEN+70 ppm group. The numbers of glutathione S-transferase placental-form positive single cells (plus mini foci) were significantly increased in the DEN+ 1,800 and DEN+3,600 ppm groups. Since those agents that induce CYP 2B1/2 isozymes

  1. Pure Laparoscopic Liver Resection for Malignant Liver Tumor: Anatomic Resection Versus Nonanatomic Resection

    Institute of Scientific and Technical Information of China (English)

    Ya-Xi Chen; Dian-Rong Xiu; Chun-Hui Yuan; Bin Jiang; Zhao-Lai Ma

    2016-01-01

    Background: Laparoscopic liver resection (LLR) has been considered to be safe and feasible.However, few studies focused on the comparison between the anatomic and nonanatomic LLR.Therefore, the purpose of this study was to compare the perioperative factors and outcomes of the anatomic and nonanatomic LLR, especially the area of liver parenchymal transection and blood loss per unit area.Methods: In this study, surgical and oncological data of patients underwent pure LLR procedures for malignant liver tumor were prospectively collected.Blood loss per unit area of liver parenchymal transection was measured and considered as an important parameter.All procedures were conducted by a single surgeon.Results: During nearly 5 years, 84 patients with malignant liver tumor received a pure LLR procedure were included.Among them, 34 patients received anatomic LLR and 50 received nonanatomic LLR, respectively.Patients of the two groups were similar in terms of demographic features and tumor characteristics, despite the tumor size was significantly larger in the anatomic LLR group than that in the nonanatomic LLR group (4.77 ± 2.57 vs.2.87 ± 2.10 cm, P =0.001).Patients who underwent anatomic resection had longer operation time (364.09 ± 131.22 vs.252.00 ± 135.21 min, P < 0.001) but less blood loss per unit area (7.85 ± 7.17 vs.14.17 ± 10.43 ml/cm2,P =0.018).Nonanatomic LLR was associated with more blood loss when the area of parenchymal transection was equal to the anatomic LLR.No mortality occurred during the hospital stay and 30 days after the operation.Moreover, there was no difference in the incidence of postoperative complications.The disease-free and overall survival rates showed no significant differences between the anatomic LLR and nonanatomic LLR groups.Conclusions: Both anatomic and nonanatomic pure LLR are safe and feasible.Measuring the area ofparenchymal transection is a simple and effective method to estimate the outcomes of the liver resection surgery

  2. Keratin 18-deficiency results in steatohepatitis and liver tumors in old mice: A model of steatohepatitis-associated liver carcinogenesis

    Science.gov (United States)

    Hofer, Eva M.; Wohlrab, Christina; Golob-Schwarzl, Nicole; Svendova, Vendula; Schimek, Michael G.; Stumptner, Cornelia; Thüringer, Andrea; Speicher, Michael R.; Lackner, Carolin; Zatloukal, Kurt; Denk, Helmut; Haybaeck, Johannes

    2016-01-01

    Backround Steatohepatitis (SH)-associated liver carcinogenesis is an increasingly important issue in clinical medicine. SH is morphologically characterized by steatosis, hepatocyte injury, ballooning, hepatocytic cytoplasmic inclusions termed Mallory-Denk bodies (MDBs), inflammation and fibrosis. Results 17-20-months-old Krt18−/− and Krt18+/− mice in contrast to wt mice spontaneously developed liver lesions closely resembling the morphological spectrum of human SH as well as liver tumors. The pathologic alterations were more pronounced in Krt18−/− than in Krt18+/− mice. The frequency of liver tumors with male predominance was significantly higher in Krt18−/− compared to age-matched Krt18+/− and wt mice. Krt18-deficient tumors in contrast to wt animals displayed SH features and often pleomorphic morphology. aCGH analysis of tumors revealed chromosomal aberrations in Krt18−/− liver tumors, affecting loci of oncogenes and tumor suppressor genes. Materials and Methods Livers of 3-, 6-, 12- and 17-20-months-old aged wild type (wt), Krt18+/− and Krt18−/− (129P2/OlaHsd background) mice were analyzed by light and immunofluorescence microscopy as well as immunohistochemistry. Liver tumors arising in aged mice were analyzed by array comparative genomic hybridization (aCGH). Conclusions Our findings show that K18 deficiency of hepatocytes leads to steatosis, increasing with age, and finally to SH. K18 deficiency and age promote liver tumor development in mice, frequently on the basis of chromosomal instability, resembling human HCC with stemness features. PMID:27689336

  3. Functional CT imaging of angiogenesis in rabbit VX2 soft-tissue tumour

    Science.gov (United States)

    Purdie, Thomas G.; Henderson, Elizabeth; Lee, Ting-Yim

    2001-12-01

    Functional parameters such as blood flow (BF), microvessel permeability surface area product (PS), blood volume (BV) and mean transit time (MTT) are physiological markers related to the changes associated with angiogenesis. In the current study we present a functional CT technique for the simultaneous measurement of these four functional parameters and the display of each parameter as a functional image over an entire tissue slice. New Zealand White rabbits with implanted VX2 thigh tumours were scanned using CT with contrast media injection. The ex vivo method of radioactive microspheres was used to evaluate the accuracy of BF measurements with the functional CT technique. There was a significant linear correlation (R = 0.96) between regional CT and microsphere-measured BF values, with a slope not significantly different from unity (0.98 +/- 0.02, P precision of our CT technique was determined by the repeated scanning under steady-state conditions. The precision of CT-measured BF, PS, BV and MTT was 14%, 18%, 20% and 24%, respectively. In conclusion, BF can be measured accurately and BF, PS, BV and MTT reproducibly using our functional CT technique. Functional CT can be readily incorporated into existing imaging protocols to assess tumour angiogenesis.

  4. Hepatic progenitor cells in human liver tumor development

    Institute of Scientific and Technical Information of China (English)

    Louis Libbrecht

    2006-01-01

    In recent years, the results of several studies suggest that human liver tumors can be derived from hepatic progenitor cells rather than from mature cell types.The available data indeed strongly suggest that most combined hepatocellular-cholangiocarcinomas arise from hepatic progenitor cells that retained their potential to differentiate into the hepatocytic and biliary lineages.Hepatic progenitor cells could also be the basis for some hepatocellular carcinomas and hepatocellular adenomas, although it is very difficult to determine the origin of an individual hepatocellular carcinoma. There is currently not enough data to make statements regarding a hepatic progenitor cell origin of cholangiocarcinoma.The presence of hepatic progenitor cell markers and the presence and extent of the cholangiocellular component are factors that are related to the prognosis of hepatocellular carcinomas and combined hepatocellularcholangiocarcinomas, respectively.

  5. Biodistribution and acute toxicity of naked gold nanoparticles in a rabbit hepatic tumor model.

    Science.gov (United States)

    Glazer, Evan S; Zhu, Cihui; Hamir, Amir N; Borne, Agatha; Thompson, Catherine Shea; Curley, Steven A

    2011-12-01

    There is a paucity of data regarding the safety of administering solid gold nanoparticles (AuNPs) in large animal tumor models. We assessed the acute toxicity and biodistribution of 5 nm and 25 nm solid AuNPs in New Zealand White rabbits (n = 6 in each) with implanted liver Vx2 tumors 24 h after intravenous injection. Gold concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP) and imaged with transmission electron microscopy (TEM). There was no clinico-pathologic evidence of renal, hepatic, pulmonary, or other organ dysfunction. After 25 nm AuNP administration, the concentration of white blood cells increased after treatment (p = 0.001). Most other blood studies were unchanged. AuNPs were distributed to the spleen, liver, and Vx2 tumors, but not to other tissues. The urinary excretion of AuNPs was bimodal as measured by ICP. 25 nm AuNPs were more evenly distributed throughout tissues and may be better tools for medical therapy.

  6. Non-functioning pancreatic neuroendocrine tumor accompanied with multiple liver metastases: remorseful case and literature review.

    Science.gov (United States)

    Hori, Tomohide; Takaori, Kyoichi; Kawaguchi, Michiya; Ogawa, Kohei; Masui, Toshihiko; Ishii, Takamichi; Nagata, Hiromitsu; Narita, Masato; Kodama, Yuzo; Uza, Norimitsu; Uemoto, Shinji

    2014-11-28

    Pancreatic neuroendocrine tumor (P-NET) is a rare and slow-growing tumor. Unfortunately, there is no clear consensus on the role and timing of surgery for primary tumor and liver metastases, although current reports refer to liver surgery including LT for unresectable liver metastases. A thirty-nine-year-old man was diagnosed with nonfunctioning pancreatic neuroendocrine tumor (P-NET) in the pancreatic head, with multiple liver metastases. The tumor was 2.5 cm in diameter and he was asymptomatic. Small but multiple metastases were detected in the liver, and no extrahepatic metastases were observed. We initially intended to control the liver metastases before resection of the primary tumor. To begin with, transarterial chemoembolization (TACE) and transcatheter arterial infusion (TAI) were repeated. Thereafter, systemic chemotherapy and biotherapy were introduced according to follow-up assessments. Unfortunately, imaging assessment at about 10 months later revealed that liver metastases were partially enlarged, although some were successfully treated. Therefore, these therapies were switched to other regimens, and TACE/TAI, systemic chemotherapies and biotherapies were repeated. Although liver metastases seemed to be stable for a while, the primary tumor was enlarged even after therapy. At 3.5 years after initial diagnosis, the primary tumor became symptomatic (pain and jaundice). Liver metastases enlarged and massive swelling of the para-aortic lymph nodes was observed. Thereafter, palliative therapy was the main course of action. He died at 4.3 years after initial diagnosis. Our young patient could have been a candidate for initial surgery for primary tumor and might have had a chance of subsequent liver transplantation for unresectable metastases. Surgeons still face questions in deciding the best surgical scenario in patients with P-NET with liver metastases.

  7. Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer

    Science.gov (United States)

    2015-05-14

    Childhood Hepatocellular Carcinoma; Papillary Thyroid Cancer; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Thyroid Cancer; Recurrent Wilms Tumor and Other Childhood Kidney Tumors

  8. Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice

    Institute of Scientific and Technical Information of China (English)

    Tamao Nishihara; Shinji Tamura; Norio Hayashi; Hiroyasu Iishi; Iichiro Shimornura; Miyako Baba; Morihiro Matsuda; Masahiro Inoue; Yasuko Nishizawa; Atsunori Fukuhara; Hiroshi Arald; Shinji Kihara; Tohru Funahashi

    2008-01-01

    AIM: To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model, and to determine the con-tribution of adiponectin deficiency to colorectal cancer development and proliferation. METHODS: We examined the influence of adiponectin deficiency on colorectal carcinogenesis induced by the administration of azoxymethane (AOM) (7.5 mg/kg, in-traperitoneal injection once a week for 8 wk), by using adiponectin-knockout (KO) mice. RESULTS: At 53 wk after the first AOM treatment, KOmice developed larger and histologically more progres-sive colorectal tumors with greater frequency com-pared with wild-type (WT) mice, although the tumor incidence was not different between WT and KO mice. KO mice showed increased cell proliferation of colorec-tal tumor cells, which correlated with the expression levels of cyclooxygenase-2 (COX-2) in the colorectal tumors. In addition, KO mice showed higher incidence and frequency of liver tumors after AOI treatment. Thirteen percent of WT mice developed liver tumors, and these WT mice had only a single tumor. In contrast, 50% of K.O mice developed liver tumors, and 58% of these KO mice had multiple tumors. CONCLUSION: Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice. This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.

  9. Carbon dioxide reactivity of computed tomography functional parameters in rabbit VX2 soft tissue tumour

    Energy Technology Data Exchange (ETDEWEB)

    Purdie, Thomas G [Department of Medical Biophysics, University of Western Ontario, London, ON (Canada); Lee, Ting-Yim [Department of Medical Biophysics, University of Western Ontario, London, ON (Canada)

    2003-04-07

    Tumour blood flow is one of the important factors limiting the efficacy of radiation therapy (hypoxic radioresistance), chemotherapy (drug delivery) and thermal therapy (heat dissipation) in treating cancer. The modification of tumour blood flow has been an area of intense investigation. In the current study, the arterial carbon dioxide tension (P{sub a}CO{sub 2}) was changed in order to investigate the tumour vascular response to carbon dioxide. Functional maps of blood flow, blood volume and mean transit time were generated at four P{sub a}CO{sub 2} levels in VX2 tumour in the rabbit thigh and normal soft tissue. The P{sub a}CO{sub 2} levels investigated were normocapnia (P{sub a}CO{sub 2} = 40.9 {+-} 1.2 mmHg), hypocapnia (27.2 {+-} 2.3 and 33.5 {+-} 2.3 mmHg) and hypercapnia (54.9 {+-} 4.4 mmHg). The carbon dioxide reactivity of the global tumour blood flow and mean transit time showed significant differences between normocapnia and the two levels of hypocapnia, but not between normocapnia and hypercapnia. The average fractional change of blood flow from normocapnia for the two levels of hypocapnia was -0.41 {+-} 0.06 and -0.29 {+-} 0.08, respectively (P < 0.05). In the case of mean transit time the fractional change was +0.39 {+-} 0.30 and +0.23 {+-} 0.24, respectively (P < 0.05). The fractional change of blood volume from normocapnia, however, was not significantly different at any capnic level, as was the case with respect to each of the functional parameters in normal tissue. The ability to reduce blood flow and increase mean transit time through hypocapnia has significant implications in thermal therapy, since heat dissipation is a major factor in limiting the effectiveness of treatment.

  10. Quantitative MRI assessment of VX2 tumour oxygenation changes in response to hyperoxia and hypercapnia

    Energy Technology Data Exchange (ETDEWEB)

    Winter, Jeff D; Cheng, Hai-Ling Margaret [Research Institute and Diagnostic Imaging, Hospital for Sick Children, Toronto M5G 1X8 (Canada); Akens, Margarete K, E-mail: Hai-Ling.Cheng@sickkids.ca [Division of Orthopaedic Surgery, Orthopaedic Biomechanics Laboratory, Sunnybrook Health Science, Toronto M4N 3M5 (Canada)

    2011-03-07

    Magnetic resonance imaging (MRI) relaxation times provide indirect estimates of tissue O{sub 2} for monitoring tumour oxygenation. This study provides insight into mechanisms underlying longitudinal (R{sub 1} = 1/T{sub 1}) and transverse effective (R{sub 2}* = 1/T{sub 2}*) relaxation rate changes during inhalation of 100% O{sub 2} and 3%, 6% and 9% CO{sub 2} (balanced O{sub 2}) in a rabbit tumour model. Quantitative R{sub 1}, R{sub 2}*, and dynamic contrast-enhanced (DCE) imaging was performed in six rabbits 12-23 days following implantation of VX2 carcinoma cells in the quadricep muscle. Invasive measurements of tissue partial pressure of O{sub 2} (pO{sub 2}) and perfusion were also performed, which revealed elevated pO{sub 2} levels in all tumour regions for all hyperoxic gases compared to baseline (air) and reduced perfusion for carbogen. During 100% O{sub 2} breathing, an R{sub 1} increase and R{sub 2}* decrease consistent with elevated pO{sub 2} were observed within tumours. DCE-derived blood flow was weakly correlated with R{sub 1} changes from air to 100% O{sub 2}. Further addition of CO{sub 2} (carbogen) did not introduce considerable changes in MR relaxation rates, but a trend towards higher R{sub 1} relative to breathing 100% O{sub 2} was observed, while R{sub 2}* changes were inconsistent. This observation supports the predominance of dissolved O{sub 2} on R{sub 1} sensitivity and demonstrates the value of R{sub 1} over R{sub 2}* for tissue oxygenation measures.

  11. Visualizing the Tumor Microenvironment of Liver Metastasis by Spinning Disk Confocal Microscopy.

    Science.gov (United States)

    Babes, Liane; Kubes, Paul

    2016-01-01

    Intravital microscopy has evolved into an invaluable technique to study the complexity of tumors by visualizing individual cells in live organisms. Here, we describe a method for employing intravital spinning disk confocal microscopy to picture high-resolution tumor-stroma interactions in real time. We depict in detail the surgical procedures to image various tumor microenvironments and different cellular components in the liver.

  12. Anechoic halo in solid liver tumors: sonographic, microangiographic, and histologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Marchal, G.J.; Pylyser, K.; Tshibwabwa-Tumba, E.A.; Verbeken, E.K.; Oyen, R.H.; Baert, A.L.; Lauweryns, J.M.

    1985-08-01

    The origin of the sonographic halo sign in liver metastases was studied after autopsy in 33 livers with macroscopic tumoral involvement. For 20 lesions a detailed comparison of findings from high-resolution 7.5- and 10-MHz sonography, microangiography, and histology was carried out. Histologic study focused on the tumor periphery and its relationship to the adjacent liver parenchyma. In particular, the type of tumor infiltration, the presence or absence of peritumoral fibrosis, and the degree of liver cell compression were assessed. In all but two cases the halo was extratumoral and was caused by peritumoral liver cell compression. In the remaining two cases the halo was tumoral and was caused by irregular fibrosis or vascularization.

  13. Surgical resection of adrenal metastasis from primary liver tumors:a report of two cases

    Institute of Scientific and Technical Information of China (English)

    Durgatosh Pandey; Kai-Chah Tan

    2008-01-01

    BACKGROUND: Although the treatment of extrahepatic metastases from primary liver tumors is essentially palliative, solitary metastasis from such tumors offers a possibility of cure by surgical resection. The adrenal gland is an uncommon site for metastasis from primary liver tumors. METHOD: We report two cases of adrenalectomy for solitary adrenal metastasis: one from intrahepatic cholangiocarcinoma and the other from hepatocellular carcinoma. RESULTS: The patient with intrahepatic cholangiocar-cinoma had a synchronous adrenal metastasis and underwent simultaneous liver resection and adrenalectomy. However, he developed recurrent disease 17 months following surgery for which he is presently on palliative chemotherapy. The other patient underwent adrenalectomy for adrenal metastasis 3 months following liver transplantation for hepatocellular carcinoma. He is presently alive and disease-free 27 months after adrenalectomy. CONCLUSION: Carefully selected patients with solitary metastasis from primary liver tumors may be considered for resection.

  14. A LIVER-TUMOR ADHESION PEPTIDE FROM RANDOM PHAGE DISPLAY LIBRARY

    Institute of Scientific and Technical Information of China (English)

    WU Miao; DU Bing; WANG Lei; ZHOU Zhong-liang; QIAN Min

    2006-01-01

    Objective: To identify and localize the synthesized targeting peptide A54 to liver cancer cell line BEL-7402 in vivo and in vitro for confirming the potential clinical application of peptide A54 in hepatocarcinoma targeting therapy. Methods: Phage A54 was confirmed by ELISA. Biotin and FAM labeled A54 peptides were identified and localized by means of immunohistochemistry and immunocytochemistry. Results: A54 peptide could target the liver-tumor tissue in vivo and adhere to several liver-tumor cells in vitro. FAM-labeled A54 peptides were localized on the membrane surface of liver-tumor cells. Conclusion: Synthesized A54 peptide obtained from in vivo phage display technology still kept special ability to adhere liver-tumor cell in vivo and in vitro. The A54 peptide could be a candidate carrier for hepatocarcinoma targeting therapy.

  15. Alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV.

    Science.gov (United States)

    Qin, Yannan; Zhong, Yaogang; Ma, Tianran; Wu, Fei; Wu, Haoxiang; Yu, Hanjie; Huang, Chen; Li, Zheng

    2016-04-01

    The incidence of hepatocellular carcinoma (HCC) is closely correlated with hepatitis B virus (HBV)-induced liver cirrhosis. Structural changes in the glycans of serum and tissue proteins are reliable indicators of liver damage. However, little is known about the alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV infection. This study compared the differential expression of liver glycopatterns in 7 sets of normal pericarcinomatous tissues (PCTs), cirrhotic, and tumor tissues from patients with liver cirrhosis and HCC induced by HBV using lectin microarrays. Fluorescence-based lectin histochemistry and lectin blotting were further utilized to validate and assess the expression and distribution of certain glycans in 9 sets of corresponding liver tissue sections. Eight lectins (e.g., Jacalin and AAL) revealed significant difference in cirrhotic tissues versus PCTs. Eleven lectins (e.g., EEL and SJA) showed significant alteration during cirrhotic and tumor progression. The expression of Galα1-3(Fucα1-2)Gal (EEL) and fucosyltransferase 1 was mainly increasing in the cytoplasm of hepatocytes during PCTs-cirrhotic-tumor tissues progression, while the expression of T antigen (ACA and PNA) was decreased sharply in cytoplasm of tumor hepatocytes. Understanding the precision alteration of liver glycopatterns related to the development of hepatitis, cirrhosis, and tumor induced by HBV infection may help elucidate the molecular mechanisms underlying the progression of chronic liver diseases and develop new antineoplastic therapeutic strategies.

  16. The Role of Lymphatic Endothelial Cells in Liver Injury and Tumor Development

    Science.gov (United States)

    Lukacs-Kornek, Veronika

    2016-01-01

    Lymphatics and lymphatic endothelial cells (LECs) possess multiple immunological functions besides affecting immune cell migration, such as inhibiting T cell proliferation and antigen presentation by dendritic cells. Moreover, they control the trans-endothelial transport of multiple molecules and antigens. Emerging evidence suggest their active involvements in immunregulation, tumor, and metastases formation. In the liver, increased lymphangiogenesis, specifically at the portal area has been associated with multiple liver diseases in particular primary biliary cirrhosis, idiopathic portal hypertension, and liver malignancies. Nevertheless, the exact role and contribution of LECs to liver diseases are poorly understood. The review summarizes the current understanding of LECs in liver diseases. PMID:27965673

  17. The role of lymphatic endothelial cells in liver injury and tumor development

    Directory of Open Access Journals (Sweden)

    Veronika Lukacs-Kornek

    2016-11-01

    Full Text Available Lymphatics and lymphatic endothelial cells (LECs possess multiple immunological functions besides affecting immune cell migration such as inhibiting T cell proliferation and antigen presentation by dendritic cells. Moreover, they control the trans-endothelial transport of multiple molecules and antigens. Emerging evidence suggests their active involvements in immunoregulation, tumor and metastases formation. In the liver, increased lymphangiogenesis, specifically at the portal area has been associated with multiple liver diseases in particular primary biliary cirrhosis, idiopathic portal hypertension, and liver malignancies. Nevertheless, the exact role and contribution of LECs to liver diseases are poorly understood. The review summarizes the current understanding of LECs in liver diseases.

  18. [A case of undifferentiated (embryonal) liver sarcoma mimicking klatskin tumor in an adult].

    Science.gov (United States)

    Lee, Ji Ae; Kim, Tae Wan; Min, Jae Hoon; Byon, Sun Jung; Jang, Seung Hoon; Choi, Seung Yeon; Kim, Hong Joo

    2010-02-01

    Undifferentiated sarcoma is an uncommon primary malignant tumor of the liver typically occurring in older children. It is also referred to as malignant mesenchymoma, fibromyxosarcoma, or mesenchymal sarcoma. We experienced a case of undifferentiated sarcoma in 72-year-old male. Contrast enhanced liver CT scan revealed a 3.4 cm heterogeneously enhancing, ill-defined, and low attenuated mass in the left liver and subtle intrahepatic duct dilatation. And, in tubogram, there were segmental stenosis and occlusion from the hilum to the proximal common bile duct. We did ultrasonography guided liver biopsy. The pathologic finding revealed infiltrative growth of atypical cells with rhabdoid features. Some atypical cells showed clear cytoplasm, but no organoid pattern was identified. The stroma around atypical cells was filled with eosinophilic hyaline material. These tumor cells were positive for vimentin only, and the tumor was consistent with undifferentiated sarcoma of the liver.

  19. Sphere-forming-like cells (squamospheres) with cancer stem-like cell traits from VX2 rabbit buccal squamous cell carcinoma.

    Science.gov (United States)

    Chen, Yuk-Kwan; Huang, Anderson Hsien-Cheng; Lin, Li-Min

    2014-12-01

    Previous studies have demonstrated that spheroid type cells grown under suspension culture conditions have cancer stem cell (CSC) traits in a number of cancers, but this phenomenon has not yet been reported in the VX2 rabbit oral cancer model. Hence, this study aimed to study the spheroid cells from VX2 rabbit buccal squamous cell carcinomas (SCCs) and assess their CSC characteristics. Five adult male New Zealand white outbred rabbits were used to generate VX2 rabbit buccal SCC. Sphere-forming cell culture was performed for the VX2 rabbit buccal SCC specimens. The self-renewal capability; cluster of designation (CD) 44, CD133, acetaldehyde dehydrogenase 1 (ALDH1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), Nestin, octamer-binding transcription factor 4 (Oct4) and reduced expression protein-1 (Rex-1) expression with reverse transcription-polymerase chain reaction (RT-PCR); chemoresistance to cisplatin and 5-fluorouracil; and in vivo tumorigenicity of spheroid cell transplantation in nude mice were evaluated to determine the CSC characteristics of the resulting spheroid cells. We successfully obtained spheroid cells from the VX2 rabbit OSCC tissues. The spheroid cells exhibited CSC traits, including the expression of CSC and stem cell markers (CD44, Bmi-1, Nestin, Oct4 and Rex-1), capacity to generate new spheroid colonies within 1 week of reseeding from single-dissociated spheroid cells, chemoresistance capacity and generation of tumour xenografts (with histological features resembling those of the original VX2 rabbit buccal SCC) from the transplantation of 10(3) undifferentiated spheroid cells into nude mice. In summary, we demonstrated that spheroid cells with CSC cell traits can be derived from VX2 rabbit buccal SCCs, indicating that this animal cancer model is applicable for studying CSCs in human oral cancers.

  20. Sphere-forming-like cells (squamospheres) with cancer stem-like cell traits from VX2 rabbit buccal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yuk-Kwan Chen; Anderson Hsien-Cheng Huang; Li-Min Lin

    2014-01-01

    Previous studies have demonstrated that spheroid type cells grown under suspension culture conditions have cancer stem cell (CSC) traits in a number of cancers, but this phenomenon has not yet been reported in the VX2 rabbit oral cancer model. Hence, this study aimed to study the spheroid cells from VX2 rabbit buccal squamous cell carcinomas (SCCs) and assess their CSC characteristics. Five adult male New Zealand white outbred rabbits were used to generate VX2 rabbit buccal SCC. Sphere-forming cell culture was performed for the VX2 rabbit buccal SCC specimens. The self-renewal capability;cluster of designation (CD) 44, CD133, acetaldehyde dehydrogenase 1 (ALDH1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), Nestin, octamer-binding transcription factor 4 (Oct4) and reduced expression protein-1 (Rex-1) expression with reverse transcription-polymerase chain reaction (RT-PCR);chemoresistance to cisplatin and 5-fluorouracil;and in vivo tumorigenicity of spheroid cell transplantation in nude mice were evaluated to determine the CSC characteristics of the resulting spheroid cells. We successfully obtained spheroid cells from the VX2 rabbit OSCC tissues. The spheroid cells exhibited CSC traits, including the expression of CSC and stem cell markers (CD44, Bmi-1, Nestin, Oct4 and Rex-1), capacity to generate new spheroid colonies within 1 week of reseeding from single-dissociated spheroid cells, chemoresistance capacity and generation of tumour xenografts (with histological features resembling those of the original VX2 rabbit buccal SCC) from the transplantation of 103 undifferentiated spheroid cells into nude mice. In summary, we demonstrated that spheroid cells with CSC cell traits can be derived from VX2 rabbit buccal SCCs, indicating that this animal cancer model is applicable for studying CSCs in human oral cancers.

  1. Associating liver partition with portal vein ligation and staged hepatectomy (ALPPS) for the treatment of liver tumors in children.

    Science.gov (United States)

    Wiederkehr, Julio Cesar; Avilla, Sylvio Gilberto; Mattos, Elisângela; Coelho, Izabel Meister; Ledesma, Jorge Alberto; Conceição, Alexandra Fernandes; Wiederkehr, Henrique Aguiar; Wiederkehr, Barbara Aguiar

    2015-07-01

    Resection is the only curative treatment option for primary and secondary malignant tumors of the liver. Although curative resection is associated with long-term survival rates, it can only be performed in 10% of patients with primary tumors and 25% of patients with liver metastases. Liver insufficiency is one of the most serious postoperative complications of patients undergoing extensive liver resections. When total liver resection is necessary liver transplant is mandatory, with the burden of long-term immunosuppression and its complications. Among several different strategies to increase the resectability of liver tumors, portal vein occlusion (embolization or ligature), bilateral tumor resection in two stages, and resection combined with loco regional therapy are the most popular. A new strategy for patients with marginally resectable liver tumors previously considered to be unresectable was formally reported by Baumgart et al. in 2011, originally developed by Hans Schlitt in 2007. This technique consists of a two-staged hepatectomy with initial portal vein ligation and in situ splitting of the liver parenchyma, and it is known as ALPPS (associating liver partition with portal vein ligation for staged hepatectomy). The aim of this study is to present the first series of pediatric patients with marginally resectable liver tumors previously considered to be unresectable treated with two-stage hepatectomy with initial portal vein ligation and in situ splitting of the liver parenchyma. Two patients were diagnosed with hepatoblastoma, and one each with rhabdomyosarcoma, hepatocellular carcinoma, and nodular focal hyperplasia. ALPPS technique was considered whenever the future liver remnant (FLR) was 40% or less of the total liver volume (TLV) determined by CT or MRI scans. The ratio of FLR to TLV before the first procedure ranged from 0.15 to 0.38, with a mean±sd of 0.253±0.07. In all patients, a rapid growth of the FLR was observed. Estimates of the FRL volume

  2. Gene expression accurately distinguishes liver metastases of small bowel and pancreas neuroendocrine tumors

    OpenAIRE

    Sherman, Scott K.; Maxwell, Jessica E.; Carr, Jennifer C.; Wang, Donghong; Bellizzi, Andrew M.; O’Dorisio, M. Sue; O’Dorisio, Thomas M.; Howe, James R.

    2014-01-01

    Small bowel (SBNETs) and pancreatic neuroendocrine tumors (PNETs) often present with liver metastases. Although liver biopsy establishes a neuroendocrine diagnosis, the primary tumor site is frequently unknown without exploratory surgery. Gene expression differences in metastases may distinguish primary SBNETs and PNETs. This study sought to determine expression differences of four genes in neuroendocrine metastases and to create a gene expression algorithm to distinguish the primary site. No...

  3. Synchronous resections of primary colorectal tumor and liver metastasis by laparoscopic approach

    OpenAIRE

    2013-01-01

    Liver metastasis of colorectal cancer is common. Resection of solitary tumors of primary and metastatic colorectal cancer can have a favorable outcome. Open resection of primary colorectal tumor and liver metastasis in one operation or in separate operations is currently common practice. Reports have shown that synchronous resections do not jeopardize short or long-term surgical outcomes and that this is a safe and effective approach in open surgery. The development of laparoscopic colorectal...

  4. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression

    NARCIS (Netherlands)

    Nantasanti, Sathidpak; Toussaint, Mathilda J. M.; Youssef, Sameh A.; Tooten, Peter C. J.; de Bruin, Alain

    2016-01-01

    The tumor suppressors Retinoblastoma (Rb) and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC) or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver f

  5. VX2恶性骨肿瘤骨髓内浸润范围MRI 与病理对照研究%Intraosseous extent in rabbit VX2 malignant bone neoplasm:comparison of MRI and pathology

    Institute of Scientific and Technical Information of China (English)

    李晓莉; 董诚; 李玉军; 陈海松; 吴增杰; 庞婧; 贾梦; 徐文坚

    2016-01-01

    目的:探讨 MRI 常用序列在判断恶性骨肿瘤骨髓内浸润范围及显示病变阳性率方面的应用价值。方法2010年6月—2012年3月选取兔龄8周、体质量2.0~3.0 kg 的雄性新西兰大白兔26只,1只制备荷瘤兔,25只接种 VX2肉瘤肿瘤组织块于兔右侧胫骨平台下2 cm 处的骨髓腔内,制备成恶性骨肿瘤模型兔。模型兔制备成功后,在全身麻醉状态下行 MRI 检查。选取肿瘤纵径最大层面,观察并测量 MR 自旋回波(SE) T1 WI、脂肪抑制 FSE T2 WI、短时间反转恢复序列(STIR)、脂肪抑制 SE T1 WI 增强序列图像中的髓内肿瘤浸润纵径。 MRI 检查完成后,处死模型兔,切取兔右下肢标本,用硬组织切片系统自 MR 扫描起始点间隔4 mm 连续切割,选取与 MRI 中骨髓内肿瘤纵径最大层面相对应的标本切片进行肿瘤髓内浸润纵径的测量和病理学观察。采用单因素方差分析和配对 t 检验,比较 MR 不同序列之间及 MR 不同序列和病理切片检查之间肿瘤髓内浸润纵径测量值的差异;并对 MR 不同序列间显示肿瘤髓内浸润的阳性率{[真阳性/(真阳性+假阳性)]×100%}进行χ2检验。结果成功制备21只模型兔。 MRI 中 SE T1 WI、脂肪抑制 FSE T2 WI、STIR、脂肪抑制 SE T1 WI 增强序列间肿瘤髓内浸润纵径的测量值分别为(44.5±10.8)mm、(41.0 ± 9.7) mm、(40.7 ± 9.4)mm、(40.3±9.5)mm,4种序列之间的差异无统计学意义(F =0.802,P >0.05)。 4种序列图像的肿瘤髓内浸润纵径测量值均大于病理标本测量值(39.3±9.3)mm,配对 t 检验分析差异均有统计学意义(t =7.053、6.334、6.445、8.150,P 值均 0. 05). The average value of group SE T1 WI, Fat-Sat FSE T2 WI, STIR and Fat-Sat SE T1 WI with contrast were (44. 5 ± 10. 8) mm, (41. 0 ± 9. 7) mm, (40. 7 ± 9. 4) mm and (40. 3 ± 9. 5) mm, respectively. The value of measuring tumor intraosseous extent in group SE T1 WI, Fat-Sat FSE T2 WI, STIR and group Fat

  6. Hepatopulmonary shunting in patients with primary and secondary liver tumors scheduled for radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Powerski, Maciej Janusz, E-mail: maciej.powerski@med.ovgu.de [Department of Radiology and Nuclear Medicine, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg (Germany); Erxleben, Christoph, E-mail: christoph.erxleben@charite.de [Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany); Scheurig-Münkler, Christian, E-mail: Christian.Scheurig@charite.de [Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany); Geisel, Dominik, E-mail: dominik.geisel@charite.de [Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany); Heimann, Uwe, E-mail: uwe.heimann@charite.de [Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany); Hamm, Bernd, E-mail: bernd.hamm@charite.de [Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany); Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.de [Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany)

    2015-02-15

    Purpose: In patients undergoing transarterial radioembolization (RE) of malignant liver tumors, hepatopulmonary shunts (HPS) can lead to nontarget irradiation of the lungs. This study aims at analyzing the HPS fraction in relation to liver volume, tumor volume, tumor-to-liver volume ratio, tumor vascularity, type of tumor, and portal vein occlusion. Materials and methods: In the presented retrospective study the percentage HPS fraction was calculated from SPECT/CT after infusion of Tc-99m macroaggregated albumin (Tc-99m MAA) into the proper hepatic artery of 233 patients evaluated for RE. Results: HPS fractions correlate very weakly with liver volume (r = 0.303), tumor volume (r = 0.345), and tumor-to-liver volume ratio (r = 0.340). Tumors with strong contrast enhancement (HPS{sub median(range)} = 11.7%(46.3%); n = 73) have significantly larger shunt fractions than tumors with little enhancement (HPS = 8.3%(16.4%); n = 61; p < 0.001). Colorectal cancer metastases (HPS = 10.6%(28.6%); n = 68) and hepatocellular cancers (HPS = 11.7%(39.4%); n = 63) have significantly larger HPS fractions than metastases from breast cancer (HPS = 7.4%(16.7%); n = 40; p = 0.012 and p = 0.001). Patients with compression (HPS = 13.9%(43.7%); n = 33) or tumor thrombosis (HPS = 15.8% (31.2%); n = 33) of a major portal vein branch have significantly higher degrees of shunting than patients with normal portal vein perfusion (HPS = 8.1% (47.0%); n = 167; both p < 0.001). The shunt fraction is largest in patients with HCC and thrombosis or occlusion of a major portal vein branch (HPS = 16.6% (31.0%); n = 32). Conclusion: The degree of hepatopulmonary shunting depends on the type of liver tumor, tumor vascularity, and portal vein perfusion. There is little to no correlation of HPS with liver volume, tumor volume, or tumor-to-liver volume ratio.

  7. Diode laser thermotherapy in the treatment of hepatic tumors in rabbits

    Science.gov (United States)

    Prudhomme, Michel; Pierredon, Marie-Ange; Tang, Jing; Lopez, Francois-Michel; Godlewski, Guilhem; Schoenenberger, Klaus; Rinck, Klauss; Delacretaz, Guy P.

    1996-01-01

    Laser induced thermotherapy (LITT) has been recently developed for treating deep seated tumors. Diode laser (830 nm) is suitable for LITT, because of its high penetration in tissue. The present animal experiment was conducted to evaluate the performance of a diode laser for treating liver tumors in rabbits. Fifty-two New Zealand rabbits were grafted in liver with a Vx2 tumor model. They were treated at a tumor size of 8 mm diameter. A laser energy of 1 350 J (power: 1.5 W; irradiation time 900 s) was delivered through a 300 micrometer fiber implanted in the center of the tumor. Our experiment was divided in two parts: (1) A survival study: we compared the medians survival between untreated tumors (Group A, n equals 21) and irradiated tumors (Group B, n equals 21), (2) An evaluation of LITT efficiency on day 7 (Group C, n equals 5) and at day 14 (Group D, n equals 5). We compared at day 7 and day 14 the radiologic data (ultrasonography and MRI realized before and after irradiation) to the microscopic examinations (haematoxylin eosine stain and picrosirius red F3BA). The results were a median survival not significantly different in group B (laser) than in group A (control) and an efficiency only at short time (on day 7). There was a good correlation between radiologic data and microscopic examinations in groups C and D. The picrosirius red F3BA estimated the extent of thermal damage. In conclusion, these disappointing results are due to an insufficient irradiation of peritumoral tissue and to the Vx2 aggressivity (undifferentiated). Using multiple optical fiber could improve the LITT efficiency. The correlation between radiological and microscopic findings would allow us to quantify the results of LITT.

  8. Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease

    Institute of Scientific and Technical Information of China (English)

    Jin-Ping Li; De-Li Zhao; Hui-Jie Jiang; Ya-Hua Huang; Da-Qing Li; Yong Wan; Xin-Ding Liu; Jin-E Wang

    2011-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhoticliverdiseasebythisfastimagingmethod. METHODS: CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. RESULTS: In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The

  9. Present status and recent advances in living donor liver transplantation for malignant hepatic tumors

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Qin; Yasutsugu Takada; Shinji Uemoto; Koichi Tanaka

    2008-01-01

    BACKGROUND:Living donor liver transplantation (LDLT) has been increasingly used to treat hepatic tumors worldwide in recent years, and is currently the most effective alternative to deceased donor liver transplantation to overcome the problem of organ shortage. LDLT has played an enormous role in treating early malignant hepatic tumors. But the indication of LDLT for malignant hepatic tumors is based on indeifnite criteria. This review summarizes the recent studies in LDLT for treating malignant hepatic tumors. DATA SOURCES:A literature research of the PubMed database was conducted and research articles were reviewed. RESULTS:The current data on LDLT for malignant hepatic tumors, combined with our hospital experience, indicated that if a patient with hepatocellular carcinoma (HCC) who meets with the conventional Milan criteria cannot undergo tumor resection because of poorly preserved liver function, and a cadaveric graft is dififcult to obtain within six months, LDLT may be selected. In a patient with recurrence of HCC after conventional therapies, feasibility, optimal timing, and efifcacy of LDLT as a second-line treatment should be determined. CONCLUSIONS:Tumor recurrence is related to the biological behavior and staging of the tumor. New immunosuppressors which have anti-tumor effects and inhibit the immune system need to be developed. The indications of LDLT for hepatic malignant tumors should be selected meticulously.

  10. Tumor lysis syndrome following endoscopic radiofrequency interstitial thermal ablation of colorectal liver metastases.

    LENUS (Irish Health Repository)

    Barry, B D

    2012-02-03

    Radiofrequency interstitial thermal ablation (RITA) provides a palliative option for patients suffering from metastatic liver disease. This procedure can be performed using a laparoscopic approach with laparoscopic ultrasound used to position the RITA probe. We describe a case of laparoscopic RITA performed for colorectal liver metastasis that was complicated by tumor lysis syndrome (TLS) following treatment. We consider RITA to be a safe procedure, as supported by the literature, but where intracorporal tumor lysis is the treatment goal we believe that the systemic release of tumor products can overwhelm the excretory capacity; therefore, TLS is an inevitable consequence in some patients.

  11. Agressive inflammatory myofibroblastic tumor of the liver with underlying schistosomiasis:A case report

    Institute of Scientific and Technical Information of China (English)

    Vera; Lucia; Pannain; Juliana; Vial; Passos; Ariovaldo; da; Rocha; Filho; Cristiane; Villela-Nogueira; Adriana; Caroli-Bottino

    2010-01-01

    Inflammatory myofibroblastic tumor(IMT)occurs infrequently in the liver.It is controversial whether it represents a low grade mesenchymal neoplasm or a reactive inflammatory lesion.Local recurrence and metastasis are rare and some tumors are associated with infectious agents.We report on a case of a large and partially resected IMT with local recurrence and diaphragm and kidney infiltration detected on routine surveillance two years later.Histologically,the tumor showed spindle cells without atypia,mitosis ...

  12. Accessory lobe of right liver mimicking a pulmonary tumor in an adult male.

    Science.gov (United States)

    Wang, Yi; Junlin, Liao; Zhang, Wei-guo; Chen, Jin-hua; He, Yong; Chen, Jian-ming

    2010-02-01

    We describe a rare case of ectopic liver tissue in the right thoracic cavity. A 39-year-old man with a suspected lung tumor underwent thoracotomy. The intraoperative finding revealed an accessory liver lobe connected to the right lobe of the liver by a small pedicle that pierced the diaphragm. A pathologic evaluation confirmed the specimen to be hepatic tissues. In retrospect, the correct diagnosis of accessory liver could have been achieved using appropriate radiologic investigations if this possibility had been considered. 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Resection of Segments 4, 5 and 8 for a Cystic Liver Tumor Using the Double Liver Hanging Maneuver

    Directory of Open Access Journals (Sweden)

    Atsushi Nanashima

    2008-03-01

    Full Text Available To achieve complete anatomic central hepatectomy for a large tumor compressing surrounding vessels, transection by an anterior approach is preferred but a skillful technique is necessary. We propose the modified technique of Belghiti’s liver hanging maneuver (LHM. The case was a 77-year-old female with a 6-cm liver cystic tumor in the central liver compressing hilar vessels and the right hepatic vein. At the hepatic hilum, the spaces between Glisson’s pedicle and hepatic parenchyma were dissected, which were (1 the space between the right anterior and posterior Glisson pedicles and (2 the space adjacent to the umbilical Glisson pedicle. Two tubes were repositioned in each space and ‘double LHM’ was possible at the two resected planes of segments 4, 5 and 8. Cut planes were easily and adequately obtained and the compressed vessels were secured. Double LHM is a useful surgical technique for hepatectomy for a large tumor located in the central liver.

  14. Detection of serum tumor marker contents of liver cancer patients and itscorrelation with JAK-STAT pathway in tumor tissue

    Institute of Scientific and Technical Information of China (English)

    Zhi-Gang Dong; Li-Li Ma; Ya-Juan Li; Zhan-Hong Zhang

    2015-01-01

    Objective: To study the serum tumor marker contents of liver cancer patients and its correlation with HAK-STAT pathway in tumor tissue. Methods: 50 cases of primary liver cancer patients diagnosed in our hospital from August 2013 to November 2014 were enrolled in liver cancer group; 50 cases of healthy persons received physical examination in our hospital during the same period were enrolled in healthy group. Then serum was collected and Livin, Xiap, Pim-1, ICAM-1, VCAM-1, CD44v6, DNMT1, DNMT2, DNMT3A, DNMT3B, HDAC1 and HDAC5 were detected; liver tissue was collected and JAK1, JAK2, STAT1, STAT3 and STAT5 were detected. Results: (1) Proliferation and adhesion molecules: compared with serum proliferation and adhesion molecule contents of the healthy group, serum Livin, Xiap, Pim-1, ICAM-1, VCAM-1 and CD44v6 contents of liver cancer group were higher; (2) Methyltransferase and histone deacetylase: compared with serum methyltransferase and histone deacetylase contents of healthy group, serum mRNA contents of DNMT1, DNMT2, DNMT3A, DNMT3B, HDAC1 and HDAC5 of liver cancer group were higher; (3) Signal molecules: compared with JAK-STAT signal molecule contents in adjacent normal liver tissue, mRNA contents of JAK1, JAK2, STAT1, STAT3 and STAT5 in hepatocellular carcinoma tissue were higher. Conclusion: Contents of serum proliferation and adhesion molecules, methyltransferase and histone deacetylase abnormally increase, which is closely related to the abnormal activation of JAK-STAT pathway in tumor tissue.

