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Adnan A, Basu S. PET-based Quantitative Techniques in Assessing Efficacy of Interventional Radiology Procedures in Oncology. PET Clin 2025:S1556-8598(25)00028-8. [PMID: 40340172 DOI: 10.1016/j.cpet.2025.03.005] [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: 05/10/2025]
Abstract
Interventional radiology (IR) is a super specialised branch where imaging modalities are employed to guide disease specific diagnostic and therapeutic interventions. IR interventions have gained popularity in various oncological and non-oncological indications due to it's ability to effectively diagnose the disease and direct specific targeted treatment. Hybrid imaging using PET CT and PET MRI combines the best of morphological and functional informations and offers improved sensitivity and specificity for detection of lesion; helps in accurate mapping of tumour burden, thereby aiding in planning curative vs palliative intent intervention; more accurate response evaluation to plan redo session in cases of residual / recurrent disease or for follow up evaluation and for prognostication and predicting response. Albeit visual analysis of PET images by specialist is most commonly performed for reading PET scans, PET has a remarkable capability to provide quantitative information. The present review provides a comprehensive assessment of the role of various aspects of quantitative PET parameters in assessing the efficacy of IR interventions. The insights provided will help clinicians, researchers, and medical professionals understand the role of PET imaging in advancing patient care and enhancing the therapeutic outcomes of IR procedures.
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Affiliation(s)
- Aadil Adnan
- Radiation Medicine Centre (B.A.R.C), Tata Memorial Centre Annexe, Parel, Mumbai, Maharahtra, India; Homi Bhabha National Institute, Mumbai, India; Department of Nuclear Medicine, Medica Cancer Center, Medica Superspeciality Hospital, 127, Eastern Metropolitean Bypass, Mukundapur, Kolkata, West Bengal, India
| | - Sandip Basu
- Radiation Medicine Centre (B.A.R.C), Tata Memorial Centre Annexe, Parel, Mumbai, Maharahtra, India; Homi Bhabha National Institute, Mumbai, India.
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Lu H, Xie X, Zeng Y, Xia X, Dong X, Bu F, Fan H, Xu S. Prognostic Comparison of Complete vs. Incomplete Radiofrequency Ablation for Colorectal Liver Metastases: A Multicenter Prospective Study. Cancer Med 2025; 14:e70735. [PMID: 40231586 PMCID: PMC11997704 DOI: 10.1002/cam4.70735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 02/09/2025] [Accepted: 02/19/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND Radiofrequency ablation (RFA) is a curative treatment for colorectal liver metastases (CLMs) in selected patients. NCCN guidelines recommend RFA for both unresectable and select resectable CLMs when complete ablation with adequate margins is feasible. While RFA can achieve oncologic outcomes comparable to surgery in well-selected patients, residual tumors are associated with a poorer prognosis. OBJECTIVES To identify predictors of residual tumor after percutaneous RFA for CLMs and evaluate their impact on overall survival (OS) and new intrahepatic metastases (NIHM). METHODS We prospectively included patients with CLMs who underwent percutaneous RFA from November 2019 to November 2022. Dynamic contrast-enhanced computed tomography assessed CLMs before and after RFA. Residual tumor was defined as active tumor visible immediately post-ablation or within 4-8 weeks, within 1 cm of the ablation zone. Data from three centers formed a developmental cohort, validated with patients from a fourth center. Cox regression and Kaplan-Meier analysis assessed local tumor progression-free survival (LTPFS), NIHM, and OS. RESULTS Among 200 patients (mean age 61 years, 126 men) with 410 tumors, independent predictors of residual tumors included perivascular tumor location (odds ratio [OR] = 6.673), tumor size ≥ 20 mm (OR = 3.925), and minimal ablative margin (OR = 0.599). These factors also predicted LTPFS. NIHM was more frequent in the residual tumor group than in the complete RFA (cRFA) group (p = 0.002). Median OS was 45 months, shorter in the residual tumor group (30 vs. 48 months, p = 0.009). Patients with NIHM who received transarterial chemoembolization combined with hepatic arterial infusion chemotherapy had a median OS of 43 months, compared to 34 months with RFA alone (p = 0.039). CONCLUSIONS A non-perivascular tumor location, tumor size < 20 mm, and a sufficient ablation margin are essential for achieving complete RFA. Residual tumors are associated with increased NIHM and shorter OS.
