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Aslam A, Kamath A, Spieler B, Maschiocchi M, Sabottke CF, Chernyak V, Lewis SC. Assessing locoregional treatment response to Hepatocellular Carcinoma: comparison of hepatobiliary contrast agents to extracellular contrast agents. Abdom Radiol (NY) 2021; 46:3565-3578. [PMID: 33856509 DOI: 10.1007/s00261-021-03076-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 03/22/2021] [Accepted: 03/27/2021] [Indexed: 12/17/2022]
Abstract
Cross-sectional imaging with contrast-enhanced magnetic resonance imaging (MRI) is routinely performed in patients with hepatocellular carcinoma (HCC) to assess tumor response to locoregional therapy (LRT). Current response assessment algorithms, such as the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (TRA), allow assessment using conventional gadolinium-based extracellular contrast agents (ECA) for accurate tumor response assessment following LRT. MRI with hepatobiliary agents (HBA) allows an acquisition of hepatobiliary phase (HBP), which is proven to increase sensitivity for detection of observations in at-risk patients, particularly for findings < 2 cm. The use of HBA is not yet incorporated into the TRA; however, it is increasingly used in clinical practice. Few published studies have evaluated the performance of LI-RADS TRA by applying ancillary features related to HBP that has resulted in category adjustment, enabling more sensitive and unequivocal diagnosis. This may help timely management of viable cases, without a significant loss of specificity in comparison with the ECA-based LI-RADS TRA assessment. In this review, we will describe and compare the imaging appearance of treated HCC on MRI using extracellular and hepatobiliary contrast agents and discuss emerging evidence and pitfalls in the assessment of tumor response following LRT with HBA.
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Affiliation(s)
- Anum Aslam
- Department of Radiology, University of Michigan Health System, 1500 E. Medical Center Dr, Ann Arbor, MI, 48109-5030, USA.
| | - Amita Kamath
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine At Mount Sinai, New York, NY, USA
| | - Bradley Spieler
- Department of Radiology, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, Rm 343, New Orleans, LA, 70112, USA
| | - Mark Maschiocchi
- Umass Memorial Medical Center- University Campus, 55 Lake Avenue North, Worcester, MA, 01655, USA
| | - Carl F Sabottke
- Department of Medical Imaging, University of Arizona College of Medicine, Tucson, AZ, USA
| | - Victoria Chernyak
- Department of Radiology and Urology, Albert Einstein College of Medicine, New York, 10467, USA
| | - Sara C Lewis
- Department of Diagnostic, Molecular and Interventional Radiology, BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Kampalath R, Tran-Harding K, Do RKG, Mendiratta-Lala M, Yaghmai V. Evaluation of Hepatocellular Carcinoma Treatment Response After Locoregional Therapy. Magn Reson Imaging Clin N Am 2021; 29:389-403. [PMID: 34243925 DOI: 10.1016/j.mric.2021.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Locoregional therapy (LRT) for hepatocellular carcinoma can be used alone or with other treatment modalities to reduce rates of progression, improve survival, or act as a bridge to cure. As the use of LRT expands, so too has the need for systems to evaluate treatment response, such as the World Health Organization and modified Response Evaluation Criteria In Solid Tumors systems and more recently, the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (TRA). Early validation results for LI-RADS TRA have been promising, and as research accrues, the TRA is expected to evolve in the near future.
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Affiliation(s)
- Rony Kampalath
- Department of Radiological Sciences, University of California Irvine, 101 The City Drive South, Orange, CA 92868, USA
| | - Karen Tran-Harding
- Department of Radiological Sciences, University of California Irvine, 101 The City Drive South, Orange, CA 92868, USA
| | - Richard K G Do
- Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Radiology, Weill Medical College of Cornell University, New York, NY, USA.