  15. Internal radiotherapy of liver cancer with rat hepato-carcinoma-intestine-pancreas gene as a liver tumor-specific promoter

    Energy Technology Data Exchange (ETDEWEB)

    Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Hop Paul Brousse, INSERM, Hepatobiliary Ctr, U785, F-94800 Villejuif (France); Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Univ Paris Sud, Fac Med, F-94800 Villejuif (France); Boisgard, R.; Tavitian, B. [INSERM, U803, F-91400 Orsay (France); Boisgard, R.; Tavitian, B. [CEA, Serv Hosp Frederic Joliot, Lab Imagerie Mol Expt, F-91400 Orsay (France); Roux, J.; Cales, P. [Univ Angers, UPRES EA 3859, Lab Hemodynam Interact Fibrose et Invas Tumorale H, Angers (France); Clerc, J. [Hop Cochin, AP HP, Dept Nucl Med, F-75014 Paris (France)

    2008-07-01

    The hepato-carcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg III {alpha}, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide sym-porter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP-NIS adeno-viral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radio-iodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and non-hepatic cells. Nuclear imaging, tissue counting and immuno-histo-chemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intra-tumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed non-hepatic cells. In rats bearing multi-nodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of {sup 131}I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated. {sup 131}I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

  16. Liver Metastasis Four Years after Whipple's Resection for Solid-Pseudopapillary Tumor of the Pancreas

    Directory of Open Access Journals (Sweden)

    Srikrishna Nagri

    2007-03-01

    Full Text Available Context Solid-pseudopapillary tumor of the pancreas is a rare tumor which usually affects young females in their second and third decade of life. Metastasis is very rare after a resection of curative intent. Case report We report a case of a 65-yearold white female who presented with metastasis to the liver four years after Whipple’s resection for a solid-pseudopapillary tumor of the pancreas. Conclusions Solid-pseudopapillary tumors of the pancreas can present with metastasis a long time after resection of the primary tumor. Long term close follow up of these patients should be done. The survival rate even after liver metastasis is good.

  17. Macrophage inflammatory protein-2 contributes to liver resection-induced acceleration of hepatic metastatic tumor growth

    Institute of Scientific and Technical Information of China (English)

    Otto Kollmar; Michael D Menger; Martin K Schilling

    2006-01-01

    AIM: To study the role of macrophage inflammatory protein (MIP)-2 in liver resection-induced acceleration of tumor growth in a mouse model of hepatic metastasis.METHODS: After a 50% hepatectomy, 1×105 CT26.WT cells were implanted into the left liver lobe of syngeneic balb/c mice (PHx). Additional animals were treated with a monoclonal antibody (MAB452) neutralizing MIP-2(PHx+mAB). Non-resected and non-mAB-treated mice (Con) served as controls. After 7 d, tumor angiogenesis and microcirculation as well as cell proliferation, tumor growth, and CXCR-2 expression were analyzed using intravital fluorescence microscopy, histology, immunohistochemistry, and flow cytometry.RESULTS: Partial hepatectomy increased (P<0.05) the expression of the MIP-2 receptor CXCR-2 on tumor cells when compared with non-resected controls, and markedly accelerated (P<0.05) angiogenesis and metastatic tumor growth. Neutralization of MIP-2 by MAB452 treatment significantly (P<0.05) depressed CXCR-2 expression. Further, the blockade of MIP-2 reduced the angiogenic response (P<0.05) and inhibited tumor growth (P< 0.05). Of interest, liver resection-induced hepatocyte proliferation was not effected by anti-MIP-2 treatment.CONCLUSION: MIP-2 significantly contributes to liver resection-induced acceleration of colorectal CT26.WT hepatic metastasis growth.

  18. PREDICTION AND PREVENTION OF LIVER FAILURE AFTER MAJOR LIVER PRIMARY AND METASTATIC TUMORS RESECTION

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2016-01-01

    Full Text Available Abstract Purpose of the study. Improvement of results of treatment in patients with primary and metastatic liver cancer by decreasing the risk of post-resection liver failure on the basis of the evaluation of the functional reserves of the liver.Materials and Methods. The study included two independent samples of patients operated about primary or metastatic lesions of the liver at the Department of abdominal Oncology, P. A. Hertsen MORI. The first group included 53 patients who carried out 13C-breath test metallimovie and dynamic scintigraphy of the liver in the preoperative stage in addition to the standard algorithm of examination. Patients of the 2nd group (n=35 had a standard clinical and laboratory examination, the patients were not performed the preoperative evaluation of the functional reserve of the liver, the incidences of total bilirubin, albumin and prothrombin time did not reveal a reduction of liver function. Post-resection liver failure have been established on the basis of the 50/50 criterion in the evaluation on day 5 after surgery.Results. Analysis of operating characteristics of the functional tests showed the absolute methacin breath test sensitivity (SE≥100%, high specificity (SP≥67% of scintigraphy of the liver and the negative predictive value of outcome (VP≥100% at complex use of two diagnostic methods. The incidence of PROPS in the study group was significantly 2 times higher in the control group –15,1% and 26.8%, respectively (p<0.001.Conclusion. The combination of preoperative dynamic scintigraphy of the liver with carrying out 13C-breath methacin test allows you to conduct a comprehensive evaluation of the liver functional reserve and can significantly improve preoperative evaluation and postoperative results of anatomic resection in patients with primary and metastatic liver lesions.

  19. A D-D/D-T fusion reaction based neutron generator system for liver tumor BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Koivunoro, H.; Lou, T.P.; Leung, K. N.; Reijonen, J.

    2003-04-02

    Boron-neutron capture therapy (BNCT) is an experimental radiation treatment modality used for highly malignant tumor treatments. Prior to irradiation with low energetic neutrons, a 10B compound is located selectively in the tumor cells. The effect of the treatment is based on the high LET radiation released in the {sup 10}B(n,{alpha}){sup 7}Li reaction with thermal neutrons. BNCT has been used experimentally for brain tumor and melanoma treatments. Lately applications of other severe tumor type treatments have been introduced. Results have shown that liver tumors can also be treated by BNCT. At Lawrence Berkeley National Laboratory, various compact neutron generators based on D-D or D-T fusion reactions are being developed. The earlier theoretical studies of the D-D or D-T fusion reaction based neutron generators have shown that the optimal moderator and reflector configuration for brain tumor BNCT can be created. In this work, the applicability of 2.5 MeV neutrons for liver tumor BNCT application was studied. The optimal neutron energy for external liver treatments is not known. Neutron beams of different energies (1eV < E < 100 keV) were simulated and the dose distribution in the liver was calculated with the MCNP simulation code. In order to obtain the optimal neutron energy spectrum with the D-D neutrons, various moderator designs were performed using MCNP simulations. In this article the neutron spectrum and the optimized beam shaping assembly for liver tumor treatments is presented.

  20. Human precision-cut liver tumor slices as a tumor patient-individual predictive test system for oncolytic measles vaccine viruses

    NARCIS (Netherlands)

    Zimmermann, Martina; Armeanu, Sorin; Smirnow, Irina; Kupka, Susan; Wagner, Silvia; Wehrmann, Manfred; Rots, Marianne G.; Groothuis, Geny M. M.; Weiss, Thomas S.; Koenigsrainer, Alfred; Gregor, Michael; Bitzer, Michael; Lauer, Ulrich M.

    2009-01-01

    Availability of an individualized preselection of oncolytic viruses to be used for virotherapy of tumor patients would be of great help. Using primary liver tumor resection specimens we evaluated the precision-cut liver slice (PCLS) technology as a novel in vitro test system for characterization of

  1. MRI visible drug eluting magnetic microspheres for transcatheter intra-arterial delivery to liver tumors.

    Science.gov (United States)

    Kim, Dong-Hyun; Chen, Jeane; Omary, Reed A; Larson, Andrew C

    2015-01-01

    Magnetic resonance imaging (MRI)-visible amonafide-eluting alginate microspheres were developed for targeted arterial-infusion chemotherapy. These alginate microspheres were synthesized using a highly efficient microfluidic gelation process. The microspheres included magnetic clusters formed by USPIO nanoparticles to permit MRI and a sustained drug-release profile. The biocompatibility, MR imaging properties and amonafide release kinetics of these microspheres were investigated during in vitro studies. A xenograft rodent model was used to demonstrate the feasibility to deliver these microspheres to liver tumors using hepatic transcatheter intra-arterial infusions and potential to visualize the intra-hepatic delivery of these microspheres to both liver tumor and normal tissues with MRI immediately after infusion. This approach offer the potential for catheter-directed drug delivery to liver tumors for reduced systemic toxicity and superior therapeutic outcomes.

  2. Regression of liver metastases of occult carcinoid tumor with slow release Lanreotide therapy

    Institute of Scientific and Technical Information of China (English)

    Marta Bondanelli; Maria Rosaria Ambrosio; Maria Chiara Zatelli; Luigi Cavazzini; Laura Al Jandali Rifa'y; Ettore C. Degli Uberti

    2005-01-01

    Few clinical studies have demonstrated an anti-proliferative activity of somatostatin (SST) analogs in carcinoids. We report the case of a woman with liver metastases of neuroendocrine tumor and no evidence of the primary tumor. The liver metastases were characterized by high proliferation indes, immunoreactiviy for somatostatin receptor (SSTR) -1,2,3 and 5and positive octreoscan. Urinary 5-hydrozyindolacetic acid, serum serotonin and chromogranin A were elevated. Slow release lanretoide (SR-LAN) therapy for 3 mo controlled clinical and biochemical signs of carcinoid tumor and caused a clear-cut reduction in the diameter of two liver metastases and disappearance of another lesion, with further reduction after 6 and 18 mo. We demonstrated a Clear-cut long-lasting antioccult carcinoid with high proliferation index and immunoreactivity for SSTR-1,2,3, and 5. Immunohistochemistry for SSTRs could be a suitable method for the selection of patients with metasatic carcinoid that may benefit from SST analog therapy.

  3. DOXORUBICIN-LOADED BORON-RICH POLYMER NANOPARTICLES FOR ORTHOTOPICALLY IMPLANTED LIVER TUMOR TREATMENT

    Institute of Scientific and Technical Information of China (English)

    Lu-zhong Zhang; Ya-jun Zhang; Wei Wu; Xi-qun Jiang

    2013-01-01

    The in vivo behaviors of doxorubicin (DOX)-loaded dextran-poly(3-acrylamidophenylboronic acid) (DextranPAPBA) nanoparticles (NPs) were studied.The DOX-loaded NPs had a narrowly distributed diameter of ca.74 nm and mainly accumulated in liver of tumor-bearing mice after intravenous injection as demonstrated by in vivo real-time near infrared fluorescent imaging.The DOX contents in various tissues were quantified and consisted well with the results of fluorescent imaging.The biodistribution pattern of DOX-loaded NPs encourages us to investigate their liver tumor treatment by using an orthotopically implanted liver tumor model,revealing that the DOX-loaded NPs formulation had better antitumor effect than free DOX.

  4. Newtype single-layer magnetic semiconductor in transition-metal dichalcogenides VX2 (X = S, Se and Te)

    Science.gov (United States)

    Fuh, Huei-Ru; Chang, Ching-Ray; Wang, Yin-Kuo; Evans, Richard F. L.; Chantrell, Roy W.; Jeng, Horng-Tay

    2016-01-01

    We present a newtype 2-dimensional (2D) magnetic semiconductor based on transition-metal dichalcogenides VX2 (X = S, Se and Te) via first-principles calculations. The obtained indirect band gaps of monolayer VS2, VSe2, and VTe2 given from the generalized gradient approximation (GGA) are respectively 0.05, 0.22, and 0.20 eV, all with integer magnetic moments of 1.0 μB. The GGA plus on-site Coulomb interaction U (GGA + U) enhances the exchange splittings and raises the energy gap up to 0.38~0.65 eV. By adopting the GW approximation, we obtain converged G0W0 gaps of 1.3, 1.2, and 0.7 eV for VS2, VSe2, and VTe2 monolayers, respectively. They agree very well with our calculated HSE gaps of 1.1, 1.2, and 0.6 eV, respectively. The gap sizes as well as the metal-insulator transitions are tunable by applying the in-plane strain and/or changing the number of stacking layers. The Monte Carlo simulations illustrate very high Curie-temperatures of 292, 472, and 553 K for VS2, VSe2, and VTe2 monolayers, respectively. They are nearly or well beyond the room temperature. Combining the semiconducting energy gap, the 100% spin polarized valence and conduction bands, the room temperature TC, and the in-plane magnetic anisotropy together in a single layer VX2, this newtype 2D magnetic semiconductor shows great potential in future spintronics. PMID:27601195

  5. Liver transplantation for hepatocellular carcinoma on cirrhosis: Strategies to avoid tumor recurrence

    Institute of Scientific and Technical Information of China (English)

    Marco Vivarelli; Andrea Risaliti

    2011-01-01

    Hepatocellular carcinoma (HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with chronic liver disease. Liver trans-plantation (LT) is potentially the optimal treatment for those patients with HCC who have a poor functional hepatic reserve due to their underlying chronic liver disease. However, due to the limited availability of donors, only those patients whose oncologic profile is favorable can be considered for LT. Despite the care-ful selection of candidates based on strict rules, 10 to 20% of liver transplant recipients who have HCC in the native cirrhotic liver develop tumor recurrence after transplantation. The selection criteria pres-ently employed to minimize the risk of recurrence are based on gross tumor characteristics defined by imaging techniques; unfortunately, the accuracy of imaging is far from being optimal. Furthermore, mi-croscopic tumor features that are strictly linked with prognosis can not be assessed prior to transplanta-tion. Pre-transplantation tumor downstaging may allow transplantation in patients initially outside the selection criteria and seems to improve the progno-sis; it also provides information on tumor biology. The main peculiarity of the transplantation setting, when this is compared with other modalities of treatment, is the need for pharmacological immunosuppression: this is based on drugs that have been demonstrated to increase the risk of tumor development. As HCC is an aggressive malignancy, immunosuppression has to be handled carefully in patients who have HCC at the time of transplantation and new categories of immu-nosuppressive agents should be considered. Adjuvant chemotherapy following transplantation has failed to show any significant advantage. The aim of the pres-ent study is to review the possible strategies to avoid recurrence of HCC after liver transplantation based on the current clinical evidence and the more recent de-velopments and to discuss possible future directions.

  6. Angiogenesis in the liver : molecular mechanisms and novel treatment strategies in liver regeneration and tumor metastasis

    NARCIS (Netherlands)

    Vogten, J.M.

    2004-01-01

    Angiogenesis in liver regeneration Liver regeneration involves the coordinated proliferation of all major hepatic cell types. There are many indirect but obvious indicators of the speculation that angiogenesis must play an important role in the regeneration process. In the first part of this thesis,

  7. Synchronous resections of primary colorectal tumor and liver metastasis by laparoscopic approach.

    Science.gov (United States)

    Cheung, Tan To; Poon, Ronnie Tung Ping

    2013-06-27

    Liver metastasis of colorectal cancer is common. Resection of solitary tumors of primary and metastatic colorectal cancer can have a favorable outcome. Open resection of primary colorectal tumor and liver metastasis in one operation or in separate operations is currently common practice. Reports have shown that synchronous resections do not jeopardize short or long-term surgical outcomes and that this is a safe and effective approach in open surgery. The development of laparoscopic colorectal surgery and laparoscopic hepatectomy has made a minimally invasive surgical approach to treating colorectal cancer with liver metastasis feasible. Synchronous resections of primary colorectal tumor and liver metastasis by laparoscopy have recently been reported. The efficacy and safety of laparoscopic colorectal resection and laparoscopic hepatectomy have been proven separately but synchronous resections by laparoscopy are in hot debate. As it has been shown that open resection of primary colorectal tumor and liver metastasis in one operation results in an equally good short-term outcome when compared with that done in separate operations, laparoscopic resection of the same in one single operation seems to be a good option. Recent evidence has shown that this new approach is a safe alternative with a shorter hospital stay. Large scale randomized controlled trials are needed to demonstrate the effectiveness of this minimally invasive approach.

  8. Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio

    Directory of Open Access Journals (Sweden)

    Dezarn William A

    2007-03-01

    Full Text Available Abstract Background Treatment records and follow-up data on 40 patients with primary and metastatic liver malignancies who underwent a single whole-liver treatment with Y-90 resin microspheres (SIR-Spheres® Sirtex Medical, Lake Forest, IL were retrospectively reviewed. The objective of the study was to evaluate the anatomic and physiologic determinants of radiation dose distribution, and the dose response of tumor and liver toxicity in patients with liver malignancies who underwent hepatic arterial Y-90 resin microsphere treatment. Methods Liver and tumor volume calculations were performed on pre-treatment CT scans. Fractional tumor and liver flow characteristics and lung shunt fractions were determined using hepatic arterial Tc-99m MAA imaging. Absorbed dose calculations were performed using the MIRD equations. Liver toxicity was assessed clinically and by liver function tests. Tumor response to therapy was assessed by CT and/or tumor markers. Results Of the 40 patients, 5 had hepatocellular cancer (HCC, and 35 had metastatic liver tumors (15 colorectal cancer, 10 neuroendocrine tumors, 4 breast cancer, 2 lung cancer, 1 ovarian cancer, 1 endometrial cancer, and 2 unknown primary adenocarcinoma. All patients were treated in a salvage setting with a 3 to 80 week follow-up (mean: 19 weeks. Tumor volumes ranged from 15.0 to 984.2 cc (mean: 294.9 cc and tumor to normal liver uptake ratios ranged from 2.8 to 15.4 (mean: 5.4. Average administered activity was 1.2 GBq (0.4 to 2.4 GBq. Liver absorbed doses ranged from 0.7 to 99.5 Gy (mean: 17.2 Gy. Tumor absorbed doses ranged from 40.1 to 494.8 Gy (mean: 121.5 Gy. None of the patients had clinical venoocclusive disease or therapy-induced liver failure. Seven patients (17.5 % had transient and 7 patients (17.5 % had persistent LFT abnormalities. There were 27 (67.5% responders (complete response, partial response, and stable disease. Tumor response correlated with higher tumor flow ratio as measured by

  9. Predisposing Factors of Liver Necrosis after Transcatheter Arterial Chemoembolization in Liver Metastases from Neuroendocrine Tumor

    Energy Technology Data Exchange (ETDEWEB)

    Joskin, Julien, E-mail: j.joskin@gmail.com; Baere, Thierry de, E-mail: Thierry.DEBAERE@igr.fr [Institut Gustave Roussy, Department of Interventional Radiology (France); Auperin, Anne, E-mail: Anne.AUPERIN@igr.fr [Institut Gustave Roussy, Department of Epidemiology (France); Tselikas, Lambros, E-mail: lambros.tselikas@gmail.com; Guiu, Boris, E-mail: boris.guiu@chu-dijon.fr; Farouil, Geoffroy, E-mail: g.farouil@gmail.com [Institut Gustave Roussy, Department of Interventional Radiology (France); Boige, Valérie, E-mail: boige@igr.fr; Malka, David, E-mail: david.malka@igr.fr [Institut Gustave Roussy, Department of Digestive Oncology (France); Leboulleux, Sophie, E-mail: sophie.leboulleux@igr.fr [Institut Gustave Roussy, Department of Nuclear Medicine and Endocrine Oncology (France); Ducreux, Michel, E-mail: ducreux@igr.fr [Institut Gustave Roussy, Department of Digestive Oncology (France); Baudin, Eric, E-mail: baudin@igr.fr [Institut Gustave Roussy, Department of Nuclear Medicine and Endocrine Oncology (France); Deschamps, Frédéric, E-mail: frederic.deschamps@igr.fr [Institut Gustave Roussy, Department of Interventional Radiology (France)

    2015-04-15

    PurposeTo investigate predictive factors for liver necrosis after transcatheter arterial chemoembolization (TACE) of neuroendocrine liver metastases.MethodsA total of 164 patients receiving 374 TACE were reviewed retrospectively to analyze predictive factors of liver necrosis. We analyzed patient age and sex; metastasis number and location; percentage of liver involvement; baseline liver function test; and pretreatment imaging abnormalities such as bile duct dilatation (BDD), portal vein narrowing (PVN), and portal vein thrombosis (PVT). We analyzed TACE technique such as Lipiodol or drug-eluting beads (DEB) as the drug’s vector; dose of chemotherapy; diameter of DEB; and number, frequency, and selectivity of TACE.ResultsLiver necrosis developed after 23 (6.1 %) of 374 TACE. In multivariate analysis, DEB > 300 μm in size induced more liver necrosis compared to Lipiodol (odds ratio [OR] 35.20; p < 0.0001) or with DEB < 300 μm in size (OR 19.95; p < 0.010). Pretreatment BDD (OR 119.64; p < 0.0001) and PVT (OR 9.83; p = 0.030) were predictive of liver necrosis. BDD or PVT responsible for liver necrosis were present before TACE in 59 % (13 of 22) and were induced by a previous TACE in 41 % (9 of 22) of cases.ConclusionDEB > 300 μm in size, BDD, and PVT are responsible for increased rate of liver necrosis after TACE. Careful analysis of BDD or PVT on pretreatment images as well as images taken between two courses can help avoid TACE complications.

  10. US-Cut: interactive algorithm for rapid detection and segmentation of liver tumors in ultrasound acquisitions

    Science.gov (United States)

    Egger, Jan; Voglreiter, Philip; Dokter, Mark; Hofmann, Michael; Chen, Xiaojun; Zoller, Wolfram G.; Schmalstieg, Dieter; Hann, Alexander

    2016-04-01

    Ultrasound (US) is the most commonly used liver imaging modality worldwide. It plays an important role in follow-up of cancer patients with liver metastases. We present an interactive segmentation approach for liver tumors in US acquisitions. Due to the low image quality and the low contrast between the tumors and the surrounding tissue in US images, the segmentation is very challenging. Thus, the clinical practice still relies on manual measurement and outlining of the tumors in the US images. We target this problem by applying an interactive segmentation algorithm to the US data, allowing the user to get real-time feedback of the segmentation results. The algorithm has been developed and tested hand-in-hand by physicians and computer scientists to make sure a future practical usage in a clinical setting is feasible. To cover typical acquisitions from the clinical routine, the approach has been evaluated with dozens of datasets where the tumors are hyperechoic (brighter), hypoechoic (darker) or isoechoic (similar) in comparison to the surrounding liver tissue. Due to the interactive real-time behavior of the approach, it was possible even in difficult cases to find satisfying segmentations of the tumors within seconds and without parameter settings, and the average tumor deviation was only 1.4mm compared with manual measurements. However, the long term goal is to ease the volumetric acquisition of liver tumors in order to evaluate for treatment response. Additional aim is the registration of intraoperative US images via the interactive segmentations to the patient's pre-interventional CT acquisitions.

  11. Intercostal Trocars Enable Easier Laparoscopic Resection of Liver Tumors in Segments 7 and 8.

    Science.gov (United States)

    Hirokawa, Fumitoshi; Hayashi, Michihiro; Asakuma, Mitsuhiro; Shimizu, Tetsunosuke; Inoue, Yoshihiro; Uchiyama, Kazuhisa

    2017-05-01

    Laparoscopic resection of posterosuperior (PS) tumors of the liver is more difficult than that of anterolateral (AL) tumors, owing to the narrow surgical field in the PS location. In this retrospective cohort study, our aim was to determine if port insertion through the intercostal space would lead to improved outcomes for laparoscopic resection of tumors in PS liver segments 7 and 8. Between January 2006 and December 2015, 153 patients underwent laparoscopic resection of solitary liver tumors at Osaka Medical College Hospital. Of these, 107 patients had AL lesions, and 46 had PS lesions. Of the 46 patients with a PS lesion, 23 underwent an abdominal-only approach, and 23 underwent the intercostal trocar approach. Multivariate analyses were performed to investigate outcomes. Conventional abdominal-only laparoscopic resection of PS liver tumors resulted in prolonged surgical time (P = 0.031), increased bleeding (P = 0.012), and a higher open conversion rate (P = 0.022) compared with AL tumors. Among patients with PS tumors, the open conversion rate was significantly higher for those treated with the abdominal-only approach than with the intercostal trocar approach (P = 0.047). Appropriate surgical margins were obtained equally using the intercostal trocar approach (P = 0.648). There was no significant difference in occurrence of complications between the abdominal-only group and the intercostal trocar group. Using the intercostal trocar approach for PS liver lesions is a safe and effective method, which significantly reduced the open conversion rate compared with the conventional abdominal-only approach.

  12. Osteoclast-like giant cell tumors of the pancreas and liver

    Institute of Scientific and Technical Information of China (English)

    Juergen Bauditz; Birgit Rudolph; Wolfram Wermke

    2006-01-01

    Osteoclast-like giant cell tumors (OGCT) are rare abdominal tumors, which mainly occur in the pancreas.The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with cystic structures. However, due to the rarity of these tumors, only very limited clinical data are available, Imaging features and sonographic appearance have hardly been characterized. Here we report on two cases of osteoclast-like giant cell tumors, one located within the pancreas, the other within the liver,in which OGCTs are extremely rare. Both patients were investigated by contrast sonography, which demonstrated a complex, partly cystic and strongly vascularized tumor within the head of the pancreas in the first patient and a large, hypervascularized neoplasm with calcifications within the liver in the second patient. The liver OGCT responded well to a combination of carboplatin,etoposide and paclitaxel. With a combination of surgical resection, radiofrequency ablation and chemotherapy,the patient's survival is currently more than 15 mo,making him the longest survivor with an OGCT of the liver to date.

  13. Surgical treatment of a rare primary renal carcinoid tumor with liver metastasis

    Directory of Open Access Journals (Sweden)

    Rowland Randall G

    2008-04-01

    Full Text Available Abstract Background Carcinoid tumors are characteristically low grade malignant neoplasms with neuroendocrine differentiation that arise in various body sites, most commonly the lung and gastrointestinal tract, but less frequently the kidneys, breasts, ovaries, testes, prostate and other locations. We report a case of a carcinoid of renal origin with synchronous single liver metastases on radiological studies. Case presentation A 45 year-old patient who presented with abdominal pain was found on CT scan to have lesions in the right ovary, right kidney, and left hepatic lobe. CA-125, CEA, and CA 19-9 were within normal limits, as were preoperative liver function tests and renal function. Biopsy of the liver mass demonstrated metastatic neuroendocrine tumor. At laparotomy, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, radical right nephrectomy with lymphadenectomy, and left hepatectomy. Pathology evaluation reported a right ovarian borderline serous tumor, well-differentiated neuroendocrine carcinoma of the kidney (carcinoid with 2 positive retroperitoneal lymph nodes, and a single liver metastasis. Immunohistochemistry revealed that this lesion was positive for synaptophysin and CD56, but negative for chromogranin as well as CD10, CD7, and CD20, consistent with a well-differentiated neuroendocrine tumor. She is doing well one year after her initial surgery, with no evidence of tumor recurrence. Conclusion Early surgical intervention, together with careful surveillance and follow-up, can achieve successful long-term outcomes in patients with this rare malignancy.

  14. Continuous Dynamic Registration of Microvascularization of Liver Tumors with Contrast-Enhanced Ultrasound

    Directory of Open Access Journals (Sweden)

    Lukas Philipp Beyer

    2014-01-01

    Full Text Available Aim. To evaluate the diagnostic value of quantification of liver tumor microvascularization using contrast-enhanced ultrasound (CEUS measured continuously from the arterial phase to the late phase (3 minutes. Material and Methods. We present a retrospective analysis of 20 patients with malignant (n=13 or benign (n=7 liver tumors. The tumors had histopathologically been proven or clearly identified using contrast-enhanced reference imaging with either 1.5 T MRI (liver specific contrast medium or triphase CT and follow-up. CEUS was performed using a multifrequency transducer (1–5 MHz and a bolus injection of 2.4 mL sulphur hexafluoride microbubbles. A retrospective perfusion analysis was performed to determine TTP (time-to-peak, RBV (regional blood volume, RBF (regional blood flow, and Peak. Results. Statistics revealed a significant difference (P<0.05 between benign and malignant tumors in the RBV, RBF, and Peak but not in TTP (P=0.07. Receiver operating curves (ROC were generated for RBV, RBF, Peak, and TTP with estimated ROC areas of 0.97, 0.96, 0.98, and 0.76, respectively. Conclusion. RBV, RBF, and Peak continuously measured over a determined time period of 3 minutes could be of valuable support in differentiating malignant from benign liver tumors.

  15. Inflammatory pseudotumor of the liver in association with a gastrointestinal stromal tumor:A case report

    Institute of Scientific and Technical Information of China (English)

    Oswens S. Lo; Ronnie T. Poon; Chi Ming Lam; Sheung Tat Fan

    2004-01-01

    Inflammatory pseudotumor of the liver is a rare benign lesion that can mimic a malignant liver neoplasm. A case of inflammatory pseudotumor of the liver found in association with a malignant gastrointestinal stromal tumor (GIST) of the small bowel was reported. The inflammatory pseudotumor was misdiagnosed as a metastasis from the GIST by frozen section. A correct diagnosis was made only after histopathological examination of the paraffin section of the resected specimen. This case is particularly interesting because of the association of the two rare pathological entities and the diagnostic dilemma that arose from the similarity of their histological appearances. To our knowledge, this association has not been reported in the literature.

  16. Research on Fuzzy Enhancement in the Diagnosis of Liver Tumor from B-mode Ultrasound Images

    Directory of Open Access Journals (Sweden)

    Wu Qiu

    2011-04-01

    Full Text Available Fuzzy enhancement is applied in computer aided diagnosis of liver cancer from B mode ultrasound images as a pre-processing procedure in this paper. It was evaluated with three classifiers including K means, back propagation neural network and support vector machine using 25 features from first order statistic (FOS, gray-level co-occurrence matrix (GLCM, gray-level run-length matrix (GLRLM, Grey level dependant matrix (GLDM and LAWS. In the analysis of 166 normal liver tissue, 30 hemangioma and 60 malignant tumor, our method improved the classification accuracy of three classifiers (K means, BP neural network and support machine vector in distinguishing liver cancer, hemangioma and normal liver cancer from B mode ultrasound images. It is proved that fuzzy enhancement as an efficient preprocessing procedure could be used in the computer aided diagnosis system of liver cancer.

  17. Perfusion CT findings in liver of patients with tumor during chemotherapy

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the microcirculation changes in liver of patients with tumor during chemotherapy by perfusion computed tomography (CT). METHODS: Sixty patients with tumor and 20 controls were enrolled in this study. Perfusion CT parameters of patients and controls were compared, including hepatic perfusion index (HPI), mean transit time (MTT), and permeability-surface area product (PS). Correlation between perfusion CT parameters, treatment cycle and alanine aminotransferase (ALT) level was studied. RES...

  18. Non-hepatic tumors change the activity of genes encoding copper trafficking proteins in the liver.

    Science.gov (United States)

    Babich, Polina S; Skvortsov, Alexey N; Rusconi, Paolo; Tsymbalenko, Nadezhda V; Mutanen, Marja; Puchkova, Ludmila V; Broggini, Massimo

    2013-07-01

    To assess the statistical relationship between tumor growth and copper metabolism, we performed a metaanalysis of studies in which patients with neoplasms were characterized according to any of the copper status indexes (atomic copper serum concentration, serum oxidase activity, ceruloplasmin protein content). Our metaanalysis shows that in the majority of cases (more than 3100 patients), tumor growth positively correlates with the copper status indexes. Nude athymic CD-1 nu/nu mice with subcutaneous tumors of human origin, C57Bl/6J mice with murine melanoma and Apc(Min) mice with spontaneously developing adenomas throughout the intestinal tract were studied to experimentally determine the relationship between tumor progression, liver copper metabolism, and copper status indexes. We showed that the copper status indexes increased significantly during tumor growth. In the liver tissue of tumor-bearing mice, ceruloplasmin gene expression, as well as the expression of genes related to ceruloplasmin metallation (CTR1 and ATP7B), increased significantly. Moreover, the presence of an mRNA splice variant encoding a form of ceruloplasmin anchored to the plasma membrane by glycosylphosphatidyl inositol, which is atypical for hepatocytes, was also detected. The ATP7A copper transporter gene, which is normally expressed in the liver only during embryonic copper metabolism, was also activated. Depletion of holo-ceruloplasmin resulted in retardation of human HCT116 colon carcinoma cell growth in nude mice and induced DNA fragmentation in tumor cells. In addition, the concentration of cytochrome c increased significantly in the cytosol, while decreasing in the mitochondria. We discuss a possible trans-effect of developing tumors on copper metabolism in the liver.

  19. THE EFFECT OF REGULAR EXERCISE ON DEVELOPMENT OF SARCOMA TUMOR AND OXIDATIVE DAMAGE IN MICE LIVER

    Directory of Open Access Journals (Sweden)

    Maria Sasvari

    2011-03-01

    Full Text Available Regular exercise has the capability of decreasing the incidence and progress of certain cancers. Murine sarcoma, (S-180 cells were transplanted to control (TC, exercise trained (10 week, 1 hour day, 5 times/ week mice, which had the swimming training terminated at the time of transplantation (ETT, and also to a group of mice that continued to exercise during tumor bearing (ETC. Continuous exercise decreased the size of tumor by about 50%. The accumulation of reactive carbonyl groups (RCD, were not significantly different for any group. The oxidative modification of proteins in the liver of the animals decreased in the exercise- trained non-tumor bearing group compared with control or tumor-bearing groups. No significant alteration was detected in the level of mutant p53. The data indicate that regular exercise retards the development of sarcoma solid tumors and it seems unlikely that massive uncompensated oxidative stress takes place in the tumor

  20. CT perfusion image processing: analysis of liver tumors

    OpenAIRE

    D’Antò, Michela

    2013-01-01

    Perfusion CT imaging of the liver has potential to improve evaluation of tumour angiogenesis. Quantitative parameters can be obtained applying mathematical models to Time Attenuation Curve (TAC). However, there are still some difficulties for an accurate quantification of perfusion parameters due, for example, to algorithms employed, to mathematical model, to patient’s weight and cardiac output and to the acquisition system. In this thesis, new parameters and alternative methodologies ab...

  1. A Case of Early-Stage Ovarian Carcinoid Tumor Metastasized to the Liver

    Directory of Open Access Journals (Sweden)

    Seiji Kanayama

    2012-01-01

    Full Text Available We report a case of ovarian carcinoid tumor that recurred with multiple liver metastases and was successfully treated with chemoembolization. A 76-year-old woman was admitted to our hospital presented with abdominal distension and abnormal uterine bleeding for about 6 months. She presented with hyperestrogenic and androgenic manifestations such as vaginal bleeding with endometrial hyperplasia and hirsutism. Magnetic resonance (MR imaging revealed a large solid and cystic ovarian tumor of 17 cm at maximum diameter. On the basis of the clinical diagnosis of sex cord stromal tumor containing a mature cystic teratoma, she underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The pathology report revealed that the mass in the left ovary was a carcinoid tumor, insular type, with mature cystic teratoma. Two years after surgical treatment, multiple liver metastases were revealed by abdominal CT. Hepatic arterial infusion of cisplatin was performed for 2 courses, and multiple metastatic nodules have remarkably reduced. No established chemotherapy or radiation therapy treatments are currently available for recurrent or advanced carcinoid tumors. Our paper suggests that chemoembolization with cisplatin may be effective in treatment of patients with multiple liver metastases of ovarian carcinoid tumor.

  2. Role of selective intra-arterial embolization in benign liver tumors.

    Science.gov (United States)

    Ferrer Puchol, M D; Parra Casado, C La; Cervera Araez, A; Sala López, R; Esteban Hernández, E; Cremades Mira, A; Ramiro Gandia, R

    To present cases of symptomatic benign liver tumors diagnosed and treated with intra-arterial embolization before surgery. We present the cases of 7 patients diagnosed with symptomatic benign liver tumors that required treatment: 1 focal nodular hyperplasia, 2 giant cavernous hemangiomas, 1 hepatic adenomatosis, and 3 hepatic adenomas. Once the feeding arteries were identified, tumors were embolized with polyvinyl alcohol particles (500μm-700μm) and then the feeding artery was plugged with coils if there was an arterial pedicle to ensure the total vascular exclusion of the tumor. The surgical intervention took place 4 to 7 days after embolization. All 7 patients were women (age range, 23-74 years); presurgical intra-arterial embolization was done in 6. In 1 patient with adenomatosis, embolization was done to control intraparenchymal hepatic hemorrhage. In the 6 patients who underwent surgery, the tumor was completely excised and no intraoperative bleeding events or postoperative complications occurred. Provided there is a consensus among the multidisciplinary team, embolization is a useful option in the perioperative management of giant and/or symptomatic benign liver tumors. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Extended postinterventional tumor necrosis-implication for outcome in liver transplant patients with advanced HCC.

    Directory of Open Access Journals (Sweden)

    Arno Kornberg

    Full Text Available BACKGROUND: Locoregional interventional bridging therapy (IBT is an accepted neoadjuvant approach in liver transplant candidates with hepatocellular carcinoma (HCC. However, the prognostic value of IBT in patients with advanced HCC is still undefined. AIM: The aim of this trial was to evaluate the impact of postinterventional tumor necrosis on recurrence-free long-term survival after liver transplantation (LT in patients with HCC, especially focusing on those exceeding the Milan criteria on pretransplant radiographic imaging. PATIENTS AND METHODS: A total of 93 consecutive liver transplant candidates with HCC were included in this trial. In 36 patients, tumors were clinically staged beyond Milan criteria prior LT. Fifty-nine patients underwent IBT by transarterial chemoembolization or radiofrequency ablation pretransplantation. Postinterventional tumor necrosis rate as assessed at liver explant pathology was correlated with outcome post-LT. RESULTS: There was no significant difference in 5-year tumor-free survival rate between the IBT- and the non-IBT subpopulation (78% versus 68%, P=0.25. However, tumor response following IBT (≥ 50% tumor necrosis rate at explant pathology resulted in a significantly better outcome 5 years post-LT (96% than tumor non-response to IBT (<50% tumor necrosis rate at explant pathology; 21%; P<0.001. Five-year recurrence-free survival rate was 80% in Milan Out patients with extended post-IBT tumor necrosis versus 0% in Milan Out patients without tumor response to IBT (P<0.001. None of macromorphological HCC features, but only the absence of increased (18F-fluoro-deoxy-glucose ((18FDG uptake on pretransplant positron emission tomography (PET was identified as independent predictor of postinterventional tumor response (P<0.001. CONCLUSION: Our results implicate that extended postinterventional tumor necrosis promotes recurrence-free long-term survival in patients with HCC beyond standard criteria. Pretransplant PET

  4. The commonly used antimicrobial additive triclosan is a liver tumor promoter.

    Science.gov (United States)

    Yueh, Mei-Fei; Taniguchi, Koji; Chen, Shujuan; Evans, Ronald M; Hammock, Bruce D; Karin, Michael; Tukey, Robert H

    2014-12-02

    Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a synthetic, broad-spectrum antibacterial chemical used in a wide range of consumer products including soaps, cosmetics, therapeutics, and plastics. The general population is exposed to TCS because of its prevalence in a variety of daily care products as well as through waterborne contamination. TCS is linked to a multitude of health and environmental effects, ranging from endocrine disruption and impaired muscle contraction to effects on aquatic ecosystems. We discovered that TCS was capable of stimulating liver cell proliferation and fibrotic responses, accompanied by signs of oxidative stress. Through a reporter screening assay with an array of nuclear xenobiotic receptors (XenoRs), we found that TCS activates the nuclear receptor constitutive androstane receptor (CAR) and, contrary to previous reports, has no significant effect on mouse peroxisome proliferation activating receptor α (PPARα). Using the procarcinogen diethylnitrosamine (DEN) to initiate tumorigenesis in mice, we discovered that TCS substantially accelerates hepatocellular carcinoma (HCC) development, acting as a liver tumor promoter. TCS-treated mice exhibited a large increase in tumor multiplicity, size, and incidence compared with control mice. TCS-mediated liver regeneration and fibrosis preceded HCC development and may constitute the primary tumor-promoting mechanism through which TCS acts. These findings strongly suggest there are adverse health effects in mice with long-term TCS exposure, especially on enhancing liver fibrogenesis and tumorigenesis, and the relevance of TCS liver toxicity to humans should be evaluated.

  5. An implantable rat liver tumor model for experimental transarterial chemoembolization therapy and its imaging features

    Institute of Scientific and Technical Information of China (English)

    Xin Li; Chuan-Sheng Zheng; Gan-Sheng Feng; Chen-Kai Zhuo; Jun-Gong Zhao; Xi Liu

    2002-01-01

    AIM: To establish an ideal implantable rat liver tumor model for interventional therapy study and examine its angiographic signs and MRI, CT features before and after embolization. METHODS: Forty male Wistar rats were implanted with Walker256 tumor in the left lateral lobe of liver. Digital subtraction angiography (DSA) and transarterial chemoembolization were performed on day 14 after implantation. Native computer tomography (CT, n=8) and native magnetic resonance (MR,n=40) were performed between the day 8 and day 21 after implantation. The radiological morphological characteristics were correlated with histological findings.RESULTS: Successful implantation was achieved in all forty rats, which was confirmed by CT and MRI. MR allowed tumor visualization from day 8 while CT from day 11 after implantation. The tumors were hypodensity on CT, hypointense on MR T1-weighted and hyperintense on T2-weighted. The model closely resembled human hepatocardnoma in growth pattem and the lesions were rich in vasculature on angiography and got its filling mainly from the hepatic artery. Before therapy, tumor size was 211.9±48.7 mm3. No ascites, satellite liver nodules or lung metastasis were found. One week after therapy, tumor size was 963.6±214.8 mm3 in the control group and 356.5±78.4mm3 in TACE group. Ascites (4/40), satellite liver nodules (7/40) or lung metastasis (3/40) could be seen on day 21.CONCLUSION: Walker-256 tumor rat model is suitable for the interventional experiment. CT and MRI are helpful in animal optioning and evaluating experimental results.

  6. Development and validation of a microRNA based diagnostic assay for primary tumor site classification of liver core biopsies

    DEFF Research Database (Denmark)

    Perell, Katharina; Vincent, Martin; Vainer, Ben;

    2015-01-01

    negatively affect the accuracy and usability of molecular classifiers. We have developed and validated a microRNA-based classifier, which predicts the primary tumor site of liver biopsies, containing a limited number of tumor cells. Concurrently we explored the influence of surrounding normal tissue...... for normal liver tissue contamination. Performance was estimated by cross-validation, followed by independent validation on 55 liver core biopsies with a tumor content as low as 10%. A microRNA classifier developed, using the statistical contamination model, showed an overall classification accuracy of 74...... on classification. MicroRNA profiling was performed using quantitative Real-Time PCR on formalin-fixed paraffin-embedded samples. 278 primary tumors and liver metastases, representing nine primary tumor classes, as well as normal liver samples were used as a training set. A statistical model was applied to adjust...

  7. Oncogenic driver genes and the inflammatory microenvironment dictate liver tumor phenotype

    DEFF Research Database (Denmark)

    Matter, Matthias S; Marquardt, Jens U; Andersen, Jesper B

    2016-01-01

    The majority of hepatocellular carcinoma (HCC) develops in the background of chronic liver inflammation caused by viral hepatitis and alcoholic or non-alcoholic steatohepatitis. However, the impact of different types of chronic inflammatory microenvironments on the phenotypes of tumors generated...

  8. Primary mixed germ cell tumor of the liver with sarcomatous components

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Germ cell tumor(GCT)of the liver is extremely rare. Here,we describe a case of hepatic mixed GCT with significant sarcomatous components and elevated serum α-fetoprotein(AFP)in a 34-year-old man.Histopathologically,the tumor was composed of two GCTs components:yolk sac tumor and immature teratoma.The predominant components of immature teratoma consisted of several types of tissue that represented different germinal layers(endoderm,mesoderm and ectoderm) and showed varying degrees of differentiation with sig...

  9. Role of Interleukin-6 in the Radiation Response of Liver Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Miao-Fen, E-mail: miaofen@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); College of Medicine, Chang Gung University, Taiwan (China); Hsieh, Ching-Chuan [College of Medicine, Chang Gung University, Taiwan (China); Department of General Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); Chen, Wen-Cheng [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); College of Medicine, Chang Gung University, Taiwan (China); Lai, Chia-Hsuan [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China)

    2012-12-01

    Purpose: To investigate the role of interleukin (IL)-6 in biological sequelae and tumor regrowth after irradiation for hepatic malignancy, which are critical for the clinical radiation response of liver tumors. Methods and Materials: The Hepa 1-6 murine hepatocellular cancer cell line was used to examine the radiation response by clonogenic assays and tumor growth delay in vivo. After irradiation in a single dose of 6 Gy in vitro or 15 Gy in vivo, biological changes including cell death and tumor regrowth were examined by experimental manipulation of IL-6 signaling. The effects of blocking IL-6 were assessed by cells preincubated in the presence of IL-6-neutralizing antibody for 24 hours or stably transfected with IL-6-silencing vectors. The correlations among tumor responses, IL-6 levels, and myeloid-derived suppressor cells (MDSC) recruitment were examined using animal experiments. Results: Interleukin-6 expression was positively linked to irradiation and radiation resistance, as demonstrated by in vitro and in vivo experiments. Interleukin-6-silencing vectors induced more tumor inhibition and DNA damage after irradiation. When subjects were irradiated with a sublethal dose, the regrowth of irradiated tumors significantly correlated with IL-6 levels and MDSC recruitment in vivo. Furthermore, blocking of IL-6 could overcome irradiation-induced MDSC recruitment and tumor regrowth after treatment. Conclusion: These data demonstrate that IL-6 is important in determining the radiation response of liver tumor cells. Irradiation-induced IL-6 and the subsequent recruitment of MDSC could be responsible for tumor regrowth. Therefore, treatment with concurrent IL-6 inhibition could be a potential therapeutic strategy for increasing the radiation response of tumors.