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Affiliation(s)
- Huilin Lu
- Department of Interventional TherapyXinxiang Central Hospital/the Fourth Clinical College of Xinxiang Medical UniversityXinxiangHenanChina
| | - Xuancheng Xie
- Department of RadiologyThe First People's Hospital of Yunnan ProvinceKunmingYunnanChina
| | - Yulan Zeng
- Cancer Center, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Xiangwen Xia
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Provincial Key Laboratory of Molecular ImagingWuhanChina
| | - Xiangjun Dong
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Provincial Key Laboratory of Molecular ImagingWuhanChina
| | - Futang Bu
- Department of Radiation Oncology, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Hongjie Fan
- Department of Radiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional MedicineWuhanChina
- Hubei Provincial Key Laboratory of Molecular ImagingWuhanChina
| | - Shufeng Xu
- Department of Radiology, The Quzhou Affiliated Hospital of Wenzhou Medical UniversityQuzhou People's HospitalQuzhouChina
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Yuan C, Zeng L, Duan H, Suksatit B. Meta-analysis of the prognostic value of serum carcinoembryonic antigen in patients with colorectal cancer liver metastases after hepatectomy. Eur J Cancer Prev 2024; 33:334-346. [PMID: 37997904 DOI: 10.1097/cej.0000000000000859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2023]
Abstract
OBJECTIVES Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. This meta-analysis was aimed at evaluating whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). METHODS PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cutoff date of 27 February 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. RESULTS This meta-analysis included 36 studies involving a total of 11 143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS: HR = 1.61, 95% CI = 1.49-1.75, P < 0.001) and recurrence-free survival (RFS: HR = 1.27, 95% CI = 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor overall survival (OS: HR = 2.66, 95% CI = 2.10-3.38, P < 0.001). CONCLUSION High preoperative and postoperative serum CEA levels in patients with CRCLM were significantly associated with poor prognosis, independent of treatment modality, mode of analysis, case origin, and cutoff value classification.
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Affiliation(s)
- Chenzhao Yuan
- Faculty of Nursing, Chiang Mai University, Chiang Mai, Thailand
| | - Lumin Zeng
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Hongxiang Duan
- Faculty of Nursing, Chiang Mai University, Chiang Mai, Thailand
- School of Nursing, Chengdu University, Chengdu, China
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Nittayacharn P, Abenojar E, Cooley MB, Berg FM, Counil C, Sojahrood AJ, Khan MS, Yang C, Berndl E, Golczak M, Kolios MC, Exner AA. Efficient ultrasound-mediated drug delivery to orthotopic liver tumors - Direct comparison of doxorubicin-loaded nanobubbles and microbubbles. J Control Release 2024; 367:135-147. [PMID: 38237687 PMCID: PMC11700473 DOI: 10.1016/j.jconrel.2024.01.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 01/11/2024] [Accepted: 01/15/2024] [Indexed: 01/28/2024]
Abstract
Liver metastasis is a major obstacle in treating aggressive cancers, and current therapeutic options often prove insufficient. To overcome these challenges, there has been growing interest in ultrasound-mediated drug delivery using lipid-shelled microbubbles (MBs) and nanobubbles (NBs) as promising strategies for enhancing drug delivery to tumors. Our previous work demonstrated the potential of Doxorubicin-loaded C3F8 NBs (hDox-NB, 280 ± 123 nm) in improving cancer treatment in vitro using low-frequency unfocused therapeutic ultrasound (TUS). In this study, we investigated the pharmacokinetics and biodistribution of sonicated hDox-NBs in orthotopic rat liver tumors. We compared their delivery and therapeutic efficiency with size-isolated MBs (hDox-MB, 1104 ± 373 nm) made from identical shell material and core gas. Results showed a similar accumulation of hDox in tumors treated with hDox-MBs and unfocused therapeutic ultrasound (hDox-MB + TUS) and hDox-NB + TUS. However, significantly increased apoptotic cell death in the tumor and fewer off-target apoptotic cells in the normal liver were found upon the treatment with hDox-NB + TUS. The tumor-to-liver apoptotic ratio was elevated 9.4-fold following treatment with hDox-NB + TUS compared to hDox-MB + TUS, suggesting that the therapeutic efficacy and specificity are significantly increased when using hDox-NB + TUS. These findings highlight the potential of this approach as a viable treatment modality for liver tumors. By elucidating the behavior of drug-loaded bubbles in vivo, we aim to contribute to developing more effective liver cancer treatments that could ultimately improve patient outcomes and decrease off-target side effects.