| | - Mishal Mendiratta-Lala
- Radiology, University of Michigan School of Medicine, 1500 East Medical Center Drive, UH B2A209R, Ann Arbor, MI 48109-5030, USA
| | - Vahid Yaghmai
- University of California, Irvine, 101 The City Drive South, Orange, CA 92868, USA
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Faiella E, Santucci D, Bernetti C, Schena E, Pacella G, Zobel BB, Grasso RF. Combined trans-arterial embolisation and microwave ablation for the treatment of large unresectable hepatic metastases (>3 cm in maximal diameter). Int J Hyperthermia 2021; 37:1395-1403. [PMID: 33342310 DOI: 10.1080/02656736.2020.1849823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Abstract
PURPOSE To assess the safety and efficacy of a two-step single-session procedure, combining transarterial embolization (TAE) and percutaneous microwave ablation (MWA), in the treatment of > 3 cm unresectable liver metastases. We also compared the final volume obtained by the two techniques (VE-T) and the expected ablation volume of the stand-alone MWA (VT). METHODS From January 2015 to December 2017, 22 consecutive patients, with a total of 24 unresectable hepatic metastases >3 cm in diameter underwent a two-step single-session combined treatment of TAE and MWA. Follow-up computed tomography scans were performed at 1-, 3-, 6-, 12, and 24 months post-procedure. VE-T as final ablation volume induced by the combined treatment (TAE-MWA), VN as initial nodule volume, VT as expected ablation volume of MWA treatment alone were evaluated and compared. RESULTS Tumor dimensions ranged from 32 to 73 mm. Technical success was achieved in all treated tumors with no local tumor recurrence. Final ablation volumes ranged from 50 to 450 cm3 and the short-axis diameter of the ablation zone ranged from 12 to 48 mm. The mean ΔV increment in the final ablation volume with respect to the stand-alone MWA was 196% (ranging from 25 cm3 - 210 cm3) (p < 0.05). The VE-T mean was four times the VN mean, while the VT mean was about twice the VN mean. No recurrence and only one case of post-embolization bleeding were observed. CONCLUSIONS This study demonstrated the safety and efficacy of a combined two-step single-session TAE-MWA treatment of unresectable hepatic metastases > 3 cm in diameter.
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Affiliation(s)
- Eliodoro Faiella
- Department of Radiology, Campus Bio-Medico University, Rome, Italy
| | | | | | - Emiliano Schena
- Center for Integrated Research, University Campus Bio-Medico di Roma, Rome, Italy
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Aslam A, Do RKG, Kambadakone A, Spieler B, Miller FH, Gabr AM, Charalel RA, Kim CY, Madoff DC, Mendiratta-Lala M. Hepatocellular carcinoma Liver Imaging Reporting and Data Systems treatment response assessment: Lessons learned and future directions. World J Hepatol 2020; 12:738-753. [PMID: 33200013 PMCID: PMC7643220 DOI: 10.4254/wjh.v12.i10.738] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 08/07/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality worldwide, with rising clinical and economic burden as incidence increases. There are a multitude of evolving treatment options, including locoregional therapies which can be used alone, in combination with each other, or in combination with systemic therapy. These treatment options have shown to be effective in achieving remission, controlling tumor progression, improving disease free and overall survival in patients who cannot undergo resection and providing a bridge to transplant by debulking tumor burden to downstage patients. Following locoregional therapy (LRT), it is crucial to provide treatment response assessment to guide management and liver transplant candidacy. Therefore, Liver Imaging Reporting and Data Systems (LI-RADS) Treatment Response Algorithm (TRA) was created to provide a standardized assessment of HCC following LRT. LI-RADS TRA provides a step by step approach to evaluate each lesion independently for accurate tumor assessment. In this review, we provide an overview of different locoregional therapies for HCC, describe the expected post treatment imaging appearance following treatment, and review the LI-RADS TRA with guidance for its application in clinical practice. Unique to other publications, we will also review emerging literature supporting the use of LI-RADS for assessment of HCC treatment response after LRT.
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Affiliation(s)
- Anum Aslam
- Department of Radiology, University of Michigan, Ann Arbor, MI 48019, United States.