  10. Solitary fibrous tumor of the liver expressing CD34 and vimentin: A case report

    Institute of Scientific and Technical Information of China (English)

    Dimitris P Korkolis; George N Zografos; Perikles P Vassilopoulos; Katerina Apostolaki; Chrysanthi Aggeli; George Plataniotis; Emmanuel Gontikakis; Dimitra Volanaki; Maria Sebastiadou; Dimitris Dimitroulopoulos; Dimitris Xinopoulos

    2008-01-01

    A case of a successfully treated solitary fibrous tumor(SFT) of the liver is reported. An 82-year-old femalepresented with left upper abdominal discomfort, afirm mass on palpation, and imaging studies revealeda large tumor, 15 cm in diameter, arising from theleft lobe of the liver. A formal left hepatectomy wasperformed. Microscopic evaluation showed spindleand fibroblast-like cells within the collagenous stroma.Immunohistochemistry disclosed diffuse CD34 andpositive vimentin, supporting the diagnosis of abenign SFT. The patient remained well 21 monthsafter surgery. SFT of the liver is a very rare neoplasmof mesenchymal origin. In most cases it is a benignlesion, although some may have malignant histologicalfeatures and recur locally or metastasize. With lessthan 30 reported cases in the literature, little canbe said regarding its natural history or the benefitsof adjuvant radiochemotherapy. Complete surgicalresection remains the cornerstone of its treatment.

  11. Claudin-2 promotes breast cancer liver metastasis by facilitating tumor cell interactions with hepatocytes.

    Science.gov (United States)

    Tabariès, Sébastien; Dupuy, Fanny; Dong, Zhifeng; Monast, Anie; Annis, Matthew G; Spicer, Jonathan; Ferri, Lorenzo E; Omeroglu, Atilla; Basik, Mark; Amir, Eitan; Clemons, Mark; Siegel, Peter M

    2012-08-01

    We previously identified claudin-2 as a functional mediator of breast cancer liver metastasis. We now confirm that claudin-2 levels are elevated in liver metastases, but not in skin metastases, compared to levels in their matched primary tumors in patients with breast cancer. Moreover, claudin-2 is specifically expressed in liver-metastatic breast cancer cells compared to populations derived from bone or lung metastases. The increased liver tropism exhibited by claudin-2-expressing breast cancer cells requires claudin-2-mediated interactions between breast cancer cells and primary hepatocytes. Furthermore, the reduction of the claudin-2 expression level, either in cancer cells or in primary hepatocytes, diminishes these heterotypic cell-cell interactions. Finally, we demonstrate that the first claudin-2 extracellular loop is essential for mediating tumor cell-hepatocyte interactions and the ability of breast cancer cells to form liver metastases in vivo. Thus, during breast cancer liver metastasis, claudin-2 shifts from acting within tight-junctional complexes to functioning as an adhesion molecule between breast cancer cells and hepatocytes.

  12. Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Guodong [Department of Surgical Oncology, Cancer Treatment Center, The Fourth Affiliated Hospital of Harbin Medical University, Harbin (China); Kong, Bo [Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ (United States); Zhu, Yan [Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing (China); Zhan, Le [Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ (United States); Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Williams, Jessica A. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Tawfik, Ossama [Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Kassel, Karen M. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Luyendyk, James P. [Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI (United States); Wang, Li [Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT (United States); Guo, Grace L., E-mail: guo@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ (United States)

    2013-10-15

    Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR{sup −/−} and SHP{sup −/−} mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR{sup −/−} mice and therefore, increased SHP expression in FXR{sup −/−} mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR{sup −/−} mice with overexpression of SHP in hepatocytes (FXR{sup −/−}/SHP{sup Tg}) and determined the contribution of SHP in HCC development in FXR{sup −/−} mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR{sup −/−} mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR{sup −/−} mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver. - Highlights: • SHP does not prevent HCC incidence nor size in FXR KO mice but reduces malignancy. • Increased SHP promotes apoptosis. • Bile acids and inflammation maybe critical for HCC formation with FXR deficiency.

  13. Wavelets in quantification of liver tumors in contrasted computed tomography images; Wavelets na quantificacao de tumores de figado em exames contrastados de tomografia computadorizada

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Bruna T.; Alvarez, Matheus; Souza, Rafael T.F.; Miranda, Jose R.A., E-mail: matheus@ibb.unesp.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP (Brazil). Instituto de Biociencias. Departamento de Fisica e Biofisica; Romeiro, Fernando G. [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP (Brazil). Fac de Mediciana. Departamento de Clinica Medica; Pina, Diana R. de; Trindade, Andre Petean [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP (Brazil). Fac. de Medicina. Departamento de Doencas Tropicais e Diagnostico por Imagem

    2012-12-15

    This paper presents an original methodology of liver tumors segmentation, based on wavelet transform. A virtual phantom was constructed with the same mean and standard deviation of the intensity of gray presented by the measured liver tissue. The optimized algorithm had a sensitivity ranging from 0.81 to 0.83, with a specificity of 0.95 for differentiation of hepatic tumors from normal tissues. We obtained a 96% agreement between the pixels segmented by an experienced radiologist and the algorithm presented here. According to the results shown in this work, the algorithm is optimal for the beginning of the tests for quantification of liver tumors in retrospective surveys. (author)

  14. Selective internal radiation therapy of liver tumors; Selektive interne Radiotherapie bei fortgeschrittenen Lebertumoren

    Energy Technology Data Exchange (ETDEWEB)

    Jakobs, Tobias F. [Krankenhaus Barmherzige Brueder Muenchen, Muenchen (Germany). Abt. Radiologie; Paprottka, Philipp Marius [Klinikum der Ludwig-Maximilians-Univ., Campus Grosshadern, Muenchen (Germany). Inst. fuer Klinische Radiologie; Reiser, Maximilian F. [Klinikum der Ludwig-Maximilians-Univ., Campus Grosshadern, Muenchen (Germany). Inst. fuer Radiologische Diagnostik

    2011-03-15

    Selective Internal Radiation Therapy (SIRT, Radioembolization) is used for the treatment of primary and secondary liver tumors. Currently, the treatment is performed when under classical and well established treatment concepts a tumor progression is detected or when the treatment has to be abandoned due to toxic effects. Microspheres are labelled with the beta-emitting isotope {sup 90}Yttrium and are infused into the hepatic arteries resulting in very high doses of radiation being selectively targeted to tumours via their arterial blood supply. The beta radiation of {sup 90}Yttrium has an average penetration in soft tissue of approximately 2,5 mm und therefore provides high doses of radiation delivered to the tumor without harming the surrounding, healthy liver parenchyma. (orig.)

  15. WE-G-18C-06: Is Diaphragm Motion a Good Surrogate for Liver Tumor Motion?

    Energy Technology Data Exchange (ETDEWEB)

    Yang, J [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); School of Information Science and Engineering, Shandong University, Jinan, Shandong (China); Cai, J; Zheng, C; Czito, B; Palta, M; Yin, F [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Wang, H [School of Information Science and Engineering, Shandong University, Jinan, Shandong (China); Bashir, M [Department of Radiology, Duke University Medical Center, Durham, NC (United States)

    2014-06-15

    Purpose: To investigate whether diaphragm motion is a good surrogate for liver tumor motion by comparing their motion trajectories obtained from cine-MRI. Methods: Fourteen patients with hepatocellular carcinoma (10/14) or liver metastases (4/14) undergoing radiation therapy were included in this study. All patients underwent single-slice 2D cine-MRI simulations across the center of the tumor in three orthogonal planes. Tumor and diaphragm motion trajectories in the superior-inferior (SI), anteriorposterior (AP), and medial-lateral (ML) directions were obtained using the normalized cross-correlation based tracking technique. Agreement between tumor and diaphragm motions was assessed by calculating the phase difference percentage (PDP), intra-class correlation coefficient (ICC), Bland-Altman analysis (Diffs) and paired t-test. The distance (D) between tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between tumor and diaphragm motions. Results: Of all patients, the means (±standard deviations) of PDP were 7.1 (±1.1)%, 4.5 (±0.5)% and 17.5 (±4.5)% in the SI, AP and ML directions, respectively. The means of ICC were 0.98 (±0.02), 0.97 (±0.02), and 0.08 (±0.06) in the SI, AP and ML directions, respectively. The Diffs were 2.8 (±1.4) mm, 2.4 (±1.1) mm, and 2.2 (±0.5) mm in the SI, AP and ML directions, respectively. The p-values derived from the paired t-test were < 0.02 in SI and AP directions, whereas were > 0.58 in ML direction primarily due to the small motion in ML direction. Tumor and diaphragmatic motion had high concordance when the distance between the tumor and tracked diaphragm areas was small. Conclusion: Preliminary results showed that liver tumor motion had good correlations with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be a reliable surrogate for liver tumor motion. NIH (1R21CA165384-01A1), Golfers Against Cancer (GAC

  16. Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

    DEFF Research Database (Denmark)

    Paiva, Carlos Eduardo; Moraes Neto, Francisco Alves; Agaimy, Abbas

    2008-01-01

    Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms, either synchronously or metachronously. In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman...... with no evidence of tuberous sclerosis. A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature. Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small...... incidental hepatic PEComa and a high risky extramural gastric GIST, respectively. The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms. To our knowledge, this is the first report of PEComa in a patient with GIST. Hepatic lesions detected synchronously...

  17. Chemotherapy for Liver Metastasis Originating from Colorectal Cancer with Portal Vein Tumor Thrombosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Atsushi Kawasaki

    2013-05-01

    Full Text Available The patient was a male in his 70s with a history of chronic renal failure and dilated cardiomyopathy. In January 2011, he underwent abdominoperineal resection of the rectum, right hepatic lobectomy, and resection of a portal vein tumor thrombus with a diagnosis of rectal cancer and metastatic liver cancer accompanied by portal vein tumor thrombosis. Although 5-fluorouracil + l-leucovorin therapy (RPMI regimen was carried out as postoperative adjuvant chemotherapy, the tumor marker (CEA and VA19-9 levels increased 8 months after surgery. Since the functions of major organs were impaired, UFT® + UZEL® therapy was started. The tumor marker levels decreased temporarily, but increased again 12 months after surgery, and so intravenous instillation of panitumumab was initiated. Nine administrations have been performed to date, with no increase in tumor marker levels or exacerbation of the condition. Also, no grade 2 or severer adverse event has been noted according to CTCAE v.4.0. The experience with this patient suggests the possibility that exacerbation of the condition of patients with liver metastasis of colorectal cancer accompanied by portal vein tumor thrombosis with abnormalities in the functions of major organs can be controlled temporarily by the administration of panitumumab alone.

  18. Regression of liver metastases of occult carcinoid tumor with slow release Lanreotide therapy

    Science.gov (United States)

    Bondanelli, Marta; Ambrosio, Maria Rosaria; Zatelli, Maria Chiara; Cavazzini, Luigi; Al Jandali Rifa’y, Laura; degli Uberti, Ettore C.

    2005-01-01

    Few clinical studies have demonstrated an anti-proliferative activity of somatostatin (SST) analogs in carcinoids. We report the case of a woman with liver metastases of neuroendocrine tumor and no evidence of the primary tumor. The liver metastases were characterized by high proliferation index, immunoreactiviy for somatostatin receptor (SSTR)-1, 2, 3 and 5 and positive octreoscan. Urinary 5-hydroxyindolacetic acid, serum serotonin and chromogranin A were elevated. Slow release lanreotide (SR-LAN) therapy for 3 mo controlled clinical and biochemical signs of carcinoid tumor and caused a clear-cut reduction in the diameter of two liver metastases and disappearance of another lesion, with further reduction after 6 and 18 mo. We demonstrated a clear-cut long-lasting anti-proliferative effect of SR-LAN on liver metastases of occult carcinoid with high proliferation index and immunoreactivity for SSTR-1, 2, 3, and 5. Immuno-histochemistry for SSTRs could be a suitable method for the selection of patients with metastatic carcinoid that may benefit from SST analog therapy. PMID:15801004

  19. Tumor diagnosis in the adult liver transplant candidate

    Energy Technology Data Exchange (ETDEWEB)

    Mahfouz, A.E. [Department of Radiology, Humboldt Univ. (Germany)]|[Department of Radiology, Cairo University Hospital, Cairo (Egypt); Vogl, T. [Department of Radiology, Humboldt Univ., Berlin (Germany).; Hamm, B. [Department of Radiology, Humboldt Univ. (Germany)

    1999-06-01

    Hepatic transplantation has emerged as a potentially curative treatment of certain malignant hepatic neoplasms such as hepatocellular carcinoma, bile duct carcinoma, fibrolamellar hepatocellular carcinoma, metastases from neuroendocrine tumors, and epithelioid hemangioendothelioma. In the early years of hepatic transplantation, there was great enthusiasm to cure patients with unresectable hepatobiliary malignancy. This early enthusiasm was tempered by the unfavorable outcome of transplantation in advanced cases of malignancy and the organ-donor shortage. Presently, patients have to be selected with predictable likelihood for long-term survival. Pre-transplantation imaging is indispensable for detection, characterization, staging, and surgical road-mapping before the procedure. The present article focuses on the role of imaging modalities in these different aspects of preoperative assessment. (orig.) With 12 figs., 2 tabs., 66 refs.

  20. Improving Surgical Resection of Metastatic Liver Tumors With Near-Infrared Optical-Guided Fluorescence Imaging.

    Science.gov (United States)

    Barabino, Gabriele; Porcheron, Jack; Cottier, Michèle; Cuilleron, Muriel; Coutard, Jean-Guillaume; Berger, Michel; Molliex, Serge; Beauchesne, Brigitte; Phelip, Jean Marc; Grichine, Alexei; Coll, Jean-Luc

    2016-08-01

    Objective The aim of this study was to investigate the feasibility and future clinical applications of near-infrared (NIR) fluorescence imaging to guide liver resection surgery for metastatic cancer to improve resection margins. Summary Background Data A subset of patients with metastatic hepatic tumors can be cured by surgery. The degree of long-term and disease-free survival is related to the quality of surgery, with the best resection defined as "R0" (complete removal of all tumor cells, as evidenced by microscopic examination of the margins). Although intraoperative ultrasonography can evaluate the surgical margins, surgeons need a new tool to perfect the surgical outcome. Methods A preliminary study was performed on 3 patients. We used NIR imaging postoperatively "ex vivo" on the resected liver tissue. The liver tumors were preoperatively labelled by intravenously injecting the patient with indocyanine green (ICG), a NIR fluorescent agent (24 hours before surgery, 0.25 mg/kg). Fluorescent images were obtained using a miniaturized fluorescence imaging system (FluoStic, Fluoptics, Grenoble, France). Results After liver resection, the surgical specimens from each patient were sliced into 10-mm sections in the operating room and analyzed with the FluoStic. All metastatic tumors presented rim-type fluorescence. Two specimens had incomplete rim fluorescence. The pathologist confirmed the presence of R1 margins (microscopic residual resection), even though the ultrasonographic analysis indicated that the result was R0. Conclusions Surgical liver resection guided by NIR fluorescence can help detect potentially uncertain anatomical areas that may be missed by preoperative imaging and by ultrasonography during surgery. These preliminary results will need to be confirmed in a larger prospective patient series.

  1. Gene expression accurately distinguishes liver metastases of small bowel and pancreas neuroendocrine tumors.

    Science.gov (United States)

    Sherman, Scott K; Maxwell, Jessica E; Carr, Jennifer C; Wang, Donghong; Bellizzi, Andrew M; Sue O'Dorisio, M; O'Dorisio, Thomas M; Howe, James R

    2014-12-01

    Small bowel (SBNETs) and pancreatic neuroendocrine tumors (PNETs) often present with liver metastases. Although liver biopsy establishes a neuroendocrine diagnosis, the primary tumor site is frequently unknown without exploratory surgery. Gene expression differences in metastases may distinguish primary SBNETs and PNETs. This study sought to determine expression differences of four genes in neuroendocrine metastases and to create a gene expression algorithm to distinguish the primary site. Nodal and liver metastases from SBNETs and PNETs (n = 136) were collected at surgery under an Institutional Review Board-approved protocol. Quantitative PCR measured expression of bombesin-like receptor-3, opioid receptor kappa-1, oxytocin receptor, and secretin receptor in metastases. Logistic regression models defined an algorithm predicting the primary tumor site. Models were developed on a training set of 21 nodal metastases and performance was validated on an independent set of nodal and liver metastases. Expression of all four genes was significantly different in SBNET compared to PNET metastases. The optimal model employed expression of bombesin-like receptor-3 and opioid receptor kappa-1. When these genes did not amplify, the algorithm used oxytocin receptor and secretin receptor expression, which allowed classification of all 136 metastases with 94.1 % accuracy. In the independent liver metastasis validation set, 52/56 (92.9 %) were correctly classified. Positive predictive values were 92.5 % for SBNETs and 93.8 % for PNETs. This validated algorithm accurately distinguishes SBNET and PNET metastases based on their expression of four genes. High accuracy in liver metastases demonstrates applicability to the clinical setting. Studies assessing this algorithm's utility in prospective clinical decision-making are warranted.

  2. Estrogen inhibits the effects of obesity and alcohol on mammary tumors and fatty liver.

    Science.gov (United States)

    Hong, Jina; Holcomb, Valerie B; Kushiro, Kyoko; Núñez, Nomelí P

    2011-12-01

    The risk of developing breast cancer and fatty liver is increased by alcohol consumption. The objective of the present study was to determine if obesity and exogenous estrogen supplementation alter the effects of alcohol on mammary tumorigenesis and fatty liver. Ovariectomized female mice were (1) fed diets to induce overweight and obese phenotypes, (2) provided water or 20% alcohol, (3) implanted with placebo, low- or high-dose estrogen pellets and (4) injected with Met-1 mouse mammary cancer cells. Alcohol-consuming mice were more insulin sensitive and developed larger tumors than water consuming mice. Obese mice developed slightly larger tumors than control mice. Alcohol consumption and obesity increased growth factors, hepatic steatosis, activation of Akt, and inhibited the caspase-3 cascade. Estrogen treatment triggered the loss of body fat, induced insulin sensitivity, suppressed tumor growth, reduced growth factors and improved hepatic steatosis. Results show that the effects of alcohol on mammary tumor and fatty liver are modified by obesity and estrogen supplementation.

  3. Mutation analysis of novel human liver-related putative tumor suppressor gene in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Cheng Liao; Tsai-Ping Li; Mu-Jun Zhao; Jing Zhao; Hai Song; Pascal Pineau; Agnès Marchio; Anne Dejean; Pierre Tiollais; Hong-Yang Wang

    2003-01-01

    AIM: To find the point mutations meaningful for inactivationof liver-related putative tumor suppressor gene (LPTS) gene,a human novel liver-related putative tumor suppressor geneand telomerase inhibitor in hepatocellular carcinoma.METHODS: The entire coding sequence of LPTS genewas examined for mutations by single strand conformationpolymorphism (SSCP) assay and PCR products directsequencing in 56 liver cancer cell lines, 7 ovarian cancerand 7 head & neck tumor cell lines and 70 pairs of HCCtissues samples. The cDNA fragment coding for the mostfrequent mutant protein was subcloned into GST fusionexpression vector. The product was expressed in E. coliand purified by glutathione-agarose column. Telomericrepeat amplification protocol (TRAP) assays wereperformed to study the effect of point mutation totelomerase inhibitory activity.RESULTS: SSCP gels showed the abnormal shifting bandsand DNA sequencing found that there were 5 differentmutations and/or polymorphisms in 12 tumor cell lineslocated at exon2, exon5 and exon7. The main alterationswere A(778)A/G and A(880)T in exon7. The change in siteof 778 could not be found in HCC tissue samples, while themutation in position 880 was seen in 7 (10 %) cases. Themutation in the site of 880 had no effect on telomeraseinhibitory activity.CONCLUSION: Alterations identified in this study arepolymorphisms of LPTS gene. LPTS mutations occur in HCCbut are infrequent and of little effect on the telomeraseinhibitory function of the protein. Epigenetics, such asmethylation, acetylation, may play the key role in inactivationof LPTS.

  4. [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 D3 mediates antitumor effects in hepatocellular carcinoma. We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D3-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 (p<0.05). The majority of the HCC samples expressed 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 D3, providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910-1918.

  5. Cyberknife Stereotactic Body Radiation Therapy for Nonresectable Tumors of the Liver: Preliminary Results

    Directory of Open Access Journals (Sweden)

    K. Goyal

    2010-01-01

    Full Text Available Purpose. Stereotactic body radiation therapy (SBRT has emerged as a treatment option for local tumor control of primary and secondary malignancies of the liver. We report on our updated experience with SBRT in patients with non-resectable tumors of the liver. Methods. Our first 17 consecutive patients (mean age 58.1 years receiving SBRT for HCC (=6, IHC (=3, and LM (=8 are presented. Mean radiation dose was 34Gy delivered over 1–3 fractions. Results. Treated patients had a mean decrease in maximum pretreatment tumor diameter from 6.9±4.6 cm to 5.0±2.1 cm at three months after treatment (<.05. The mean total tumor volume reduction was 44% at six months (<.05. 82% of all patients (14/17 achieved local control with a median follow-up of 8 months. 100% of patients with HCC (=6 achieved local control. Patients with surgically placed fiducial markers had no complications related to marker placement. Conclusion. Our preliminary results showed that SBRT is a safe and effective local treatment modality in selected patients with liver malignancies with minimal adverse events. Further studies are needed to define its role in the management of these malignancies.

  6. Multimodal Imaging of Nanocomposite Microspheres for Transcatheter Intra-Arterial Drug Delivery to Liver Tumors

    Science.gov (United States)

    Kim, Dong-Hyun; Li, Weiguo; Chen, Jeane; Zhang, Zhuoli; Green, Richard M.; Huang, Sui; Larson, Andrew C.

    2016-01-01

    A modern multi-functional drug carrier is critically needed to improve the efficacy of image-guided catheter-directed approaches for the treatment of hepatic malignancies. For this purpose, a nanocomposite microsphere platform was developed for selective intra-arterial transcatheter drug delivery to liver tumors. In our study, continuous microfluidic methods were used to fabricate drug-loaded multimodal MRI/CT visible microspheres that included both gold nanorods and magnetic clusters. The resulting hydrophilic, deformable, and non-aggregated microspheres were mono-disperse and roughly 25 um in size. Sustained drug release and strong MRI T2 and CT contrast effects were achieved with the embedded magnetic nano-clusters and radiopaque gold nanorods. The microspheres were successfully infused through catheters selectively placed within the hepatic artery in rodent models and subsequent distribution in the targeted liver tissues and hepatic tumors confirmed with MRI and CT imaging. These multimodal nanocomposite drug carriers should be ideal for selective intra-arterial catheter-directed administration to liver tumors while permitting MRI/CT visualization for patient-specific confirmation of tumor-targeted delivery. PMID:27405824

  7. Expression of phosphatase of regenerating liver-3 is associated with prognosis of Wilms’ tumor

    Directory of Open Access Journals (Sweden)

    Sun F

    2017-01-01

    Full Text Available Fengyin Sun,1 Wenyi Li,2,3 Lie Wang,2 Changfeng Jiao3 1Department of Pediatric Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, 2Department of General Surgery, Fuzhou General Hospital of Nanjing Command, PLA, Fuzhou, Fujian Province, 3Department of Vascular Surgery, Xinzhou City People’s Hospital, Xinzhou, Shanxi Province, People’s Republic of China Objective: The current study was undertaken to explore the clinical and prognostic value of phosphatase of regenerating liver-3 (PRL-3 expression in Wilms’ tumor. Methods: Seventy-six patients with Wilms’ tumor in Qilu Hospital from January 2003 to July 2009 were enrolled in the study. Protein expression level of PRL-3 was examined by immunohistochemical staining, and the correlation between PRL-3 expression and histopathological parameters, clinical variables, and outcome of patients with Wilms’ tumor were analyzed. Results: We found that 19% of patients with unfavorable histology had tumor recurrence and 16% of patients died following the operation. PRL-3 was expressed in 15 out of 76 tumors (19% and expressed highly in unfavorable histology Wilms’ tumor (P=0.04. PRL-3 protein expression level was correlated to 2.5-fold increase in recurrence rate of Wilms’ tumor (P=0.06 without any statistically significant difference. However, in favorable histology Wilms’ tumor, PRL-3 expression was correlated to an increase of 3.4-fold in recurrence rate (P=0.03. Conclusion: The expression of PRL-3 protein was correlated with an increased recurrence rate of favorable histology Wilms’ tumor. PRL-3 may serve as a promising biomarker for predicting patients with high risk of Wilms’ tumor. Further investigations are warranted to investigate the clinical function of PRL-3 in Wilms’ tumor. Keywords: Wilms’ tumor, prognosis, tumorigenesis, recurrence

  8. Transarterial Fiducial Marker Placement for Image-guided Proton Therapy for Malignant Liver Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, Kengo, E-mail: yesterday.is.yesterday@gmail.com; Shimohira, Masashi, E-mail: mshimohira@gmail.com [Nagoya City University Graduate School of Medical Sciences, Department of Radiology (Japan); Sasaki, Shigeru, E-mail: ssasaki916@yahoo.co.jp; Iwata, Hiromitsu, E-mail: h-iwa-ncu@nifty.com; Nishikawa, Hiroko, E-mail: piroko1018@gmail.com; Ogino, Hiroyuki, E-mail: oginogio@gmail.com; Hara, Masaki, E-mail: mhara@med.nagoya-cu.ac.jp [Nagoya City West Medical Center, Department of Radiation Oncology, Nagoya Proton Therapy Center (Japan); Hashizume, Takuya, E-mail: tky300@gmail.com; Shibamoto, Yuta, E-mail: yshiba@med.nagoya-cu.ac.jp [Nagoya City University Graduate School of Medical Sciences, Department of Radiology (Japan)

    2015-10-15

    PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors.

  9. Expression of tumor necrosis factor-alpha converting enzyme in liver regeneration after partial hepatectomy

    Institute of Scientific and Technical Information of China (English)

    Xian-Ming Lin; Ying-Bin Liu; Fan Zhou; Yu-Lian Wu; Li Chen; He-Qing Fang

    2008-01-01

    AIM:To study the expression of tumor necrosis factor-alpha converting enzyme (TACE) and evaluate its significance in liver regeneration after partial hepatectomy in vivo.METHODS:Male SD rats underwent 70% partial hepatec-tomy.The remaining liver and spleen tissue samples were collected at indicated time points after hepatectomy.TACE expression was investigated by Western blotting,immunohistochemistry,and serial section immunostaining.RESULTS:Expression of TACE in liver and spleen tissues after partial hepatectomy was a time-dependent alteration,reaching a maximal level between 24 and 48 h and remaining elevated for more than 168 h.TACE protein was localized to mononuclear cells (MNC),which infiltrated the liver from the spleen after hepatectomy.The kinetics of TACE expression was in accordance with the number of TACE-staining MNCs and synchronized with those of transforming growth factor-α(TGFα).In addition,TACE-staining MNC partially overlapped with CD3+ T lymphocytes.CONCLUSION:TACE may be involved in liver regenera-tion by pathway mediated with TGFα-EGFR in the cell-cycle progressive phase in vivo.TACE production and effect by paracrine may be a pathway of involvement in liver regeneration for the activated CD3+ T lymphocytes.

  10. Solid, non-skin, post-liver transplant tumors: Key role of lifestyle and immunosuppression management.

    Science.gov (United States)

    Carenco, Christophe; Faure, Stéphanie; Ursic-Bedoya, José; Herrero, Astrid; Pageaux, Georges Philippe

    2016-01-07

    Liver transplantation has been the treatment of choice for end-stage liver disease since 1983. Cancer has emerged as a major long-term cause of death for liver transplant recipients. Many retrospective studies that have explored standardized incidence ratio have reported increased rates of solid organ cancers post-liver transplantation; some have also studied risk factors. Liver transplantation results in a two to five-fold mean increase in the rate of solid organ cancers. Risk of head and neck, lung, esophageal, cervical cancers and Kaposi's sarcoma is high, but risk of colorectal cancer is not clearly demonstrated. There appears to be no excess risk of developing breast or prostate cancer. Environmental risk factors such as viral infection and tobacco consumption, and personal risk factors such as obesity play a key role, but recent data also implicate the role of calcineurin inhibitors, whose cumulative and dose-dependent effects on cell metabolism might play a direct role in oncogenesis. In this paper, we review the results of studies assessing the incidence of non-skin solid tumors in order to understand the mechanisms underlying solid cancers in post-liver transplant patients and, ultimately, discuss how to prevent these cancers. Immunosuppressive protocol changes, including a calcineurin inhibitor-free regimen, combined with dietary guidelines and smoking cessation, are theoretically the best preventive measures.

  11. The role of chemokines in regualating mast cell recruitment around rat liver tumor

    Institute of Scientific and Technical Information of China (English)

    ZHANGZhi-Yong; RUANYou-Bing

    2001-01-01

    Aim To explore the correlation of stem cell factor (SCF)and monocyte chemoattractant protein-1 (MCP-1) with number difference of mast cell (MC) around the liver tumor.Methods 40 male wistar rats with liver neoplasm were divided into three different groups by numbers of MC in the surroundings of tumor. We performed ELISA for SCF and MCP-1 in serums. And chemotaxis assays of rat peritoneal MCs to SCF and MCP-1 in serums were measured in 48-wellmicroboyden chambers. We also used immunohistochemistryto investigate whether rat MCs express SCF positively.RESULTE There were marked differences in MC numbersaround tumor between different groups. The group that has more MCs around tumor has the higher levels of SCF andMCP-1 in serums and the stronger chemotaxis to ratperitoneal MCs. SCF washigher than MCP-1 in bothchemotactic activity to MCs and levels in serums. And ratMCs positively express SCF.Conclusion SCF and MCP-1 were found to be two particularly efficacious chemoattractants for MCs. The levels of SCF and MCP-1 in serums may be closely correlated with MCs numbers around tumor. The production of SCF by MCs might act on mast cell migration and proliferation of MC.

  12. Direct Liver Invasion from a Gastric Adenocarcinoma as an Initial Presentation of Extranodal Tumor Spread

    Directory of Open Access Journals (Sweden)

    Mitanshu Shah

    2012-01-01

    Full Text Available Gastric cancer often carries a poor prognosis, with an estimated 740,000 deaths from the malignancy occurring yearly worldwide (Dicken et al., 2005. The mortality of disease is largely dependent on the extent of tumor spread, as gastric cancer has a predilection to metastasize to other visceral secondaries via hematogenous and lymphatic dissemination. Direct invasion of a gastric adenocarcinoma to adjacent organs secondary to gastric wall perforation does occur; however, it is often present in the setting of advanced disease. Rarely does direct tumor invasion to adjacent organs from a gastric adenocarcinoma present as the initial manifestation of extranodal tumor spread. We present a case of a 40-year-old male with direct tumor extension to the liver as an initial presentation of extranodal tumor spread from a gastric adenocarcinoma. Clinicians should be aware of such an occurrence, as treatment modalities in direct liver extension from a gastric adenocarcinoma vary and may be directed towards palliation rather than curative intent.

  13. Advances in SPECT for Optimizing the Liver Tumors Radioembolization Using Yttrium-90 Microspheres.

    Science.gov (United States)

    Roshan, Hoda Rezaei; Azarm, Ahmadreza; Mahmoudian, Babak; Islamian, Jalil Pirayesh

    2015-01-01

    Radioembolization (RE) with Yttrium-90 ((90)Y) microspheres is an effective treatment for unresectable liver tumors. The activity of the microspheres to be administered should be calculated based on the type of microspheres. Technetium-99m macroaggregated albumin ((99m)Tc-MAA) single photon emission computed tomography/computed tomography (SPECT/CT) is a reliable assessment before RE to ensure the safe delivery of microspheres into the target. (90)Y bremsstrahlung SPECT imaging as a posttherapeutic assessment approach enables the reliable determination of absorbed dose, which is indispensable for the verification of treatment efficacy. This article intends to provide a review of the methods of optimizing (90)Y bremsstrahlung SPECT imaging to improve the treatment efficacy of liver tumor RE using (90)Y microspheres.

  14. Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

    Institute of Scientific and Technical Information of China (English)

    Carlos Eduardo Paiva; Francisco Alves Moraes Neto; Abbas Agaimy; Maria Aparecida Custódio Domingues; Silvia Regina Rogatto

    2008-01-01

    Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms,either synchronously or metachronously.In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman with no evidence of tuberous sclerosis.A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature.Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small incidental hepatic PEComa and a high risky extramural gastric GIST,respectively.The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms.To our knowledge,this is the first report of PEComa in a patient with GIST.Hepatic lesions detected synchronously or metachronously in patients with GISTs may represent histogenetically distinct lesions and should be sampled to confirm or exclude metastatic GISTs.

  15. Avaliação dos tumores hepáticos ao Doppler Doppler evaluation of liver tumors

    Directory of Open Access Journals (Sweden)

    Márcio Martins Machado

    2004-10-01

    Full Text Available Os avanços recentes na ultra-sonografia têm ampliado a possibilidade de detecção de tumores hepáticos. Isto tem auxiliado na perspectiva de melhora do prognóstico destes pacientes, à medida que novas técnicas terapêuticas têm surgido. Neste artigo os autores relatam achados ao Doppler que podem auxiliar na identificação e caracterização dos tumores hepáticos, avaliando dados do Doppler colorido, pulsado e do Doppler de amplitude ("power Doppler". Fazem, também, referência a novas modalidades de imagem, como o uso da harmônica.Recent advances in ultrasound have optimized the detection of liver tumors and helped to improve the prognosis of patients with this condition as newly developed and improved therapeutic modalities have been established. The authors review important Doppler findings which may help in the identification and characterization of some hepatic tumors through the evaluation of color Doppler, pulsed Doppler and power Doppler features. New imaging methods such as the use of harmonics imaging are also reviewed.

  16. Stereotactic body radiation therapy for liver oligo-recurrence and oligo-progression from various tumors

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Yu Jin; Kim, Mi Sook; Jang, Won Il; Seo, Young Seok; Cho, Chul Koo; Yoo, Hyung Jun; Paik, Eun Kyung [Dept. of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2017-06-15

    To evaluate the outcomes of stereotactic body radiation therapy (SBRT) for patients with liver oligo-recurrence and oligo-progression from various primary tumors. Between 2002 and 2013, 72 patients with liver oligo-recurrence (oligo-metastasis with a controlled primary tumor) and oligo-progression (contradictory progression of a few sites of disease despite an overall tumor burden response to therapy) underwent SBRT. Of these, 9 and 8 patients with uncontrollable distant metastases and patients immediate loss to follow-up, respectively, were excluded. The total planning target volume was used to select the SBRT dose (median, 48 Gy; range, 30 to 60 Gy, 3–4 fractions). Toxicity was evaluated using the Common Toxicity Criteria for Adverse Events v4.0. We evaluated 55 patients (77 lesions) treated with SBRT for liver metastases. All patients had controlled primary lesions, and 28 patients had stable lesions at another site (oligo-progression). The most common primary site was the colon (36 patients), followed by the stomach (6 patients) and other sites (13 patients). The 2-year local control and progression-free survival rates were 68% and 22%, respectively. The 2- and 5-year overall survival rates were 56% and 20%, respectively. The most common adverse events were grade 1–2 fatigue, nausea, and vomiting; no grade ≥3 toxicities were observed. Univariate analysis revealed that oligo-progression associated with poor survival. SBRT for liver oligo-recurrence and oligo-progression appears safe, with similar local control rates. For liver oligo-progression, criteria are needed to select patients in whom improved overall survival can be expected through SBRT.

  17. Vascular Profile Characterization of Liver Tumors by Magnetic Resonance Imaging Using Hemodynamic Response Imaging in Mice

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    Yifat Edrei

    2011-03-01

    Full Text Available Recently, we have demonstrated the feasibility of using hemodynamic response imaging (HRI, a functional magnetic resonance imaging (MRI method combined with hypercapnia and hyperoxia, for monitoring vascular changes during liver pathologies without the need of contrast material. In this study, we evaluated HRI ability to assess changes in liver tumor vasculature during tumor establishment, progression, and antiangiogenic therapy. Colorectal adenocarcinoma cells were injected intrasplenically to model colorectal liver metastasis (CRLM and the Mdr2 knockout mice were used to model primary hepatic tumors. Hepatic perfusion parameters were evaluated using the HRI protocol and were compared with contrast-enhanced (CE MRI. The hypovascularity and the increased arterial blood supply in well-defined CRLM were demonstrated by HRI. In CRLM-bearing mice, the entire liver perfusion was attenuated as the HRI maps were significantly reduced by 35%. This study demonstrates that the HRI method showed enhanced sensitivity for small CRLM (1–2 mm detection compared with CE-MRI (82% versus 38%, respectively. In addition, HRI could demonstrate the vasculature alteration during CRLM progression (arborized vessels, which was further confirmed by histology. Moreover, HRI revealed the vascular changes induced by rapamycin treatment. Finally, HRI facilitates primary hepatic tumor characterization with good correlation to the pathologic differentiation. The HRI method is highly sensitive to subtle hemodynamic changes induced by CRLM and, hence, can function as an imaging tool for understanding the hemodynamic changes occurring during CRLM establishment, progression, and antiangiogenic treatment. In addition, this method facilitated the differentiation between different types of hepatic lesions based on their vascular profile noninvasively.

  18. Totally laparoscopic anatomical liver resection for centrally located tumors: A single center experience.

    Science.gov (United States)

    Kim, Wan-Joon; Kim, Ki-Hun; Shin, Min-Ho; Yoon, Young-In; Lee, Sung-Gyu

    2017-01-01

    Laparoscopic major hepatectomy is a common procedure that has been reported frequently; however, laparoscopic resection of centrally located tumors involving segments 4, 5, and 8 remains a technically difficult procedure because it requires 2 transection planes and dissection of numerous branches of the hepatic vein and glissonean capsule compared to hemi-hepatectomy. Here, we present 7 cases of totally laparoscopic right anterior sectionectomy (Lap-RAS) and 3 cases of totally laparoscopic central bisectionectomy (Lap-CBS).Between May 2013 and January 2015, 10 totally laparoscopic anatomical resections of centrally located tumors were performed in our institution. The median age of the patients was 54.2 (38-72) years and the median ICG-R15 was 10.4 (3.9-17.4). There were 8 patients with hepatocellular carcinoma (HCC) and 2 with metastatic colorectal cancer. All the HCC patients has the liver function impairment on the degree of Child-Pugh score A.The mean operation time was 330 ± 92.7 minutes with an estimated blood loss of 325 ± 234.5 mL. Only 1 patient required transfusion during surgery. Mean postoperative hospital stay was 9.5 ± 3.4 day and postop complication was reported only 1 case that has the fluid collection at the resection margin of the liver. Mean resection margin was 8.5 ± 6.1 mm and tumor size was 2.9 ± 1.9 cm.Totally lap-RAS and lap-CBS are feasible operative procedures in patients with centrally located tumor of the liver and particularly in patients with limited liver function such as those with cirrhosis.

  19. Undifferentiated sarcoma of the liver: a case study of an erythropoietin-secreting tumor.

    Science.gov (United States)

    Lin, JoAnn M; Heath, Jonathon E; Twaddell, William S; Castellani, Rudy J

    2014-09-01

    Undifferentiated embryonal sarcoma of the liver (UESL) is an uncommon hepatic tumor usually found in children, with rare cases reported in adults. We present a case of a 53-year-old woman with an undifferentiated sarcoma of the liver (USL), which resembles UESL, who initially presented with a markedly elevated hematocrit (61.2%). Cytogenetic studies for polycythemia vera were negative, but the patient's erythropoietin (EPO) was elevated. A computed tomography scan and subsequent partial hepatectomy revealed a well-circumscribed, partially cystic mass in the right lobe of the liver measuring 34 cm. Following surgery, the patient's EPO level and hematocrit dropped to within normal range and remained so for 1 year, at which point it rose again. A subsequent magnetic resonance imaging scan showed a liver mass at the previous resection margin, consistent with a recurrence. In this case study, we describe the first reported USL resembling an UESL that secretes EPO, which was a useful marker of tumor recurrence. © The Author(s) 2013.

  20. BMP9-Induced Survival Effect in Liver Tumor Cells Requires p38MAPK Activation

    Directory of Open Access Journals (Sweden)

    María García-Álvaro

    2015-08-01

    Full Text Available The study of bone morphogenetic proteins (BMPs role in tumorigenic processes, and specifically in the liver, has gathered importance in the last few years. Previous studies have shown that BMP9 is overexpressed in about 40% of hepatocellular carcinoma (HCC patients. In vitro data have also shown evidence that BMP9 has a pro-tumorigenic action, not only by inducing epithelial to mesenchymal transition (EMT and migration, but also by promoting proliferation and survival in liver cancer cells. However, the precise mechanisms driving these effects have not yet been established. In the present work, we deepened our studies into the intracellular mechanisms implicated in the BMP9 proliferative and pro-survival effect on liver tumor cells. In HepG2 cells, BMP9 induces both Smad and non-Smad signaling cascades, specifically PI3K/AKT and p38MAPK. However, only the p38MAPK pathway contributes to the BMP9 growth-promoting effect on these cells. Using genetic and pharmacological approaches, we demonstrate that p38MAPK activation, although dispensable for the BMP9 proliferative activity, is required for the BMP9 protective effect on serum withdrawal-induced apoptosis. These findings contribute to a better understanding of the signaling pathways involved in the BMP9 pro-tumorigenic role in liver tumor cells.

  1. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression.

    Directory of Open Access Journals (Sweden)

    Sathidpak Nantasanti

    Full Text Available The tumor suppressors Retinoblastoma (Rb and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver for metabolizing therapeutic drugs or toxins. We demonstrate that Rb and p53 cooperate to metabolize the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC. DDC is metabolized mainly by cytochrome P450 (Cyp3a enzymes resulting in inhibition of heme synthesis and accumulation of protoporphyrin, an intermediate of heme pathway. Protoporphyrin accumulation causes bile injury and ductular reaction. We show that loss of Rb and p53 resulted in reduced Cyp3a expression decreased accumulation of protoporphyrin and consequently less ductular reaction in livers of mice fed with DDC for 3 weeks. These findings provide strong evidence that synergistic functions of Rb and p53 are essential for metabolism of DDC. Because Rb and p53 functions are frequently disabled in liver diseases, our results suggest that liver patients might have altered ability to remove toxins or properly metabolize therapeutic drugs. Strikingly the reduced biliary injury towards the oxidative stress inducer DCC was accompanied by enhanced hepatocellular injury and formation of HCCs in Rb and p53 deficient livers. The increase in hepatocellular injury might be related to reduce protoporphyrin accumulation, because protoporphrin is well known for its anti-oxidative activity. Furthermore our results indicate that Rb and p53 not only function as tumor suppressors in response to carcinogenic injury, but also in response to non-carcinogenic injury such as DDC.

  2. The c-Met Inhibitor MSC2156119J Effectively Inhibits Tumor Growth in Liver Cancer Models

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    Bladt, Friedhelm, E-mail: Friedhelm.Bladt@merckgroup.com; Friese-Hamim, Manja; Ihling, Christian; Wilm, Claudia; Blaukat, Andree [EMD Serono, and Merck Serono Research and Development, Merck KGaA, Darmstadt 64293 (Germany)

    2014-08-19

    The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth factor (HGF) as its only high-affinity ligand. Aberrant activation of c-Met is associated with many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy of the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude mice were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected according to c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and induced complete regression in mice bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 weeks of MSC2156119J treatment, and the number of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation showed increased responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterized by low c-Met expression were less sensitive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy did not improve efficacy. These findings indicate that selective c-Met/HGF inhibition with MSC2156119J is associated with marked regression of c-Met high-expressing tumors, supporting its clinical development as an antitumor treatment for HCC patients with active c-Met signaling.

  3. Activatable Water-Soluble Probes Enhance Tumor Imaging by Responding to Dysregulated pH and Exhibiting High Tumor-to-Liver Fluorescence Emission Contrast.

    Science.gov (United States)

    Xiong, Hu; Kos, Petra; Yan, Yunfeng; Zhou, Kejin; Miller, Jason B; Elkassih, Sussana; Siegwart, Daniel J

    2016-07-20

    Dysregulated pH has been recognized as a universal tumor microenvironment signature that can delineate tumors from normal tissues. Existing fluorescent probes that activate in response to pH are hindered by either fast clearance (in the case of small molecules) or high liver background emission (in the case of large particles). There remains a need to design water-soluble, long circulating, pH-responsive nanoprobes with high tumor-to-liver contrast. Herein, we report a modular chemical strategy to create acidic pH-sensitive and water-soluble fluorescent probes for high in vivo tumor detection and minimal liver activation. A combination of a modified Knoevenagel reaction and PEGylation yielded a series of NIR BODIPY fluorophores with tunable pKas, high quantum yield, and optimal orbital energies to enable photoinduced electron transfer (PeT) activation in response to pH. After intravenous administration, Probe 5c localized to tumors and provided excellent tumor-to-liver contrast (apparent T/L = 3) because it minimally activates in the liver. This phenomenon was further confirmed by direct ex vivo imaging experiments on harvested organs. Because no targeting ligands were required, we believe that this report introduces a versatile strategy to directly synthesize soluble probes with broad potential utility including fluorescence-based image-guided surgery, cancer diagnosis, and theranostic nanomedicine.

  4. Metastases of pancreatic neuroendocrine tumor to the liver as extremely rare indication for liver transplantation in children. Case report and review of the literature.