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Affiliation(s)
- Pinunta Nittayacharn
- Department of Radiology, Case Western Reserve University, Cleveland, OH, USA; Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Puttamonthon, Nakorn Pathom, Thailand
| | - Eric Abenojar
- Department of Radiology, Case Western Reserve University, Cleveland, OH, USA
| | - Michaela B Cooley
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Felipe M Berg
- Department of Radiology, Case Western Reserve University, Cleveland, OH, USA; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
| | - Claire Counil
- Department of Radiology, Case Western Reserve University, Cleveland, OH, USA
| | - Amin Jafari Sojahrood
- Department of Physics, Toronto Metropolitan University, Toronto, Canada; Institute for Biomedical Engineering, Science and Technology (iBEST), a partnership between St. Michael's Hospital, a site of Unity Health Toronto and Toronto Metropolitan University, Toronto, Canada
| | - Muhammad Saad Khan
- Department of Physics, Toronto Metropolitan University, Toronto, Canada; Institute for Biomedical Engineering, Science and Technology (iBEST), a partnership between St. Michael's Hospital, a site of Unity Health Toronto and Toronto Metropolitan University, Toronto, Canada
| | - Celina Yang
- Department of Physics, Toronto Metropolitan University, Toronto, Canada; Institute for Biomedical Engineering, Science and Technology (iBEST), a partnership between St. Michael's Hospital, a site of Unity Health Toronto and Toronto Metropolitan University, Toronto, Canada
| | - Elizabeth Berndl
- Department of Physics, Toronto Metropolitan University, Toronto, Canada; Institute for Biomedical Engineering, Science and Technology (iBEST), a partnership between St. Michael's Hospital, a site of Unity Health Toronto and Toronto Metropolitan University, Toronto, Canada
| | - Marcin Golczak
- Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA
| | - Michael C Kolios
- Department of Physics, Toronto Metropolitan University, Toronto, Canada; Institute for Biomedical Engineering, Science and Technology (iBEST), a partnership between St. Michael's Hospital, a site of Unity Health Toronto and Toronto Metropolitan University, Toronto, Canada
| | - Agata A Exner
- Department of Radiology, Case Western Reserve University, Cleveland, OH, USA; Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
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Tang F, Huang CW, Tang ZH, Lu SL, Bai T, Huang Q, Li XZ, Zhang B, Wu FX. Prognostic role of serum carcinoembryonic antigen in patients receiving liver resection for colorectal cancer liver metastasis: A meta-analysis. World J Gastrointest Surg 2023; 15:2890-2906. [PMID: 38222018 PMCID: PMC10784827 DOI: 10.4240/wjgs.v15.i12.2890] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 11/03/2023] [Accepted: 11/28/2023] [Indexed: 12/27/2023] Open
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. AIM To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). METHODS PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cut-off date of February 27, 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. RESULTS This meta-analysis included 36 studies involving a total of 11143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS) [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.49-1.75, P < 0.001] and recurrence-free survival (HR = 1.27, 95%CI: 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor OS (HR = 2.66, 95%CI: 2.10-3.38, P < 0.001). A comparison by treatment modality, analysis modality, patient source, and cutoff-value showed that overall, high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis. CONCLUSION This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.