| | - Richard Kinh Gian Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States
| | - Avinash Kambadakone
- Abdominal Imaging and Interventional Radiology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, United States
| | - Bradley Spieler
- Department of Radiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States
| | - Frank H Miller
- Department of Radiology, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
| | - Ahmed M Gabr
- Department of Interventional Radiology, OHSU and Tanta University, Egypt, Portland, OR 97239, United States
| | - Resmi A Charalel
- Department of Radiology, Weill Cornell Medicine, New York, NY 10065, United States
| | - Charles Y Kim
- Department of Radiology, Duke University Medical Center, Duke University, Durham, NC 27710, United States
| | - David C Madoff
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT 06520, United States
| | - Mishal Mendiratta-Lala
- School of Medicine, 1500 East Medical Center Drive, University of Michigan, Ann Arbor, MI 48109, United States
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Albrecht KC, Aschenbach R, Diamantis I, Eckardt N, Teichgräber U. Response rate and safety in patients with hepatocellular carcinoma treated with transarterial chemoembolization using 40-µm doxorubicin-eluting microspheres. J Cancer Res Clin Oncol 2020; 147:23-32. [PMID: 32880029 PMCID: PMC7810642 DOI: 10.1007/s00432-020-03370-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 08/19/2020] [Indexed: 12/22/2022]
Abstract
Purpose To evaluate the response rate and safety of superselective drug-eluting beats transarterial chemoembolization (DEB-TACE) with doxorubicin-loaded 40-µm microspheres in patients with hepatocellular carcinoma (HCC). Methods One hundred and forty-one treatments with doxorubicin-loaded 40-µm microspheres in 83 patients between 2012 and 2017 were retrospectively evaluated. Images of the treated lesions were analyzed before and after each treatment according to mRECIST (modified Response Evaluation Criteria in Solid Tumors). Therapy response (complete response [CR] + partial response [PR]) and disease control (CR + PR + stable disease [SD]) rates were determined, and the correlation between the longitudinal axis (longest diameter of the tumor) and volume was investigated using a newly developed software for systematic tumor response assessment. Additional endpoints were progression-free survival (PFS) and time to progression (TTP). Results In the target tumors, a therapy response rate of 63.1% and a disease control rate of 95.7% were achieved. There was a good correlation between the measurement of the longitudinal axis and volume of the measured lesion (r value, 0.954). The median PFS was 2.23 months, and the median TTP was 5.91 months. The serious adverse event rate (SAE) was 10.64%. Conclusion Superselective DEB-TACE with 40-µm sized Embozene Tandem™ can be considered an effective and safe treatment, given the number of procedure-related complications. Electronic supplementary material The online version of this article (10.1007/s00432-020-03370-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Katharina Carolin Albrecht
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Jena IDIR, Am Klinikum 1, 07747, Jena, Germany
| | - René Aschenbach
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Jena IDIR, Am Klinikum 1, 07747, Jena, Germany
| | - Ioannis Diamantis
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Jena IDIR, Am Klinikum 1, 07747, Jena, Germany
| | - Niklas Eckardt
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Jena IDIR, Am Klinikum 1, 07747, Jena, Germany
| | - Ulf Teichgräber
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Jena IDIR, Am Klinikum 1, 07747, Jena, Germany.
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Mendiratta-Lala M, Masch WR, Shampain K, Zhang A, Jo AS, Moorman S, Aslam A, Maturen KE, Davenport MS. MRI Assessment of Hepatocellular Carcinoma after Local-Regional Therapy: A Comprehensive Review. Radiol Imaging Cancer 2020; 2:e190024. [PMID: 33778692 DOI: 10.1148/rycan.2020190024] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 07/29/2019] [Accepted: 09/10/2019] [Indexed: 12/13/2022]
Abstract
Nearly 80% of cirrhotic patients diagnosed with hepatocellular carcinoma (HCC) are not eligible for surgical resection and instead undergo local-regional treatment. After therapy for HCC, patients undergo imaging surveillance to assess treatment efficacy and identify potential sites of progressive tumor elsewhere within the liver. Accurate interpretation of posttreatment imaging is essential for guiding further management decisions, and radiologists must understand expected treatment-specific imaging findings for each of the local-regional therapies. Of interest, expected imaging findings seen after radiation-based therapies (transarterial radioembolization and stereotactic body radiation therapy) are different than those seen after thermal ablation and transarterial chemoembolization. Given differences in expected posttreatment imaging findings, the current radiologic treatment response assessment algorithms used for HCC (modified Response Evaluation Criteria in Solid Tumors classification, European Association for the Study of Liver Diseases criteria, and Liver Imaging and Reporting Data System Treatment Response Algorithm) must be applied cautiously for radiation-based therapies in which persistent arterial phase hyperenhancement in the early posttreatment period is common and expected. This article will review the concept of tumor response assessment for HCC, the forms of local-regional therapy for HCC, and the expected posttreatment findings for each form of therapy. Keywords: Abdomen/GI, Liver, MR-Imaging, Treatment Effects, Tumor Response © RSNA, 2020.