    Science.gov (United States)

    Ismail, Hor; Broniszczak, Dorota; Markiewicz-Kijewska, Małgorzata; Ciopiński, Mateusz; Teisseyre, Joanna; Kluge, Przemysław; Dembowska-Bagińska, Bożenna; Kościesza, Andrzej; Socha, Piotr; Kaliciński, Piotr

    2016-09-01

    Neuroendocrine tumors (NET) are extremely rare in children (0.75 cases per 100,000 children and adolescents a year) and the majority of these tumors are benign or present low grade of malignancy. According to the American registry Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, less than 2% of all neuroendocrine tumors in children occur in the pancreas, making it a rare site for these tumors. The majority of them are found in children over 10years of age, especially those with malignant potential. Treatment of NET consists of different methods: surgery, somatostatin analogues and chemotherapy. Radical surgical resection remains the standard of treatment; however, it is not always feasible because of distant metastases. The authors present a case report of pancreatic NET with multiple metastases to the liver. The patient was treated with pancreatic resection and liver transplantation for liver metastases. Prior to liver transplantation, the patient was treated with somatostatin analogues, sunitinib and chemotherapy. Management of liver metastases with liver transplantation is discussed.

  5. Comprehensive treatment of a functional pancreatic neuroendocrine tumor with multifocal liver metastases.

    Science.gov (United States)

    Wang, Wei; Seeruttun, Sharvesh Raj; Fang, Cheng; Zhou, Zhiwei

    2014-08-01

    A 64-year-old man was admitted to the Sun Yat-Sen University Cancer Center with chief complaints of recurrent abdominal pain and diarrhea for about 3 years and with a history of surgical repair for intestinal perforation owing to stress ulcer. Positron emission tomography (PET)/computed tomography (CT) demonstrated a primary tumor on the pancreatic tail with multifocal liver metastases. Pathological and immunohistochemistry staining revealed the lesion to be a pancreatic neuroendocrine tumor (pNET). According to the latest World Health Organization (WHO, 2013) classification, the tumor was classified as stage IV functional G1 pNET. After referral to the multidisciplinary treatment board (MDT), the patient was started on periodic dose of omeprazole, somatostatin analogues and Interferon α (IFNα) and had scanning follow-ups. Based upon the imaging results, CT-guided radioactive iodine-125 ((125)I) seeds implantation therapy, radiofrequency ablation therapy (RFA) or microwave ablation technique were chosen for the treatment of the primary tumor. Transarterial chemoembolization (TACE), RFA and microwave ablation techniques were decided upon for liver metastases. The patient showed beneficial response to the treatment with clinically manageable low-grade side effects and attained partial remission (RECIST criteria) with a good quality of life.

  6. 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

  7. Usefulness of examination of some tumor markers in diagnostics of liver cancer.

    Science.gov (United States)

    Snarska, Jadwiga; Szajda, Slawomir Dariusz; Puchalski, Zbigniew; Szmitkowski, Maciej; Chabielska, Ewa; Kaminski, Fabian; Zwierz, Piotr; Zwierz, Krzysztof

    2006-01-01

    Diagnostics of liver cancer is mainly based on imaging methods: which are ultrasound and computer tomography. Determination of tumor markers is an accessory investigation enabling us to detect cancer, to evaluate the effectiveness of its operative and postoperative treatment and to diagnose early cancer relapse or distant metastases. Alpha-fetoprotein (AFP) is a basic well-known marker in diagnostics of liver cancer. Carcinoembryonic antigen (CEA) and cancer procoagulant (CP) are also important in case of metastases to this organ, especially from the colon. The purpose of this study was to evaluate the usefulness of AFP, CEA and CP in detection of liver cancer. The material of the study was the blood serum from 25 patients with liver cancer diagnosed histopathologically and 12 healthy individuals as a control group. The concentrations of AFP and CEP were assessed by immunoenzymatic method (MEIA) in the Axsym analyzer of Abbott and expressed in ng/mL. CP activity was determined by coagulation method worked out by Gordon and Benson and expressed as coagulation time in seconds (s). Based on the results obtained in our study, the concentrations of AFP and CEP were several fold higher in the serum of patients with liver cancer than the relevant values of these markers. CP activity was higher in the serum of patients with liver cancer than the mean values of patients in the control group. The differences found in the study between the groups examined and the control group were statistically significant atp<0.001. The results confirmed a high diagnostic value of AFP and CEA testing and suggest the possibility of using CP activity to detect liver cancer.

  8. A MULTISTAGE BIOLOGICALLY BASED MATHEMATICAL MODEL FOR MOUSE LIVER TUMORS INDUCED BY DICHLOROACETIC ACID (DCA) - EXPLORATION OF THE MODEL

    Science.gov (United States)

    A biologically based mathematical model for the induction of liver tumors in mice by dichloroacetic acid (DCA) has been developed from histopathologic analysis of the livers of exposed mice. This analysis suggests that following chronic exposure to DCA, carcinomas can arise dire...

  9. Free breathing DCE-MRI with motion correction and its values for benign and malignant liver tumor differentiation

    Directory of Open Access Journals (Sweden)

    Xiaolin Zheng

    2015-09-01

    Conclusion: Dynamic contrast-enhanced MRI combined with tracer kinetic model and non-rigid registration was a feasible method for diagnosing of liver lesions under free breezing mode. In our approach, the contrast agent transfer rate Ktrans was a good biomarker to differentiate benign and malignant tumors of liver.

  10. Analysis of factors affecting local tumor progression of colorectal cancer liver metastasis after radiofrequency ablation

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    Jeon, Seong Hee; Cho, Yun Ku; Choi, Seung A; Kim, Mi Young; Lee, Ho Suk [Veterans Health Service Medical Center, Seoul (Korea, Republic of)

    2017-03-15

    The purpose of this study was to evaluate the independent predictive factors for local tumor progression (LTP) of colorectal liver metastasis (CRLM) after radiofrequency ablation (RFA). Patients with CRLM were included in the analysis if nodules were up to five in number, each nodule was ≤ 5 cm, and RFA was performed in our center from January 2006 to December 2015. Univariate and multivariate analyses to identify the predictors of LTP were performed by using a Cox proportional hazard model. Overall, 58 tumors from 38 patients were included in this study. LTP occurred in 14 tumors from 9 patients. The overall 1- and 3-year LTP rates were 23.5% and 29.4%, respectively. Multivariate analysis showed that tumor size > 2 cm and insufficient ablative margin were two independently significant adverse prognostic factors for LTP (p = 0.045 and 0.022, respectively). The 3-year LTP rates for 33 and 25 tumors with and without sufficient ablative margin were 4.5% and 61.2%, respectively. The difference was statistically significant (p < 0.001). The difference in the 3-year LTP rates according to the tumor size was not statistically significant (p = 0.791). Insufficient ablative margin seems to be the most potent predictor of LTP after RFA of CRLM.

  11. Ultrasound-guided percutaneous radiofrequency ablation of liver tumors: How we do it safety and completely

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    Kim, Jin Woong; Shin, Sang Soo; Heo, Suk Hee; Hong, Jun Hyung; Lim, Hyo Soon; Seon, Hyun Ju; Hur, Young Hoe; Park, Chang Hwan; Jeong, Yong Yeon; Kang, Heoung Keun [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2015-12-15

    Ultrasound-guided percutaneous radiofrequency (RF) ablation has become one of the most promising local cancer therapies for both resectable and nonresectable hepatic tumors. Although RF ablation is a safe and effective technique for the treatment of liver tumors, the outcome of treatment can be closely related to the location and shape of the tumors. There may be difficulties with RF ablation of tumors that are adjacent to large vessels or extrahepatic heat-vulnerable organs and tumors in the caudate lobe, possibly resulting in major complications or treatment failure. Thus, a number of strategies have been developed to overcome these challenges, which include artificial ascites, needle track ablation, fusion imaging guidance, parallel targeting, bypass targeting, etc. Operators need to use the right strategy in the right situation to avoid the possibility of complications and incomplete thermal tissue destruction; with the right strategy, RF ablation can be performed successfully, even for hepatic tumors in high-risk locations. This article offers technical strategies that can be used to effectively perform RF ablation as well as to minimize possible complications related to the procedure with representative cases and schematic illustrations.

  12. Combined transarterial chemoembolization and arterial administration of Bletilla striata in treatment of liver tumor in rats

    Institute of Scientific and Technical Information of China (English)

    Jun Qian; Daryusch Vossoughi; Dirk Woitaschek; Elsie Oppermann; Wolf O.Bechstein; Wei-Yong Li; Gan-Sheng Feng; Thomas Vogl

    2003-01-01

    AIM: To evaluate and compare the effect of combined transarterial chemoembolization (TACE) and arterial administration of Bletilla striata (a Chinese traditionalmedicine against liver tumor) versusTACE alone for the treatment of hepatocellular carcinoma (HCC) in ACI rats.METHODS: Subcapsular implantation of a solid Morris hepatoma 3 924A (2 mm3) in the liver was carried out in 30 male ACI rats. Tumor volume (V1) was measured by magnetic resonance imaging (MRI) on day 13 after implantation. The following different agents of interventional treatment were injected after retrograde catheterization via gastroduodenal artery (on day 14), namely, (A) TACE (0.1 mg mitomycin +0.1 mi Lipiodol) + Bletilla striata (1.0 mg) (n= 10); (B) TACE + Blebilla stnata(1.0 mg) + ligation of hepatic artery (n=10),(C) TACE alone (control group, n=10). Tumor volume (V2)was assessed by MRI (on day 13 after treatment) and the tumor growth ratio (V2/V1) was calculated.RESULTS: The mean tumor volume before (V1) and after (V2) treatment was 0.0355 cm3 and 0.2248 cm3 in group A,0.0374 cm3 and 0.0573 cm3 in group B, 0.0380 cm3 and 0.3674 cm3 in group C, respectively. The mean ratio (V2/V1)was 6.2791 in group A, 1.5324 in group B and 9.1382 in group C. Compared with the control group (group C), group B showed significant inhibition of tumor growth (P<0.01),while group A did not (P>0.05). None of the animals died during implantation or in the postoperative period.CONCLUSION: Combination of TACE and arterial administration of Bletilla striata plus ligation of hepatic artery is more effective than TACE alone in the treatment of HCC in rats.

  13. Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion

    Energy Technology Data Exchange (ETDEWEB)

    Baere, Thierry de, E-mail: thierry.debaere@gustaveroussy.fr [Gustave Roussy, Department of Interventional Radiology (France); Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp [National Cancer Center, Department of Diagnostic Radiology (Japan); Lencioni, Riccardo, E-mail: riccardo.lencioni@med.unipi.it [Pisa University School of Medicine, Division of Diagnostic Imaging and Intervention (R.L.) (Italy); Geschwind, Jean-Francois, E-mail: jfg@jhmi.edu [The Johns Hopkins Hospital, Vascular and Interventional Radiology (United States); Rilling, William, E-mail: wrilling@mcw.edu [Medical College of Wisconsin, Division of Vascular and Interventional Radiology Rm2803 (United States); Salem, Riad, E-mail: r-salem@northwestern.edu [Northwestern University, Department of Radiology (United States); Matsui, Osamu, E-mail: matsuio@med.kanazawa-u.ac.jp [Kanazawa University Graduate School of Medical Sciences, Department of Advanced Medical Imaging (Japan); Soulen, Michael C., E-mail: michael.soulen@uphs.upenn.edu [University of Pennsylvania, Division of Interventional Radiology (MCS) (United States)

    2016-03-15

    Transarterial chemoembolization with Lipiodol (Lipiodol TACE), also called conventional TACE, was developed in the early 1980s and widely adopted worldwide after randomized control trials and meta-analysis demonstrated superiority of Lipiodol TACE to best supportive care. Presently, there is no level one evidence that other TACE techniques are superior to Lipiodol TACE for intermediate stage hepatocellular carcinoma (HCC), which includes patients with preserved liver function and nonsurgical large or multinodular HCC without distant metastases. In addition, TACE is part of the treatment for progressive or symptomatic liver metastases from gastroenteropancreatic neuroendocrine tumors. When injected into the hepatic artery, Lipiodol has the unique property of selective uptake and retention in hyperarterialyzed liver tumors. Lipiodol/drug emulsion followed by particle embolization has been demonstrated to improve the pharmacokinetic of the drug and tumor response. Radio opacity of Lipiodol helps to monitor treatment delivery, with retention of Lipiodol serving as an imaging biomarker for tumor response. For 30 years, Lipiodol TACE has been inconsistently referenced in many publications with various levels of details for the method of preparation and administration, with reported progressive outcomes following improvements in the technique and the devices used to deliver the treatment and better patient selection. Consequently, there is no consensus on the standard method of TACE regarding the use of anticancer agents, embolic material, technical details, and the treatment schedule. In order to develop an internationally validated technical recommendation to standardize the Lipiodol TACE procedure, a worldwide panel of experts participated in a consensus meeting held on May 10, 2014.

  14. Cyclophilin A enhances cell proliferation and tumor growth of liver fluke-associated cholangiocarcinoma

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    Sawanyawisuth Kanlayanee

    2011-08-01

    Full Text Available Abstract Background Cyclophilin A (CypA expression is associated with malignant phenotypes in many cancers. However, the role and mechanisms of CypA in liver fluke-associated cholangiocarcinoma (CCA are not presently known. In this study, we investigated the expression of CypA in CCA tumor tissues and CCA cell lines as well as regulation mechanisms of CypA in tumor growth using CCA cell lines. Methods CypA expression was determined by real time RT-PCR, Western blot or immunohistochemistry. CypA silence or overexpression in CCA cells was achieved using gene delivery techniques. Cell proliferation was assessed using MTS assay or Ki-67 staining. The effect of silencing CypA on CCA tumor growth was determined in nude mice. The effect of CypA knockdown on ERK1/2 activation was assessed by Western blot. Results CypA was upregulated in 68% of CCA tumor tissues. Silencing CypA significantly suppressed cell proliferation in several CCA cell lines. Likewise, inhibition of CypA peptidyl-prolyl cis-trans isomerase (PPIase activity using cyclosporin A (CsA decreased cell proliferation. In contrast, overexpression of CypA resulted in 30% to 35% increases in proliferation of CCA cell lines. Interestingly, neither silence nor overexpression of CypA affected cell proliferation of a non-tumor human cholangiocyte cell line, MMNK1. Suppression of CypA expression attenuated ERK1/2 activity in CCA M139 cells by using both transient and stable knockdown methods. In the in vivo study, there was a 43% reduction in weight of tumors derived from CypA-silenced CCA cell lines compared with control vector CCA tumors in mice; these tumors with stable CypA silencing showed a reduced cell proliferation. Conclusions CypA is upregulated in majority of CCA patients' tissues and confers a significant growth advantage in CCA cells. Suppression of CypA expression decreases proliferation of CCA cell lines in vitro and reduces tumor growth in the nude mouse model. Inhibition of Cyp

  15. A Glycyrrhetinic Acid-Modified Curcumin Supramolecular Hydrogel for liver tumor targeting therapy

    Science.gov (United States)

    Chen, Guoqin; Li, Jinliang; Cai, Yanbin; Zhan, Jie; Gao, Jie; Song, Mingcai; Shi, Yang; Yang, Zhimou

    2017-03-01

    Curcumin (Cur), a phenolic anti-oxidant compound obtained from Curcuma longa plant, possesses a variety of therapeutic properties. However, it is suffered from its low water solubility and low bioavailability property, which seriously restricts its clinical application. In this study, we developed a glycyrrhetinic acid (GA) modified curcumin supramolecular pro-gelator (GA-Cur) and a control compound Nap-Cur by replacing GA with the naphthylacetic acid (Nap). Both compounds showed good water solubility and could form supramolecular gels by disulfide bond reduction triggered by glutathione (GSH) in vitro. Both formed gels could sustainedly release Cur in buffer solutions. We also investigated the cytotoxicity of pro-gelators to HepG2 cells by a MTT assay and determined the cellular uptake behaviours of them by fluorescence microscopy and LC-MS. Due to the over expression of GA receptor in liver cancer cells, our pro-gelator of GA-Cur showed an enhanced cellular uptake and better inhibition capacity to liver tumor cells than Nap-Cur. Therefore, the GA-Cur could significantly inhibit HepG2 cell growth. Our study provides a novel nanomaterial for liver tumor chemotherapy.

  16. A Glycyrrhetinic Acid-Modified Curcumin Supramolecular Hydrogel for liver tumor targeting therapy

    Science.gov (United States)

    Chen, Guoqin; Li, Jinliang; Cai, Yanbin; Zhan, Jie; Gao, Jie; Song, Mingcai; Shi, Yang; Yang, Zhimou

    2017-01-01

    Curcumin (Cur), a phenolic anti-oxidant compound obtained from Curcuma longa plant, possesses a variety of therapeutic properties. However, it is suffered from its low water solubility and low bioavailability property, which seriously restricts its clinical application. In this study, we developed a glycyrrhetinic acid (GA) modified curcumin supramolecular pro-gelator (GA-Cur) and a control compound Nap-Cur by replacing GA with the naphthylacetic acid (Nap). Both compounds showed good water solubility and could form supramolecular gels by disulfide bond reduction triggered by glutathione (GSH) in vitro. Both formed gels could sustainedly release Cur in buffer solutions. We also investigated the cytotoxicity of pro-gelators to HepG2 cells by a MTT assay and determined the cellular uptake behaviours of them by fluorescence microscopy and LC-MS. Due to the over expression of GA receptor in liver cancer cells, our pro-gelator of GA-Cur showed an enhanced cellular uptake and better inhibition capacity to liver tumor cells than Nap-Cur. Therefore, the GA-Cur could significantly inhibit HepG2 cell growth. Our study provides a novel nanomaterial for liver tumor chemotherapy. PMID:28281678

  17. Quantifying Rigid and Nonrigid Motion of Liver Tumors During Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Qianyi, E-mail: xuqianyi@gmail.com [Department of Radiation Oncology, MD Anderson Cancer Center at Cooper, Camden, New Jersey (United States); Hanna, George [Department of Radiation Oncology, MD Anderson Cancer Center at Cooper, Camden, New Jersey (United States); Grimm, Jimm [Department of Radiation Oncology, Holy Redeemer Hospital, Bott Cancer Center, Meadowbrook, Pennsylvania (United States); Kubicek, Gregory [Department of Radiation Oncology, MD Anderson Cancer Center at Cooper, Camden, New Jersey (United States); Pahlajani, Niraj [Department of Radiation Oncology, First Radiation and Oncology Group, Jacksonville, Florida (United States); Asbell, Sucha [Department of Radiation Oncology, MD Anderson Cancer Center at Cooper, Camden, New Jersey (United States); Fan, Jiajin [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Chen, Yan; LaCouture, Tamara [Department of Radiation Oncology, MD Anderson Cancer Center at Cooper, Camden, New Jersey (United States)

    2014-09-01

    Purpose: To quantify rigid and nonrigid motion of liver tumors using reconstructed 3-dimensional (3D) fiducials from stereo imaging during CyberKnife-based stereotactic body radiation therapy (SBRT). Methods and Materials: Twenty-three liver patients treated with 3 fractions of SBRT were used in this study. After 2 orthogonal kilovoltage images were taken during treatment, the 3D locations of the fiducials were generated by the CyberKnife system and validated using geometric derivations. A total of 4824 pairs of kilovoltage images from start to end of treatment were analyzed. For rigid motion, the rotational angles and translational shifts were reported by aligning 3D fiducial groups from different image pairs, using least-squares fitting. For nonrigid motion, we quantified interfractional tumor volume variations by using the proportional volume derived from the fiducials, which correlates to the sum of interfiducial distances. The individual fiducial displacements were also reported (1) after rigid corrections and (2) without angle corrections. Results: The proportional volume derived by the fiducials demonstrated a volume-increasing trend in the second (101.9% ± 3.6%) and third (101.0 ± 5.9%) fractions among most patients, possibly due to radiation-induced edema. For all patients, the translational shifts in left-right, anteroposterior, and superoinferior directions were 2.1 ± 2.3 mm, 2.9 ± 2.8 mm, and 6.4 ± 5.5 mm, respectively. The greatest translational shifts occurred in the superoinferior direction, likely due to respiratory motion from the diaphragm. The rotational angles in roll, pitch, and yaw were 1.2° ± 1.8°, 1.8° ± 2.4°, and 1.7° ± 2.1°, respectively. The 3D individual fiducial displacements with rigid corrections were 0.2 ± 0.2 mm and increased to 0.5 ± 0.4 mm without rotational corrections. Conclusions: Accurate 3D locations of internal fiducials can be reconstructed from stereo imaging during treatment. As an

  18. Thiamethoxam induced mouse liver tumors and their relevance to humans. Part 2: species differences in response.

    Science.gov (United States)

    Green, Trevor; Toghill, Alison; Lee, Robert; Waechter, Felix; Weber, Edgar; Peffer, Richard; Noakes, James; Robinson, Mervyn

    2005-07-01

    Thiamethoxam is a neonicotinoid insecticide that is not a mutagen, but it did cause a significant increase in liver cancer in mice, but not rats, in chronic dietary feeding studies. Previous studies in mice have characterized a carcinogenicity mode of action that involved depletion of plasma cholesterol, cell death, both as single cell necrosis and as apoptosis, and sustained increases in cell replication rates. In a study reported in this article, female rats have been exposed to thiamethoxam in their diet at concentrations of 0, 1000, and 3000 ppm for 50 weeks, a study design directly comparable to the mouse study in which the mode of action changes were characterized. In rats, thiamethoxam had no adverse effects on either the biochemistry or histopathology of the liver at any time point during the study. Cell replication rates were not increased, in fact they were significantly decreased at several time points. The lack of effect on the rat liver is entirely consistent with the lack of liver tumor formation in the two-year cancer bioassay. Comparisons of the metabolism of thiamethoxam in rats and mice have shown that concentrations of the parent chemical were either similar or higher in rat blood than in mouse blood in both single dose and the dietary studies strongly indicating that thiamethoxam itself is unlikely to play a role in the development of liver tumors. In contrast, the concentrations of the two metabolites, CGA265307 and CGA330050, shown to play a role in the development of liver damage in the mouse, were 140- (CGA265307) and 15- (CGA330050) fold lower in rats than in mice following either a single oral dose, or dietary administration of thiamethoxam for up to 50 weeks. Comparisons of the major metabolic pathways of thiamethoxam in vitro using mouse, rat, and human liver fractions have shown that metabolic rates in humans are lower than those in the rat suggesting that thiamethoxam is unlikely to pose a hazard to humans exposed to this chemical at

  19. 5-Fluorouracil concentration in blood, liver and tumor tissues and apoptosis of tumor cells after preoperative oral 5'-deoxy-5-fluorouridine in patients with hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jin-Fang Zheng; Hai-Dong Wang

    2005-01-01

    AIM: To study the levels of 5-fluorouracail (5-FU) in plasma,liver and tumor in patients with hepatocellular carcinoma after oral administration of 5'-deoxy-5-fluorouridine (5'-DFUR).METHODS: Thirty-nine patients with hepatocellular carcinoma were treated with oral 5'-DFUR for more than 4 d before operation. The contents of 5-FU in plasma,liver and tumor were measured by high performance liquid chromatography (HPLC) and apoptosis of tumor cells was evaluated by in-situ TUNEL after resection of tumor.RESULTS: The concentrations of 5-FU were 1.1 μg/mL,5.6, 5.9, and 10.5 μg/g in plasma, the liver tissue, the center of tumor and the periphery of tumor, respectively.5-FU concentration was significantly higher in the periphery of tumor than that in the liver tissue and the center of tumor (10.5±1.6 μg/g vs 5.6±0.8 μg/g, t= 21.38, P<0.05;10.5±1.6 μg/g vs 5.9±0.9 μg/g, t= 20.07, P<0.05). 5-FU level was significantly lower in plasma than that in the liver and the tumor (1.1±0.3 μg/mL vs 5.6±0.8 μg/g, t= 19.63,P<0.05; 1.1±0.3 μg/mL vs 10.5±1.6 μg/g, t= 41.01, P<0.05).Apoptosis of tumor cells was significantly increased after oral 5'-DFUR compared to the control group without 5'-DFUR treatment.CONCLUSION: There is a higher concentration of 5-FU distributed in the tumor compared with liver tissue and apoptosis of tumor cells is increased following oral 5'-DFUR compared with the control group. The results indicate that 5'-DFUR is hopeful as neo-adjuvant chemotherapy to prevent recurrence after resection of hepatocellular carcinoma.

  20. An initial clinical study on the efficacy of cisplatin-releasing gelatin microspheres for metastatic liver tumors

    Energy Technology Data Exchange (ETDEWEB)

    Nitta, Norihisa [Department of Radiology, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga 520-2192 (Japan)], E-mail: r34nitta@yahoo.co.jp; Ohta, Shinichi; Tanaka, Toyohiko; Takazakura, Ryutaro; Toyama, Tetsuya; Sonoda, Akinaga; Seko, Ayumi; Furukawa, Akira; Takahashi, Masashi; Murata, Kiyoshi [Department of Radiology, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga 520-2192 (Japan); Kurumi, Yoshimasa; Tani, Toru [Department of Surgery, Shiga University of Medical Science, Shiga (Japan); Sakamoto, Tsutomu [Department of Radiology, Kohka General Hospital, Shiga (Japan); Tabata, Yasuhiko [Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan)

    2009-09-15

    Purpose: To evaluate the antitumor effect and side effects of cisplatin-releasing gelatin microspheres (Cis-GMSs) for metastatic liver tumors. Methods: Cis-GMSs that degraded over 14 days were employed. The subjects comprised a total of nine cases. Transcatheter hepatic artery embolization (TAE) using Cis-GMSs (Cis-GMSs-TAE) was performed 13 times in total. Six cases, each containing one to five tumors in a single segment to an entire lobe were treated by Cis-GMSs-TAE. In the remaining three cases with six or more metastatic liver tumors, the right and left lobes were treated by Cis-GMSs-TAE at a 2-week interval. Results: There were two complete response (CR), one partial response (PR) and six stable disease (SD) cases. The response rate was 33.3%. The average rate of reduction in tumor diameter was 32%. Disappearance of metastatic liver tumors was observed in only two of the nine cases. As for side effects and complications, post-embolization syndrome was observed in eight cases, but no severe complications such as cholangitis or liver abscess were observed. Conclusion: Considering the mild side effects by Cis-GMSs-TAE, it is suggested that Cis-GMSs-TAE should be tried at least once as topical therapy for metastatic liver tumors when the response to systemic chemotherapy and other treatments is not satisfactory.

  1. Is There a Role for Liver Transplantation in Metastatic Pancreatic Neuroendocrine Tumors (PNET?

    Directory of Open Access Journals (Sweden)

    Anthony Paul Gulati

    2012-05-01

    Full Text Available Dear Sir, recently, we published an important report on the role of radiotherapy in pancreatic neuroendocrine tumors (PNET consisting of our experience and the data presented at the 2012 ASCO Gastrointestinal Cancers Symposium by the University of Maryland School of Medicine, Baltimore, MD, USA and Johns Hopkins University School of Medicine, Baltimore, MD, USA [1, 2]. We received multiple calls, emails as well as questions by the patients about the role of liver transplant in this population of patients with PNET. This question probably received a lot of attention in the media with the unfortunate passing of Steve Jobs in 2011. In 2009, Mr. Jobs was the recipient of a liver transplant, an unusual treatment for this disease.

  2. Protective effects of tumor necrosis factor antibody and ulinastatin on liver ischemic reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Xiao-Ping Xu; Ke-Feng Dou; Shu-Qiang Yue; Kai-Zong Li

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor α(TNFα) antibody and ulinastatin on liver ischemic reperfusion in rats.METHODS: One hundred and twenty male SD rats were randomly divided into four groups: normal control group,ischemic group, TNFα antibody group and TNFα antibody + ulinastatin group. The animals were killed at 0, 3, 6, 9,12 h after ischemia for 60 min and followed by reperfusion.Serum alanine aminotransferase (ALT), malondialdehyde (MDA) and liver histopathology were observed.RESULTS: After ischemic reperfusion, the serum ALT and MDA were remarkably increased, and the hepatic congestion was obvious. Treatment of TNFα antibody and ulinastatin could significantly decrease serum ALT and MDA levels,and relieve hepatic congestion.CONCLUSION: Ulinastatin and TNFα antibody can suppress the inflammatory reaction induced by hepatic ischemic reperfusion, and have protective effects on rat hepatic ischemic reperfusion injury.

  3. Lack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3β pathways in vivo.

    Directory of Open Access Journals (Sweden)

    Alexandra Fullár

    Full Text Available Matrilin-2 (Matn2 is a multidomain adaptor protein which plays a role in the assembly of extracellular matrix (ECM. It is produced by oval cells during stem cell-driven liver regeneration. In our study, the impact of Matn2 on hepatocarcinogenesis was investigated in Matn2(-/- mice comparing them with wild-type (WT mice in a diethylnitrosamine (DEN model. The liver tissue was analyzed macroscopically, histologically and immunohistochemically, at protein level by Proteome Profiler Arrays and Western blot analysis. Matn2(-/- mice exhibited higher susceptibility to hepatocarcinogenesis compared to wild-type mice. In the liver of Matn2(-/- mice, spontaneous microscopic tumor foci were detected without DEN treatment. After 15 μg/g body weight DEN treatment, the liver of Matn2(-/- mice contained macroscopic tumors of both larger number and size than the WT liver. In contrast with the WT liver, spontaneous phosphorylation of EGFR, Erk1/2 GSK-3α/β and retinoblastoma protein (p-Rb, decrease in p21/CIP1 level, and increase in β-Catenin protein expression were detected in Matn2(-/- livers. Focal Ki-67 positivity of these samples provided additional support to our presumption that the lack of Matn2 drives the liver into a pro-proliferatory state, making it prone to tumor development. This enhanced proliferative capacity was further increased in the tumor nodules of DEN-treated Matn2(-/- livers. Our study suggests that Matn2 functions as a tumor suppressor in hepatocarcinogenesis, and in this process activation of EGFR together with that of Erk1/2, as well as inactivation of GSK-3β, play strategic roles.

  4. Inhibition of mammary tumor growth and metastases to bone and liver by dietary grape polyphenols.

    Science.gov (United States)

    Castillo-Pichardo, Linette; Martínez-Montemayor, Michelle M; Martínez, Joel E; Wall, Kristin M; Cubano, Luis A; Dharmawardhane, Suranganie

    2009-01-01

    The cancer preventive properties of grape products such as red wine have been attributed to polyphenols enriched in red wine. However, much of the studies on cancer preventive mechanisms of grape polyphenols have been conducted with individual compounds at concentrations too high to be achieved via dietary consumption. We recently reported that combined grape polyphenols at physiologically relevant concentrations are more effective than individual compounds at inhibition of ERalpha(-), ERbeta(+) MDA-MB-231 breast cancer cell proliferation, cell cycle progression, and primary mammary tumor growth (Schlachterman et al., Transl Oncol 1:19-27, 2008). Herein, we show that combined grape polyphenols induce apoptosis and are more effective than individual resveratrol, quercetin, or catechin at inhibition of cell proliferation, cell cycle progression, and cell migration in the highly metastatic ER (-) MDA-MB-435 cell line. The combined effect of dietary grape polyphenols (5 mg/kg each resveratrol, quercetin, and catechin) was tested on progression of mammary tumors in nude mice created from green fluorescent protein-tagged MDA-MB-435 bone metastatic variant. Fluorescence image analysis of primary tumor growth demonstrated a statistically significant decrease in tumor area by dietary grape polyphenols. Molecular analysis of excised tumors demonstrated that reduced mammary tumor growth may be due to upregulation of FOXO1 (forkhead box O1) and NFKBIA (IkappaBalpha), thus activating apoptosis and potentially inhibiting NfkappaB (nuclear factor kappaB) activity. Image analysis of distant organs for metastases demonstrated that grape polyphenols reduced metastasis especially to liver and bone. Overall, these results indicate that combined dietary grape polyphenols are effective at inhibition of mammary tumor growth and site-specific metastasis.

  5. Tumors of the liver; a ten year study in Children Medical Center

    Directory of Open Access Journals (Sweden)

    Farahmand F

    2007-06-01

    Full Text Available Background: The aim of this study was to review the frequency, histopathology and outcome in children with tumors of the liver. Methods: Included in this retrospective/descriptive study were 30 children treated for liver tumors from 1375-1384 (ca. 1996-2005, at Children’s Hospital Medical Center, Tehran, Iran. We included the clinical, radiologic, and pathologic data of our patients, focusing on the frequency, etiology and outcome. Results: Patient ages ranged from three months to 12 years (median 3.8 years, with 18 males (60% and 12 females (40%. Of these, 17 patients had hepatoblastoma (55.66%, including 13 males and four females, with an age range of six months to five years. Four cases (13.33% had neuroblastoma. Hepatocellular carcinoma (HCC was found in three cases (10%, all of whom were carriers of hepatitis B. Two cases (6.66% were diagnosed with mesenchymal hamartoma, two cases (6.66% with hemangioendothelioma and two cases (6.66% with rhabdomyosarcoma and leiomyosarcoma of the biliary tract. Abdominal swelling and hepatomegaly were seen in all of patients. Jaundice was observed in two cases. Serum alpha-fetoprotein levels greater than 500 ng/ml were seen in 17 cases (56.66%. All patients were receiving specific treatment. The three-year survival rate was 65% for hepatoblastoma and 2% for HCC Conclusion: With the introduction of specific treatment, the survival rate for children with tumors of the liver has significantly increased. Further improvement can be achieved using diagnostic biopsy for hepatoblastoma, although it may result in complications, and preoperative chemotherapy followed by complete surgical excision (per International Society of Pediatric Oncology guidelines, yielding an outstanding survival rate of 80%.

  6. 5-Amino-4-oxopentanoic acid photodynamic diagnosis guided microsurgery and photodynamic therapy on VX2 brain tumour implanted in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    XIAO Hong; LIAO Qiong; CHENG Ming; LI Fei; XIE Bing; LI Mei; FENG Hua

    2009-01-01

    Background Complete tumour resection is important for improving the prognosis of brain tumour patients. However,extensive resection remains controversial because the tumour margin is difficult to be distinguished from surrounding brain tissue. It has been established that 5-amino-4-oxopentanoic acid (5-aminolevulinic acid, ALA) can be used as a photodynamic diagnostic marker and a photosensitizer for photodynamic therapy in surgical treatment of brain tumours. We investigated the efficacy of ALA photodynamically guided microsurgery and photodynamic therapy on VX2 brain tumour implanted in a rabbit model.Methods Eighty New Zealand rabbits implanted with VX2 brain tumours were randomly assigned to five groups: control, conventional white light microsurgery, a photodynamic therapy group, a photodynamically guided microsurgery group and a group in which guided microsurgery was followed by photodynamic therapy. The VX2 tumour was resected under a surgical microscope. The tumour resection was confirmed with histological analysis. All animals were examined with MRI for presence of any residual tumour tissue. The survival time of each rabbit was recorded.Results All treatment groups showed a significantly extended survival time compared with the control group.Photodynamically guided microsurgery combined with photodynamic therapy significantly prolonged survival time, compared with guided microsurgery alone. MRI and the autopsy results confirmed removal of most of the tumours.Conclusions Our results suggest that photodynamically guided surgery and photodynamic therapy significantly reduce or delay local recurrence, increase the effectiveness of radical resection and prolong the survival time of tumour bearing rabbits, Their combination has the potential to be used as a rapid and highly effective treatment of metastatic brain tumours.

  7. Mixed germ-cell testicular tumor in a liver transplant recipient

    Directory of Open Access Journals (Sweden)

    Mehdi Salehipour

    2012-01-01

    Full Text Available The development of malignancies after solid organ transplants is a well-known complication. Cancer is associated with significant consequences for the organ transplant patient. It is expected that cancer will surpass cardiovascular complications as the leading cause of death in transplant patients within the next few years. We report on a 36-year-old male patient who developed mixed germ-cell testicular tumor seven years after liver transplantation for alcoholic cirrhosis. He was treated with orchiectomy, retroperitoneal lymph node dissection and post-operative chemotherapy.

  8. Cationized gelatin-HVJ envelope with sodium borocaptate improved the BNCT efficacy for liver tumors in vivo

    Directory of Open Access Journals (Sweden)

    Ono Koji

    2011-01-01

    Full Text Available Abstract Background Boron neutron capture therapy (BNCT is a cell-selective radiation therapy that uses the alpha particles and lithium nuclei produced by the boron neutron capture reaction. BNCT is a relatively safe tool for treating multiple or diffuse malignant tumors with little injury to normal tissue. The success or failure of BNCT depends upon the 10B compound accumulation within tumor cells and the proximity of the tumor cells to the body surface. To extend the therapeutic use of BNCT from surface tumors to visceral tumors will require 10B compounds that accumulate strongly in tumor cells without significant accumulation in normal cells, and an appropriate delivery method for deeper tissues. Hemagglutinating Virus of Japan Envelope (HVJ-E is used as a vehicle for gene delivery because of its high ability to fuse with cells. However, its strong hemagglutination activity makes HVJ-E unsuitable for systemic administration. In this study, we developed a novel vector for 10B (sodium borocaptate: BSH delivery using HVJ-E and cationized gelatin for treating multiple liver tumors with BNCT without severe adverse events. Methods We developed cationized gelatin conjugate HVJ-E combined with BSH (CG-HVJ-E-BSH, and evaluated its characteristics (toxicity, affinity for tumor cells, accumulation and retention in tumor cells, boron-carrying capacity to multiple liver tumors in vivo, and bio-distribution and effectiveness in BNCT therapy in a murine model of multiple liver tumors. Results CG-HVJ-E reduced hemagglutination activity by half and was significantly less toxic in mice than HVJ-E. Higher 10B concentrations in murine osteosarcoma cells (LM8G5 were achieved with CG-HVJ-E-BSH than with BSH. When administered into mice bearing multiple LM8G5 liver tumors, the tumor/normal liver ratios of CG-HVJ-E-BSH were significantly higher than those of BSH for the first 48 hours (p . In suppressing the spread of tumor cells in mice, BNCT treatment was as

  9. Liver and circulating NK1.1(+)CD3(-) cells are increased in infection with attenuated Salmonella typhimurium and are associated with reduced tumor in murine liver cancer.

    Science.gov (United States)

    Feltis, B A; Miller, J S; Sahar, D A; Kim, A S; Saltzman, D A; Leonard, A S; Wells, C L; Sielaff, T D

    2002-09-01

    An attenuated (DeltacyA, Deltacrp) strain of Salmonella typhimurium (chi4550) containing a gene for human IL-2 (chi4550pIL2) reduces hepatic tumor burden when orally inoculated into mice with liver cancer; however, wild-type S. typhimurium is also associated with cancer regression. Therefore, experiments were designed to clarify the invasiveness and the anti-tumor properties of three strains of S. typhimurium. S. typhimurium chi4550pIL2, chi4550, or wild type (WT) was incubated with mature Caco-2 and HT-29 enterocytes, and S. typhimurium internalization was assessed. For infectivity experiments, mice were orally inoculated with saline or 10(9)S. typhimurium chi4550pIL2, chi4550, or WT; 48 h later mice were sacrificed for analysis of cecal bacteria and S. typhimurium translocation to mesenteric lymph nodes. For experiments involving tumor implantation, four groups were studied: saline control, tumor alone, chi4550pIL2+tumor, and chi4550+tumor. Mice were orally inoculated with saline or S. typhimurium and underwent laparotomy 24 h later with 5 x 10(4) MCA38 murine adenocarcinoma cells injected into the spleen. On day 14, liver tumors were counted and peripheral blood and hepatic lymphocyte populations were analyzed by FACScan. Attenuated S. typhimurium exhibited decreased internalization by cultured enterocytes and decreased infectivity after oral inoculation. Mice treated with chi4550pIL2 or chi4550 had fewer liver tumors and increased populations of hepatic and circulating NK1.1(+)CD3(-) lymphocytes compared to mice treated with saline (P < 0.01). These data suggest that attenuated S. typhimurium may have an application as an anti-tumor agent.

  10. 经皮超声造影检测兔 VX2乳腺癌前哨淋巴结的实验研究%Experimental study of contrast-enhanced ultrasonography for sentinel lymph node detection in rabbit with VX2 breast cancer

    Institute of Scientific and Technical Information of China (English)

    李艳; 尹立雪; 李文华

    2013-01-01

    Objective To investigate the value of contrast-enhanced ultrasonography (CEUS) for the detection of sentinel lymph node (SLN) in breast cancer.Methods Eighteen VX2 breast cancer lymph node metastasis models in rabbit were established .Experimental methods:(1)Conventional two-dimensional, color and energy Doppler images and Doppler velocity tracings of axillary lymph nodes were obtained after injection of tumor cell suspension for 4 to 5 weeks;(2)After injected subcutaneously with SonoVue around the tumor,nodes perfusion images were collected;(3) Methylene blue tracer was subcutaneously injected around the tumor;(4)Axillary lymph nodes resected for pathological examination .Results Fifteen VX2 breast cancer lymph node metastasis models in rabbit were successfully established .A total of 39 lymph nodes were resected for pathologic examination and 30 were metastasis.(1)A total of 35 lymph nodes were detected by gray-scale ultrasound,of which,23 metastasized and 12 non-metastasized.The results showed that metastatic lymph nodes were mostly with rounded shape ( aspect ratio 0.05].The detection accuracy,sensitivity,specificity rate of metastatic lymph node by CEUS was higher than that by gray-scale ultrasound,but there was no statistically significant differences (χ2 =0.36,P>0.05;Fisher′s exact test,P=0.05).The detection accuracy rate of metastatic lymph node by CEUS was lower than that by gray-scale ultrasound,and there was no statistically significant differences too (Fisher′s exact test,P=0.08).Conclusions CEUS can be used for real-time observing both lymphatic perfusion and lymph node metastasis,and for non-invasive localization of SLN.It has the potential ability to determine lymph node metastases.CEUS has similar detection rate ,accuracy and sensitivity to blue dye test .It is suggested that the CEUS-guided method using SonoVue may be a novel useful method for SLN identification .%  目的探讨经皮超声造影在实验兔VX2乳腺癌前哨淋巴结

  11. Mode of action and human relevance of THF-induced mouse liver tumors.

    Science.gov (United States)

    Choi, Christopher J; Rushton, Erik K; Vardy, Audrey; Higgins, Larry; Augello, Andrea; Parod, Ralph J

    2017-07-05

    In a National Toxicology Program (NTP) bioassay, inhalation of tetrahydrofuran (THF) induced liver tumors in female B6C3F1 mice but not in male mice or rats of either sex. Since THF is not genotoxic, the NTP concluded this carcinogenic activity was likely mediated via non-genotoxic modes of action (MOA). Based on evidence that THF and phenobarbital share a similar MOA, female Car/Pxr knock-out mice were orally exposed to THF to evaluate the potential role of CAR activation in the MOA for THF-induced liver tumors. Because data from this oral study with Car/Pxr knock-out mice (C57Bl/6) and the inhalation studies with wild type mice (B6C3F1) reported by NTP and others were derived from different strains, oral studies with wild type B6C3F1 and C57Bl/6 mice were conducted to ensure THF responses in both strains were comparable. As seen in inhalation studies with THF, oral exposure of wild type female mice to a maximum tolerated dose of THF increased total P450 content, CAR-related P450 activities, and hepatocyte proliferation; these effects were not observed in Car/Pxr knock-out female mice. This finding supports the hypothesis THF-induced carcinogenicity is likely mediated via CAR activation that has limited, if any, relevance to humans. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Selective internal radiotherapy (SIRT) of liver tumors; Selektive interne Radiotherapie (SIRT) von Lebertumoren

    Energy Technology Data Exchange (ETDEWEB)

    Duan, H. [Universitaetsklinik fuer Radiologie und Nuklearmedizin, Medizinische Universitaet Wien, Klinische Abteilung fuer Nuklearmedizin, Wien (Austria); Hoffmann, M. [Institut fuer Nuklearmedizin, Radiology-Center, Wien (Austria)

    2014-12-19

    Selective internal radiotherapy (SIRT) is a safe and efficacious, minimally invasive procedure to treat primary and secondary unresectable liver tumors. For hepatocellular carcinoma (HCC), SIRT has proven to be a well-tolerated therapy option even in advanced stages of disease. In cases of portal vein thrombosis SIRT is the alternative to transarterial chemoembolization (TACE). The role of SIRT regarding downstaging and bridging to transplantation is promising and SIRT has also been shown to be highly effective and well-tolerated in metastastic liver disease. The results of prospective randomized trials are awaited to prove the efficiency and safety of SIRT described in numerous retrospective and prospective non-randomized studies. The indications are established within the framework of a tumor board. (orig.) [German] Die SIRT ist ein sicheres und effizientes, minimal-invasives nuklearmedizinisch-radiologisches Verfahren zur Therapie von primaeren und sekundaeren nicht resezierbaren Lebertumoren. Beim hepatozellulaerem Karzinom (HCC) stellt die SIRT eine gut vertraegliche Therapieoption auch in fortgeschrittenem Stadium dar. Im Falle einer Pfortaderthrombose ist SIRT eine Alternative zur transarteriellen Chemoembolisation (TACE). Die Rolle der SIRT beim Downstaging/Bridging zur Transplantation ist vielversprechend. Auch bei sekundaeren Lebertumoren zeigt die SIRT gute Ansprechraten und ausgezeichnete Vertraeglichkeit. Ergebnisse prospektiver randomisierter Studien stehen noch aus, um die in zahlreichen retrospektiven oder prospektiven nichtrandomisierten Studien beschriebene Effektivitaet zu bestaetigen. Die Indikation wird im Rahmen eines Tumorboards gestellt. (orig.)