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Affiliation(s)
- Fan Tang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Cheng-Wen Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zhi-Hong Tang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Shao-Long Lu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Tao Bai
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Qing Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xing-Zhi Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Bin Zhang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Key Laboratory of High-Incidence-Tumor Prevention & Treatment, Ministry of Education, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Qin S, Zhou J, Cui R, Chen Y, Wang Y, Liu G. Percutaneous ablation of colorectal liver metastases: a comparison between the outcomes of grayscale US guidance and Sonazoid CEUS Kupffer phase guidance using propensity score matching. Int J Hyperthermia 2023; 40:2260573. [PMID: 37788806 DOI: 10.1080/02656736.2023.2260573] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 09/13/2023] [Indexed: 10/05/2023] Open
Abstract
PURPOSE To assess the utility of Sonazoid contrast-enhanced ultrasound (CEUS) for guiding percutaneous microwave ablation (MWA) for colorectal liver metastases (CRLMs). MATERIALS AND METHODS The medical records of patients who had undergone ultrasound (US)-guided percutaneous MWA between July 2020 and June 2022, were reviewed. Propensity score matching (PSM) with a ratio of 1:1 was used to balance the potential bias between the grayscale US-guided and Sonazoid CEUS-guided groups. Local tumor progression (LTP), intrahepatic recurrence (IR), and complication rates were compared between the two groups. RESULTS Of 252 patients enrolled, 247 achieved complete ablation, and the technical effectiveness was 98.0% (247/252). Of these 247 patients, 158 were in the grayscale US-guided group and 89 in the Sonazoid CEUS-guided group. The median follow-up period was 14.6 months. After PSM, there were no significant differences in LTP, IR, or complication rates between the two groups (p = 0.100, p = 0.511, p > 0.99, respectively). Multivariate analysis identified tumor size ≥ 3 cm (hazard ratio [HR], 7.945; 95% CI, 2.591-24.370; p < 0.001), perivascular (HR, 2.331; 95% CI, 1.068-5.087; p = 0.034), and tumor depth > 8 cm (HR, 3.194; 95% CI, 1.439-7.091; p = 0.004) as significant factors associated with LTP. For tumors with poor vision on grayscale US, Sonazoid CEUS-guided ablation achieved a better LTP rate than grayscale US-guided ablation (3.7% vs.14.8%, p = 0.032). CONCLUSION For tumors with poor vision on grayscale US, Sonazoid CEUS guidance is recommended for better local tumor control.
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Affiliation(s)
- Si Qin
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Jingwen Zhou
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Rui Cui
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Yao Chen
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Yimin Wang
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Guangjian Liu
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
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Nittayacharn P, Abenojar E, Cooley M, Berg F, Counil C, Sojahrood AJ, Khan MS, Yang C, Berndl E, Golczak M, Kolios MC, Exner AA. Efficient ultrasound-mediated drug delivery to orthotopic liver tumors - Direct comparison of doxorubicin-loaded nanobubbles and microbubbles. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.09.01.555196. [PMID: 37732235 PMCID: PMC10508722 DOI: 10.1101/2023.09.01.555196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/22/2023]
Abstract
Liver metastasis is a major obstacle in treating aggressive cancers, and current therapeutic options often prove insufficient. To overcome these challenges, there has been growing interest in ultrasound-mediated drug delivery using lipid-shelled microbubbles (MBs) and nanobubbles (NBs) as promising strategies for enhancing drug delivery to tumors. Our previous work demonstrated the potential of Doxorubicin-loaded C3F8 NBs (hDox-NB, 280 ± 123 nm) in improving cancer treatment in vitro using low-frequency ultrasound. In this study, we investigated the pharmacokinetics and biodistribution of sonicated hDox-NBs in orthotopic rat liver tumors. We compared their delivery and therapeutic efficiency with size-isolated MBs (hDox-MB, 1104 ± 373 nm). Results showed a similar accumulation of hDox in tumors treated with hDox-MBs and unfocused therapeutic ultrasound (hDox-MB+TUS) and hDox-NB+TUS. However, significantly increased apoptotic cell death in the tumor and fewer off-target apoptotic cells in the normal liver were found upon the treatment with hDox-NB+TUS. The tumor-to-liver apoptotic ratio was elevated 9.4-fold following treatment with hDox-NB+TUS compared to hDox-MB+TUS, suggesting that the therapeutic efficacy and specificity are significantly increased when using hDox-NB+TUS. These findings highlight the potential of this approach as a viable treatment modality for liver tumors. By elucidating the behavior of drug-loaded bubbles in vivo, we aim to contribute to developing more effective liver cancer treatments that could ultimately improve patient outcomes and decrease off-target side effects.