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Affiliation(s)
- Mishal Mendiratta-Lala
- Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr, UH B2A209R, Ann Arbor, MI 48109-5030
| | - William R Masch
- Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr, UH B2A209R, Ann Arbor, MI 48109-5030
| | - Kimberly Shampain
- Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr, UH B2A209R, Ann Arbor, MI 48109-5030
| | - Andrew Zhang
- Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr, UH B2A209R, Ann Arbor, MI 48109-5030
| | - Alexandria S Jo
- Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr, UH B2A209R, Ann Arbor, MI 48109-5030
| | - Sarah Moorman
- Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr, UH B2A209R, Ann Arbor, MI 48109-5030
| | - Anum Aslam
- Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr, UH B2A209R, Ann Arbor, MI 48109-5030
| | - Katherine E Maturen
- Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr, UH B2A209R, Ann Arbor, MI 48109-5030
| | - Matthew S Davenport
- Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr, UH B2A209R, Ann Arbor, MI 48109-5030
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7
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Yang ZW, He W, Zheng Y, Zou RH, Liu WW, Zhang YP, Wang CW, Wang YJ, Yuan YC, Li BK, Yuan YF. The efficacy and safety of long- versus short-interval transarterial chemoembolization in unresectable hepatocellular carcinoma. J Cancer 2018; 9:4000-4008. [PMID: 30410605 PMCID: PMC6218788 DOI: 10.7150/jca.24250] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 06/16/2018] [Indexed: 12/25/2022] Open
Abstract
Background: To compare the efficacy and safety of long- versus short-interval of transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) patients. Methods: This retrospective analysis enrolled 574 patients with unresectable HCC who underwent at least two sessions of TACE between January 2007 and December 2014. The patients were divided into a short-interval group (SIG) and a long-interval group (LIG) based on the median TACE interval of the first two sessions. Propensity score matching (PSM) identified 476 patients for a comparison of overall survival (OS) and safety. Results: Before matching, the LIG had a longer OS than the SIG (Median: 12.1 vs. 8.7 months; P = 0.003). After matching, median OS in the SIG and LIG were 9.1 and 14.2 months (P < 0.001). The 1-, 2-, and 3-year survival rates were 37.5%, 17.1%, and 9.9% for SIG and 50.1%, 19.3%, and 11.6% for LIG, respectively. The TACE interval was an independent prognostic factor for OS. The LIG had a longer OS than the SIG in Barcelona Clinic liver cancer (BCLC) stage C patients (Median: 10.2 vs. 5.8 months; P < 0.001), but not in BCLC-A or B. The postoperative adverse rates were similar in matched SIG and LIG patients (29.4% vs. 33.6%, P = 0.324). Conclusions: A long interval between the first two sessions of TACE resulted in a better OS than a short interval in patients with unresectable BCLC C-stage HCC.
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Affiliation(s)
- Zhi-Wen Yang
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Wei He
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yun Zheng
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Ru-Hai Zou
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Wen-Wu Liu
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yuan-Ping Zhang
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Chen-Wei Wang
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yong-Jin Wang
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yi-Chuan Yuan
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Bin-Kui Li
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yun-Fei Yuan
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
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Sulfamethazine-based pH-sensitive hydrogels with potential application for transcatheter arterial chemoembolization therapy. Acta Biomater 2016; 41:253-63. [PMID: 27184404 DOI: 10.1016/j.actbio.2016.05.018] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2015] [Revised: 05/10/2016] [Accepted: 05/11/2016] [Indexed: 02/07/2023]
Abstract
UNLABELLED Transcatheter arterial chemoembolization (TACE) is the most common palliative therapy for unresectable hepatocellular carcinoma (HCC). The conventional TACE technique, which employs the Lipiodol® emulsion, has been widely used for human cancer treatments. However, this delivery system seems to be inconsistent and unstable in maintaining a high concentration of drugs at tumor sites. An alternative approach for TACE is loading drugs into a liquid embolic solution that exists as an injectable solution and can exhibit a sol-to-gel phase transition to form a solidified state once delivered to the tumor site. Here, we develop a novel sulfamethazine-based anionic pH-sensitive block copolymer with potential application as a radiopaque embolic material. The copolymer, named PCL-PEG-SM, and comprised of poly(ε-caprolactone), sulfamethazine, and poly(ethylene glycol), was fabricated by free radical polymerization. An aqueous solution of the developed copolymer underwent a sol-to-gel phase transition upon lowering the environmental pH to create a gel region that covered the physiological condition (pH 7.4, 37°C) and the low pH conditions at tumor sites (pH 6.5-7.0, 37°C). The release of doxorubicin (DOX) from DOX-loaded copolymer hydrogels could be sustained for more than 4weeks in vitro, and the released DOX retained its fully bioactivity via inhibition the proliferation of hepatic cancer cells. The radiopaque embolic formulations that were prepared by mixing copolymer solutions at pH 8.0 with Lipiodol®, a long-lasting X-ray contrast agent, could exhibit the gelation inside the tumor after intratumoral injection or intraarterial administration using a VX2 carcinoma hepatic tumor rabbit model. These results suggest that a novel anionic pH-sensitive copolymer has been developed with a potential application as a liquid radiopaque embolic solution for TACE of HCC. STATE OF SIGNIFICANCE Transcatheter arterial chemoembolization (TACE) has been widely used as a palliative treatment therapy for unresectable hepatocellular carcinoma (HCC). Conventional TACE technique, which usually employs emulsion of DOX-in-Lipiodol®, followed by an embolic agent, has significant limitation of inconsistency and lack of controlled release ability. To address these limitations of conventional TACE material system, we introduced a novel liquid radiopaque embolic material from our pH-sensitive hydrogel. The material has low viscosity that can be injected via a microcatheter, rather biocompatibility, and drug controlled release ability. Importantly, it can form gel in the tumor as well as tumoral vasculature in response to the lowered pH at the tumor site, which proved the potential for the use to treat HCC by TACE therapy.
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Chiu RYW, Yap WW, Patel R, Liu D, Klass D, Harris AC. Hepatocellular Carcinoma Post Embolotherapy: Imaging Appearances and Pitfalls on Computed Tomography and Magnetic Resonance Imaging. Can Assoc Radiol J 2016; 67:158-72. [PMID: 26961737 DOI: 10.1016/j.carj.2015.09.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Revised: 08/26/2015] [Accepted: 09/07/2015] [Indexed: 02/07/2023] Open
Abstract
Embolotherapies used in the treatment of hepatocellular carcinoma (HCC) include bland embolization, conventional transarterial chemoembolization (cTACE) using ethiodol as a carrier, TACE with drug-eluting beads and super absorbent polymer microspheres (DEB-TACE), and selective internal radiation therapy (SIRT). Successfully treated HCC lesions undergo coagulation necrosis, and appear as nonenhancing hypoattenuating or hypointense lesions in the embolized region on computed tomography (CT) and magnetic resonance. Residual or recurrent tumours demonstrate arterial enhancement with portal venous phase wash-out of contrast, features characteristic of HCC, in and/or around the embolized area. Certain imaging features that result from the procedure itself may limit assessment of response. In conventional TACE, the high-attenuating retained ethiodized oil may obscure arterially-enhancing tumours and limit detection of residual tumours; thus a noncontrast CT on follow-up imaging is important post-cTACE. Hyperenhancement within or around the treated zone can be seen after cTACE, DEB-TACE, or SIRT due to physiologic inflammatory response and may mimic residual tumour. Recognition of these pitfalls is important in the evaluation embolotherapy response.
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Affiliation(s)
- Rita Y W Chiu
- Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
| | - Wan W Yap
- Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Roshni Patel
- Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - David Liu
- Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Darren Klass
- Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Alison C Harris
- Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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10
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Transarterial Embolization for Hepatocellular Carcinoma: A Comparison between Nonspherical PVA and Microspheres. BIOMED RESEARCH INTERNATIONAL 2015; 2015:435120. [PMID: 26413523 PMCID: PMC4564629 DOI: 10.1155/2015/435120] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 05/04/2015] [Accepted: 05/14/2015] [Indexed: 12/13/2022]
Abstract
Transarterial chemoembolization (TACE) and transarterial embolization (TAE) have improved the survival rates of patients with unresectable hepatocellular carcinoma (HCC); however, the optimal TACE/TAE embolic agent has not yet been identified. The aim of this study was to compare the effect of two different embolic agents such as microspheres (ME) and polyvinyl alcohol (PVA) on survival, tumor response, and complications in patients with HCC submitted to transarterial embolization (TAE). Eighty HCC patients who underwent TAE between June 2008 and December 2012 at a single center were retrospectively studied. A total of 48 and 32 patients were treated with PVA and ME, respectively. There were no significant differences in survival (P = 0.679) or tumoral response (P = 0.369) between groups (PVA or ME). Overall survival rates at 12, 18, 24, 36, and 48 months were 97.9, 88.8, 78.9, 53.4, and 21.4% in the PVA-TAE group and 100, 92.9, 76.6, 58.8, and 58% in the ME-TAE group (P = 0.734). Patients submitted to TAE with ME presented postembolization syndrome more frequently when compared with the PVA group (P = 0.02). According to our cohort, the choice of ME or PVA as embolizing agent had no significant impact on overall survival.