  13. Serum sialic acid in malignant tumors, bacterial infections, and chronic liver diseases.

    Science.gov (United States)

    Stefenelli, N; Klotz, H; Engel, A; Bauer, P

    1985-01-01

    The total serum sialic acid concentration was determined in 2,264 persons with various malignant tumors, bacterial infections, rheumatic diseases, and chronic liver diseases, and in a control group. The thiobarbiturate method according to Warren was used. The upper limit (95% percentile) in the control group was 2.23 mumol/ml. Higher values were found in the groups with neoplasms (mean: 3.04 mumol/ml), inflammatory diseases (e.g., pneumonia: 3.02 mumol/ml), and active rheumatoid arthritis (3.05 mumol/ml). In the group with malignant diseases, the sialic acid concentration at the time of diagnosis was highest for bronchial carcinoma (3.29 mumol/ml) and lowest for breast cancer (2.58 mumol/ml). In chronic liver diseases the mean sialic acid level was lower than in a heterogeneous group of noninflammatory and nonneoplastic diseases. The estimation of the serum sialic acid concentration could be useful in the detection of tumor burden and metastases, and in the evaluation of the later course and prognosis of malignant neoplasms if bacterial/inflammatory and active rheumatoid processes can be excluded.

  14. Malignant insulinoma presenting as metastatic liver tumor. Case report and review of the literature.

    Science.gov (United States)

    Baldelli, R; Ettorre, G; Vennarecci, G; Pasimeni, G; Carboni, F; Lorusso, R; Barnabei, A; Appetecchia, M

    2007-12-01

    Insulin-secreting tumors are the commonest hormone-producing neoplasm of the gastrointestinal tract. They occur with an incidence of 4 cases per million per year. About 10% of them are metastatic and malignant insulinomas very rarely observed in children and in elderly. We report a rare case of very large malignant insulinoma in a 71-year-old woman admitted in our Oncological Institute on October 2005. She presented with fasting hypoglicemia (blood glucose 35 mg/dl) and high serum insulin levels (insulin 115.9 microU/ml). A computerized tomographic scan showed a pancreatic tail lesion of about 6 cm in max diameter and multiple liver metastases. A whole body scintiscan using 111In-DTPA-D-Phe1-octreotide was made and an increased uptake in the tail of the pancreas has been found. The patient was submitted to liver biopsy and the diagnosis of a metastatic insulin-secreting tumor was immunoistochemically confirmed. Due to the presence of some hypoglicemic episodes uncontrolled by medical treatment, on December 2005 the patient was admitted to surgical intervention with a body and tail pancreatic resection. Post-operatively the patient experienced again syncope with hypoglycemia and hyperinsulinemia. It was then decided to start a schedule of treatment with somatostatin analog (octreotide subcutaneously 500 microg three times a day) with a good control of blood glucose levels (101 mg/dl). A trans-arterial chemioembolization was planned but the patient died for pancreatic and cardiovascular complications before this treatment started.

  15. The Long-term Benefit of Liver Transplantation for Hepatic Metastases from Neuroendocrine Tumors.

    Science.gov (United States)

    Mazzaferro, V; Sposito, C; Coppa, J; Miceli, R; Bhoori, S; Bongini, M; Camerini, T; Milione, M; Regalia, E; Spreafico, C; Gangeri, L; Buzzoni, R; de Braud, F G; De Feo, T; Mariani, L

    2016-05-01

    Selection criteria and benefit of liver transplantation for hepatic metastases from neuroendocrine tumors (NETs) remains uncertain. Eighty-eight consecutive patients with metastatic NETs eligible for liver transplantation according to Milan-NET criteria were offered transplant (n.42) vs. non-transplant options (n.46) depending on list dynamics, patient disposition and age. Tumor burden between groups did not differ. Transplant patients were younger (40.5 vs. 55.5 years; p<0.001). Long-term outcomes were compared after matching between groups made on multiple Cox models adjusted for propensity score built on logistic models. Survival-benefit was the difference in mean survival between transplant vs. non-transplant options. No patients were lost or died without recurrence. Median follow-up was 122 months. Transplant group showed significant advantage over non-transplant strategies at 5 and 10-yrs in survival (97.2% and 88.8% vs. 50.9% and 22.4% respectively; p<0.001) and time-to-progression (13.1% and 13.1% vs. 83.5% and 89%; p<0.001). After adjustment for propensity score, survival advantage of transplant group was significant (HR=7.4; 95%CI: 2.4-23.0; p=0.001). Adjusted transplant-related survival-benefit was 6.82 months (95%CI: 1.10-12.54; p=0.019) and 38.43 months (95%CI: 21.41-55.45; p<0.001) at 5 and 10-yrs respectively. Liver transplantation for metastatic NETs under restrictive criteria provides excellent long-term outcome. Transplant-related survival-benefit increases over time and maximizes after 10 yrs. This article is protected by copyright. All rights reserved.

  16. GRP78 as a regulator of liver steatosis and cancer progression mediated by loss of the tumor suppressor PTEN.

    Science.gov (United States)

    Chen, W-T; Zhu, G; Pfaffenbach, K; Kanel, G; Stiles, B; Lee, A S

    2014-10-16

    Glucose-regulated protein 78 (GRP78), a molecular chaperone widely elevated in human cancers, is critical for endoplasmic reticulum (ER) protein folding, stress signaling and PI3K/AKT activation. Genetic knockout models of GRP78 revealed that GRP78 maintains homeostasis of metabolic organs, including liver, pancreas and adipose tissues. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the most common liver cancers. There is a lack of effective therapeutics for HCC and CC, highlighting the need to further understand liver tumorigenic mechanisms. PTEN (phosphatase and tenson homolog deleted on chromosome 10), a tumor suppressor that antagonizes the PI3K/AKT pathway, is inactivated in a wide range of tumors, including 40-50% of human liver cancers. To elucidate the role of GRP78 in liver cancer, we created a mouse model with biallelic liver-specific deletion of Pten and Grp78 mediated by Albumin-Cre-recombinase (cP(f/f)78(f/f)). Interestingly, in contrast to PTEN, deletion of GRP78 was progressive but incomplete. At 3 months, cP(f/f)78(f/f) livers showed hepatomegaly, activation of lipogenic genes, exacerbated steatosis and liver injury, implying that GRP78 protects the liver against PTEN-null-mediated pathogenesis. Furthermore, in response to liver injury, we observed increased proliferation and expansion of bile duct and liver progenitor cells in cP(f/f)78(f/f) livers. Strikingly, bile duct cells in cP(f/f)78(f/f) livers maintained wild-type (WT) GRP78 level, whereas adjacent areas showed GRP78 reduction. Analysis of signaling pathways revealed selective JNK activation, β-catenin downregulation, along with PDGFRα upregulation, which was unique to cP(f/f)78(f/f) livers at 6 months. Development of both HCC and CC was accelerated and was evident in cP(f/f)78(f/f) livers at 8-9 months, coinciding with intense GRP78 expression in the cancer lesions, and GRP78 expression in adjacent normal areas reverted back to the WT level. In contrast, c78(f/f) livers

  17. Expert consensus on precise diagnosis and treatment of complicated liver tumor guided by three-dimensional visualization technology

    Directory of Open Access Journals (Sweden)

    Chinese Society of Digital Medicine

    2017-01-01

    Full Text Available The three-dimensional (3D visualization technology in liver tumor could offer decision-making support to preoperative diagnosis, individualized surgical planning, and choosing an operative approach. In addition, the hepatic 3D printing helps to realize the leapfrog development from 3D images to 3D physical models and provides better guidance of the precise surgery of complicated liver tumors. To standardize the application of 3D visualization and 3D printing technology in the precise diagnosis and treatment of complicated liver tumors, Chinese experts in relevant fields were organized by Chinese Society of Digital Medicine and Chinese Research Hospital Association of Digital Surgery Committee to formulate this expert consensus.

  18. Chemoprevention and cytotoxic effect of Bauhinia variegata against N-nitrosodiethylamine induced liver tumors and human cancer cell lines.

    Science.gov (United States)

    Rajkapoor, B; Jayakar, B; Murugesh, N; Sakthisekaran, D

    2006-04-06

    The chemopreventive and cytotoxic effect of ethanol extract of Bauhinia variegata (EBV) was evaluated in N-nitrosodiethylamine (DEN, 200 mg/kg) induced experimental liver tumor in rats and human cancer cell lines. Oral administration of ethanol extract of Bauhinia variegata (250 mg/kg) effectively suppressed liver tumor induced by DEN as revealed by decrease in DEN induced elevated levels of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO), glutathione peroxidase (GPx) and glutathione S-transferase (GST). The extract produced an increase in enzymatic antioxidant (superoxide dismutase and catalase) levels and total proteins when compared to those in liver tumor bearing rats. The histopathological changes of liver samples were compared with respective controls. EBV was found to be cytotoxic against human epithelial larynx cancer (HEp2) and human breast cancer (HBL-100) cells. These results show a significant chemopreventive and cytotoxic effect of ethanol extract of Bauhinia variegata against DEN induced liver tumor and human cancer cell lines.

  19. Transient mTOR inhibition facilitates continuous growth of liver tumors by modulating the maintenance of CD133+ cell populations.

    Directory of Open Access Journals (Sweden)

    Zhaojuan Yang

    Full Text Available The mammalian target of the rapamycin (mTOR pathway, which drives cell proliferation, is frequently hyperactivated in a variety of malignancies. Therefore, the inhibition of the mTOR pathway has been considered as an appropriate approach for cancer therapy. In this study, we examined the roles of mTOR in the maintenance and differentiation of cancer stem-like cells (CSCs, the conversion of conventional cancer cells to CSCs and continuous tumor growth in vivo. In H-Ras-transformed mouse liver tumor cells, we found that pharmacological inhibition of mTOR with rapamycin greatly increased not only the CD133+ populations both in vitro and in vivo but also the expression of stem cell-like genes. Enhancing mTOR activity by over-expressing Rheb significantly decreased CD133 expression, whereas knockdown of the mTOR yielded an opposite effect. In addition, mTOR inhibition severely blocked the differentiation of CD133+ to CD133- liver tumor cells. Strikingly, single-cell culture experiments revealed that CD133- liver tumor cells were capable of converting to CD133+ cells and the inhibition of mTOR signaling substantially promoted this conversion. In serial implantation of tumor xenografts in nude BALB/c mice, the residual tumor cells that were exposed to rapamycin in vivo displayed higher CD133 expression and had increased secondary tumorigenicity compared with the control group. Moreover, rapamycin treatment also enhanced the level of stem cell-associated genes and CD133 expression in certain human liver tumor cell lines, such as Huh7, PLC/PRC/7 and Hep3B. The mTOR pathway is significantly involved in the generation and the differentiation of tumorigenic liver CSCs. These results may be valuable for the design of more rational strategies to control clinical malignant HCC using mTOR inhibitors.

  20. Liver Tumor Segmentation from MR Images Using 3D Fast Marching Algorithm and Single Hidden Layer Feedforward Neural Network

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    Trong-Ngoc Le

    2016-01-01

    Full Text Available Objective. Our objective is to develop a computerized scheme for liver tumor segmentation in MR images. Materials and Methods. Our proposed scheme consists of four main stages. Firstly, the region of interest (ROI image which contains the liver tumor region in the T1-weighted MR image series was extracted by using seed points. The noise in this ROI image was reduced and the boundaries were enhanced. A 3D fast marching algorithm was applied to generate the initial labeled regions which are considered as teacher regions. A single hidden layer feedforward neural network (SLFN, which was trained by a noniterative algorithm, was employed to classify the unlabeled voxels. Finally, the postprocessing stage was applied to extract and refine the liver tumor boundaries. The liver tumors determined by our scheme were compared with those manually traced by a radiologist, used as the “ground truth.” Results. The study was evaluated on two datasets of 25 tumors from 16 patients. The proposed scheme obtained the mean volumetric overlap error of 27.43% and the mean percentage volume error of 15.73%. The mean of the average surface distance, the root mean square surface distance, and the maximal surface distance were 0.58 mm, 1.20 mm, and 6.29 mm, respectively.

  1. Tumor deposit is a poor prognostic indicator in patients who underwent simultaneous resection for synchronous colorectal liver metastases

    Directory of Open Access Journals (Sweden)

    Lin Q

    2015-01-01

    Full Text Available Qi Lin,# Ye Wei,# Li Ren,# Yunshi Zhong,# Chunzhi Qin, Peng Zheng, Pingping Xu, Dexiang Zhu, Meiling Ji, Jianmin XuDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China#These authors contributed equally to this workBackground: Tumor deposits are one of the important influencing factors among the different editions of Tumor, Node, Metastasis classification. Incidence and prognosis of tumor deposits in stage I, II, and III colorectal cancer patients has been explored. The aim of this study was to determine the prognostic value of tumor deposits in stage IV colorectal cancer patients who underwent simultaneous resection for synchronous colorectal liver metastases (SCRLM.Methods: Clinicopathological and outcome data of 146 consecutive SCRLM patients who underwent simultaneous R0 resection between July 2003 and July 2013 were collected from our prospectively established SCRLM database. The prognostic value of tumor deposits was evaluated by Kaplan–Meier and Cox regression analysis.Results: Tumor deposits were detected in 41.8% (61/146 of these SCRLM patients. Tumor deposits were significantly correlated with lymph node metastasis and nerve invasion of the primary tumors (P=0.002, P=0.041; respectively. The Kaplan–Meier survival analysis revealed that the overall survival (OS and disease-free survival (DFS of SCRLM patients with tumor deposits were significantly poorer than those with no tumor deposits (P=0.039, P=0.001; respectively. And with multivariate analysis, we found that positive tumor deposits were significantly associated with shorter DFS independent of lymph node status (P=0.002. Subgroup analysis found that of the 57 SCRLM patients with negative lymph node status, the OS and DFS of patients with positive tumor deposits were significantly shorter than those with negative tumor deposits (P=0.002 and P=0.031, respectively. Of the 89 patients with positive lymph node status, the OS of

  2. The impact of share wave elastography in differentiation of hepatic hemangioma from malignant liver tumors in pediatric population

    Energy Technology Data Exchange (ETDEWEB)

    Özmen, Evrim, E-mail: evrimkilicdr@gmail.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Adaletli, İbrahim, E-mail: iadaletli@yahoo.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Kayadibi, Yasemin, E-mail: ysmnkurdoglu@gmail.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Emre, Şenol, E-mail: senolemre@hotmail.com [Department of Pediatric Surgery, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Kılıç, Fahrettin, E-mail: fahrettinkilic@hotmail.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Dervişoğlu, Sergülen, E-mail: selozmen@gmail.com [Department of Pathology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Kuruğoğlu, Sebuh, E-mail: sebuhk@yahoo.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Şenyüz, Osman Faruk, E-mail: ofsenyuz@gmail.com [Department of Pediatric Surgery, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey)

    2014-09-15

    Highlights: • We evaluated the impact of share wave elastography technique in differentiation hepatic hemangiomas from malignant liver tumors in pediatric population. • Share wave technique can increase the diagnostic capability of conventional ultrasonography in the differential diagnosis of liver tumors in children. • Share wave elastography is a potential adjunctive diagnostic technique for pediatric liver tumors. - Abstract: Objective: In children it is crucial to differentiate malignant liver tumors from the most common benign tumor, hepatic hemangiomas since the treatment strategies are quite different. We aimed to evaluate the efficiency of shear wave elastography (SWE) technique in differentiation of malignant hepatic tumors and hepatic hemangiomas. Methods: Twenty patients with hepatic tumor were included in our study. Two radiologists performed SWE for 13 patients with malignant hepatic tumors including hepatoblastoma (n = 7), hepatocellular carcinoma (n = 3), metastasis (n = 2), embryonal sarcoma (n = 1) and 7 patients with hepatic hemangioma. All of our patients were between the age of 1 and 192 months (mean age: 56.88 months). Receiver operating characteristic analysis was achieved to evaluate the diagnostic accuracy of SWE and to determine the optimal cut-off value in differentiation hepatic hemangioma from malignant hepatic tumors. Results: The mean SWE values (in kPa) for the first observer were 46.94 (13.8–145) and 22.38 (6.6–49.6) and those for the second observer were 57.91 (11–237) and 23.87 (6.4–57.5), respectively for malignant hepatic tumors and hepatic hemangiomas. The SWE values of malignant hepatic tumors were significantly higher than those of hepatic hemangioma (p = 0.02). The inter-observer agreement was almost perfect (0.81). The area under the receiver operating characteristic curve of SWE for differentiating the hepatic hemangioma from malignant hepatic tumors was 0.77 with a sensitivity of 72.7% and a specificity of 66

  3. Syphilis presenting as inflammatory tumors of the liver in HIV-positive homosexual men.

    Science.gov (United States)

    Hagen, Catherine E; Kamionek, Michal; McKinsey, David S; Misdraji, Joseph

    2014-12-01

    Syphilis, a sexually transmitted infection caused by the spirochete Treponema pallidum, has seen a resurgence since 2001, particularly in men who have sex with men. Syphilis can affect the liver during the secondary stage as syphilitic hepatitis and during the tertiary stage as gummas. We describe 3 cases of syphilis in human immunodeficiency virus-positive homosexual men that presented as hepatic mass lesions clinically suspected of being malignant tumors. Histologically, 2 of the 3 cases showed a plump spindle cell proliferation, mixed inflammatory infiltrate with numerous neutrophils, and abscesses, whereas the third case showed granulomas and pericholangitis/cholangitis. Immunohistochemical staining for T. pallidum showed innumerable organisms in 2 of the cases. Pathologists must be aware of the possibility of syphilis causing hepatic inflammatory masses in human immunodeficiency virus-positive men who have sex with men in order to avoid misdiagnosis or delayed treatment.

  4. Contrast-enhanced ultrasonography parameters in neural network diagnosis of liver tumors

    Institute of Scientific and Technical Information of China (English)

    Costin Teodor Streba; Mihaela Ionescu; Dan Ionut Gheonea; Larisa Sandulescu; Tudorel Ciurea; Adrian Saftoiu; Cristin Constantin Vere

    2012-01-01

    AIM:To study the role of time-intensity curve (TIC) analysis parameters in a complex system of neural networks designed to classify liver tumors.METHODS:We prospectively included 112 patients with hepatocellular carcinoma (HCC) (n =41),hypervascular (n =20) and hypovascular (n =12) liver metastases,hepatic hemangiomas (n =16) or focal fatty changes (n =23) who underwent contrast-enhanced ultrasonography in the Research Center of Gastroenterology and Hepatology,Craiova,Romania.We recorded full length movies of all contrast uptake phases and post-processed them offline by selecting two areas of interest (one for the tumor and one for the healthy surrounding parenchyma) and consecutive TIC analysis.The difference in maximum intensities,the time to reaching them and the aspect of the late/portal phase,as quantified by the neural network and a ratio between median intensities of the central and peripheral areas were analyzed by a feed forward back propagation multi-layer neural network which was trained to classify data into five distinct classes,corresponding to each type of liver lesion.RESULTS:The neural network had 94.45% training accuracy (95% CI:89.31%-97.21%) and 87.12% testing accuracy (95% CI:86.83%-93.17%).The automatic classification process registered 93.2% sensitivity,89.7% specificity,94.42% positive predictive value and 87.57% negative predictive value.The artificial neural networks (ANN) incorrectly classified as hemangyomas three HCC cases and two hypervascular metastases,while in turn misclassifying four liver hemangyomas as HCC (one case) and hypervascular metastases (three cases).Comparatively,human interpretation of TICs showed 94.1% sensitivity,90.7% specificity,95.11% positive predictive value and 88.89% negative predictive value.The accuracy and specificity of the ANN diagnosis system was similar to that of human interpretation of the TICs (P =0.225 and P =0.451,respectively).Hepatocellular carcinoma cases showed

  5. Nanodiamond-Manganese dual mode MRI contrast agents for enhanced liver tumor detection.

    Science.gov (United States)

    Hou, Weixin; Toh, Tan Boon; Abdullah, Lissa Nurrul; Yvonne, Tay Wei Zheng; Lee, Kuan J; Guenther, Ilonka; Chow, Edward Kai-Hua

    2017-04-01

    Contrast agent-enhanced magnetic resonance (MR) imaging is critical for the diagnosis and monitoring of a number of diseases, including cancer. Certain clinical applications, including the detection of liver tumors, rely on both T1 and T2-weighted images even though contrast agent-enhanced MR imaging is not always reliable. Thus, there is a need for improved dual mode contrast agents with enhanced sensitivity. We report the development of a nanodiamond-manganese dual mode contrast agent that enhanced both T1 and T2-weighted MR imaging. Conjugation of manganese to nanodiamonds resulted in improved longitudinal and transverse relaxivity efficacy over unmodified MnCl2 as well as clinical contrast agents. Following intravenous administration, nanodiamond-manganese complexes outperformed current clinical contrast agents in an orthotopic liver cancer mouse model while also reducing blood serum concentration of toxic free Mn(2+) ions. Thus, nanodiamond-manganese complexes may serve as more effective dual mode MRI contrast agent, particularly in cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Portal vein-circulating tumor cells predict liver metastases in patients with resectable pancreatic cancer.

    Science.gov (United States)

    Bissolati, Massimiliano; Sandri, Maria Teresa; Burtulo, Giovanni; Zorzino, Laura; Balzano, Gianpaolo; Braga, Marco

    2015-02-01

    Pancreatic cancer patients underwent surgical resection often present distant metastases early after surgery. Detection of circulating tumor cells (CTCs) has been correlated to a worse oncological outcome in patients with advanced pancreatic cancer. The objective of this pilot study is to investigate the possible prognostic role of CTCs in patients undergoing surgery for pancreatic cancer. In 20 patients undergoing pancreatic resection, 10 mL blood sample was collected intraoperatively from both systemic circulation (SC) and portal vein (PV). Blood sample was analyzed for CTCs with CellSearch® system. All patients underwent an oncologic follow-up for at least 3 years, quarterly. CTCs were detected in nine (45%) patients: five patients had CTCs in PV only, three patients in both SC and PV, and one patient in SC only. CTC-positive and CTC-negative patients were similar for demographics and cancer stage pattern. No significant differences were found in both overall and disease-free survival between CTC-positive and CTC-negative patients. At 3-year follow-up, portal vein CTC-positive patients presented a higher rate of liver metastases than CTC-negative patients (53 vs. 8%, p = 0.038). CTCs were found in 45% of the patients. No correlation between CTCs and survival was found. The presence of CTCs in portal vein has been associated to higher rate of liver metastases after surgery.

  7. Evaluation of potential internal target volume of liver tumors using cine-MRI.

    Science.gov (United States)

    Akino, Yuichi; Oh, Ryoong-Jin; Masai, Norihisa; Shiomi, Hiroya; Inoue, Toshihiko

    2014-11-01

    Four-dimensional computed tomography (4DCT) is widely used for evaluating moving tumors, including lung and liver cancers. For patients with unstable respiration, however, the 4DCT may not visualize tumor motion properly. High-speed magnetic resonance imaging (MRI) sequences (cine-MRI) permit direct visualization of respiratory motion of liver tumors without considering radiation dose exposure to patients. Here, the authors demonstrated a technique for evaluating internal target volume (ITV) with consideration of respiratory variation using cine-MRI. The authors retrospectively evaluated six patients who received stereotactic body radiotherapy (SBRT) to hepatocellular carcinoma. Before acquiring planning CT, sagittal and coronal cine-MRI images were acquired for 30 s with a frame rate of 2 frames/s. The patient immobilization was conducted under the same condition as SBRT. Planning CT images were then acquired within 15 min from cine-MRI image acquisitions, followed by a 4DCT scan. To calculate tumor motion, the motion vectors between two continuous frames of cine-MRI images were calculated for each frame using the pyramidal Lucas-Kanade method. The target contour was delineated on one frame, and each vertex of the contour was shifted and copied onto the following frame using neighboring motion vectors. 3D trajectory data were generated with the centroid of the contours on sagittal and coronal images. To evaluate the accuracy of the tracking method, the motion of clearly visible blood vessel was analyzed with the motion tracking and manual detection techniques. The target volume delineated on the 50% (end-exhale) phase of 4DCT was translated with the trajectory data, and the distribution of the occupancy probability of target volume was calculated as potential ITV (ITV Potential). The concordance between ITV Potential and ITV estimated with 4DCT (ITV 4DCT) was evaluated using the Dice's similarity coefficient (DSC). The distance between blood vessel positions

  8. Evaluation of potential internal target volume of liver tumors using cine-MRI

    Energy Technology Data Exchange (ETDEWEB)

    Akino, Yuichi, E-mail: akino@radonc.med.osaka-u.ac.jp [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 5650871, Japan and Miyakojima IGRT Clinic, Miyakojima-ku, Osaka 5340021 (Japan); Oh, Ryoong-Jin; Masai, Norihisa; Shiomi, Hiroya; Inoue, Toshihiko [Miyakojima IGRT Clinic, Miyakojima-ku, Osaka 5340021 (Japan)

    2014-11-01

    Purpose: Four-dimensional computed tomography (4DCT) is widely used for evaluating moving tumors, including lung and liver cancers. For patients with unstable respiration, however, the 4DCT may not visualize tumor motion properly. High-speed magnetic resonance imaging (MRI) sequences (cine-MRI) permit direct visualization of respiratory motion of liver tumors without considering radiation dose exposure to patients. Here, the authors demonstrated a technique for evaluating internal target volume (ITV) with consideration of respiratory variation using cine-MRI. Methods: The authors retrospectively evaluated six patients who received stereotactic body radiotherapy (SBRT) to hepatocellular carcinoma. Before acquiring planning CT, sagittal and coronal cine-MRI images were acquired for 30 s with a frame rate of 2 frames/s. The patient immobilization was conducted under the same condition as SBRT. Planning CT images were then acquired within 15 min from cine-MRI image acquisitions, followed by a 4DCT scan. To calculate tumor motion, the motion vectors between two continuous frames of cine-MRI images were calculated for each frame using the pyramidal Lucas–Kanade method. The target contour was delineated on one frame, and each vertex of the contour was shifted and copied onto the following frame using neighboring motion vectors. 3D trajectory data were generated with the centroid of the contours on sagittal and coronal images. To evaluate the accuracy of the tracking method, the motion of clearly visible blood vessel was analyzed with the motion tracking and manual detection techniques. The target volume delineated on the 50% (end-exhale) phase of 4DCT was translated with the trajectory data, and the distribution of the occupancy probability of target volume was calculated as potential ITV (ITV {sub Potential}). The concordance between ITV {sub Potential} and ITV estimated with 4DCT (ITV {sub 4DCT}) was evaluated using the Dice’s similarity coefficient (DSC). Results

  9. Assessment of metastatic liver disease in patients with primary extrahepatic tumors by contrast-enhanced sonography versus CT & MRI

    NARCIS (Netherlands)

    Dietrich, Christoph F.; Kratzer, Wolfgang; Strobel, Deike; Danse, Etienne; Fessl, Robert; Bunk, Alfred; Vossas, Udo; Hauenstein, Karlheinz; Koch, Wilhelm; Blank, Wolfgang; Oudkerk, Matthijs; Hahn, Dietbert; Greis, Christian

    2006-01-01

    AIM: To evaluate contrast-enhanced ultrasonography (CEUS) using SonoVue (R) in the detection of liver metastases in patients with known extrahepatic primary tumors versus the combined gold standard comprising CT, MRI and clinical/histological data. METHODS: It is an international multicenter study,

  10. Suppression of breast tumor growth by DNA vaccination against phosphatase of regenerating liver 3.

    Science.gov (United States)

    Lv, J; Liu, C; Huang, H; Meng, L; Jiang, B; Cao, Y; Zhou, Z; She, T; Qu, L; Wei Song, S; Shou, C

    2013-08-01

    Phosphatase of regenerating liver (PRL)-3 is highly expressed in multiple cancers and has important roles in cancer development. Some small-molecule inhibitors and antibodies targeting PRL-3 have been recently reported to inhibit tumor growth effectively. To determine whether PRL-3-targeted DNA vaccination can induce immune response to prevent or inhibit the tumor growth, we established mouse D2F2 breast cancer cells expressing PRL-3 (D2F2/PRL-3) and control cells (D2F2/NC) with lentivirus, and constructed pVAX1-Igκ-PRL-3 plasmid (named as K-P3) as DNA vaccine to immunize BALB/c mice. We found that the K-P3 vaccine delivered by gene gun significantly prevented the growth of D2F2/PRL-3 compared with pVAX1-vector (Padjuvants, such as Mycobacterium tuberculosis heat-shock protein, CTL antigen 4 and M. tuberculosis T-cell stimulatory epitope (MT), into K-P3 vaccine for expressing the fusion proteins. We found that these adjuvant molecules did not significantly improve the antitumor activity of PRL-3 vaccine, but enhanced the production of PRL-3 antibodies in immunized mice. Summarily, our findings demonstrate that PRL-3-targeted DNA vaccine can generate significantly preventive and therapeutic effects on the growth of breast cancer expressing PRL-3 through the induction of cellular immune responses to PRL-3.

  11. Effects of high volume hemofiltration on HMGB1,TNF-a,IL-6 in serum and live,lung, kidney tissues of sepsis dog model with acute renal failure%DMSA-Fe3O4纳米磁流体介导热疗对兔VX2肿瘤的影响

    Institute of Scientific and Technical Information of China (English)

    臧汉杰; 冯耀良; 余超; 祖庆泉; 马明; 顾宁

    2012-01-01

    Objective To investigate the effects of high volume hemofiltration(HVHF) on high mobility group box chromosomal protein 1 ( HMGB1), TNF-a, IL-6 in serum and live, lung, kidney tissues of sepsis dog model with acute kidney failure. Methods The bilateral ureters of twelve male Beagle dogs were ligated and lipopolysaccharide( LPS) 1.0 mg/kg was injected to establish the sepstic dog models with acute kidney failure. The dogs were equally randomized to model group and HVHF group( treated with HVHF for 24 h after injection of LPS immediately). Venous blood was collected to check blood routine, liver and kidney functions and electrolytes before and at 2,4,8,16,24 h after injection of LPS. Arterial blood gas analysis was performed before and at 24 h after injection of LPS. EILSA was used to determine the concentrations of HMGB1, TNF-a, IL-6 in serum at different time points above and in supernatant of liver, lung and kidney tissues at 24 h after injection of LPS. Results Compared with model group, the levels of HMGB1, TNF-o, IL-6 in serum and liver, lung, kidney tissues were decreased, peak time of HMGB1 level in serum was delayed, liver, lung and kidney functions were improved in HVHF group (P<0. 05). Conclusion HVHF therapy can decrease the concentrations of HMGB1,TNF-a and IL-6 in serum and liver,lung and kidney tissues and protect the liver, lung and kidney functions of septic dog with acute kidney failure.%目的 探讨交变磁场介导的二巯基丁二酸(DMSA)-Fe3O4纳米磁流体热疗治疗兔VX2肿瘤的疗效.方法 建立20只兔后肢VX2软组织肿瘤模型,随机分为4组:A组(对照组)、B组(磁流体局部注射组十热疗)、C组(磁流体动脉灌注组十热疗)、D组(磁流体静脉注射组十热疗),每组5只.成瘤2周后CT测量肿瘤大小.结果 B组和C组的肿瘤中心区[(46.01±1.97)℃和(40.38±1.50)℃]和肿瘤边缘区[(40.35±1.36)℃和(42.57±1.80)℃]的温度显著高于正常肌肉组织[(35.73±1.32)℃和(35.37±1.55)

  12. Activation-induced cytidine deaminase is dispensable for virus-mediated liver and skin tumor development in mouse models.

    Science.gov (United States)

    Nguyen, Tung; Xu, Jianliang; Chikuma, Shunsuke; Hiai, Hiroshi; Kinoshita, Kazuo; Moriya, Kyoji; Koike, Kazuhiko; Marcuzzi, Gian Paolo; Pfister, Herbert; Honjo, Tasuku; Kobayashi, Maki

    2014-07-01

    Activation-induced cytidine deaminase (AID) not only promotes immune diversity by initiating somatic hypermutation and class switch recombination in immunoglobulin genes but also provokes genomic instability by introducing translocations and mutations into non-immunoglobulin genes. To test whether AID is essential for virus-induced tumor development, we used two transgenic tumor models: mice expressing hepatitis C virus (HCV) core proteins (HCV-Tg), driven by the hepatitis B virus promoter, and mice expressing human papillomavirus type 8 proteins (HPV8-Tg), driven by the Keratin 14 promoter. Both strains were analyzed in the absence and presence of AID by crossing each with AID (-/-) mice. There was no difference in the liver tumor frequency between the HCV-Tg/AID (+/+) and HCV-Tg/AID (-/-) mice at 20 months of age although the AID (+/+) mice showed more severe histological findings and increased cytokine expression. Furthermore, a low level of AID transcript was detected in the HCV-Tg/AID (+/+) liver tissue that was not derived from hepatocytes themselves but from intra-hepatic immune cells. Although AID may not be the direct cause of HCV-induced oncogenesis, AID expressed in B cells, not in hepatocytes, may prolong steatosis and cause increased lymphocyte infiltration into HCV core protein-induced liver lesions. Similarly, there was no difference in the time course of skin tumor development between the HPV8-Tg/AID (-/-) and HPV8-Tg/AID (+/+) groups. In conclusion, AID does not appear to be required for tumor development in the two virus-induced tumor mouse models tested although AID expressed in infiltrating B cells may promote inflammatory reactions in HCV core protein-induced liver pathogenesis.

  13. Clinicopathological and prognostic implications of endoglin (CD105) expression in hepatocellular carcinoma and its adjacent non-tumorous liver

    Institute of Scientific and Technical Information of China (English)

    Joanna W. Ho; Ronnie T. Poon; Chris K. Sun; Wei-Cheng Xue; Sheung-Tat Fan

    2005-01-01

    AIM: The expression pattern of endoglin (CD105) in hepatocellular carcinoma (HCC) has not been reported so far. We hypothesized that CD105 could differentially highlight a subset of microvessels in HCC, and intratumoral microvessel density (IMVD) by CD105 immunostaining (IMVD-CD105) could provide better prognostic information than IMVD by CD34 immunostaining (IMVD-CD34).METHODS: Paraffin blocks of tumor and adjacent nontumorous liver tissues from 86 patients who underwent curative resection of HCC were used for this study. Serial sections were stained for CD105 and CD34, respectively,to highlight the microvessels. IMVD was counted according to a standard protocol.RESULTS: In the HCC tissues, CD105 was either negatively or positively stained only in a subset of microvessels. In contrast, CD34 showed positive and more extensive microvessel staining in all cases examined. However, in the adjacent non-tumorous liver sections, CD105 showed a diffuse pattern of microvessel staining in 20 of 86 cases,while CD34 showed negative or only focal staining of the sinusoids around portal area. Correlation with clinicopathological data demonstrated that lower scores of IMVD-CD105 were found in larger sized tumors [mean 41.4/0.74 mm2 (>5 cm tumor) vs 65.9/0.74 mm2(≤ 5 cm tumor), P = 0.043] and more aggressive tumors,as indicated by venous infiltration [36.8/0.74 mm2 (present)vs 64.2/0.74 mm2 (absent), P = 0.020], microsatellite nodules [35.1/0.74 mm2 (present) vs 65.9/0.74 mm2(absent), P = 0.012], and advanced TNM tumor stage [38.8/0.74 mm2 (stage 3 or 4) vs 68.3/0.74 mm2 (stage 1or 2), P = 0.014]. No prognostic significance was observed when median values were used as cut-off points using either IMVD-CD105 or IMVD-CD34. However, the presence of the diffuse pattern of CD105 expression in the adjacent non-tumorous liver tissues predicted a poorer disease-free survival (median 8.6 vs 21.5 mo, P = 0.026).CONCLUSION: Our data demonstrate that a lower IMVDCD105 is associated with

  14. 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...

  15. Stereotactic body radiotherapy for liver tumors. Principles and practical guidelines of the DEGRO Working Group on Stereotactic Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Sterzing, Florian [Deutsches Krebsforschungszentrum (DKFZ), Klinische Kooperationseinheit Strahlentherapie, Heidelberg (Germany); Radiologische Universitaetsklinik, Abteilung fuer Radioonkologie und Strahlentherapie, Heidelberg (Germany); Brunner, Thomas B. [Universitaetsklinikum Freiburg, Klinik fuer Strahlenheilkunde, Radiologische Klinik, Freiburg (Germany); Ernst, Iris; Greve, Burkhard [Universitaetsklinikum Muenster, Klinik fuer Strahlentherapie - Radioonkologie, Muenster (Germany); Baus, Wolfgang W. [Universitaetsklinikum Koeln, Klinik und Poliklinik fuer Strahlentherapie, Koeln (Germany); Herfarth, Klaus [Radiologische Universitaetsklinik, Abteilung fuer Radioonkologie und Strahlentherapie, Heidelberg (Germany); Guckenberger, Matthias [UniversitaetsSpital Zuerich, Klinik fuer Radio-Onkologie, Zuerich (Switzerland)

    2014-10-15

    This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a practical guideline for safe and effective stereotactic body radiotherapy (SBRT) of liver tumors. The literature on the clinical evidence of SBRT for both primary liver tumors and liver metastases was reviewed and analyzed focusing on both physical requirements and special biological characteristics. Recommendations were developed for patient selection, imaging, planning, treatment delivery, motion management, dose reporting, and follow-up. Radiation dose constraints to critical organs at risk are provided. SBRT is a well-established treatment option for primary and secondary liver tumors associated with low morbidity. (orig.) [German] Die Arbeitsgruppe Stereotaxie der Deutschen Gesellschaft fuer Radioonkologie (DEGRO) legt hier eine Empfehlung zur sicheren und effektiven Durchfuehrung der SBRT von Lebertumoren vor. Eine Literaturrecherche zur Untersuchung der Evidenz der SBRT sowohl fuer primaere Lebertumore als auch fuer Lebermetastasen wurde durchgefuehrt. Auf dieser Basis werden Empfehlungen fuer technisch-physikalische Voraussetzungen wie auch fuer die taegliche Praxis der Leber-SBRT gegeben. Weiterhin werden radiobiologische Besonderheiten dieses Verfahrens dargestellt. Praktische Vorgaben werden fuer Patientenselektion, Bildgebung, Planung, Applikation, Bewegungsmanagement, Dosisdokumentation und Follow-up gegeben. Dosisempfehlungen fuer die kritischen Risikoorgane werden dargestellt. Die SBRT stellt eine etablierte Behandlungsmethode fuer primaere und sekundaere Lebertumore dar und ist mit niedriger Morbiditaet assoziiert. (orig.)

  16. The Role of the Superior Order GLCM in the Characterization and Recognition of the Liver Tumors from Ultrasound Images

    Directory of Open Access Journals (Sweden)

    D. Mitrea

    2012-04-01

    Full Text Available The hepatocellular carcinoma (HCC is the most frequent malignant liver tumor. It often has a similar visual aspect with the cirrhotic parenchyma on which it evolves and with the benign liver tumors. The golden standard for HCC diagnosis is the needle biopsy, but this is an invasive, dangerous method. We aim to develop computerized,noninvasive techniques for the automatic diagnosis of HCC, based on information obtained from ultrasound images. The texture is an important property of the internal organs tissue, able to provide subtle information about the pathology. We previously defined the textural model of HCC, consisting in the exhaustive set of the relevant textural features, appropriate for HCC characterization and in the specific values of these features. In this work, we analyze the role that the superior order Grey Level Cooccurrence Matrices (GLCM and the associated parameters have in the improvement of HCC characterization and automatic diagnosis. We also determine the best spatial relations between the pixels that lead to the highest performances, for the third, fifth and seventh order GLCM. The following classes will be considered: HCC, cirrhotic liver parenchyma on which it evolves and benign liver tumors.

  17. Angled Cool-Tip Electrode for Radiofrequency Ablation of Small Superficial Subcapsular Tumors in the Liver: A Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Il [Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of); Kim, Il Jung [Department of Radiology, Bucheon St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647 (Korea, Republic of); Lee, Shin Jae [Department of Radiology, CHA Bundang Medical Center, CHA University, Seongnam 13496 (Korea, Republic of); Shin, Min Woo; Shin, Won Sun; Chung, Yong Eun; Kim, Gyoung Min; Kim, Man Deuk; Won, Jong Yun; Lee, Do Yun [Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of); Choi, Jin Sub [Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of); Han, Kwang-Hyub [Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of)

    2016-11-01

    To evaluate the feasibility of angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular liver tumors abutting abdominal wall, in order to traverse normal liver parenchyma, and thereby, obtain favorable configuration of ablation margin. In this study, we retrospectively analyzed 15 small superficial subcapsular liver tumors abutting abdominal wall in 15 patients, treated with radiofrequency ablation from March 2013 to June 2015 using a cool-tip electrode manually modified to create 25–35° angle at the junction between exposed and insulated segments. The tumors were hepatocellular carcinoma (n = 13) and metastases (n = 2: cholangiocellular carcinoma and rectosigmoid cancer), with maximum diameter of 10–26 mm (mean, 15.68 ± 5.29 mm). Under ultrasonographic guidance, the electrode tip was advanced to the depth of the tumors' epicenter about 1 cm from the margin. The tip was re-directed to penetrate the tumor for radiofrequency ablation. Minimal ablation margin was measured at immediate post-treatment CT. Radiological images and medical records were evaluated for success rate, length of minimal ablation margin and complications. Technical success rate of obtaining complete necrosis of the tumors was 100%, with no procedure-related complication. Minimal ablation margin ranged from 3–12 mm (mean, 7.07 ± 2.23 mm). CT/MRI follow-up at 21–1022 days (mean, 519.47 ± 304.51 days) revealed no local recurrence, but distant recurrence in 9 patients. Using an angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular tumors abutting abdominal wall may be a feasible technique for obtaining adequate ablation margin and lower complication rate.

  18. Angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular tumors in the liver: A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Il; Shin, Min Woo; Shin, Won Seon [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); and others

    2016-09-15

    To evaluate the feasibility of angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular liver tumors abutting abdominal wall, in order to traverse normal liver parenchyma, and thereby, obtain favorable configuration of ablation margin. In this study, we retrospectively analyzed 15 small superficial subcapsular liver tumors abutting abdominal wall in 15 patients, treated with radiofrequency ablation from March 2013 to June 2015 using a cool-tip electrode manually modified to create 25–35° angle at the junction between exposed and insulated segments. The tumors were hepatocellular carcinoma (n = 13) and metastases (n = 2: cholangiocellular carcinoma and rectosigmoid cancer), with maximum diameter of 10–26 mm (mean, 15.68 ± 5.29 mm). Under ultrasonographic guidance, the electrode tip was advanced to the depth of the tumors' epicenter about 1 cm from the margin. The tip was re-directed to penetrate the tumor for radiofrequency ablation. Minimal ablation margin was measured at immediate post-treatment CT. Radiological images and medical records were evaluated for success rate, length of minimal ablation margin and complications. Technical success rate of obtaining complete necrosis of the tumors was 100%, with no procedure-related complication. Minimal ablation margin ranged from 3–12 mm (mean, 7.07 ± 2.23 mm). CT/MRI follow-up at 21–1022 days (mean, 519.47 ± 304.51 days) revealed no local recurrence, but distant recurrence in 9 patients. Using an angled cool-tip electrode for radiofrequency ablation of small superficial subcapsular tumors abutting abdominal wall may be a feasible technique for obtaining adequate ablation margin and lower complication rate.

  19. Therapeutic efficacy of tumor-targeting Salmonella typhimurium A1-R on human colorectal cancer liver metastasis in orthotopic nude-mouse models.

    Science.gov (United States)

    Murakami, Takashi; Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2015-10-13

    Liver metastasis is the most frequent cause of death from colon and other cancers. Generally, liver metastasis is recalcitrant to treatment. The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R on liver metastasis in orthotopic mouse models. HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used in the present study. S. typhimurium A1-R infected HT-29 cells in a time-dependent manner, inhibiting cancer-cell proliferation in vitro. S. typhimurium A1-R promoted tumor necrosis and inhibited tumor growth in a subcutaneous tumor mouse model of HT-29-RFP. In orthotopic mouse models, S. typhimurium A1-R targeted liver metastases and significantly reduced their growth. The results of this study demonstrate the future clinical potential of S. typhimurium A1-R targeting of liver metastasis.

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

    Directory of Open Access Journals (Sweden)

    Ling Ye

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

  1. SIRT1 and c-Myc Promote Liver Tumor Cell Survival and Predict Poor Survival of Human Hepatocellular Carcinomas

    Science.gov (United States)

    Jang, Kyu Yun; Noh, Sang Jae; Lehwald, Nadja; Tao, Guo-Zhong; Bellovin, David I.; Park, Ho Sung; Moon, Woo Sung; Felsher, Dean W.; Sylvester, Karl G.

    2012-01-01

    The increased expression of SIRT1 has recently been identified in numerous human tumors and a possible correlation with c-Myc oncogene has been proposed. However, it remains unclear whether SIRT1 functions as an oncogene or tumor suppressor. We sought to elucidate the role of SIRT1 in liver cancer under the influence of c-Myc and to determine the prognostic significance of SIRT1 and c-Myc expression in human hepatocellular carcinoma. The effect of either over-expression or knock down of SIRT1 on cell proliferation and survival was evaluated in both mouse and human liver cancer cells. Nicotinamide, an inhibitor of SIRT1, was also evaluated for its effects on liver tumorigenesis. The prognostic significance of the immunohistochemical detection of SIRT1 and c-Myc was evaluated in 154 hepatocellular carcinoma patients. SIRT1 and c-Myc regulate each other via a positive feedback loop and act synergistically to promote hepatocellular proliferation in both mice and human liver tumor cells. Tumor growth was significantly inhibited by nicotinamide in vivo and in vitro. In human hepatocellular carcinoma, SIRT1 expression positively correlated with c-Myc, Ki67 and p53 expression, as well as high á-fetoprotein level. Moreover, the expression of SIRT1, c-Myc and p53 were independent prognostic indicators of hepatocellular carcinoma. In conclusion, this study demonstrates that SIRT1 expression supports liver tumorigenesis and is closely correlated with oncogenic c-MYC expression. In addition, both SIRT1 and c-Myc may be useful prognostic indicators of hepatocellular carcinoma and SIRT1 targeted therapy may be beneficial in the treatment of hepatocellular carcinoma. PMID:23024800

  2. A semi-automated technique determining the liver standardized uptake value reference for tumor delineation in FDG PET-CT.

    Directory of Open Access Journals (Sweden)

    Kenji Hirata

    Full Text Available BACKGROUND: 18F-fluorodeoxyglucose (FDG positron emission tomography (PET-computed tomography (CT has been an essential modality in oncology. We propose a semi-automated algorithm to objectively determine liver standardized uptake value (SUV, which is used as a threshold for tumor delineation. METHODS: A large spherical volume of interest (VOI was placed manually to roughly enclose the right lobe (RL of the liver. For each voxel in this VOI, a coefficient of variation of voxel values (CVv was calculated for neighboring voxels within a radius of d/2. The voxel with the minimum CVv was then selected, where a 30-mm spherical VOI was placed at that voxel in accordance with PERCIST criteria. Two nuclear medicine physicians independently defined 30-mm VOIs manually on 124 studies in 62 patients to generate the standard values, against which the results from the new method were compared. RESULTS: The semi-automated method was successful in determining the liver SUV that was consistent between the two physicians in all the studies (d = 80 mm. The liver SUV threshold (mean +3 SD within 30-mm VOI determined by the new semi-automated method (3.12±0.61 was not statistically different from those determined by the manual method (Physician-1: 3.14±0.58, Physician-2: 3.15±0.58. The semi-automated method produced tumor volumes that were not statistically different from those by experts' manual operation. Furthermore, the volume change in the two sequential studies had no statistical difference between semi-automated and manual methods. CONCLUSIONS: Our semi-automated method could define the liver SUV robustly as the threshold value used for tumor volume measurements according to PERCIST. The method could avoid possible subjective bias of manual liver VOI placement and is thus expected to improve clinical performance of volume-based parameters for prediction of cancer treatment response.

  3. Surgical treatment of double primary liver cancer: An observational study for a rare type of tumor.

    Science.gov (United States)

    Li, Aijun; Ma, Senlin; Pawlik, Timothy; Wu, Bin; Yang, Xiaoyu; Cui, Longjiu; Wu, Mengchao

    2016-08-01

    Double primary liver cancer (DPLC) is a special type of clinical situation. As such, a detailed analysis of the surgical management and prognosis of patients with DPLC is lacking. The objective of the current study was to define the management and outcome of patients undergoing surgery for DPLC at a major hepatobiliary center.A total of 87 patients treated by surgical resection at the Eastern Hepatobiliary Surgery Hospital from January 1st, 2007 to October 31st, 2013 who had DPLC demonstrated by final pathological diagnosis were identified. Among these, 50 patients had complete clinical and prognostic data. Demographic and tumor characteristics as well as the prognosis were analyzed.The proportion of hepatitis B surface antigen (HBsAg) (+) and hepatitis B virus e antigen (HBeAg) (+), HBsAg (+), and HBeAg (-) hepatocirrhosis in all patients was 21.84%, 67.82%, and 63.22%, respectively. Incidental findings accounted for 58.62% of patients; among those who had symptoms, the main symptom was abdominal pain (31.03%). Nonanatomic wedge resection was the main operative approach (62.07%). Postoperatively, the main complications included seroperitoneum (11.49%), hypoproteinemia (10.34%), and pleural effusion (8.05%). Factors associated with disease-free survival (DFS) included intrahepatic cholangiocarcinoma (ICC) tumor size (P = 0.002) and use of postoperative prophylactic transcatheter arterial chemoembolization (TACE) treatment (P = 0.015). Meanwhile, hepatocellular carcinoma (HCC) size (P = 0.045), ICC size (P < 0.001), and liver function (including aspartate aminotransferase [P = 0.001] and r-glutamyl transferase [P < 0.001]) were associated with overall survival (OS).Hepatitis B virus (HBV)-related hepatitis or cirrhosis is also an important factor in the pathogenesis of DPLC and surgical treatment is safe for it with low complication rates. In addition, it is effective to prolong DFS that DPLC patients undergo postoperative prophylactic TACE

  4. Pattern of Retained Contrast on Immediate Postprocedure Computed tomography (CT) After Particle Embolization of Liver Tumors Predicts Subsequent Treatment Response

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xiaodong, E-mail: wangxde@gmail.com; Erinjeri, Joseph P., E-mail: erinjerj@mskcc.org [Memorial Sloan-Kettering Cancer Center, Interventional Radiology Service, Department of Radiology (United States); Jia Xiaoyu, E-mail: jiax@mskcc.org; Gonen, Mithat, E-mail: gonenm@mskcc.org [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics (United States); Brown, Karen T., E-mail: brown6@mskcc.org; Sofocleous, Constantinos T., E-mail: sofoclec@mskcc.org; Getrajdman, George I., E-mail: getrajdg@mskcc.org; Brody, Lynn A., E-mail: brodyl@mskcc.org; Thornton, Raymond H., E-mail: throntor@mskcc.org; Maybody, Majid, E-mail: maybodym@mskcc.org; Covey, Ann M., E-mail: covey@mskcc.org; Siegelbaum, Robert H., E-mail: siegelbr@mskcc.org; Alago, William, E-mail: alagow@mskcc.org; Solomon, Stephen B., E-mail: solomons@mskcc.org [Memorial Sloan-Kettering Cancer Center, Interventional Radiology Service, Department of Radiology (United States)

    2013-08-01

    PurposeTo determine if the pattern of retained contrast on immediate postprocedure computed tomography (CT) after particle embolization of hepatic tumors predicts modified Response Evaluation Criteria in Solid Tumors (mRECIST) response.Materials and MethodsThis study was approved by the Institutional Review Board with a waiver of authorization. One hundred four liver tumors were embolized with spherical embolic agents (Embospheres, Bead Block, LC Bead) and polyvinyl alcohol. Noncontrast CT was performed immediately after embolization to assess contrast retention in the targeted tumors, and treatment response was assessed by mRECIST criteria on follow-up CT (average time 9.0 {+-} 7.7 weeks after embolization). Tumor contrast retention (TCR) was determined based on change in Hounsfield units (HUs) of the index tumors between the preprocedure and immediate postprocedure scans; vascular contrast retention (VCR) was rated; and defects in contrast retention (DCR) were also documented. The morphology of residual enhancing tumor on follow-up CT was described as partial, circumferential, or total. Association between TCR variables and tumor response were assessed using multivariate logistic regression.ResultsOf 104 hepatic tumors, 51 (49 %) tumors had complete response (CR) by mRECIST criteria; 23 (22.1 %) had partial response (PR); 21 (20.2 %) had stable disease (SD); and 9 (8.7 %) had progressive disease (PD). By multivariate analysis, TCR, VCR, and tumor size are independent predictors of CR (p = 0.02, 0.05, and 0.005 respectively). In 75 tumors, DCR was found to be an independent predictor of failure to achieve complete response (p < 0.0001) by imaging criteria.ConclusionTCR, VCR, and DCR on immediate posttreatment CT are independent predictors of CR by mRECIST criteria.

  5. Therapy response of liver tumors after selective internal radiation therapy; Therapieresponse von Lebertumoren nach selektiver interner Radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Jakobs, T.F.; Hoffmann, R.T.; Trumm, C.; Reiser, M.F. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen, Institut fuer Klinische Radiologie, Muenchen (Germany); Tatsch, K. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen, Klinik und Poliklinik fuer Nuklearmedizin, Muenchen (Germany)

    2008-09-15

    Selective internal radiation therapy (SIRT) is used for the treatment of patients with liver tumors, especially for those with hepatocellular carcinoma (HCC) or liver metastases from various primary tumors. Currently this innovative treatment concept is recommended when established state-of-the-art treatment regimes have failed and tumor progression is noted or if the treatment has to be abandoned because of intolerable toxic effects. For SIRT small biocompatible microspheres (SIR-Spheres {sup registered}) are labelled with the radioactive isotope 90Yttrium, a pure beta emitter, and are superselectively infused into the hepatic arteries. The microspheres are collected in the precapillary vessels in and surrounding the tumor. The beta radiation of 90Yttrium has an average penetration in tissue of approximately 2.5 mm and results in very high doses of radiation being selectively targeted to metastases providing protection to the surrounding healthy liver tissue. In this paper we review the results of SIRT in patients with hepatic metastases from colorectal cancer, breast cancer, neuroendocrine tumors and primary liver cancer (HCC). (orig.) [German] Die selektive interne Radiotherapie (SIRT) wird zur Behandlung primaerer Lebertumoren, insbesondere dem hepatozellulaeren Karzinom (HCC) und von Lebermetastasen verschiedener Primaertumoren eingesetzt. Derzeit wird diese innovative Therapieform empfohlen, wenn unter klassischen und etablierten Therapiekonzepten eine Progression der Lebererkrankung zu verzeichnen ist oder diese Therapien auf Grund intolerabler Toxizitaet abgebrochen werden muessen. Bei der SIRT werden kleine biokompatible Harzmikrosphaeren (SIR-Spheres {sup registered}), die Betastrahlen emittierendes Yttrium-90 enthalten, ueber einen transarteriellen Zugangsweg superselektiv in die Leberarterien injiziert. Die Mikrosphaeren sammeln sich in praekapillaren Gefaessen in und um das Tumorgewebe an. Hier entfalten die Betastrahlen aufgrund ihrer geringen

  6. Visualization of risk structures for interactive planning of image guided radiofrequency ablation of liver tumors

    Science.gov (United States)

    Rieder, Christian; Schwier, Michael; Weihusen, Andreas; Zidowitz, Stephan; Peitgen, Heinz-Otto

    2009-02-01

    Image guided radiofrequency ablation (RFA) is becoming a standard procedure as a minimally invasive method for tumor treatment in the clinical routine. The visualization of pathological tissue and potential risk structures like vessels or important organs gives essential support in image guided pre-interventional RFA planning. In this work our aim is to present novel visualization techniques for interactive RFA planning to support the physician with spatial information of pathological structures as well as the finding of trajectories without harming vitally important tissue. Furthermore, we illustrate three-dimensional applicator models of different manufactures combined with corresponding ablation areas in homogenous tissue, as specified by the manufacturers, to enhance the estimated amount of cell destruction caused by ablation. The visualization techniques are embedded in a workflow oriented application, designed for the use in the clinical routine. To allow a high-quality volume rendering we integrated a visualization method using the fuzzy c-means algorithm. This method automatically defines a transfer function for volume visualization of vessels without the need of a segmentation mask. However, insufficient visualization results of the displayed vessels caused by low data quality can be improved using local vessel segmentation in the vicinity of the lesion. We also provide an interactive segmentation technique of liver tumors for the volumetric measurement and for the visualization of pathological tissue combined with anatomical structures. In order to support coagulation estimation with respect to the heat-sink effect of the cooling blood flow which decreases thermal ablation, a numerical simulation of the heat distribution is provided.

  7. Feasibility of Quantitative Parameter Measurements at Reduced X-ray Dose CT Perfusion in Rabbits with Implanted VX2 Lung Tumours%兔VX2肺肿瘤低剂量CT灌注成像的可行性研究

    Institute of Scientific and Technical Information of China (English)

    崔磊; 龚沈初; 何书; 尹剑兵; 杨巨顺; 杨红

    2011-01-01

    Objective To prospectively assess the reproducibility of CT perfusion parameters acquired with normal dose and low dose in rabbits with implanted VX2 lung tumours. Methods Two times of perfusion CT were performed with 24-hour interval in 10 New Zealand white rabbits with implanted VX2 lung tumours by means of using routine (120 kV, 100 mAs) and low (120 kV, 50 mAs) dose. The volume, maximum diameter, blood volume(BV) , blood flow(BF) , time to peak(TTP) , permeability surface (PS), patlak BV(PBV), Patlak R square (PatRsq) and Patlak residual ( PatRVX2 lungtumours.%目的 前瞻性评估兔VX2肺种植肿瘤低剂量和常规剂量CT灌注检查测量参数的可重复性.方法 10只肺种植肿瘤新西兰大白兔间隔24h行两次CT灌注检查(常规剂量120 kV,100 mAs;低剂量120 kV,50 mAs),分别测量肿瘤体积、最大径、血容量(BV)、血流量(BF)、达峰时间(TTP)、表面通透性(PS)、Patlak血容量(PBV)、Patlak R方程(PatRsq)及Patlak残差(PatRes).使用配对t检验和Bland-Altman法分析2组CT测量数据的一致性和可重复性.结果 两次CT检查所有的CT灌注参数均显示较好的一致性.配对t检验

  8. Comparative assessment of liver tumor motion using cine-magnetic resonance imaging versus 4-dimensional computed tomography.

    Science.gov (United States)

    Fernandes, Annemarie T; Apisarnthanarax, Smith; Yin, Lingshu; Zou, Wei; Rosen, Mark; Plastaras, John P; Ben-Josef, Edgar; Metz, James M; Teo, Boon-Keng

    2015-04-01

    To compare the extent of tumor motion between 4-dimensional CT (4DCT) and cine-MRI in patients with hepatic tumors treated with radiation therapy. Patients with liver tumors who underwent 4DCT and 2-dimensional biplanar cine-MRI scans during simulation were retrospectively reviewed to determine the extent of target motion in the superior-inferior, anterior-posterior, and lateral directions. Cine-MRI was performed over 5 minutes. Tumor motion from MRI was determined by tracking the centroid of the gross tumor volume using deformable image registration. Motion estimates from 4DCT were performed by evaluation of the fiducial, residual contrast (or liver contour) positions in each CT phase. Sixteen patients with hepatocellular carcinoma (n=11), cholangiocarcinoma (n=3), and liver metastasis (n=2) were reviewed. Cine-MRI motion was larger than 4DCT for the superior-inferior direction in 50% of patients by a median of 3.0 mm (range, 1.5-7 mm), the anterior-posterior direction in 44% of patients by a median of 2.5 mm (range, 1-5.5 mm), and laterally in 63% of patients by a median of 1.1 mm (range, 0.2-4.5 mm). Cine-MRI frequently detects larger differences in hepatic intrafraction tumor motion when compared with 4DCT most notably in the superior-inferior direction, and may be useful when assessing the need for or treating without respiratory management, particularly in patients with unreliable 4DCT imaging. Margins wider than the internal target volume as defined by 4DCT were required to encompass nearly all the motion detected by cine-MRI for some of the patients in this study. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Comparative Assessment of Liver Tumor Motion Using Cine–Magnetic Resonance Imaging Versus 4-Dimensional Computed Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Annemarie T. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Apisarnthanarax, Smith [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Yin, Lingshu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Zou, Wei [Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Rosen, Mark [Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Plastaras, John P.; Ben-Josef, Edgar; Metz, James M. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Teo, Boon-Keng, E-mail: kevin.teo@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2015-04-01

    Purpose: To compare the extent of tumor motion between 4-dimensional CT (4DCT) and cine-MRI in patients with hepatic tumors treated with radiation therapy. Methods and Materials: Patients with liver tumors who underwent 4DCT and 2-dimensional biplanar cine-MRI scans during simulation were retrospectively reviewed to determine the extent of target motion in the superior–inferior, anterior–posterior, and lateral directions. Cine-MRI was performed over 5 minutes. Tumor motion from MRI was determined by tracking the centroid of the gross tumor volume using deformable image registration. Motion estimates from 4DCT were performed by evaluation of the fiducial, residual contrast (or liver contour) positions in each CT phase. Results: Sixteen patients with hepatocellular carcinoma (n=11), cholangiocarcinoma (n=3), and liver metastasis (n=2) were reviewed. Cine-MRI motion was larger than 4DCT for the superior–inferior direction in 50% of patients by a median of 3.0 mm (range, 1.5-7 mm), the anterior–posterior direction in 44% of patients by a median of 2.5 mm (range, 1-5.5 mm), and laterally in 63% of patients by a median of 1.1 mm (range, 0.2-4.5 mm). Conclusions: Cine-MRI frequently detects larger differences in hepatic intrafraction tumor motion when compared with 4DCT most notably in the superior–inferior direction, and may be useful when assessing the need for or treating without respiratory management, particularly in patients with unreliable 4DCT imaging. Margins wider than the internal target volume as defined by 4DCT were required to encompass nearly all the motion detected by cine-MRI for some of the patients in this study.

  10. Complications of Microwave Ablation for Liver Tumors: Results of a Multicenter Study

    Energy Technology Data Exchange (ETDEWEB)

    Livraghi, Tito, E-mail: lalivra@tin.it [IRCCS Istituto Clinico Humanitas, Department of Interventional Radiology (Italy); Meloni, Franca, E-mail: meloni@yahoo.it [San Gerardo Hospital, Department of Radiology (Italy); Solbiati, Luigi, E-mail: lusolbia@tin.it [Azienda Ospedaliera di Busto Arsizio, Department of Interventional Radiology (Italy); Zanus, Giorgio, E-mail: zanus@unipd.it [Azienda Universita di Padova, General Surgery and Organ Transplantation (Italy); Collaboration: For the Collaborative Italian Group using AMICA system

    2012-08-15

    Purpose: New technologies for microwave ablation (MWA) have been conceived, designed to achieve larger areas of necrosis compared with radiofrequency ablation (RFA). The purpose of this study was to report complications by using this technique in patients with focal liver cancer. Methods: Members of 14 Italian centers used a 2.45-GMHz generator delivering energy through a cooled miniature-choke MW antenna and a standardized protocol for follow-up. They completed a questionnaire regarding number and type of deaths, major and minor complications and side effects, and likelihood of their relationship to the procedure. Enrollment included 736 patients with 1.037 lesions: 522 had hepatocellular carcinoma with cirrhosis, 187 had metastases predominantly from colorectal cancer, and 27 had cholangiocellular carcinoma. Tumor size ranged from 0.5 to 10 cm. In 13 centers, the approach used was percutaneous, in 4 videolaparoscopic, and in 3 laparotomic. Results: No deaths were reported. Major complications occurred in 22 cases (2.9%), and minor complications in 54 patients (7.3%). Complications of MWA do not differ from those RFA, both being based on the heat damage. Conclusion: Results of this multicenter study confirmed those of single-center experiences, indicating that MWA is a safe procedure, with no mortality and a low rate of major complications. The low rate of complications was probably due to precautions adopted, knowing in advance possible risk conditions, on the basis of prior RFA experience.

  11. Perfusion CT Changes in Liver Metastases from Pancreatic Neuroendocrine Tumors During Everolimus Treatment.

    Science.gov (United States)

    D'Onofrio, Mirko; Cingarlini, Sara; Ortolani, Silvia; Crosara, Stefano; DE Robertis, Riccardo; Vallerio, Paola; Grego, Elisabetta; Ciaravino, Valentina; Ruzzenente, Andrea; Landoni, Luca; Scarpa, Aldo; Bassi, Claudio; Tortora, Giampaolo

    2017-03-01

    To evaluate modifications of perfusional parameters assessed by perfusion computed tomography (P-CT) of liver metastases (LM) from pancreatic neuroendocrine tumors (PanNETs) during everolimus treatment. All patients with LMs from G1-2 PanNETs undergoing everolimus treatment between January 2013 and January 2015 were prospectively evaluated with P-CT at baseline, and after 2 and 4 months of therapy. Size, perfusion, blood volume (BV), peak enhancement intensity (PEI) and time to peak for each lesion were calculated. A total of 33 LMs in nine patients with G1-2 PanNETs were prospectively evaluated: 23/33 (69.7%) were responders, 10/33 (30.3%) were non-responders. Among perfusional parameters, only numerical peak enhancement intensity values significantly differed between the two groups at baseline (p=0.043). BV increase was the most significant perfusional modification identifying responding lesions, even at an early stage of treatment, with a high positive predictive value (89.47%). P-CT seems to be useful for prediction of response to everolimus of LMs from PanNETs. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Finite element analysis of constant-power invasive microwave coagulation of liver tumors

    Institute of Scientific and Technical Information of China (English)

    陈新; 南群; 彭见曙; 曾衍钧; 梁萍; 于晓玲; 董宝玮

    2002-01-01

    Invasive microwave coagulation (IMC) therapy is a newly developed method for the treatment of liver tumors. In this paper, the constant-power IMC therapy is discussed. Three-dimensional finite element analysis for "alternative" heating pattern and a large blood vessel bioheat model are performed. The objective is to study: (i) the effects of "alternative" heating pattern of invasive microwave antennas on reducing the peak temperature which can be up to 140℃. Therefore, "alternative" heating pattern can improve the security of IMC; (ii) modeling impact of large vessels on heat transfer of surrounding tissue and the formation of the coagulation lesion. Corresponding in vivo pig experiments are provided to compare with the simulation results. The results indicate that: (i) the "alternative" heating pattern was efficient in reducing the peak temperature and diminishing the dimension of "super hot" area; (ii) the heat loss due to the cooling of the large blood vessel is so great that attempting to compensate the cool area by thermal method is unfeasible, which explains why occluding the blood vessel is a practical approach to dealing with this problem during the invasive microwave coagulation therapy; (iii) the radius of effect of large vessels (Rev) was brought forward to provide theoretical basis for clinical practice.

  13. State of the art in computer-assisted planning, intervention, and assessment of liver-tumor ablation.

    Science.gov (United States)

    Schumann, Christian; Rieder, Christian; Bieberstein, Jennifer; Weihusen, Andreas; Zidowitz, Stephan; Moltz, Jan Hendrik; Preusser, Tobias

    2010-01-01

    Percutaneous, image-guided thermal tumor ablation procedures are used increasingly for minimally invasive, local treatment of tumors in the liver. The planning of these procedures; the support of targeting, monitoring, and controlling during the intervention itself; and the assessment of the treatment response can all benefit significantly from computer assistance. The outcome can be optimized by supporting the physician in the process of determining an intervention strategy that enables complete destruction of the targeted tumor while reducing the danger of complications. During the intervention, computer-assisted methods can be used to guide the physician in the implementation of the intended strategy by providing planning information. Assessment of the intervention result is carried out by comparison of the achieved coagulation with the target tumor volume. Supporting this comparison facilitates the early detection of potential recurrences. This report provides an overview of state-of-the-art computer-assisted methods for the support of thermal tumor ablations in the liver. Proper approaches for image segmentation, access-path determination, simulation, visualization, interventional guidance, and post-interventional assessment, as well as integrated work flow-oriented solutions, are reviewed with respect to technical aspects and applicability in the clinical setting.

  14. Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

    Institute of Scientific and Technical Information of China (English)

    Sung Yi Hong; Myun Hee Lee; Kyung Sup Kim; Hyun Cheol Jung; Jae Kyung Roh; Woo Jin Hyung; Sung Hoon Noh; Seung Ho Choi

    2004-01-01

    AIM: rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer. However,a sustained and high protein delivery is required to achieve the desired therapeutic effects. We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model.METHODS: rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines. To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin, Western blotting and ELISA were performed. The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays.The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor, etoposide, were evaluated in a mouse liver tumor model.RESULTS: Topoisomerase inhibitors, including camptothecin and etoposide, were found to increase the endostatin expression level in vitro. The over-expressed endostatin,as a result of pretreatment with a topoisomerase inhibitor,was also biologically active. In animal experiments, the combined therapy of topoisomerase inhibitor, etoposide with the rAAV-endostatin vector had the best tumorsuppressive effect and tumor foci were barely observed in livers of the treated mice. Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice. Finally, the mice treated with rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models.CONCLUSION: rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.

  15. {sup 188}Re-HTDD-lipiodol solution as a new therapeutic agent for transhepatic arterial administration in liver cancer: a preclinical study using liver-cancer model in rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Paeng, J. C.; Jeong, J. M.; Lee, Y. S. [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)] [and others

    2001-07-01

    {sup 188}Re-HTDD-lipiodol solution was developed and reported to be a new therapeutic material for transhepatic arterial embolization (TAE) of liver cancer. In this study we compared the tissue retention of {sup 188}Re-HTDD-lipiodol with that of {sup 188}Re-TDD-lipiodol using liver-cancer model in rabbit. Cancer cell line VX2 was inoculated into 7 rabbits and grown up to larger than 3 cm. TAE was performed with {sup 188}Re-TDD-lipiodol in 3 rabbits and with {sup 188}Re-HTDD-lipiodol in 4 rabbits. Conjugated planar scans were performed at 1, 2, 6, 24, 48 hours after TAE. From these images, the mean life of radioactivity retention in tumor was calculated, and the required dose for human application as also calculated from the mean life and MIRDOSE3 software. The mean lifes of radioactivity in liver were 10.2{+-}1.0 hr in TDD group and 17.6{+-}0.8 hr in HTDD group (p<0.001). The required dose for the tumor to be irradiated 50 Gy of radiation was calculated to be 18 mCi of {sup 188}Re-HTDD-lipiodol for 5.7 cm-sized tumor and 88 mCi for 9,7 cm-sized tumor. By the introduction of long chain alkyl group, {sup 188}Re-HTDD-lipiodol showed significantly better tumor retention than that of {sup 188}Re-TDD-lipiodol. And the required dose of radiation for human application was calculated to be 18 {approx} 88 mCi when using {sup 188}Re-HTDD-lipiodol.

  16. Semiautomatic technique for defining the internal gross tumor volume of lung tumors close to liver/spleen cupola by 4D-CT

    Energy Technology Data Exchange (ETDEWEB)

    Mancosu, Pietro; Sghedoni, Roberto; Bettinardi, Valentino; Aquilina, Mark Anthony; Navarria, Piera; Cattaneo, Giovanni Mauro; Di Muzio, Nadia; Cozzi, Luca; Scorsetti, Marta [Department of Radiotherapy, IRCCS Istituto Clinico Humanitas, Rozzano, 20089 Milano (Italy); Department of Medical Physics, Arcispedale S. Maria Nuova, Reggio, 42100 Emilia (Italy); Department of Nuclear Medicine, Scientific Institute H. S. Raffaele, 20089 Milan (Italy); Department of Radiotherapy, IRCCS Istituto Clinico Humanitas, 20089 Rozzano, Milano (Italy); Department of Medical Physics, San Raffaele Scientific Institute, 20133 Milan (Italy); Department of Radiotherapy, San Raffaele Scientific Institute, 20133 Milan (Italy); Medical Physics Unit, Oncology Institute of Southern Switzerland, 6504 Bellinzona (Switzerland); Department of Radiotherapy, IRCCS Istituto Clinico Humanitas, 20089 Rozzano, Milano (Italy)

    2010-09-15

    Purpose: It has been shown that in cases of lung tumors close to the liver cupola, the four dimensional (4D)-CT postprocessing maximum intensity projection (MIP) algorithm does not fully recover the radiotherapy internal gross tumor volume (IGTV). In this work, a semiautomatic technique was evaluated by which the residual IGTV that was not included into the IGTV by MIP algorithm was actually added. Methods: A moving phantom and five selected patients were considered. The various IGTVs produced by the semiautomatic approach were compared to those generated by 4D-CT manual contouring. Results: In all cases, the radiation oncologist qualitatively concurred with the semiautomatic IGTV. A quantitative difference in volume of 2.6% was found in the phantom study, whereas a mean difference of 0.1{+-}4.6% was obtained in the patient studies. Conclusions: A semiautomatic technique to include the residual part of IGTV covered by liver/spleen cupola when using MIP algorithm was validated on phantom and on selected patients, revealing the possibility of defining the IGTV for patients with lesions located near liver/spleen cupola by performing only the contours on the MIP series.

  17. Biocompatible Low-Retention Superparamagnetic Iron Oxide Nanoclusters as Contrast Agents for Magnetic Resonance Imaging of Liver Tumor.

    Science.gov (United States)

    Wei, Yushuang; Liao, Rufang; Liu, Haijuan; Li, Huan; Xu, Haibo; Zhou, Qibing

    2015-05-01

    Although superparamagnetic iron oxide (SPIO) nanoparticles have been developed as a contrast agent for magnetic resonance imaging (MRI), acute iron overload due to the persistently high retention of SPIOs in the liver and spleen that are slowly converted to ferroproteins is a serious safety concern. Here, we report that the addition of poly-L-lysine polymers to an SPIO hydroxyethyl starch solution produced tightly controlled, monodispersed nanoparticles in a size-dependent manner as effective contrast agents for the MRI of liver tumors. High MRI contrast was demonstrated with an orthotopic liver tumor model at a low injection dose. Simultaneously, rapid bioclearance of excess iron in the lung and spleen and in blood serum was observed within 24 h post-injection. The full excretion of excess iron was confirmed in urine post-intravenous injection, suggesting that the effective clearance of SPIOs could be achieved with our SPIO nanoclusters as a liver imaging contrast agent to resolve acute iron overload in the clinical usage of SPIOs as a contrast agent.

  18. Imatinib mesylate induces responses in patients with liver metastases from gastrointestinal stromal tumor failing intra-arterial hepatic chemotherapy

    Directory of Open Access Journals (Sweden)

    Fiorentini Giammaria

    2006-01-01

    Full Text Available Background: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST, due to the typically hypervascular pattern of the tumor. Aims: We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. Materials and Methods: Three patients (pts with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. Results: We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. Conclusion: No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.

  19. Protective Effect of Prosopis cineraria Against N-Nitrosodiethylamine Induced Liver Tumor by Modulating Membrane Bound Enzymes and Glycoproteins

    Directory of Open Access Journals (Sweden)

    Naina Mohamed Pakkir Maideen

    2012-06-01

    Full Text Available Purpose: The objective of the present study was to evaluate the protective effect of methanol extract of Prosopis cineraria (MPC against N-nitrosodiethylamine (DEN, 200mg/kg induced Phenobarbital promoted experimental liver tumors in male Wistar rats. Methods: The rats were divided into four groups, each group consisting of six animals. Group 1 served as control animals. Liver tumor was induced in group 2, 3, and 4 and Group 3 animals received MPC 200mg/kg and Group 4 animals received MPC 400mg/kg. Results: Administration of DEN has brought down the levels of membrane bound enzymes like Na+/ K+ ATPase, Mg2+ ATPase and Ca2+ATPase which were later found to be increased by the administration of Prosopis cineraria (200 and 400mg/kg in dose dependent manner. The MPC extract also suppressed the levels of glycoproteins like Hexose, Hexosamine and Sialic acid when compared to liver tumor bearing animals. Conclusions: Our study suggests that MPC may extend its protective role by modulating the levels of membrane bound enzymes and suppressing glycoprotein levels.

  20. Electroporation-based treatment planning for deep-seated tumors based on automatic liver segmentation of MRI images.

    Science.gov (United States)

    Pavliha, Denis; Mušič, Maja M; Serša, Gregor; Miklavčič, Damijan

    2013-01-01

    Electroporation is the phenomenon that occurs when a cell is exposed to a high electric field, which causes transient cell membrane permeabilization. A paramount electroporation-based application is electrochemotherapy, which is performed by delivering high-voltage electric pulses that enable the chemotherapeutic drug to more effectively destroy the tumor cells. Electrochemotherapy can be used for treating deep-seated metastases (e.g. in the liver, bone, brain, soft tissue) using variable-geometry long-needle electrodes. To treat deep-seated tumors, patient-specific treatment planning of the electroporation-based treatment is required. Treatment planning is based on generating a 3D model of the organ and target tissue subject to electroporation (i.e. tumor nodules). The generation of the 3D model is done by segmentation algorithms. We implemented and evaluated three automatic liver segmentation algorithms: region growing, adaptive threshold, and active contours (snakes). The algorithms were optimized using a seven-case dataset manually segmented by the radiologist as a training set, and finally validated using an additional four-case dataset that was previously not included in the optimization dataset. The presented results demonstrate that patient's medical images that were not included in the training set can be successfully segmented using our three algorithms. Besides electroporation-based treatments, these algorithms can be used in applications where automatic liver segmentation is required.

  1. Electroporation-based treatment planning for deep-seated tumors based on automatic liver segmentation of MRI images.

    Directory of Open Access Journals (Sweden)

    Denis Pavliha

    Full Text Available Electroporation is the phenomenon that occurs when a cell is exposed to a high electric field, which causes transient cell membrane permeabilization. A paramount electroporation-based application is electrochemotherapy, which is performed by delivering high-voltage electric pulses that enable the chemotherapeutic drug to more effectively destroy the tumor cells. Electrochemotherapy can be used for treating deep-seated metastases (e.g. in the liver, bone, brain, soft tissue using variable-geometry long-needle electrodes. To treat deep-seated tumors, patient-specific treatment planning of the electroporation-based treatment is required. Treatment planning is based on generating a 3D model of the organ and target tissue subject to electroporation (i.e. tumor nodules. The generation of the 3D model is done by segmentation algorithms. We implemented and evaluated three automatic liver segmentation algorithms: region growing, adaptive threshold, and active contours (snakes. The algorithms were optimized using a seven-case dataset manually segmented by the radiologist as a training set, and finally validated using an additional four-case dataset that was previously not included in the optimization dataset. The presented results demonstrate that patient's medical images that were not included in the training set can be successfully segmented using our three algorithms. Besides electroporation-based treatments, these algorithms can be used in applications where automatic liver segmentation is required.

  2. Minimally invasive liver resection to obtain tumor-infiltrating lymphocytes for adoptive cell therapy in patients with metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Alvarez-Downing Melissa M

    2012-06-01

    Full Text Available Abstract Background Adoptive cell therapy (ACT with tumor-infiltrating lymphocytes (TIL in patients with metastatic melanoma has been reported to have a 56% overall response rate with 20% complete responders. To increase the availability of this promising therapy in patients with advanced melanoma, a minimally invasive approach to procure tumor for TIL generation is warranted. Methods A feasibility study was performed to determine the safety and efficacy of laparoscopic liver resection to generate TIL for ACT. Retrospective review of a prospectively maintained database identified 22 patients with advanced melanoma and visceral metastasis (AJCC Stage M1c who underwent laparoscopic liver resection between 1 October 2005 and 31 July 2011. The indication for resection in all patients was to receive postoperative ACT with TIL. Results Twenty patients (91% underwent resection utilizing a closed laparoscopic technique, one required hand-assistance and another required conversion to open resection. Median intraoperative blood loss was 100 mL with most cases performed without a Pringle maneuver. Median hospital stay was 3 days. Three (14% patients experienced a complication from resection with no mortality. TIL were generated from 18 of 22 (82% patients. Twelve of 15 (80% TIL tested were found to have in vitro tumor reactivity. Eleven patients (50% received the intended ACT. Two patients were rendered no evidence of disease after surgical resection, with one undergoing delayed ACT with generated TIL after relapse. Objective tumor response was seen in 5 of 11 patients (45% who received TIL, with one patient experiencing an ongoing complete response (32+ months. Conclusions Laparoscopic liver resection can be performed with minimal morbidity and serve as an effective means to procure tumor to generate therapeutic TIL for ACT to patients with metastatic melanoma.

  3. Radiofrequency thermal ablation (RFA) of liver tumors: open surgical or percutaneous approach?

    Science.gov (United States)

    Crucitti, A; Danza, F M; Pirulli, P G V; Antinori, A; Antonacci, V; La Greca, A; Bock, E; Magistrelli, P

    2004-11-01

    RFA was used to ablate 81 liver lesions: 61 liver metastases and 20 hepatomas. An open surgical approach was adopted in 19 instances (27.5%), 12 of which were simultaneously treated for associated diseases, and percutaneous treatment was adopted in 50 instances (72.5%). The CT liver control at 6 months showed a complete necrosis in 50 lesions (66.3%). The advantages of the percutaneous approach include less invasiveness, reduced postoperative pain, shorter hospitalization, reduced costs and less discomfort in repeating the procedure. In conclusion, radiofrequency liver nodule ablation could be considered, today, as one of the promising and versatile techniques for loco-regional liver cancer control.

  4. Fusion of intravenous contrast-enhanced C-arm CT and pretreatment imaging for ablation margin assessment of liver tumors: A preliminary study

    Directory of Open Access Journals (Sweden)

    Jin Iwazawa

    2012-01-01

    Full Text Available The aim of this preliminary study was to evaluate the feasibility of assessing ablation margins after radiofrequency ablation (RFA of liver tumors from fusion images of post-treatment C-arm computed tomography (CT images fused to pretreatment images. Five patients with liver tumors underwent RFA. Intravenous contrast-enhanced C-arm CT images were obtained for all patients immediately after RFA, and multi-detector CT (MDCT images were obtained 3-7 days later. The C-arm CT and MDCT images were fused to pretreatment images using a multimodality image fusion software. The minimum ablation margins were assessed in the C-arm CT and MDCT fusion images. Ablation margins after RFA of liver tumors can be measured using intravenous contrast-enhanced C-arm CT images fused with pretreatment images. This technique has the potential for use in the intra-procedural assessment of liver tumor ablation.

  5. Erlotinib in Treating Patients With Solid Tumors and Liver or Kidney Dysfunction

    Science.gov (United States)

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Primary Hepatocellular Carcinoma; Adult Subependymoma; Advanced Adult Primary Liver Cancer; Advanced Malignant Mesothelioma; Male Breast Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Brain Tumor; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Malignant Mesothelioma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Pancreatic Cancer; Recurrent Prostate Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage II Esophageal Cancer; Stage II Pancreatic Cancer; Stage III Esophageal Cancer

  6. Critical Role of Myeloid-Derived Suppressor Cells in Tumor-Induced Liver Immune Suppression through Inhibition of NKT Cell Function

    Science.gov (United States)

    Zhang, Hongru; Li, Zheng; Wang, Li; Tian, Gaofei; Tian, Jun; Yang, Zishan; Cao, Guangchao; Zhou, Hong; Zhao, Liqing; Wu, Zhenzhou; Yin, Zhinan

    2017-01-01

    Metastasis followed by the tumor development is the primary cause of death for cancer patients. However, the underlying molecular mechanisms of how the growth of tumor resulted in the immune suppression, especially at the blood-enriched organ such as liver, were largely unknown. In this report, we studied the liver immune response of tumor-bearing (TB) mice using concanavalin A (Con A)-induced hepatitis model. We demonstrated that TB mice displayed an immune suppression phenotype, with attenuated alanine aminotransferase levels and liver damage upon Con A treatment. We also elucidated that large amounts of myeloid-derived suppressor cells (MDSCs) being influx into the liver in TB mice and these MDSCs were essential for liver immune suppression through both depletion and reconstitution approaches. We further determined that these MDSCs selectively suppressed the IFN-γ production deriving from NKT cells through membrane-bound transforming growth factor β (TGF-β). Finally, we defined a tumor-derived TGF-β-triggered CXCL1/2/5- and CXCR2-dependent recruitment of MDSC into the liver. In summary, our results defined a novel mechanism of liver immune suppression triggered by growing living tumor and provided possible therapeutic targets against these MDSCs.

  7. Feedback control of temperature evolution in rabbit kidney in vivo using MRI guided focused ultrasound. Application to renal VX2 carcinoma ablation

    Science.gov (United States)

    Delemazure, A. S.; Salomir, R.; Grenier, N.; Palussière, J.; Deminière, C.; Mougenot, C.; Moonen, C. W.

    2005-03-01

    A significant number of patients with small renal tumours may get benefit from in situ thermo-ablation techniques. Focused ultrasound is a non-invasive approach which offers excellent flexibility. On the other hand, real time MR thermometry is a valuable tool for monitoring and controlling therapy. In this study, coupling of focused ultrasound with PRF-based, respiratory-gated MR thermometry was used to provide temperature feedback control for local hyperthermia in the rabbit kidney. Two heating protocols were initially used in healthy kidneys (medulla and cortex): 1. fixed focal point heating; 2. spiral trajectories of the focal point. Further, five VX2 renal carcinomas were treated with multiple focal point heating in each tumour. Post-treatment MRI follow up and post mortem histology were performed. The shape and size of the lesions (MRI, histology) were compared to the calculated thermal dose map. The standard deviation of the MR thermometry ranged from 0.5°C to 1°C. The temperature controller matched the objective curve with approximately 1°C precision (fixed focal point mode). Several technical and physiological difficulties for spiral heating could not be overcome with the available setup. Thermal ablation with temperature feedback control in healthy and tumour bearing kidney was demonstrated to be feasible and effective, despite specific challenges (deep seated organ, respiratory motion, high blood perfusion).

  8. Structural and magnetic properties in the quantum S=1/2 dimer systems Ba3(Cr1-xVx)2O8 with site disorder

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Tao [ORNL; Zhu, L. Y. [Argonne National Laboratory (ANL); Ke, X. [Michigan State University, East Lansing; Garlea, Vasile O [ORNL; Qiu, Y. [National Institute of Standards and Technol/University of Maryland, College Park; Nambu, Y. [Tohoku University, Sendai, Japan; Yoshizawa, H. [University of Tokyo, Tokyo, Japan; Zhu, M. [Michigan State University, East Lansing; Granroth, Garrett E [ORNL; Savici, Andrei T [ORNL; Gai, Zheng [ORNL; Zhou, H. D. [Department of Physics and Astronomy, University of Tennessee

    2013-01-01

    We report a comprehensive study of the DC susceptibility, specific heat, neutron diffraction, and inelastic neutron scattering measurements on the polycrystalline Ba3(Cr1-xVx)2O8 samples, where x=0, 0.06, 0.15, and 0.53. A Jahn-Teller structure transition occurs for x=0, 0.06, and 0.15 samples and the transition temperature is reduced upon vanadium substitution from 70(2) K at x=0 to 60(2) K at x=0.06 and 0.15. The structure becomes less distorted as x increases and such transition disappears at x=0.53. The observed magnetic excitation spectrum indicates that the singlet ground state remains unaltered and spin gap energy =1.3(1) meV is identical within the instrument resolution for all x. In addition, the dispersion bandwidth W decreases with increase of x. At x=0.53, W is reduced to 1.4(1) meV from 2.0(1) meV at x=0.

  9. Radiofrequency ablation of malignant liver tumors: use of a volumetric necrosis-tumor ratio for local control; Radiofrequenzablation von malignen Lebertumoren: Erlaubt ein volumetrischer Nekrose-/Tumor-Quotient eine Vorhersage zur lokalen Tumorkontrolle?

    Energy Technology Data Exchange (ETDEWEB)

    Kuehl, H. [Inst. fuer Diagnostische und Interventionelle Radiologie, Universitaetsklinik Essen (Germany); Stattaus, J.; Antoch, G.; Forsting, M. [Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie, Universitaetsklinik Essen (Germany); Kuehl, B. [Klinik fuer Strahlentherapie, Universitaetsklinik Essen (Germany); Boes, T. [Inst. fuer Medizinische Informatik, Biometrie und Epidemiologie, Universitaetsklinik Essen (Germany); Frilling, A. [Klinik fuer Allgemein-, Viszeral- und Transplantationschirurgie, Universitaetsklinik Essen (Germany)

    2006-12-15

    Purpose: Sufficient safety margins are essential for preventing local tumor recurrence after radiofrequency ablation RFA of malignant liver tumors. The aim was to determine the initial tumor volume, ablation necrosis volume, and the necrosis-tumor quotient in order to compare these parameters with the rate of local control during follow-up. Materials and Methods: 35 patients with 53 tumor nodules (29 colorectal metastases and 24 HCC nodules) were enrolled. RFA procedures were performed under CT guidance with intravenous conscious sedation. Tumor volumes were measured based on CT data sets and the necrosis volume was assessed using the sum-of-area method. A volumetric necrosis/tumor quotient (NTQ) was calculated for all lesions. Follow-up examinations were performed after 3, 6, and 12 months and then on a yearly basis to identify local recurrent tumors. Results: The CRC metastases and HCC nodules had a median tumor volume of 8.3 ml and 7.4 ml, respectively. The mean ablation volumes were 37.6 ml and 29.5 ml, respectively. This resulted in a median NTQ of 3.9 for metastases and 3.4 for HCC. The follow-up (mean time 18 months) revealed local tumor recurrence in 16 of 29 (55%) metastases and 10 of 24 (42%) HCC nodules. In lesions with local recurrence, the initial tumor volume was significantly greater and the NTQ was significantly smaller. A threshold value of 3.4 for NTQ has the highest predictive value for local tumor recurrence. (orig.)