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11
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Liu M, Lin MX, Lu MD, Xu ZF, Zheng KG, Wang W, Kuang M, Zhuang WQ, Xie XY. Comparison of contrast-enhanced ultrasound and contrast-enhanced computed tomography in evaluating the treatment response to transcatheter arterial chemoembolization of hepatocellular carcinoma using modified RECIST. Eur Radiol 2015; 25:2502-11. [DOI: 10.1007/s00330-015-3611-9] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2014] [Revised: 10/21/2014] [Accepted: 01/16/2015] [Indexed: 01/15/2023]
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12
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MDCT findings after hepatic chemoembolization with DC-beads: what the radiologist needs to know. ACTA ACUST UNITED AC 2013; 38:778-84. [PMID: 23053454 DOI: 10.1007/s00261-012-9963-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Transcatheter arterial chemoembolization with drug-eluting beads (TACE-DC-beads) is a new local treatment for primary or metastatic liver tumors. Despite technical efforts to achieve highly selective embolization of the tumor-supplying vessels, small, or large insults to the non-tumorous parenchyma are inevitably induced by the embolic materials or procedure itself. Parenchymal changes following TACE-DC-beads include bile duct injuries (bile duct dilatation, periportal edema, and bilomas), obliteration of intrahepatic portal vein branches, hypodense ill-defined areas, and perilesional parenchymal enhancement. The radiologist must be familiar with the changes induced by this treatment in order to distinguish therapeutic effect and collateral findings from complications and residual or recurrent tumor.
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Giunchedi P, Maestri M, Gavini E, Dionigi P, Rassu G. Transarterial chemoembolization of hepatocellular carcinoma – agents and drugs: an overview. Part 2. Expert Opin Drug Deliv 2013; 10:799-810. [DOI: 10.1517/17425247.2013.796359] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Tzeng SY, Higgins LJ, Pomper MG, Green JJ. Student award winner in the Ph.D. category for the 2013 society for biomaterials annual meeting and exposition, april 10-13, 2013, Boston, Massachusetts : biomaterial-mediated cancer-specific DNA delivery to liver cell cultures using synthetic poly(beta-amino ester)s. J Biomed Mater Res A 2013; 101:1837-45. [PMID: 23559534 DOI: 10.1002/jbm.a.34616] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Accepted: 01/22/2013] [Indexed: 12/21/2022]
Abstract
Liver cancer is a leading cause of cancer death. Most patients are treated by arterial injection of chemoembolizing agents, providing a convenient avenue for local treatment by novel therapies, including gene therapy. Poly(beta-amino ester)s (PBAEs) were synthesized and used to form nanoparticles for non-viral transfection of buffalo rat hepatoma (MCA-RH7777) and hepatocyte (BRL-3A) lines with eGFP and luciferase DNA. Hepatoma cells were transfected with up to (98 ± 0.4)% efficacy with no measurable cytotoxicity. Hepatocytes were transfected with as high as (73 ± 0.4)% efficacy with (10 ± 4)% non-specific cytotoxicity. In contrast, positive controls (branched polyethylenimine, Lipofectamine™ 2000, and X-tremeGENE(®) DNA HP) caused 30-90% toxicity in BRL-3A cells at doses required for >50% transfection. Of the 21 optimized PBAE-DNA formulations tested, 12 showed significant specificity for hepatoma cells over hepatocytes in monoculture (p < 0.05 for both percentage transfected and eGFP expression intensity). Top polymers from eGFP studies also delivered luciferase DNA with 220 ± 30-fold and 470 ± 30-fold greater specificity for hepatoma cells than hepatocytes. Transfections of co-cultures of hepatoma and hepatocytes with eGFP DNA also showed high specificity (1.9 ± 0.1- to 5.8± 1.4-fold more transfected hepatoma cells than hepatocytes, measured by percentage transfected and flow cytometry). By eGFP intensity, up to 530 ±60-fold higher average expression per cell was measured in hepatoma cells. One top formulation caused (95 ± 0.2)% transfection in hepatoma cells and (27 ± 0.2)% in hepatocytes [(96 ± 9)% relative hepatocyte viability]. PBAE-based nanoparticles are a viable strategy for liver cancer treatment, delivering genes to nearly 100% of cancer cells while maintaining high biomaterial-mediated specificity to prevent toxic side-effects on healthy hepatocytes.