  10. Imaging findings of rare tumors or tumor-like lesions in liver grafts after liver transplantation%移植肝少见肿瘤或肿瘤样病变的影像学表现

    Institute of Scientific and Technical Information of China (English)

    陈炳辉; 谢佩怡; 全力; 谢斯栋; 孟晓春; 单鸿

    2014-01-01

    Objective To investigate the imaging findings of rare tumors or tumor-like lesions in liver grafts after liver transplantation.Methods Imaging data of 4 patients with rare tumors or tumor-like lesions in the liver grafts of patients after liver transplantation from December 2006 to August 2013 in the Third Affiliated Hospital of Sun Yat-sen University were reviewed.Findings of computerized tomography ( CT ) and ( or ) magnetic resonance imaging ( MRI) plain scan and dynamic enhanced MRI of liver lesions in these patients were analyzed specially.Results In the 4 patients, 3 cases were misdiagnosed , including undifferentiated liver sarcoma , secondary lymphoma and eosinophilic granuloma.One case was diagnosed correctly with hepatic metastases of gallbladder carcinoma.The undifferentiated liver sarcomas appeared as cystic and solid space occupying masses with significant and persistent enhancement in the surrounding solid and separating parts .No enhancement was observed in the cystic parts , which increased rapidly in a short term.No edema area around the lesions was observed , but many calcifications were detected.The secondary hepatic lymphoma appeared as intrahepatic multiple nodules , most of which presented uniform signal intensity with moderate enhancement in every phase.No intrahepatic vascular invasion was observed but extrahepatic lymphadenectasis was detected .Bleeding was observed in a few lesions.The liver eosinophilic granuloma appeared as multiple liver lesions with variable signal intensity and enhancement modes , which suggested that the lesions were consisted of variety of elements and in the different disease stages.Most of the lesions were observed with progressive circled enhancement.The recurrence of gallbladder carcinoma and hepatic metastasis after liver transplantation appeared as a intrahepatic hypodensity lesion with slight enhancement in arterial phase and slight hypodensity in portal phase.Retroperitoneal lymph nodes were observed

  11. Assessment of metastatic liver disease in patients with primary extrahepatic tumors by contrast-enhanced sonography versus CT and MRI

    Institute of Scientific and Technical Information of China (English)

    Christoph F Dietrich; Wolfgang Blank; Matthijs Oudkerk; Dietbert Hahn; Christian Greis; Wolfgang Kratzer; Deike Strobel; Etienne Danse; Robert Fessl; Alfred Bunk; Udo Vossas; Karlheinz Hauenstein; Wilhelm Koch

    2006-01-01

    AIM: To evaluate contrast-enhanced ultrasonography (CEUS) using SonoVue(R) in the detection of liver metastases in patients with known extrahepatic primary tumors versus the combined gold standard comprising CT,MRI and clinical/histological data.METHODS: It is an international multicenter study, and there were 12 centres and 125 patients (64 males, 61 females, aged 59 ± 11 years) involved, with 102 patients per protocol. Primary tumors were colorectal in 35%,breast in 27%, pancreatic in 17% and others in 21%.CEUS using SonoVue(R) was employed with a low-mechanical-index technique and contrast-specific software using Siemens Elegra, Philips HDI 5000 and Acuson Sequoia;continuous scanning for at least five minutes.RESULTS: CEUS with SonoVue(R) increased significantly the number of focal liver lesions detected versus unenhanced sonography. In 31.4% of the patients, more lesions were found after contrast enhancement. The total numbers of lesions detected were comparable with CEUS (55), triple-phase spiral CT (61) and MRI with a liverspecific contrast agent (53). Accuracy of detection of metastatic disease (i.e. at least one metastatic lesion) was significantly higher for CEUS (91.2%) than for unenhanced sonography (81.4%) and was similar to that of triple-phase spiral CT (89.2%). In 53 patients whose CEUS examination was negative, a follow-up examination 3-6 months later confirmed the absence of metastatic lesions in 50 patients (94.4 %).CONCLUSION: CEUS is proved to be reliable in the detection of liver metastases in patients with known extrahepatic primary tumors and suspected liver lesions.

  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. Differential diagnosis between metastatic tumors and nonsolid benign lesions of the liver using ferucarbotran-enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Higashihara, Hiroki [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 5650871 (Japan)], E-mail: h-higashihara@radiol.med.osaka-u.ac.jp; Murakami, Takamichi [Department of Radiology, Kinki University School of Medicine 377-2 Oonohigashi, Osakasayama, Osaka 5898511 (Japan); Kim, Tonsok; Hori, Masatoshi; Onishi, Hiromitsu [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 5650871 (Japan); Nakata, Saki [Department of Radiology, Toyonaka Municipal Hospital, 4-14-1 Shibahara Chou, Toyonaka, Osaka 5608565 (Japan); Osuga, Keigo; Tomoda, Kaname; Nakamura, Hironobu [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 5650871 (Japan)

    2010-01-15

    Purpose: To evaluate ability of ferucarbotran-enhanced MR imaging (MRI) in differentiating metastases from nonsolid benign lesions of the liver according to signal-intensity characteristics. Materials and methods: Sixty-six consecutive patients, who had 138 focal hepatic lesions (26 cysts, 11 hemangiomas, and 101 metastases), underwent ferucarbotran-enhanced MRI. The signal-intensity pattern of each kind of lesion relative to the liver parenchyma on ferucarbotran-enhanced T2* and heavily T1-weighted gradient-echo images were assessed and categorized into the following three categories: high-intensity and iso-intensity, respectively (category A), high and low (category B), and iso- and low-intensity (category C). For category B, lesions were subdivided into two groups based on single-shot half-Fourier RARE images: category B1 (not significantly high-intensity) and category B2 (significantly high-intensity). Results: Category A had 11 hemangiomas and 2 metastatic tumors, category B1 had 97 metastatic tumors, category B2 had 2 metastatic tumors and 9 cysts, and category C had 17 cysts. When a tumor with a signal intensity of category A was considered to be hemangioma, category B1 metastasis, and category B2 and C cyst, the diagnostic accuracy for differentiating these lesions was 97% (134/138). Conclusion: The combination of signal-intensity pattern on ferucarbotran-enhanced T2*- and heavily T1-weighted gradient-echo MRI has ability to differentiate liver metastases from nonsolid benign lesions. However, T2-weighted single-shot half-Fourier RARE imaging should also be employed to achieve better performance.

  14. Hypofractionated stereotactic body radiotherapy for primary and metastatic liver tumors using the novalis image-guided system: preliminary results regarding efficacy and toxicity.

    Science.gov (United States)

    Iwata, Hiromitsu; Shibamoto, Yuta; Hashizume, Chisa; Mori, Yoshimasa; Kobayashi, Tatsuya; Hayashi, Naoki; Kosaki, Katsura; Ishikawa, Tetsuya; Kuzuya, Teiji; Utsunomiya, Setsuo

    2010-12-01

    www.tcrt.org The purpose of this study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for primary and metastatic liver tumors using the Novalis image-guided radiotherapy system. After preliminarily treating liver tumors using the Novalis system from July 2006, we started a protocol-based study in February 2008. Eighteen patients (6 with primary hepatocellular carcinoma and 12 with metastatic liver tumor) were treated with 55 or 50 Gy, depending upon their planned dose distribution and liver function, delivered in 10 fractions over 2 weeks. Four non-coplanar and three coplanar static beams were used. Patient age ranged from 54 to 84 years (median: 72 years). The Child-Pugh classification was Grade A in 17 patients and Grade B in 1. Tumor diameter ranged from 12 to 35 mm (median: 23 mm). Toxicities were evaluated according to the Common Terminology Criteria of Adverse Events version 4.0, and radiation-induced liver disease (RILD) was defined by Lawrence's criterion. The median follow-up period was 14.5 months. For all patients, the 1-year overall survival and local control rates were 94% and 86%, respectively. A Grade 1 liver enzyme change was observed in 5 patients, but no RILD or chronic liver dysfunction was observed. SBRT using the Novalis image-guided system is safe and effective for treating primary and metastatic liver tumors. Further investigation of SBRT for liver tumors is warranted. In view of the acceptable toxicity observed with this protocol, we have moved to a new protocol to shorten the overall treatment time and escalate the dose.

  15. C-arm CT for chemo-embolization of liver tumors; C-Arm-CT bei der Chemoembolisation von Lebertumoren

    Energy Technology Data Exchange (ETDEWEB)

    Huppert, P.E. [Klinikum Darmstadt, Institut fuer Diagnostische und Interventionelle Radiologie, Darmstadt (Germany); Firlbeck, G. [Universitaet Tuebingen, Klinik fuer Dermatologie, Tuebingen (Germany); Meissner, O.A. [Siemens AG, Forchheim, Healthcare Sector, Forchheim (Germany); Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Institut fuer Klinische Radiologie, Muenchen (Germany); Wietholtz, H. [Klinikum Darmstadt, Medizinische Klinik II, Darmstadt (Germany)

    2009-09-15

    Local efficacy of transarterial chemo-embolization (TACE) is enhanced if selective treatment is performed. Selectivity of TACE mainly depends on vascular anatomy but also on the identification and catheterization of tumor feeding arteries. Correlation of vascular territories and target tumor volume in angiographic projection images is more difficult if tumors are not hypervascularized and contrast of liver parenchyma is inhomogeneous. C-arm CT offers the option of selective perfusion imaging via tumor-feeding arteries. This allows the comparison of perfusion images and baseline cross-sectional imaging to evaluate if tumors are covered completely by local treatment and to change the catheter position if necessary. Furthermore the uptake of embolization material, such as lipiodol can be checked by C-arm CT. In a prospective study of 75 TACE of liver tumors and liver metastases we evaluated the appropriateness of 85 catheter positions ready for delivery by perfusion C-arm CT and compared the diagnostic confidence of angiography and perfusion C-arm CT in terms of judgment of correct catheter position for the planned treatment. Diagnostic confidence was improved by perfusion C-arm CT in 55% of cases and in 11 cases (13%) catheter positions were inappropriate and had to be corrected. The reasons for catheter repositioning were incomplete coverage of the target tumor by perfusion volume (mismatch) in 6 cases, inappropriate perfusion of adjacent liver parenchyma in 2 cases and non-selective tumor perfusion via collateral arteries in 3 cases. C-arm CT allowed sufficient visualization of uptake of lipiodol in all cases evaluated. The diagnostic benefit of C-arm CT increases if tumors are treated more selectively, are not strongly hypervascular, are located centrally and if the enhancement of liver parenchyma is inhomogeneous. C-arm CT causes additional working time and contrast load, which is relatively low compared to angiography. Radiation exposure of 151 {mu}Gy per C

  16. Thiamethoxam induced mouse liver tumors and their relevance to humans. Part 1: mode of action studies in the mouse.

    Science.gov (United States)

    Green, Trevor; Toghill, Alison; Lee, Robert; Waechter, Felix; Weber, Edgar; Noakes, James

    2005-07-01

    Thiamethoxam, a neonicotinoid insecticide, which is not mutagenic either in vitro or in vivo, caused an increased incidence of liver tumors in mice when fed in the diet for 18 months at concentrations in the range 500 to 2500 ppm. A number of dietary studies of up to 50 weeks duration have been conducted in order to identify the mode of action for the development of the liver tumors seen at the end of the cancer bioassay. Both thiamethoxam and its major metabolites have been tested in these studies. Over the duration of a 50-week thiamethoxam dietary feeding study in mice, the earliest change, within one week, is a marked reduction (by up to 40%) in plasma cholesterol. This was followed 10 weeks later by evidence of liver toxicity including single cell necrosis and an increase in apoptosis. After 20 weeks there was a significant increase in hepatic cell replication rates. All of these changes persisted from the time they were first observed until the end of the study at 50 weeks. They occurred in a dose-dependent manner and were only observed at doses (500, 1250, 2500 ppm) where liver tumors were increased in the cancer bioassay. There was a clear no-effect level of 200 ppm. The changes seen in this study are consistent with the development of liver cancer in mice and form the basis of the mode of action. When the major metabolites of thiamethoxam, CGA322704, CGA265307, and CGA330050 were tested in dietary feeding studies of up to 20 weeks duration, only metabolite CGA330050 induced the same changes as those seen in the liver in the thiamethoxam feeding study. It was concluded that thiamethoxam is hepatotoxic and hepatocarcinogenic as a result of its metabolism to CGA330050. Metabolite CGA265307 was also shown to be an inhibitor of inducible nitric oxide synthase and to increase the hepatotoxicity of carbon tetrachloride. It is proposed that CGA265307, through its effects on nitric oxide synthase, exacerbates the toxicity of CGA330050 in thiamethoxam treated mice.

  17. Cushing syndrome as presenting symptom of calcifying nested stromal-epithelial tumor of the liver in an adolescent boy: a case report

    NARCIS (Netherlands)

    Weeda, V.B.; Reuver, P.R.; Bras, H.; Zsiros, J.; Lamers, W.H.; Aronson, D.C.

    2016-01-01

    BACKGROUND: Ectopic adrenocorticotropic hormone-producing primary liver tumors are rare, especially in children. We report the case of an adolescent boy of mixed Dutch and Moroccan descent with an adrenocorticotropic hormone-producing calcifying nested stromal-epithelial tumor with long-term

  18. Celecoxib and Ibuprofen Restore the ATP Content and the Gluconeogenesis Activity in the Liver of Walker-256 Tumor-Bearing Rats

    Directory of Open Access Journals (Sweden)

    Camila Oliveira de Souza

    2015-07-01

    Full Text Available Background/Aims: The main purpose of this study was to investigate the effects of celecoxib and ibuprofen, both non-steroidal anti-inflammatory drugs (NSAIDs, on the decreased gluconeogenesis observed in liver of Walker-256 tumor-bearing rats. Methods: Celecoxib and ibuprofen (both at 25 mg/Kg were orally administered for 12 days, beginning on the same day when the rats were inoculated with Walker-256 tumor cells. Results: Celecoxib and ibuprofen treatment reversed the reduced production of glucose, pyruvate, lactate and urea from alanine as well as the reduced production of glucose from pyruvate and lactate in perfused liver from tumor-bearing rats. Besides, celecoxib and ibuprofen treatment restored the decreased ATP content, increased triacylglycerol levels and reduced mRNA expression of carnitine palmitoyl transferase 1 (CPT1, while ibuprofen treatment restored the reduced mRNA expression of peroxisome proliferator-activated receptor alpha (PPARα in the liver of tumor-bearing rats. Both treatments tended to decrease TNFα, IL6 and IL10 in the liver of tumor-bearing rats. Finally, the treatment with celecoxib, but not with ibuprofen, reduced the growth of Walker-256 tumor. Conclusion: Celecoxib and ibuprofen restored the decreased gluconeogenesis in the liver of Walker-256 tumor-bearing rats. These effects did not involve changes in tumor growth and probably occurred by anti-inflammatory properties of these NSAIDs, which increased expression of genes associated with fatty acid oxidation (PPARα and CPT1 and consequently the ATP production, normalizing the energy status in the liver of tumor-bearing rats.

  19. Liver tumor formation by a mutant retinoblastoma protein in the transgenic mice is caused by an upregulation of c-Myc target genes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bo; Hikosaka, Keisuke; Sultana, Nishat; Sharkar, Mohammad Tofael Kabir [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Noritake, Hidenao [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Kimura, Wataru; Wu, Yi-Xin [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Kobayashi, Yoshimasa [Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Uezato, Tadayoshi [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Miura, Naoyuki, E-mail: nmiura@hama-med.ac.jp [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Fifty percent of the mutant Rb transgenic mice produced liver tumors. Black-Right-Pointing-Pointer In the tumor, Foxm1, Skp2, Bmi1 and AP-1 mRNAs were up-regulated. Black-Right-Pointing-Pointer No increase in expression of the Myc-target genes was observed in the non-tumorous liver. Black-Right-Pointing-Pointer Tumor formation depends on up-regulation of the Myc-target genes. -- Abstract: The retinoblastoma (Rb) tumor suppressor encodes a nuclear phosphoprotein that regulates cellular proliferation, apoptosis and differentiation. In order to adapt itself to these biological functions, Rb is subjected to modification cycle, phosphorylation and dephosphorylation. To directly determine the effect of phosphorylation-resistant Rb on liver development and function, we generated transgenic mice expressing phosphorylation-resistant human mutant Rb (mt-Rb) under the control of the rat hepatocyte nuclear factor-1 gene promoter/enhancer. Expression of mt-Rb in the liver resulted in macroscopic neoplastic nodules (adenomas) with {approx}50% incidence within 15 months old. Interestingly, quantitative reverse transcriptase-PCR analysis showed that c-Myc was up-regulated in the liver of mt-Rb transgenic mice irrespective of having tumor tissues or no tumor. In tumor tissues, several c-Myc target genes, Foxm1, c-Jun, c-Fos, Bmi1 and Skp2, were also up-regulated dramatically. We determined whether mt-Rb activated the Myc promoter in the HTP9 cells and demonstrated that mt-Rb acted as an inhibitor of wild-type Rb-induced repression on the Myc promoter. Our results suggest that continued upregulation of c-Myc target genes promotes the liver tumor formation after about 1 year of age.

  20. Liver Cancer and Its Tumor Microenvironment: the Role of Mesenchymal Stromal Cells and SMADs

    NARCIS (Netherlands)

    P.Y. Hernanda (Pratika)

    2014-01-01

    markdownabstract__Abstract__ Liver cancer is one of most devastating malignancies. Hepatocellular carcinoma (HCC) accounts for >90% of primary liver malignancies and is the third leading cause of cancer-related deaths worldwide. Major risk factors for hepatocellular carcinoma include infection with

  1. Cushing syndrome as presenting symptom of calcifying nested stromal-epithelial tumor of the liver in an adolescent boy: a case report.

    Science.gov (United States)

    Weeda, V B; de Reuver, Ph R; Bras, H; Zsíros, J; Lamers, W H; Aronson, D C

    2016-06-16

    Ectopic adrenocorticotropic hormone-producing primary liver tumors are rare, especially in children. We report the case of an adolescent boy of mixed Dutch and Moroccan descent with an adrenocorticotropic hormone-producing calcifying nested stromal-epithelial tumor with long-term follow-up. Thus far, only two such cases have been reported. A 16-year-old boy of mixed Dutch and Moroccan descent presented with Cushing syndrome and a palpable abdominal mass. A calcifying nested stromal-epithelial tumor was diagnosed. Postoperatively, his plasma adrenocorticotropic hormone concentration normalized. He remains in complete remission 13 years after tumor resection. Calcifying nested stromal-epithelial tumor should be in the differential diagnosis of liver tumors, especially if associated with Cushing syndrome as significant morbidity and mortality may be associated. Literature on the topics involved is comprehensively reviewed.

  2. Poly(γ-glutamic acid)-coated lipoplexes loaded with Doxorubicin for enhancing the antitumor activity against liver tumors

    Science.gov (United States)

    Qi, Na; Tang, Bo; Liu, Guang; Liang, Xingsi

    2017-05-01

    The study was to develop poly-γ-glutamic acid (γ-PGA)-coated Doxorubicin (Dox) lipoplexes that enhance the antitumor activity against liver tumors. γ-PGA-coated lipoplexes were performed by electrostatistically attracting to the surface of cationic charge liposomes with anionic γ-PGA. With the increasing of γ-PGA concentration, the particle size of γ-PGA-coated Dox lipoplexes slightly increased, the zeta potential from positive shifted to negative, and the entrapment efficiency (EE) were no significant change. The release rate of γ-PGA-coated Dox lipoplexes slightly increased at acidic pH, the accelerated Dox release might be attributed to greater drug delivery to tumor cells, resulting in a higher antitumor activity. Especially, γ-PGA-coated Dox lipoplexes exhibited higher cellular uptake, significant in vitro cytotoxicity in HepG2 cells, and improved in vivo antitumor efficacy toward HepG2 hepatoma-xenografted nude models in comparison with Dox liposomes and free Dox solution. In addition, the analysis results via flow cytometry showed that γ-PGA-coated Dox lipoplexes induce S phase cell cycle arrest and significantly increased apoptosis rate of HepG2 cells. In conclusion, the presence of γ-PGA on the surface of Dox lipoplexes enhanced antitumor effects of liver tumors.

  3. Hepatic perfusion in a tumor model using DCE-CT: an accuracy and precision study

    Science.gov (United States)

    Stewart, Errol E.; Chen, Xiaogang; Hadway, Jennifer; Lee, Ting-Yim

    2008-08-01

    In the current study we investigate the accuracy and precision of hepatic perfusion measurements based on the Johnson and Wilson model with the adiabatic approximation. VX2 carcinoma cells were implanted into the livers of New Zealand white rabbits. Simultaneous dynamic contrast-enhanced computed tomography (DCE-CT) and radiolabeled microsphere studies were performed under steady-state normo-, hyper- and hypo-capnia. The hepatic arterial blood flows (HABF) obtained using both techniques were compared with ANOVA. The precision was assessed by the coefficient of variation (CV). Under normo-capnia the microsphere HABF were 51.9 ± 4.2, 40.7 ± 4.9 and 99.7 ± 6.0 ml min-1 (100 g)-1 while DCE-CT HABF were 50.0 ± 5.7, 37.1 ± 4.5 and 99.8 ± 6.8 ml min-1 (100 g)-1 in normal tissue, tumor core and rim, respectively. There were no significant differences between HABF measurements obtained with both techniques (P > 0.05). Furthermore, a strong correlation was observed between HABF values from both techniques: slope of 0.92 ± 0.05, intercept of 4.62 ± 2.69 ml min-1 (100 g)-1 and R2 = 0.81 ± 0.05 (P liver diseases.

  4. Adjuvant treatment with tumor-targeting Salmonella typhimurium A1-R reduces recurrence and increases survival after liver metastasis resection in an orthotopic nude mouse model.

    Science.gov (United States)

    Murakami, Takashi; Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2015-12-01

    Colon cancer liver metastasis is often the lethal aspect of this disease. Well-isolated metastases are candidates for surgical resection, but recurrence is common. Better adjuvant treatment is therefore needed to reduce or prevent recurrence. In the present study, HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used to establish liver metastases in nude mice. Mice with a single liver metastasis were randomized into bright-light surgery (BLS) or the combination of BLS and adjuvant treatment with tumor-targeting S. typhimurium A1-R. Residual tumor fluorescence after BLS was clearly visualized at high magnification by fluorescence imaging. Adjuvant treatment with S. typhimurium A1-R was highly effective to increase survival and disease-free survival after BLS of liver metastasis. The results suggest the future clinical potential of adjuvant S. typhimurium A1-R treatment after liver metastasis resection.

  5. One-stage laparoscopic resection for a large gastric gastrointestinal stromal tumor and synchronous liver metastases following preoperative imatinib therapy: A case report

    OpenAIRE

    2013-01-01

    Laparoscopic partial gastrectomy without lymph node dissection has been accepted worldwide for the treatment of small gastric gastrointestinal stromal tumors (GISTs). However, the role of laparoscopic surgery in the treatment of large gastric GISTs remains under debate due to the risk of tumor spillage or rupture of the tumor capsule leading to peritoneal seeding. To the best of our knowledge, one-stage laparoscopic resection for a large gastric GIST and synchronous liver metastases following...

  6. Efficiency of high- and low-voltage pulse combinations for gene electrotransfer in muscle, liver, tumor, and skin

    DEFF Research Database (Denmark)

    André, F M; Gehl, J; Sersa, G;

    2008-01-01

    Gene electrotransfer is gaining momentum as an efficient methodology for nonviral gene transfer. In skeletal muscle, data suggest that electric pulses play two roles: structurally permeabilizing the muscle fibers and electrophoretically supporting the migration of DNA toward or across......, but not to liver; and (4) efficient gene electrotransfer was achieved with HV field strengths below the detectability thresholds for permeabilization; and (5) the lag time interval between the HV and LV pulses decreased sensitivity to the HV pulses, enabling a wider HV amplitude range. In conclusion, HV plus LV...... the permeabilized membrane. To investigate this further, combinations of permeabilizing short high-voltage pulses (HV; hundreds of V/cm) and mainly electrophoretic long low-voltage pulses (LV; tens of V/cm) were investigated in muscle, liver, tumor, and skin in rodent models. The following observations were made...

  7. Pathologic complete response confirmed by surgical resection for liver metastases of gastrointestinal stromal tumor after treatment with imatinib mesylate

    Institute of Scientific and Technical Information of China (English)

    Seiji Suzuki; Shotaro Maeda; Takashi Tajiri; Koji Sasajima; Masayuki Miyamoto; Hidehiro Watanabe; Tadashi Yokoyama; Hiroshi Maruyama; Takeshi Matsutani; Aimin Liu; Masaru Hosone

    2008-01-01

    A 39-year-old male underwent distal gastrectomy for a high grade gastrointestinal stromal tumor (GIST). Computed tomography (CT) and magnetic resonance imaging (MRI) 107 mo after the operation, revealed a cystic mass (14 cm in diameter) and a solid mass (9 cm in diameter) in the right and left lobes of the liver, respectively. A biopsy specimen of the solid mass showed a liver metastasis of GIST. The patient received imatinib mesylate (IM) treatment, 400mg/day orally. Following the IM treatment for a period of 35 mo, the patient underwent partial hepatectomy (S4+S5). The effect of IM on the metastatic lesions was interpreted as pathologic complete response (CR). Pathologically verified cases showing therapeutic efficacy of IM have been rarely reported.

  8. Is Antibiotic Prophylaxis for Percutaneous Radiofrequency Ablation (RFA) of Primary Liver Tumors Necessary? Results From a Single-Center Experience

    Energy Technology Data Exchange (ETDEWEB)

    Bhatia, Shivank S., E-mail: sbhatia1@med.miami.edu [University of Miami, Vascular/Interventional Radiology, Department of Radiology, Miller School of Medicine (United States); Spector, Seth, E-mail: sspector@med.miami.edu [University of Miami, Department of Surgery, VA Hospital (Veterans Affairs Medical Center) (United States); Echenique, Ana, E-mail: aechenique@med.miami.edu; Froud, Tatiana, E-mail: tfroud@med.miami.edu; Suthar, Rekha, E-mail: rsuthar@med.miami.edu; Lawson, Ivy, E-mail: i.lawson1@med.miami.edu; Dalal, Ravi, E-mail: rdalal@med.miami.edu [University of Miami, Vascular/Interventional Radiology, Department of Radiology, Miller School of Medicine (United States); Dinh, Vy, E-mail: vdinh@med.miami.edu [VA Hospital (Veterans Affairs Medical Center), Department of Medicine (United States); Yrizarry, Jose, E-mail: jyrizarr@med.miami.edu; Narayanan, Govindarajan, E-mail: gnarayanan@med.miami.edu [University of Miami, Vascular/Interventional Radiology, Department of Radiology, Miller School of Medicine (United States)

    2015-08-15

    PurposeThe purpose of this study was to evaluate need for antibiotic prophylaxis for radiofrequency ablation (RFA) of liver tumors in patients with no significant co-existing risk factors for infection.Materials and MethodsFrom January 2004 to September 2013, 83 patients underwent 123 percutaneous RFA procedures for total of 152 hepatocellular carcinoma (HCC) lesions. None of the patients had pre-existing biliary enteric anastomosis (BEA) or any biliary tract abnormality predisposing to ascending biliary infection or uncontrolled diabetes mellitus. No pre- or post-procedure antibiotic prophylaxis was provided for 121 procedures. Data for potential risk factors were reviewed retrospectively and analyzed for the frequency of infectious complications, including abscess formation.ResultsOne patient (1/121 (0.8 %) RFA sessions) developed a large segment 5 liver abscess/infected biloma communicating with the gallbladder 7 weeks after the procedure, successfully treated over 10 weeks with IV and PO antibiotic therapy and percutaneous catheter drainage. This patient did not receive any antibiotics prior to RFA. During the procedure, there was inadvertent placement of RFA probe tines into the gallbladder. No other infectious complications were documented.ConclusionThese data suggest that the routine use of prophylactic antibiotics for liver RFA is not necessary in majority of the patients undergoing liver ablation for HCC and could be limited to patients with high-risk factors such as the presence of BEA or other biliary abnormalities, uncontrolled diabetes mellitus, and large centrally located tumors in close proximity to central bile ducts. Larger randomized studies are needed to confirm this hypothesis.

  9. Image guided respiratory gated hypofractionated Stereotactic Body Radiation Therapy (H-SBRT) for liver and lung tumors: Initial experience

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    Wurm, R.E.; Gum, F.; Erbel, S. [Charite Campus Mitte, Berlin (Germany). Dept. of Radiation Oncology

    2006-09-15

    To evaluate our initial experience with image guided respiratory gated H-SBRT for liver and lung tumors. The system combines a stereoscopic x-ray imaging system (ExacTrac{sup R} X-Ray 6D) with a dedicated conformal stereotactic radiosurgery and radiotherapy linear accelerator (Novalis) and ExacTrac{sup R} Adaptive Gating for dynamic adaptive treatment. Moving targets are located and tracked by x-ray imaging of implanted fiducial markers defined in the treatment planning computed tomography (CT). The marker position is compared with the position in verification stereoscopic x-ray images, using fully automated marker detection software. The required shift for a correct, gated set-up is calculated and automatically applied. We present our acceptance testing and initial experience in patients with liver and lung tumors. For treatment planning CT and Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) as well as magnetic resonance imaging (MRI) taken at free breathing and expiration breath hold with internal and external fiducials present were used. Patients were treated with 8-11 consecutive fractions to a dose of 74.8-79.2 Gy. Phantom tests demonstrated targeting accuracy with a moving target to within {+-}1 mm. Inter- and intrafractional patient set-up displacements, as corrected by the gated set-up and not detectable by a conventional set-up, were up to 30 mm. Verification imaging to determine target location during treatment showed an average marker position deviation from the expected position of up to 4 mm on real patients. This initial evaluation shows the accuracy of the system and feasibility of image guided real-time respiratory gated H-SBRT for liver and lung tumors.

  10. Role of PINCH and its partner tumor suppressor Rsu-1 in regulating liver size and tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Shashikiran Donthamsetty

    Full Text Available Particularly interesting new cysteine-histidine-rich protein (PINCH protein is part of the ternary complex known as the IPP (integrin linked kinase (ILK-PINCH-Parvin-α complex. PINCH itself binds to ILK and to another protein known as Rsu-1 (Ras suppressor 1. We generated PINCH 1 and PINCH 2 Double knockout mice (referred as PINCH DKO mice. PINCH2 elimination was systemic whereas PINCH1 elimination was targeted to hepatocytes. The genetically modified mice were born normal. The mice were sacrificed at different ages after birth. Soon after birth, they developed abnormal hepatic histology characterized by disorderly hepatic plates, increased proliferation of hepatocytes and biliary cells and increased deposition of extracellular matrix. After a sustained and prolonged proliferation of all epithelial components, proliferation subsided and final liver weight by the end of 30 weeks in livers with PINCH DKO deficient hepatocytes was 40% larger than the control mice. The livers of the PINCH DKO mice were also very stiff due to increased ECM deposition throughout the liver, with no observed nodularity. Mice developed liver cancer by one year. These mice regenerated normally when subjected to 70% partial hepatectomy and did not show any termination defect. Ras suppressor 1 (Rsu-1 protein, the binding partner of PINCH is frequently deleted in human liver cancers. Rsu-1 expression is dramatically decreased in PINCH DKO mouse livers. Increased expression of Rsu-1 suppressed cell proliferation and migration in HCC cell lines. These changes were brought about not by affecting activation of Ras (as its name suggests but by suppression of Ras downstream signaling via RhoGTPase proteins. In conclusion, our studies suggest that removal of PINCH results in enlargement of liver and tumorigenesis. Decreased levels of Rsu-1, a partner for PINCH and a protein often deleted in human liver cancer, may play an important role in the development of the observed phenotype.

  11. Clinical utility and limitations of tumor-feeder detection software for liver cancer embolization

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    Iwazawa, Jin, E-mail: iwazawa.jin@nissay-hp.or.jp [Department of Radiology, Nissay Hospital, 6-3-8 Itachibori, Nishiku, Osaka 550-0012 (Japan); Ohue, Shoichi, E-mail: ponpoko_tanuki.1125@softbank.ne.jp [Department of Radiology, Komatsu Hospital, 11-6 Kawakatsucho, Neyagawa 572-8567 (Japan); Hashimoto, Naoko, E-mail: nhashimoto0316@gmail.com [Department of Radiology, Nissay Hospital, 6-3-8 Itachibori, Nishiku, Osaka 550-0012 (Japan); Muramoto, Osamu, E-mail: muramoto.osamu@nissay-hp.or.jp [Department of Gastroenterology, Nissay Hospital, 6-3-8 Itachibori, Nishiku, Osaka 550-0012 (Japan); Mitani, Takashi, E-mail: mitani.takashi@nissay-hp.or.jp [Department of Radiology, Nissay Hospital, 6-3-8 Itachibori, Nishiku, Osaka 550-0012 (Japan)

    2013-10-01

    Purpose: To evaluate the clinical utility and limitations of a computer software program for detecting tumor feeders of hepatocellular carcinoma (HCC) during transarterial chemoembolization (TACE). Materials and methods: Forty-six patients with 59 HCC nodules underwent nonselective digital subtraction angiography (DSA) and C-arm computed tomography (CT) in the same hepatic artery. C-arm CT data sets were analyzed using the software to identify potential tumor feeders during each TACE session. For DSA analysis, 3 radiologists were independently assigned to identify tumor feeders using the DSA images in a separate session. The sensitivity of the 2 techniques in detecting tumor feeders was compared, with TACE findings as the reference standard. Factors affecting the failure of the software to detect tumor feeders were assessed by univariate and multivariate analyses. Results: We detected 65 tumor feeders supplying 59 HCC nodules during TACE sessions. The sensitivity of the software to detect tumor feeders was significantly higher than that of the manual assessment using DSA (87.7% vs. 71.8%, P < 0.001). Multivariate analysis showed that a tumor feeder diameter of <1.0 mm (hazard ratio [HR], 56.3; P = 0.003) and lipiodol accumulation adjacent to the tumor (HR, 11.4; P = 0.044) were the significant predictors for failure to detect tumor feeders. Conclusion: The software analysis was superior to manual assessment with DSA in detecting tumor feeders during TACE for HCC. However, the capability of the software to detect tumor feeders was limited by vessel caliber and by prior lipiodol accumulation to the tumor.

  12. A novel three-dimensional print of liver vessels and tumors in hepatectomy.

    Science.gov (United States)

    Oshiro, Yukio; Mitani, Jun; Okada, Toshiyuki; Ohkohchi, Nobuhiro

    2017-04-01

    Creating a three-dimensional (3D)-printed liver model is costly, and the visibility of the inner structures is slightly hindered. We developed a novel structure that simultaneously solves both of these problems. The outer frames were set up along the liver surface. Our structure did not use the transparent loading material because this material increases the printing cost. Therefore, we were able to directly observe the inside of the structure. We performed hepatectomy using this novel 3D-printed liver model. Using this model, we were able to clearly simulate the resection line and safely perform the surgery. Our process was more cost effective, had a shorter production time, and improved the visibility than other processes. We developed a novel 3D-printed liver for hepatectomy, which made the procedure easier, reduced the production cost, and improved the visibility; this approach may be useful for future surgeries.

  13. Simultaneous laparoscopic resection of colorectal cancer and synchronous metastatic liver tumor.

    Science.gov (United States)

    Hayashi, Michihiro; Komeda, Koji; Inoue, Yoshihiro; Shimizu, Tetsunosuke; Asakuma, Mitsuhiro; Hirokawa, Fumitoshi; Okuda, Junji; Tanaka, Keitaro; Kondo, Keisaku; Tanigawa, Nobuhiko

    2011-01-01

    Laparoscopic colorectal resection has been applied to advanced colorectal cancer. Synchronous liver metastasis of colorectal cancer would be treated safely and effectively by simultaneous laparoscopic colorectal and hepatic resection. Seven patients with colorectal cancer and synchronous liver metastasis treated by simultaneous laparoscopic resection were analyzed retrospectively. Three patients received a hybrid operation using a small skin incision, 2 patients underwent hand-assisted laparoscopic surgery using a small incision produced for colonic anastomosis, and 2 patients were treated with pure laparoscopic resection. The mean total operation duration was 407 minutes, and mean blood loss was 207 mL. Negative surgical margins were achieved in all cases. Mean postoperative hospital stay was 16.4 days. No recurrence at the surgical margin was observed in the liver. For selected patients with synchronous liver metastasis of colorectal cancer, simultaneous laparoscopic resection is useful for minimizing operative invasiveness while maintaining safety and curability, with satisfying short- and long-term results.

  14. Semi-automatic liver tumor segmentation with hidden Markov measure field model and non-parametric distribution estimation.

    Science.gov (United States)

    Häme, Yrjö; Pollari, Mika

    2012-01-01

    A novel liver tumor segmentation method for CT images is presented. The aim of this work was to reduce the manual labor and time required in the treatment planning of radiofrequency ablation (RFA), by providing accurate and automated tumor segmentations reliably. The developed method is semi-automatic, requiring only minimal user interaction. The segmentation is based on non-parametric intensity distribution estimation and a hidden Markov measure field model, with application of a spherical shape prior. A post-processing operation is also presented to remove the overflow to adjacent tissue. In addition to the conventional approach of using a single image as input data, an approach using images from multiple contrast phases was developed. The accuracy of the method was validated with two sets of patient data, and artificially generated samples. The patient data included preoperative RFA images and a public data set from "3D Liver Tumor Segmentation Challenge 2008". The method achieved very high accuracy with the RFA data, and outperformed other methods evaluated with the public data set, receiving an average overlap error of 30.3% which represents an improvement of 2.3% points to the previously best performing semi-automatic method. The average volume difference was 23.5%, and the average, the RMS, and the maximum surface distance errors were 1.87, 2.43, and 8.09 mm, respectively. The method produced good results even for tumors with very low contrast and ambiguous borders, and the performance remained high with noisy image data.

  15. Carcinoid syndrome, acromegaly, and hypoglycemia due to an insulin-secreting neuroendocrine tumor of the liver.

    Science.gov (United States)

    Furrer, J; Hättenschwiler, A; Komminoth, P; Pfammatter, T; Wiesli, P

    2001-05-01

    We report a patient with a hepatic neuroendocrine tumor showing an extraordinary change of the tumor's humoral manifestations from a clinically documented extrapituitary acromegaly and a typical carcinoid syndrome toward a hyperinsulinemic hypoglycemia syndrome. At the primary manifestation of the tumor, an increased serum level of insulin-like growth factor I due to overproduction of GHRH and an increased urinary excretion of 5-hydroxyindoleacetic acid were found. The clinical manifestation of the GHRH excess was an arthralgia, which resolved completely after operative tumor debulking and normalization of insulin-like growth factor I and GHRH serum levels. The secretion of serotonin from the tumor resulted in a typical carcinoid syndrome including right-sided valvular heart disease. On the later course of the disease, the humoral manifestations of the tumor were supplemented by the secretion of insulin, leading to recurrent severe hyperinsulinemic hypoglycemia. The hepatic origin of hyperinsulinism was demonstrated by selective arterial calcium stimulation. Moreover, tumor cells revealed insulin and C-peptide immunoreactivity in the immunohistochemical analysis. The patient died 8 yr after the initial diagnosis of the tumor, and a carefully performed autopsy procedure confirmed the absence of any extrahepatic tumor manifestation.

  16. Evaluation of an anti-tumor necrosis factor therapeutic in a mouse model of Niemann-Pick C liver disease.

    Directory of Open Access Journals (Sweden)

    Melanie Vincent

    Full Text Available BACKGROUND: Niemann-Pick type C (NPC disease is a lysosomal storage disease characterized by the accumulation of cholesterol and glycosphingolipids. The majority of NPC patients die in their teen years due to progressive neurodegeneration; however, half of NPC patients also suffer from cholestasis, prolonged jaundice, and hepatosplenomegaly. We previously showed that a key mediator of NPC liver disease is tumor necrosis factor (TNF α, which is involved in both proinflammatory and apoptotic signaling cascades. In this study, we tested the hypothesis that blocking TNF action with an anti-TNF monoclonal antibody (CNTO5048 will slow the progression of NPC liver disease. METHODOLOGY/PRINCIPAL FINDINGS: Treatment of wild-type C57BL/6 mice with NPC1-specific antisense oligonucleotides led to knockdown of NPC1 protein expression in the liver. This caused classical symptoms of NPC liver disease, including hepatic cholesterol accumulation, hepatomegaly, elevated serum liver enzymes, and lipid laden macrophage accumulation. In addition, there was a significant increase in the number of apoptotic cells and a proliferation of stellate cells. Concurrent treatment of NPC1 knockdown mice with anti-TNF had no effect on the primary lipid storage or accumulation of lipid-laden macrophages. However, anti-TNF treatment slightly blunted the increase in hepatic apoptosis and stellate cell activation that was seen with NPC1 knockdown. CONCLUSIONS/SIGNIFICANCE: Current therapeutic options for NPC disease are limited. Our results provide proof of principle that pharmacologically blocking the TNF-α inflammatory cascade can slightly reduce certain markers of NPC disease. Small molecule inhibitors of TNF that penetrate tissues and cross the blood-brain barrier may prove even more beneficial.

  17. Lysophospholipid profile in serum and liver by high-fat diet and tumor induction in obesity-resistant BALB/c mice.

    Science.gov (United States)

    Kim, Hyang Yeon; Kim, Minhee; Park, Hye Min; Kim, Jiyoung; Kim, Eun Ji; Lee, Choong Hwan; Park, Jung Han Yoon

    2014-01-01

    Our previous study revealed that chronic consumption of a high-fat diet (HFD) stimulates colon cancer progression in obesity-resistant BALB/c mice. The aim of the present study was to investigate the significant alteration of metabolites caused by tumor progression and an HFD in the serum and liver in the same mouse model. Male BALB/c mice were fed either a control diet or a HFD for 20.5 wk. The syngeneic CT26 colon carcinoma cells were injected into the right rear flank of mice after 16 wk of feeding. Metabolites in serum and liver samples were analyzed by ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry-based metabolomics. HFD feeding and tumor injection induced changes in the choline-containing phospholipids, namely, phosphatidylcholines and lysophosphatidylcholines (lysoPCs), and lysophosphatidylethanolamines in the serum and liver. The majority of these metabolite changes were due to HFD feeding (11 in sera and 5 in livers) rather than tumors (3 in sera and 1 in livers). The HFD- and tumor-related metabolite alterations of phospholipids, especially lysoPCs, in the liver and serum of obesity-resistant mice, suggesting that the lysoPCs are potential biomarkers for the chronic consumption of HFD in nonobese individuals. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. An Oral Salmonella-Based Vaccine Inhibits Liver Metastases by Promoting Tumor-Specific T-Cell-Mediated Immunity in Celiac and Portal Lymph Nodes: A Preclinical Study.

    Science.gov (United States)

    Vendrell, Alejandrina; Mongini, Claudia; Gravisaco, María José; Canellada, Andrea; Tesone, Agustina Inés; Goin, Juan Carlos; Waldner, Claudia Inés

    2016-01-01

    Primary tumor excision is one of the most widely used therapies of cancer. However, the risk of metastases development still exists following tumor resection. The liver is a common site of metastatic disease for numerous cancers. Breast cancer is one of the most frequent sources of metastases to the liver. The aim of this work was to evaluate the efficacy of the orally administered Salmonella Typhi vaccine strain CVD 915 on the development of liver metastases in a mouse model of breast cancer. To this end, one group of BALB/c mice was orogastrically immunized with CVD 915, while another received PBS as a control. After 24 h, mice were injected with LM3 mammary adenocarcinoma cells into the spleen and subjected to splenectomy. This oral Salmonella-based vaccine produced an antitumor effect, leading to a decrease in the number and volume of liver metastases. Immunization with Salmonella induced an early cellular immune response in mice. This innate stimulation rendered a large production of IFN-γ by intrahepatic immune cells (IHIC) detected within 24 h. An antitumor adaptive immunity was found in the liver and celiac and portal lymph nodes (LDLN) 21 days after oral bacterial inoculation. The antitumor immune response inside the liver was associated with increased CD4(+) and dendritic cell populations as well as with an inflammatory infiltrate located around liver metastatic nodules. Enlarged levels of inflammatory cytokines (IFN-γ and TNF) were also detected in IHIC. Furthermore, a tumor-specific production of IFN-γ and TNF as well as tumor-specific IFN-γ-producing CD8 T cells (CD8(+)IFN-γ(+)) were found in the celiac and portal lymph nodes of Salmonella-treated mice. This study provides first evidence for the involvement of LDLN in the development of an efficient cellular immune response against hepatic tumors, which resulted in the elimination of liver metastases after oral Salmonella-based vaccination.

  19. An oral Salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T cell-mediated immunity in celiac & portal lymph nodes. A preclinical study.

    Directory of Open Access Journals (Sweden)

    Alejandrina eVendrell

    2016-03-01

    Full Text Available Primary tumor excision is one of the therapies of cancer most widely used. However, the risk of metastases development still exists following tumor resection. The liver is a common site of metastatic disease for numerous cancers. Breast cancer is one of the most frequent source of metastases to the liver. The aim of this work was to evaluate the efficacy of the orally-administered Salmonella Typhi vaccine strain CVD 915 on the development of liver metastases in a mouse model of breast cancer. To this end, one group of BALB/c mice was immunized with CVD 915 via o.g. while another received PBS as a control. After 24 h, mice were injected with LM3 mammary adenocarcinoma cells into the spleen and subjected to splenectomy. This oral Salmonella-based vaccine produced an antitumor effect, leading to a decrease in the number and volume of liver metastases. Immunization with Salmonella induced an early cellular immune response in mice. This innate stimulation rendered a large production of IFN-γ by intrahepatic immune cells (IHIC detected within 24 h. An antitumor adaptive immunity was found in the liver and celiac & portal lymph nodes (LDLN 21 days after oral bacterial inoculation. The antitumor immune response inside the liver was associated with increased CD4+ and DC cell populations as well as with an inflammatory infiltrate located around liver metastatic nodules. Enlarged levels of inflammatory cytokines (IFN-γ and TNF were also detected in IHIC. Furthermore, a tumor-specific production of IFN-γ and TNF as well as tumor-specific IFN-γ-producing CD8 T cells (CD8+IFN-γ+ were found in the celiac & portal lymph nodes of Salmonella-treated mice. This study provides first evidence for the involvement of LDLN in the development of an efficient cellular immune response against hepatic tumors, which resulted in the elimination of liver metastases after oral Salmonella-based vaccination.

  20. Margin Size is an Independent Predictor of Local Tumor Progression After Ablation of Colon Cancer Liver Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xiaodong; Sofocleous, Constantinos T., E-mail: sofoclec@mskcc.org; Erinjeri, Joseph P.; Petre, Elena N. [Memorial Sloan-Kettering Cancer Center, Section of Interventional Radiology, Department of Radiology (United States); Gonen, Mithat [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics (United States); Do, Kinh G. [Memorial Sloan-Kettering Cancer Center, Department of Radiology (United States); Brown, Karen T.; Covey, Anne M.; Brody, Lynn A.; Alago, William; Thornton, Raymond H. [Memorial Sloan-Kettering Cancer Center, Section of Interventional Radiology, Department of Radiology (United States); Kemeny, Nancy E. [Memorial Sloan-Kettering Cancer Center, Department of Medicine (United States); Solomon, Stephen B. [Memorial Sloan-Kettering Cancer Center, Section of Interventional Radiology, Department of Radiology (United States)

    2013-02-15

    This study was designed to evaluate the relationship between the minimal margin size and local tumor progression (LTP) following CT-guided radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLM). An institutional review board-approved, HIPPA-compliant review identified 73 patients with 94 previously untreated CLM that underwent RFA between March 2003 and May 2010, resulting in an ablation zone completely covering the tumor 4-8 weeks after RFA dynamic CT. Comparing the pre- with the post-RFA CT, the minimal margin size was categorized to 0, 1-5, 6-10, and 11-15 mm. Follow-up included CT every 2-4 months. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the effect of the minimal margin size, tumor location, size, and proximity to a vessel on LTP. Forty-five of 94 (47.9 %) CLM progressed locally. Median LTP-free survival (LPFS) was 16 months. Two-year LPFS rates for ablated CLM with minimal margin of 0, 1-5 mm, 6-10 mm, 11-15 mm were 26, 46, 74, and 80 % (p < 0.011). Minimal margin (p = 0.002) and tumor size (p = 0.028) were independent risk factors for LTP. The risk for LTP decreased by 46 % for each 5-mm increase in minimal margin size, whereas each additional 5-mm increase in tumor size increased the risk of LTP by 22 %. An ablation zone with a minimal margin uniformly larger than 5 mm 4-8 weeks postablation CT is associated with the best local tumor control.

  1. Geometrical features assessment of liver's tumor with application of artificial neural network evolved by imperialist competitive algorithm.

    Science.gov (United States)

    Keshavarz, M; Mojra, A

    2015-05-01

    Geometrical features of a cancerous tumor embedded in biological soft tissue, including tumor size and depth, are a necessity in the follow-up procedure and making suitable therapeutic decisions. In this paper, a new socio-politically motivated global search strategy which is called imperialist competitive algorithm (ICA) is implemented to train a feed forward neural network (FFNN) to estimate the tumor's geometrical characteristics (FFNNICA). First, a viscoelastic model of liver tissue is constructed by using a series of in vitro uniaxial and relaxation test data. Then, 163 samples of the tissue including a tumor with different depths and diameters are generated by making use of PYTHON programming to link the ABAQUS and MATLAB together. Next, the samples are divided into 123 samples as training dataset and 40 samples as testing dataset. Training inputs of the network are mechanical parameters extracted from palpation of the tissue through a developing noninvasive technology called artificial tactile sensing (ATS). Last, to evaluate the FFNNICA performance, outputs of the network including tumor's depth and diameter are compared with desired values for both training and testing datasets. Deviations of the outputs from desired values are calculated by a regression analysis. Statistical analysis is also performed by measuring Root Mean Square Error (RMSE) and Efficiency (E). RMSE in diameter and depth estimations are 0.50 mm and 1.49, respectively, for the testing dataset. Results affirm that the proposed optimization algorithm for training neural network can be useful to characterize soft tissue tumors accurately by employing an artificial palpation approach. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Quantitative evaluation of six graph based semi-automatic liver tumor segmentation techniques using multiple sets of reference segmentation

    Science.gov (United States)

    Su, Zihua; Deng, Xiang; Chefd'hotel, Christophe; Grady, Leo; Fei, Jun; Zheng, Dong; Chen, Ning; Xu, Xiaodong

    2011-03-01

    Graph based semi-automatic tumor segmentation techniques have demonstrated great potential in efficiently measuring tumor size from CT images. Comprehensive and quantitative validation is essential to ensure the efficacy of graph based tumor segmentation techniques in clinical applications. In this paper, we present a quantitative validation study of six graph based 3D semi-automatic tumor segmentation techniques using multiple sets of expert segmentation. The six segmentation techniques are Random Walk (RW), Watershed based Random Walk (WRW), LazySnapping (LS), GraphCut (GHC), GrabCut (GBC), and GrowCut (GWC) algorithms. The validation was conducted using clinical CT data of 29 liver tumors and four sets of expert segmentation. The performance of the six algorithms was evaluated using accuracy and reproducibility. The accuracy was quantified using Normalized Probabilistic Rand Index (NPRI), which takes into account of the variation of multiple expert segmentations. The reproducibility was evaluated by the change of the NPRI from 10 different sets of user initializations. Our results from the accuracy test demonstrated that RW (0.63) showed the highest NPRI value, compared to WRW (0.61), GWC (0.60), GHC (0.58), LS (0.57), GBC (0.27). The results from the reproducibility test indicated that GBC is more sensitive to user initialization than the other five algorithms. Compared to previous tumor segmentation validation studies using one set of reference segmentation, our evaluation methods use multiple sets of expert segmentation to address the inter or intra rater variability issue in ground truth annotation, and provide quantitative assessment for comparing different segmentation algorithms.

  3. Evaluation of quantitative contrast harmonic imaging to assess malignancy of liver tumors: A prospective controlled two-center study

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To establish the extent to which contrast enhancement with SonoVue in combination with quantitative evaluation of contrast-medium dynamics facilitates the detection of hepatic tumors.METHODS: One hundred patients with histologically confirmed malignant or benign hepatic tumor (maximum size 5 cm) were analyzed. Contrast-enhanced ultrasound (bolus injection 2.5 mL SonoVue) was carried out with intermittent breath-holding technique using a multifrequency transducer (2.5-4 MHz). Native vascularization was analyzed with power Doppler. The contrast-enhanced dynamic ultrasound investigation was carried out with contrast harmonic imaging in true detection mode during the arterial, portal venous and late phases. Mechanical index was set at 0.15. Perfusion analysis was performed by post-processing of the raw data [time intensity curve (TIC) analysis]. The cutoff of the gray value differences between tumor and normal liver tissue was established using Receiver Operating Characteristic (ROC) analysis 64-line multislice computed tomography served as reference method in all cases. Magnetic resonance tomography was used additionally in 19 cases.RESULTS: One hundred patients with 59 malignant (43 colon, 5 breast, 2 endocrine metastases, 7 hepatocellular carcinomas and 2 kidney cancers) and 41 benign (15 hemangiomas, 7 focal nodular hyperplasias, 5 complicated cysts, 2 abscesses and 12 circumscribed fatty changes) tumors were included. The late venous phase proved to be the most sensitive for classification of the tumor type. Fifty-eight of the 59 malignant tumors were classified as true positive, and one as false negative. This resulted in a sensitivity of 98.3%. Of the 41 benign tumors, 37 were classified as true negative and 4 as false negative, which corresponds to a specificity of 90.2%. Altogether, 95.0% of the diagnoses were classified as correct on the basis of the histological classification. No investigator-dependency (P = 0.23) was noted.CONCLUSION: The results show

  4. Successful Re-resection for Locally Recurrent Retroperitoneal Liposarcoma at Four Years After Ex Vivo Tumor Resection and Autotransplantation of the Liver: A Case Report.

    Science.gov (United States)

    Kobayashi, T; Miura, K; Ishikawa, H; Soma, D; Zhang, Z; Yuza, K; Hirose, Y; Takizawa, K; Nagahashi, M; Sakata, J; Kameyama, H; Kosugi, S; Wakai, T

    2016-05-01

    Surgical resection should be considered for isolated locally recurrent retroperitoneal liposarcomas. We experienced a case of successful re-resection for locally recurrent retroperitoneal liposarcomas 4 years after ex vivo tumor resection and autotransplantation of the liver. A 75-year-old man was admitted to our hospital. His diagnosis was local recurrence of liposarcomas. He had previously undergone ex vivo tumor resection and autologous orthotopic liver transplantation for a retroperitoneal tumor 4 years earlier. The resected tumor size was 23.5 × 15.5 × 12.5 cm. The tumor was revealed by means of histopathologic study to be a myxoid liposarcoma. Follow-up computerized tomography showed 2 recurrent tumors in the retropancreatic and para-aortic lesions. Although adhesion was severe within the operative field, we successfully performed complete en bloc re-resection of each recurrent tumor. The operative time was 250 minutes, and blood loss was 300 mL. The resected tumor sizes were 3.9 × 3.2 × 1.5 cm and 4.5 × 3.3 × 3.0 cm. The tumors were revealed by means of histopathologic study to be dedifferentiated liposarcomas. Postoperative complications included intestinal obstruction and colocutaneous fistula formation, both of which were treated surgically. The patient was discharged in an ambulatory state at 80 days after re-resection of the recurrent tumors. At the time of writing, he was alive with no evidence of recurrence, 14 months after re-resection and 62 months after primary ex vivo tumor resection. This is the first case of successful surgical re-resection for locally recurrent liposarcoma after ex vivo tumor resection and autotransplantation of the liver.

  5. Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90 microspheres for unresectable primary and metastatic liver tumors

    Directory of Open Access Journals (Sweden)

    Ozkan Elgin

    2011-08-01

    Full Text Available Abstract Background The aim of this study was to evaluate the success of selective intraarterial radionuclide therapy (SIRT with Yttrium-90 (Y-90 microspheres in liver metastases of different tumors. We also interpreted the contribution of SIRT to survival times according to responder- non responder and hepatic- extra hepatic disease. Methods The clinical and follow-up data of 124 patients who were referred to our department for SIRT between June 2006 and October 2010 were evaluated retrospectively. SIRT has been applied to 78 patients who were suitable for treatment. All the patients had primary liver tumor or unresectable liver metastasis of different malignancies. The treatment was repeated at least one more time in 5 patients to the same or other lobes. Metabolic treatment response evaluated by fluorine-18 fluorodeoxyglucose (F18-FDG positron emission tomography/computed tomography (PET/CT in the 6th week after treatment. F18-FDG PET/CT was repeated in per six weeks periods. The response criterion had been described as at least 20% decrease of SUV value. Also in patients with neuroendocrine tumor serial Gallium-68 (Ga-68 PET/CT was used for evaluation of response. Patients were divided into 2 groups according to their treatment response. Results 68 patients received treatment for the right lobe, seven patients received treatment for the left lobe and 3 patients for both lobes. The mean treatment dose was estimated at 1.62 GBq. In the evaluation of treatment response; 43(55% patients were responder (R and 35 (45% patients were non-responder (NR in the sixth week F18-FDG PET/CT. Mean pretreatment SUVmax value of R group was 11.6 and NR group was 10.7. While only 11 (31% out of 35 NR patients had H disease, 30 (69% out of 43 R patients had H disease (p Conclusions SIRT is a useful treatment method which can contribute to the lengthening of survival times in patients with primary or metastatic unresectable liver malignancies. Also F18-FDG PET

  6. 超声激励荧光微泡对兔乳腺癌转移淋巴结的释放作用%Sonorelease of DiO-microspheres to the lymph nodes metastasis of rabbits VX2 breast cancer

    Institute of Scientific and Technical Information of China (English)

    乔璐; 朱梅; 高文宏; 张莉; 李露; 刘政

    2013-01-01

    Objective To observe the sonorelease of fluresence ricrobubbles to the lymph nodes metastasis of rabbits VX2 breast cancer by ultrasound excitation.Methods DiO-labeled microbubbles were prepared with lipid microbubbles and mixed Dimethyl sulfoxide (DMSO) dissolved DiO.The fluorescence microbubbles were made by high speed mechanical agitation.Rabbits models of VX2 breast carcinoma were established by means of injection of tissue mass suspension and were divided into fluorescent microbubbles combined ultrasonic cavitation group and fluorescence of microbubbles group (each n=8).In fluorescent microbubbles combined ultrasonic cavitation group,the fluorescent microbubbles (total 1 ml) were injected subcutaneously around tumor and massaged to drainage of lymph nodes The lymph nodes were exposured to pulse ultrasound intermittent treatment for 5 times,total 30 min.In fluorescence of microbubbles group,the same injection without ultrasound irradiation was performed.Laser confocal microscope was used to observe the deposition of green fluorescein in a small portion of frozen section lymph node tissues and to analyze the fluorescence of the area integrated optical density (IOD) and average optical density (AOD).Results Compared with fluorescence of microbubbles group,the fluorescence area,IOD and AOD of lymph node were higher in fluorescent microbubbles combined ultrasonic cavitation group (all P<0.05).Condusion Flurescence microbubbles can not only enter lymph vessel to make lymph node development,but also deliver a high concentration of fluorescence microbubbles in the regional lymph node by lowpressure ultrasound in rabbit models.%目的 观察超声激励荧光微泡空化对兔乳腺癌转移淋巴结的荧光释放作用.方法 使用二甲基亚砜(DMSO)溶解绿色细胞膜荧光分子探针(DiO),抽取少量溶解液与脂质微泡混和,通过高速机械振荡制成荧光微泡.选取16只荷VX2乳腺癌的新西兰大白兔随机分成荧光微

  7. Role of wild type p53 and double suicide genes in interventional therapy of liver cancer in rabbits Papel do p53 selvagem e do duplo genes suicidas na terapia intervencionista do câncer de fígado em coelhos

    Directory of Open Access Journals (Sweden)

    Hong-xin Niu

    2012-08-01

    Full Text Available PURPOSE: To investigate the feasibility of interventional lipiodol embolism and multigene therapy in combination with focal chemotherapy in the treatment of VX2 liver cancer in rabbits. METHODS: Forty five rabbits with cancer larger than 2cm in diameter were randomly divided into five groups (n=9 per group. In Group 1, animals were treated with 0.9% sodium chloride. In Group 2, animals received lipiodol embolism. In Group 3, animals received lipiodol embolism and p53 gene therapy. In Group 4, animals received lipiodol embolism and TK/CD gene therapy. In Group 5, animals received lipiodol embolism and p53 and TK/CD gene therapy. Ultrasonography and CT were performed before and at ten days after interventional therapy. RESULTS: The VX2 model of liver cancer was successfully established in rabbits and interventional therapy smoothly performed. At ten days after interventional therapy, significant difference in the tumor volume was noted among five groups (pOBJETIVO: Investigar a possibilidade de terapia multigênica e intervenção por embolização com lipiodol em combinação com quimioterapia focal no tratamento de câncer de fígado VX2 em coelhos. MÉTODOS: Quarenta e cinco coelhos com câncer maior do que 2cm de diâmetro foram distribuídos, aleatoriamente, em cinco grupos (n=9 por grupo. Grupo 1: animais foram tratados com cloreto de sódio 0,9% e no grupo 2 os animais receberam embolização com lipidol. Grupo 3: animais receberam embolização com lipiodol e terapia do gene p53 e grupo 4 animais receberam embolização com lipiodol e terapia do gene TK/CD. Grupo 5: animais receberam embolização com lipiodol e terapia do gene p53 e do gene TK/CD. Ultrassonografia e tomografia computadorizada foram realizadas antes e dez dias após a intervenção terapêutica. RESULTADOS: O modelo VX2 de câncer de fígado foi estabelecido com sucesso em coelhos e a terapia intervencionista foi bem executada. Dez dias após a intervenção terap

  8. Selective internal radiotherapy (SIRT) with radioactive microspheres in unresectable liver tumors; Selektive interne Radiotherapie (SIRT) inoperabler Lebertumoren mit radioaktiv markierten Mikrosphaeren

    Energy Technology Data Exchange (ETDEWEB)

    Tatsch, K.; Poepperl, G. [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum der Univ. Muenchen, Grosshadern (Germany); Hoffmann, R.T. [Inst. fuer Klinische Radiologie, Klinikum der Univ. Muenchen, Grosshadern (Germany)

    2008-06-15

    Selective internal radiotherapy (SIRT) is a method for local treatment of primary liver tumors and metastatic liver disease. SIRT is based on the delivery of radioactive labeled microspheres into the vascular bed of the liver via angiographically placed catheters in branches of the hepatic artery. Currently this therapeutic approach is predominantly applied, if surgical resection or other local forms of ablative therapies are not indicated and commonly applied chemotherapy regimen have failed to prevent progression of liver involvement. This article briefly summarizes the pathophysiologic principle of SIRT, addresses the criteria for patient selection, describes how to perform the therapeutic procedure in combination with adjuvant actions and reports on side effects and possible complications. Finally, the results obtained with this therapy are summarized for the most relevant tumor entities and some future perspectives are discussed. (orig.)

  9. Role of Prosopis cineraria against N-nitrosodiethylamine-induced liver tumor in rats with reference to marker enzymes and nucleic acid contents

    Directory of Open Access Journals (Sweden)

    Naina mohamed Pakkir Maideen

    2011-06-01

    Full Text Available The effect of methanol extract of Prosopis cineraria against experimental liver tumor in rats was studied. Liver tumor was induced by the administration of N-nitrosodiethylamine (200 mg/kg and it was promoted by phenobarbital administration. Methanol extract (200 and 400 mg/kg was administered to determine the protective activity. Administration of methanol extract suppressed the liver tumor effectively as revealed by the decrease in elevated levels of aryl hydrocarbon hydroxylase, lactate dehydrogenase, g-glutamyl transpeptidase (g-GTP, 5’nucleotidase, deoxyribonucleic acid (DNA and ribonucleic acid (RNA. We found that methanol extract may extend its protective role by modifying the levels of marker enzymes and nucleic acid contents.

  10. Clinical evaluation of synthetic aperture sequential beamforming ultrasound in patients with liver tumors

    DEFF Research Database (Denmark)

    Hansen, Peter Møller; Hemmsen, Martin Christian; Brandt, Andreas Hjelm

    2014-01-01

    Medical ultrasound imaging using synthetic aperture sequential beamforming (SASB) has for the first time been used for clinical patient scanning. Nineteen patients with cancer of the liver (hepatocellular carcinoma or colorectal liver metastases) were scanned simultaneously with conventional...... maintained despite the data reduction. A total of 117 sequences were recorded and evaluated blinded by five radiologists from a clinical perspective. Forty-eight percent of the evaluations were in favor of SASB, 33% in favor of conventional ultrasound and 19%were equal, that is, a clear, but non...

  11. Characterization and propagation of tumor initiating cells derived from colorectal liver metastases: trials, tribulations and a cautionary note.

    Directory of Open Access Journals (Sweden)

    Mark I James

    Full Text Available Tumor initiating cells (TIC are increasingly being put forward as a potential target for intervention within colorectal cancer. Whilst characterisation and outgrowth of these cells has been extensively undertaken in primary colorectal cancers, few data are available describing characteristics within the metastatic setting. Tissue was obtained from patients undergoing surgical resection for colorectal liver metastases, and processed into single cell suspension for assessment. Tumor initiating cells from liver metastases were characterised using combinations of EPCAM, Aldehyde dehydrogenase activity, CD133 and CD26. CD133 expression was significantly lower in patients who had received chemotherapy, but this was accounted for by a decrease observed in the male patient cohort only. ALDHhigh populations were rare (0.4 and 0.3% for EPCAM+/ALDHhigh/CD133- and EPCAM+/ALDHhigh/CD133+ populations respectively and below the limits of detection in 28% of samples. Spheroid outgrowth of metastatic tumor cells across all samples could not be readily achieved using standard spheroid-formation techniques, thus requiring further method validation to reliably propagate cells from the majority of tissues. Spheroid formation was not enhanced using additional growth factors or fibroblast co-culture, but once cells were passaged through NOD-SCID mice, spheroid formation was observed in 82% samples, accompanied by a significant increase in CD26. Order of spheroid forming ability was ALDHhigh>CD133>CD26. Samples sorted by these markers each had the ability to reform ALDHhigh, CD133 and CD26 positive populations to a similar extent, suggestive of a high degree of plasticity for each population. Ex vivo TIC models are increasingly being utilised to assess efficacy of therapeutic interventions. It is therefore essential that such investigations use well-characterised models that are able to sustain TIC populations across a large patient cohort in order that the inherent

  12. Mechanically assisted 3D ultrasound for pre-operative assessment and guiding percutaneous treatment of focal liver tumors

    Science.gov (United States)

    Sadeghi Neshat, Hamid; Bax, Jeffery; Barker, Kevin; Gardi, Lori; Chedalavada, Jason; Kakani, Nirmal; Fenster, Aaron

    2014-03-01

    Image-guided percutaneous ablation is the standard treatment for focal liver tumors deemed inoperable and is commonly used to maintain eligibility for patients on transplant waitlists. Radiofrequency (RFA), microwave (MWA) and cryoablation technologies are all delivered via one or a number of needle-shaped probes inserted directly into the tumor. Planning is mostly based on contrast CT/MRI. While intra-procedural CT is commonly used to confirm the intended probe placement, 2D ultrasound (US) remains the main, and in some centers the only imaging modality used for needle guidance. Corresponding intraoperative 2D US with planning and other intra-procedural imaging modalities is essential for accurate needle placement. However, identification of matching features of interest among these images is often challenging given the limited field-of-view (FOV) and low quality of 2D US images. We have developed a passive tracking arm with a motorized scan-head and software tools to improve guiding capabilities of conventional US by large FOV 3D US scans that provides more anatomical landmarks that can facilitate registration of US with both planning and intra-procedural images. The tracker arm is used to scan the whole liver with a high geometrical accuracy that facilitates multi-modality landmark based image registration. Software tools are provided to assist with the segmentation of the ablation probes and tumors, find the 2D view that best shows the probe(s) from a 3D US image, and to identify the corresponding image from planning CT scans. In this paper, evaluation results from laboratory testing and a phase 1 clinical trial for planning and guiding RFA and MWA procedures using the developed system will be presented. Early clinical results show a comparable performance to intra-procedural CT that suggests 3D US as a cost-effective alternative with no side-effects in centers where CT is not available.

  13. An unusual case of fatty liver in a patient with desmoid tumor

    Institute of Scientific and Technical Information of China (English)

    Francesca De Felice; Daniela Musio; Rossella Caiazzo; Bartolomeo Dipalma; Lavinia Grapulin; Camilla Proietti Semproni; Vincenzo Tombolini

    2012-01-01

    A desmoid tumor,also known as aggressive fibromatosis,is a rare benign neoplasm that arises from fascial or musculoaponeurotic tissues.It can occur in any anatomical location,most commonly the abdominal wall,shoulder girdle and retroperitoneum.The typical clinical presentation is a painless mass with a slow and progressive invasion of contiguous structures.It is associated with a high local recurrence rate after resection.Many issues regarding the optimal treatment of desmoid tumors remain controversial.Aggressive surgical resection with a wide margin (2-3 cm) remains the gold standard treatment with regard to preserving quality of life.Radiotherapy alone has been shown to be effective for the control of unresectable or recurrent lesions.Desmoid tumors tend to be locally infiltrative,therefore,the fields must be generous to prevent marginal recurrence.The radiation dose appropriate for treating desmoid tumors remains controversial.We present a 25-year-old Caucasian man with local recurrence of a desmoid tumor after repeated surgical resection,treated with radiotherapy.The patient achieved complete tumor regression at 4 mo after radiotherapy,and he is clinically free of disease at 12 mo after the end of treatment,with an acceptable quality of life.The patient developed short bowel syndrome as a complication of second surgical resection.Consequently,radiotherapy might have worsened an already present malabsorption and so led to steatohepatitis.

  14. Focal peliosis hepatis in a colon cancer patient resembling metastatic liver tumor

    Institute of Scientific and Technical Information of China (English)

    Wu-Jun Xiong; Li-Juan Hu; Yi-Cheng Jian; Yi He; Wei Zhou; Xin-Lai Guo; Ya-Xin Zheng

    2012-01-01

    Peliosis hepatis (PH) is a rare benign condition characterized by the presence of multiple,randomly distributed,blood filled cystic areas of variable size within the liver parenchyma.PH is difficult to recognize and may be mistaken for neoplasm,metastases or multiple abscesses.A 75-year-old female with a previous history of colon cancer was admitted when a liver mass in the right liver lobe was found 11 mo after surgery during the follow-up period.Computed tomography and magnetic resonance imaging scan of the abdomen were performed.The initial possible diagnosis was metastatic hepatocellular carcinoma.The patient underwent excision of the hepatic segment where the nodule was located.The pathological diagnosis of the surgical specimen was PH.PH should be considered in the differential diagnosis of new liver lesions in patients whose clinical settings do not clearly favor metastasization.Clinicians and radiologists must recognize these lesions to minimize the probability of misdiagnosis and inappropriate treatment.

  15. Mode of Action Profiles for Pesticide Compounds with Rodent Liver Tumor Outcomes

    Science.gov (United States)

    Mode of action (MOA) provides a central framework for assessing human relevance of adverse health outcomes observed in nonclinical safety studies. The goal of this study was to characterize MOA profiles for known rodent liver tumorigens identified from a database of pesticides as...

  16. Metabolism of indole alkaloid tumor promoter, (-)-indolactam V, which has the fundamental structure of teleocidins, by rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Hagiwara, N.; Irie, K.; Tokuda, H.; Koshimizu, K.

    1987-07-01

    Metabolic activation and/or deactivation of indole alkaloid tumor promoter, (-)-indolactam V (ILV), was examined using rat liver microsomes. Reaction of ILV with the microsomes supplemented with NADPH and MgCl/sub 2/ gave three major metabolites, which were identified as (-)-N13-desmethylindolactam V and two diastereomers of (-)-2-oxyindolactam V at C-3. The tumor-promoting activities of these metabolites were evaluated by induction of Epstein-Barr virus early antigen and inhibition of specific binding of (/sup 3/H)-12-O-tetradecanoylphorbol-13-acetate to a mouse epidermal particulate fraction, and proved to be conspicuously lower than that of ILV. These results demonstrate that the metabolism of ILV results in detoxification, and that it itself is the tumor-promoting entity. Studies on the enzymes concerned with this metabolism suggested the involvement of cytochrome P-450-containing mixed-function oxidases. Similar deactivation seems to be possible by skin, where the mixed-function oxidases are known to exist.

  17. Transferrin-targeted magnetic/fluorescence micelles as a specific bi-functional nanoprobe for imaging liver tumor

    Science.gov (United States)

    Qi, Hui; Li, Zhengzheng; Du, Kai; Mu, Ketao; Zhou, Qing; Liang, Shuyan; Zhu, Wenzhen; Yang, Xiangliang; Zhu, Yanhong

    2014-10-01

    In order to delineate the location of the tumor both before and during operation, we developed targeted bi-functional polymeric micelles for magnetic resonance (MR) and fluorescence imaging in liver tumors. Hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) were loaded into the polymeric micelles through self-assembly of an amphiphilic block copolymer poly(ethylene glycol)-poly(ɛ-caprolactone). After, transferrin (Tf) and near-infrared fluorescence molecule Cy5.5 were conjugated onto the surface of the polymeric micelles to obtain the nanosized probe SPIO@PEG- b-PCL-Tf/Cy5.5 (SPPTC). Imaging capabilities of this nanoprobe were evaluated both in vitro and in vivo. The accumulation of SPPTC in HepG2 cells increased over SPIO@PEG- b-PCL-Cy5.5 (SPPC) by confocal microscopy. The targeted nanoprobe SPPTC possessed favorable properties on the MR and fluorescence imaging both in vitro and in vivo. The MTT results showed that the nanoprobes were well tolerated. SPPTC had the potential for pre-operation evaluation and intra-operation navigation of tumors in clinic.

  18. Effects of intra-arterial chemotherapy with a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol on experimental liver tumor in rats

    Energy Technology Data Exchange (ETDEWEB)

    Egawa, H.; Maki, A.; Mori, K.; Yamamoto, Y.; Mitsuhashi, S.; Bannai, K.; Asano, K.; Ozawa, K. (Kyoto Univ. (Japan))

    1990-06-01

    Anticancer effects and biodistribution of a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol (LPD) were investigated as an intra-arterial chemotherapy (IAC) on Walker 256 carcinosarcoma grown in the liver of 136 Wistar rats. All rats treated with KM2210 (10 mg)-LPD survived for 90 days after administration, whereas none of the rats with LPD alone were alive for more than 19 days. Histological examination revealed that there was no viable tumor cell in the encapsulated necrotic tumor at 21 days after administration. There was no significant liver dysfunction or leukopenia due to KM2210. The biodistribution study using (14C, 3H)KM2210-LPD solution showed that KM2210 accumulated selectively in tumor and that the tumor-to-normal-liver and tumor-to-blood ratios were 10 and 1,000, respectively, at 21 days after administration. These results suggest that KM2210 has potential clinical application in the treatment of human liver cancer.

  19. Mechanisms of tumor necrosis factor-α and interleukin-6 induction during human liver transplantation

    Directory of Open Access Journals (Sweden)

    Gerhard Hamilton

    1993-01-01

    Full Text Available In human orthotopic liver transplantation (LTX intraoperative elevations of TNF-α (> 100 pg/ml and IL-6 (>800 pg/ml have been found to correlate with early post-operative rejections and infections respectively. In this study the possible mechanism responsible for the induction of these cytokines has been investigated during liver allografting in 38 recipients. Intraoperative elevations of TNF-α (> 100 pg/ml were detected in the majority of pre-transplant endotoxin positive recipients (8/12, > 10 endotoxin units/ml, the patients turning endotoxin positive until the end of grafting (3/5, and in a subgroup (6/21 patients, apparently endotoxin negative for the whole operation. Therefore endotoxin (ET seems to stimulate release of TNF-α in approximately 50% of the patients, whereas sensitized Kupffer graft cells or immediate allograft reactivity of the host are likely to account for the remaining TNF-α positive cases. Elevations of IL-6 > 800 pg/ml were found in approximately 50% of the TNF-α positive cases, indicating partially independent regulatory pathways for IL-6 induction in the TNF-α negative patients. In agreement with a previous study, 11/13 (85% of the intraoperative TNF-α positive recipients rejected their grafts within the first 10 days post-operatively. These data demonstrate that ET/infection associated as well as ET independent/reperfusion associated intraoperative TNF-α elevations, promote the initiation of allograft rejection in human liver transplantation. The transient and low endotoxaemia caused by the liver grafting procedure performed without veno-venous bypass seems to be of minor importance in the intraoperative induction of TNF-α.

  20. Association between polycyclic aromatic hydrocarbons and human rectal tumor or liver cancer

    Institute of Scientific and Technical Information of China (English)

    Guohong Jiang; Limin Lun; Liyuan Cong

    2012-01-01

    Objective: The aim of this study was to investigate the effect of polycyclic aromatic hydrocarbons (PAHs) in rectal carcinoma and hepatocarcinoma genesis. Methods: The PAHs in the human rectal cancer and liver cancer tissues, the adjacent tissues and homologous tissues without rectal cancer or liver cancer were extracted by ultrasonic wave. The extracts were then cleaned up and enriched by solid phase extraction, analyzed by high performance liquid chromatography (HPLC) with fluorescence spectroscopy. Results: Four kinds of PAHs were detected in human rectal and hepatic tissues. The contents of pyrene, 2-methylanthracene and benzo (a) pyrene in both rectal cancer tissues and adjacent homologous tissues were higher than rectal tissues without rectal cancer, the differences were statistically significant (P 0.05). The differences of the content of each PAHs between rectal cancer and adjacent tissue were not significant (P > 0.05). The contents of the four PAHs in the three kinds of liver tis-sues were not statistically significant (P > 0.05). Conclusion: PAHs are found in human rectal tissues or hepatic tissues. The contents of PAHs in human rectal tissue may have an effect on the occurrence of human rectal cancer while the contents of PAHs in human hepatic tissues may have not ones.

  1. Undifferentiated embryonal sarcoma of the liver presenting as a hemorrhagic cystic tumor in an adult

    Institute of Scientific and Technical Information of China (English)

    Ho Hyun Kim; Jung Chul Kim; Eun Kyu Park; Young Hoe Hur; Yang Seok Koh; Chol Kyoon Cho; Hyung Seok Kim; Hyun Jong Kim

    2011-01-01

    BACKGROUND: Undifferentiated  embryonal  sarcoma  (UES) of the liver is a rare, highly malignant neoplasm with a poor prognosis occurring almost exclusively in late childhood (6-10 years  of  age).  Only  a  few  cases  have  been  reported  in  adults, accounting for less than 1% of all primary liver neoplasms. METHODS: A 47-year-old woman presented with a palpable mass in the left upper abdomen. Magnetic resonance imaging revealed  a  12×10  cm  cystic  mass  with  hemorrhage  in  the left lateral segment of the liver. The initial impression was a hemorrhagic cystic tumor of the liver. The patient underwent a left lateral sectionectomy of the liver. Histopathology and immunohistochemistry helped make a diagnosis of UES. RESULTS: The  patient  recovered  uneventfully  and  received systemic chemotherapy. Radiologic examination for follow-up revealed a metastatic lesion in the lumbar spine (L5). She was subjected to radiotherapy at the lumbar spine. She survived 48 months. CONCLUSION: Although  hepatic  cyst  as  UES  of  the  liver  is difficult  to  diagnose  because  of  its  rarity  in  adults  and  lack of  specific  findings,  it  should  be  considered  in  a  differential diagnosis.

  2. Laser-induced thermotherapy (LITT) of tumors of the liver in central location: results and complications; Laserinduzierte Thermotherapie (LITT) von Lebertumoren in zentraler Lokalisation: Ergebnisse und Komplikationen

    Energy Technology Data Exchange (ETDEWEB)

    Mensel, B.; Weigel, C.; Hosten, N. [Abt. fuer Diagnostische und Interventionelle Radiologie, Klinikum der Ernst-Moritz-Arndt-Univ. Greifswald (Germany); Heidecke, C.D.; Stier, A. [Klinik und Poliklinik fuer Chirurgie, Klinikum der Ernst-Moritz-Arndt-Univ. Greifswald (Germany)

    2005-09-01

    Purpose: to investigate whether laser-induced thermotherapy (LITT) for tumors of the liver in central location is a sufficient and safe therapeutic option. Material and methods: according to predefined criteria, 23 of 136 patients were chosen to be treated with LITT because of malignant liver tumors. At the time of the first LITT, the patients had 28 central tumors (27 metastases, one HCC), which were treated in 34 sessions with 64 laser applications and had a clinical and imaging follow-up every 3 months. Results: the primary effectiveness rate was 74.1% and the secondary effectiveness rate 82.1%. The mortality rate was 0%. Major complications occurred in one patient (hemorrhagic pleural effusion), while minor complications occurred in 10 patients. During the median follow-up of 20 months (range 3-57 months), local tumor progression developed in 22% of the tumors. The effectiveness rate was 78.6%, 71.4% and 64.3% after 3, 6 and 9 months. The median survival was 46.0 months (95% confidence interval: 28.6-47.1 months). Conclusion: in our patients, complications and ablation rate of laser-induced thermotherapy for central liver tumors do not differ from those in peripheral location as described in the literature. (orig.)

  3. T1-Weighted MR imaging of liver tumor by gadolinium-encapsulated glycol chitosan nanoparticles without non-specific toxicity in normal tissues

    Science.gov (United States)

    Na, Jin Hee; Lee, Sangmin; Koo, Heebeom; Han, Hyounkoo; Lee, Kyung Eun; Han, Seung Jin; Choi, Seung Hong; Kim, Hyuncheol; Lee, Seulki; Kwon, Ick Chan; Choi, Kuiwon; Kim, Kwangmeyung

    2016-05-01

    Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the amine groups on the surface of Gd(iii)-CNPs could be protonated and could induce fast cellular uptake at acidic pH in tumor tissue. To assay the tumor-targeting ability of Cy5.5-labeled Gd(iii)-CNPs, near-infrared fluorescence (NIRF) imaging and MR imaging were used in a liver tumor model as well as a subcutaneous tumor model. Cy5.5-labeled Gd(iii)-CNPs generated highly intense fluorescence and T1 MR signals in tumor tissues after intravenous injection, while DOTAREM®, the commercialized control MR contrast agent, showed very low tumor-targeting efficiency on MR images. Furthermore, damaged tissues were found in the livers and kidneys of mice injected with DOTAREM®, but there were no obvious adverse effects with Gd(iii)-CNPs. Taken together, these results demonstrate the superiority of Gd(iii)-CNPs as a tumor-targeting T1 MR agent.Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the

  4. Prognostication and response assessment in liver and pancreatic tumors: The new imaging

    Science.gov (United States)

    De Robertis, Riccardo; Tinazzi Martini, Paolo; Demozzi, Emanuele; Puntel, Gino; Ortolani, Silvia; Cingarlini, Sara; Ruzzenente, Andrea; Guglielmi, Alfredo; Tortora, Giampaolo; Bassi, Claudio; Pederzoli, Paolo; D’Onofrio, Mirko

    2015-01-01

    Diffusion-weighted imaging (DWI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) are technical improvements of morphologic imaging that can evaluate functional properties of hepato-bilio-pancreatic tumors during conventional MRI or CT examinations. Nevertheless, the term “functional imaging” is commonly used to describe molecular imaging techniques, as positron emission tomography (PET) CT/MRI, which still represent the most widely used methods for the evaluation of functional properties of solid neoplasms; unlike PET or single photon emission computed tomography, functional imaging techniques applied to conventional MRI/CT examinations do not require the administration of radiolabeled drugs or specific equipments. Moreover, DWI and DCE-MRI can be performed during the same session, thus providing a comprehensive “one-step” morphological and functional evaluation of hepato-bilio-pancreatic tumors. Literature data reveal that functional imaging techniques could be proposed for the evaluation of these tumors before treatment, given that they may improve staging and predict prognosis or clinical outcome. Microscopic changes within neoplastic tissues induced by treatments can be detected and quantified with functional imaging, therefore these techniques could be used also for post-treatment assessment, even at an early stage. The aim of this editorial is to describe possible applications of new functional imaging techniques apart from molecular imaging to hepatic and pancreatic tumors through a review of up-to-date literature data, with a particular emphasis on pathological correlations, prognostic stratification and post-treatment monitoring. PMID:26078555

  5. Liposomal phosphatidylserine inhibits tumor cytotoxicity of liver macrophages induced by muramyl dipeptide and lipopolysaccharide

    NARCIS (Netherlands)

    Daemen, T; Regts, J; Scherphof, GL

    1996-01-01

    Liposomes can very efficiently deliver immunomodulators to macrophages so as to induce tumor cytotoxicity. Liposomes most widely used for that purpose contain negatively charged lipids, in particular phosphatidylserine (PS), to enhance liposome uptake by the macrophages. We investigated the effect o

  6. p53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer

    DEFF Research Database (Denmark)

    Tschaharganeh, Darjus F; Xue, Wen; Calvisi, Diego F

    2014-01-01

    nestin in an Sp1/3 transcription-factor-dependent manner and that Nestin is required for tumor initiation in vivo. Moreover, loss of p53 facilitates dedifferentiation of mature hepatocytes into nestin-positive progenitor-like cells, which are poised to differentiate into hepatocellular carcinomas (HCCs...

  7. Liu-stain quick cytodiagnosis of ultrasound-guided fine needle aspiration in diagnosis of liver tumors

    Institute of Scientific and Technical Information of China (English)

    Chi-Sin Changchien; Jing-Houng Wang; Sheng-Nan Lu; Chao-Hung Hung; Chien-Hung Chen; Chuan-Mo Lee

    2007-01-01

    AIM: To combine ultrasound-guided fine-needle aspiration (US-FNA) and Liu (Riu) stain to make a quick study on liver tumor lesions.METHODS: Two hundred and twenty-eight aspirations from 232 patients were completely studied. The operator himself made the quick cytodiagnosis of US-FNA smear stained by Liu method within thirty minutes. The US-FNA specimen was also sent to the pathological department for cytological study and cellblock histology. The result of our Liu-stain quick cytodiagnosis in each patient was confirmed by the final cytopathological diagnosis from pathological report.RESULTS: Among 228 samples, the quick cytodiagnosis revealed 146 malignancies, 81 benign lesions and one inadequate specimen. Cytopathological diagnosis from the pathological department revealed 150 malignancies,and 78 benign lesions. Four well-differentiated hepatocellular carcinomas (HCCs) were under-diagnosed by quick cytodiagnosis as benign and 3 benign lesions were over-diagnosed as well-differentiated HCCs. Compared with cytopathological diagnosis, quick cytodiagnosis correctly diagnosed 143 malignancies and 77 benign lesions. Except for the one inadequate specimen in quick cytodiagnosis, the accuracy of quick cytodiagnosis was 96.9% (220/227), and its sensitivity, specificity and positive and negative predictive values were 97.9%, 95.1%,97.3% and 96.3%, respectively.CONCLUSION: Liu-stain quick cytodiagnosis is a fast,convenient, safe and effective method for hepatologists in clinic practice to diagnose liver tumor. In few cases of well-differentiated HCC, Liu-stain quick cytodiagnosis has its limitation.

  8. A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer

    Science.gov (United States)

    Nam, Soo Jeong; Yeo, Hyun Yang; Chang, Hee Jin; Kim, Bo Hyun; Hong, Eun Kyung; Park, Joong-Won

    2016-01-01

    Purpose We developed a new method of detecting circulating tumor cells (CTCs) in liver cancer patients by constructing cell blocks from peripheral blood cells, including CTCs, followed by multiple immunohistochemical analysis. Materials and Methods Cell blockswere constructed from the nucleated cell pellets of peripheral blood afterremoval of red blood cells. The blood cell blocks were obtained from 29 patients with liver cancer, and from healthy donor blood spikedwith seven cell lines. The cell blocks and corresponding tumor tissues were immunostained with antibodies to seven markers: cytokeratin (CK), epithelial cell adhesion molecule (EpCAM), epithelial membrane antigen (EMA), CK18, α-fetoprotein (AFP), Glypican 3, and HepPar1. Results The average recovery rate of spiked SW620 cells from blood cell blocks was 91%. CTCs were detected in 14 out of 29 patients (48.3%); 11/23 hepatocellular carcinomas (HCC), 1/2 cholangiocarcinomas (CC), 1/1 combined HCC-CC, and 1/3 metastatic cancers. CTCs from 14 patients were positive for EpCAM (57.1%), EMA (42.9%), AFP (21.4%), CK18 (14.3%), Gypican3 and CK (7.1%, each), and HepPar1 (0%). Patients with HCC expressed EpCAM, EMA, CK18, and AFP in tissue and/or CTCs, whereas CK, HepPar1, and Glypican3 were expressed only in tissue. Only EMA was significantly associated with the expressions in CTC and tissue. CTC detection was associated with higher T stage and portal vein invasion in HCC patients. Conclusion This cell block method allows cytologic detection and multiple immunohistochemical analysis of CTCs. Our results show that tissue biomarkers of HCC may not be useful for the detection of CTC. EpCAM could be a candidate marker for CTCs in patients with HCC. PMID:27034142

  9. Tumor

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008479 Preliminary study of MR elastography in brain tumors. XU Lei(徐磊), et al.Neurosci Imaging Center, Beijing Tiantan Hosp, Capital Med Univ, Beijing 100050.Chin J Radiol 2008;42(6):605-608. Objective To investigate the potential values of magnetic resonance elastography (MRE) for evaluating the brain tumor consistency in vivo. Methods Fourteen patients with known solid brain tumor (5 male, 9 female; age range: 16-63 years)

  10. Therapeutic value of 3-D printing template-assisted 125I-seed implantation in the treatment of malignant liver tumors

    Directory of Open Access Journals (Sweden)

    Han T

    2017-07-01

    Full Text Available Tao Han,1,* Xiaodan Yang,1,* Ying Xu,2,* Zhendong Zheng,1,* Ying Yan,2 Ning Wang2 1Department of Oncology, 2Department of Radiotherapy, General Hospital of Shenyang Military Region, Shenyang, China *These authors contributed equally to this work Objective: To explore the therapeutic value of 3-D printing template-assisted 125I-seed implantation in the treatment of malignant liver tumors.Materials and methods: Fifteen liver cancer patients with 47 total lesions were treated with 3-D printing template-assisted radioactive seed implantation (group A, and 25 liver-tumor patients with 66 total lesions were treated with 125I-seed implantation without a template auxiliary (group B. Operation time, in-hospital time, operation complications, dose distribution, and response rate (number were compared between the two groups. Results: Shorter operation times and better dose distribution were observed in group A than in group B, and the differences were statistically significant. The response rate after 2 months was 86.7% (13 of 15 in group A and 84% (21 of 25 in group B; differences between the two groups were not significant.Conclusion: Application of 3-D printing template-assisted radioactive seed implantation in the treatment of malignant liver tumors can help shorten operation time and optimize radiation-dose distribution, is worthy of further study, and has clinical significance. Keywords: brachytherapy, stereotactic techniques, iodine isotopes, liver, carcinoma 

  11. Preoperative Y-90 microsphere selective internal radiation treatment for tumor downsizing and future liver remnant recruitment: a novel approach to improving the safety of major hepatic resections

    Directory of Open Access Journals (Sweden)

    Gulec Seza A

    2009-01-01

    Full Text Available Abstract Background Extended liver resections are being performed more liberally than ever. The extent of resection of liver metastases, however, is restricted by the volume of the future liver remnant (FLR. An intervention that would both accomplish tumor control and induce compensatory hypertrophy, with good patient tolerability, could improve clinical outcomes. Case presentation A 53-year-old woman with a history of cervical cancer presented with a large liver mass. Subsequent biopsy indicated poorly differentiated carcinoma with necrosis suggestive of squamous cell origin. A decision was made to proceed with pre-operative chemotherapy and Y-90 microsphere SIRT with the intent to obtain systemic control over the disease, downsize the hepatic lesion, and improve the FLR. A surgical exploration was performed six months after the first SIRT (three months after the second. There was no extrahepatic disease. The tumor was found to be signi