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Affiliation(s)
- Stephany Y Tzeng
- Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Huo X, Zhang Q, Liu AM, Tang C, Gong Y, Bian J, Luk JM, Xu Z, Chen J. Overexpression of Yes-associated protein confers doxorubicin resistance in hepatocellullar carcinoma. Oncol Rep 2012; 29:840-6. [PMID: 23232767 DOI: 10.3892/or.2012.2176] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2012] [Accepted: 11/21/2012] [Indexed: 11/06/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies worldwide and is highly resistant to chemotherapy. Yes-associated protein (YAP) is the downstream effector of the Hippo signaling pathway, which is frequently overexpressed in many types of cancers. Amplification of the YAP gene and overexpression of YAP in HCC have previously been reported to contribute to hepatocyte malignant transformation and tumor progression. In this study, we aimed to investigate the potential role of YAP in HCC chemoresistance. Overexpression of YAP resulted in resistance against doxorubicin-induced apoptosis in HCC cell lines, whereas suppression of the endogenous YAP expression by RNA interference demonstrated the reverse effect. Western blotting revealed that, following exposure to doxorubicin, YAP-overexpressing cells exhibited decreased cleaved PARP, increased phosphorylation of Akt and ERK1/2, and elevated Bcl-xL expression in comparison to the vector control. Inhibition of YAP expression sensitized HCC cells to doxorubicin, by exhibiting increased cleaved PARP, decreased levels of phosphorylated Akt, phosphorylated ERK1/2 and Bcl-xL expression. In addition, pretreatment with the MEK1/2 inhibitor U0126 but not the PI3-K inhibitor LY294002 significantly enhanced doxorubicin-induced apoptosis and decreased Bcl-xL expression in YAP-overexpressing HCC cells. Our data provide evidence that overexpression of YAP plays an important role in conferring doxorubicin resistance to HCC, which is at least partially mediated by YAP-induced activation of the MAP kinase pathway. Targeting YAP may be a promising adjunct for overcoming doxorubicin resistance in HCC.
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Affiliation(s)
- Xinying Huo
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, PR China
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Fatima S, Lee NP, Luk JM. Dickkopfs and Wnt/β-catenin signalling in liver cancer. World J Clin Oncol 2011; 2:311-25. [PMID: 21876852 PMCID: PMC3163259 DOI: 10.5306/wjco.v2.i8.311] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2011] [Revised: 07/07/2011] [Accepted: 07/14/2011] [Indexed: 02/06/2023] Open
Abstract
Liver cancer is the fifth and seventh most common cause of cancer in men and women, respectively. Wnt/β-catenin signalling has emerged as a critical player in both the development of normal liver as well as an oncogenic driver in hepatocellular carcinoma (HCC). Based on the current understanding, this article summarizes the possible mechanisms for the aberrant activation of this pathway with specific focus on HCC. Furthermore, we will discuss the role of dickkopfs (DKKs) in regulating Wnt/β-catenin signalling, which is poorly understood and understudied. DKKs are a family of secreted proteins that comprise at least four members, namely DKK1-DKK4, which act as inhibitors of Wnt/β-catenin signalling. Nevertheless, not all members antagonize Wnt/β-catenin signalling. Their functional significance in hepatocarcinogenesis remains to be further characterized for which these studies should provide new insights into the regulatory role of DKKs in Wnt/β-catenin signalling in hepatic carcinogenesis. Because of the important oncogenic roles, there are an increasing number of therapeutic molecules targeting β-catenin and the Wnt/β-catenin pathway for potential therapy of HCC.
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Affiliation(s)
- Sarwat Fatima
- Sarwat Fatima, Nikki P Lee, Department of Surgery, The University of Hong Kong, Hong Kong, China
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