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Affiliation(s)
| | - Eric Abenojar
- Department of Radiology, Case Western Reserve University, Cleveland, OH, USA
| | - Michaela Cooley
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Felipe Berg
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
- Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
| | - Claire Counil
- Department of Radiology, Case Western Reserve University, Cleveland, OH, USA
| | | | | | - Celina Yang
- Department of Physics, Toronto Metropolitan University, Toronto, Canada
| | - Elizabeth Berndl
- Department of Physics, Toronto Metropolitan University, Toronto, Canada
| | - Marcin Golczak
- Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA
| | - Michael C. Kolios
- Department of Physics, Toronto Metropolitan University, Toronto, Canada
| | - Agata A. Exner
- Department of Radiology, Case Western Reserve University, Cleveland, OH, USA
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
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Szemitko M, Golubinska-Szemitko E, Sienko J, Falkowski A, Wiernicki I. Efficacy of Liver Chemoembolization after Prior Cetuximab Monotherapy in Patients with Metastatic Colorectal Cancer. Cancers (Basel) 2023; 15:cancers15020541. [PMID: 36672489 PMCID: PMC9856261 DOI: 10.3390/cancers15020541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/09/2023] [Accepted: 01/13/2023] [Indexed: 01/18/2023] Open
Abstract
Purpose: Chemoembolization of liver lesions, metastatic from colorectal cancer (CRC), with irinotecan-loaded microspheres shows less efficacy if applied after previous systemic chemotherapy. This is because cancer cells acquire resistance to previously used chemotherapeutic agents, e.g., irinotecan or perhaps via, e.g., modulations of EGFR receptors after use of anti-EGFR antibodies. Objective: To evaluate the effects of prior treatment with anti-EGFR (cetuximab) antibodies on the efficacy of chemoembolization, with irinotecan-loaded microspheres, of liver lesions metastatic from CRC. Patients and methods: The study included 50 patients (27 female, 23 male) with inoperable liver metastases in the course of CRC who underwent a total of 192 chemoembolization procedures with microspheres loaded with 100 mg of irinotecan. Chemoembolization of the right or left liver lobes was performed alternately at three-week intervals. Patients were divided into two groups: group A (n = 26): patients who had previously received anti-EGFR (cetuximab) antibodies; and group B (n = 24): patients who had never received anti-EGFR antibodies. Response to treatment was assessed according to mRECIST criteria. Overall survival time (OS) was calculated using the Kaplan−Meier method. Evaluation of adverse effects was performed according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (Version 5.0). Results: Analysis did not show a statistically significant difference in radiological response between the two groups: partial response: 36.2% in group A and 32.9% in group B (p = 0.139); and stable disease: 19.2% in group A and 21.7% in group B (p = 0.224). Post-treatment progression was comparable at 46.2% in group A and 41.6% in group B (p = 0.343). There was a significant difference in OS (p = 0.043 log-rank test), however, prior treatment with cetuximab showed no significant effect on OS in a Cox proportional hazards regression model HR 1.906 (0.977−3.716), p = 0.058. Mean OS was 15.2 months (95% confidence interval (Cl): 6 to 23 months) in group A and 13.1 months (95% Cl: 7 to 22 months) in group B. In both groups, there was a negative correlation between carcinoembryonic antigen (CEA) levels below 10 mg/mL before surgery and OS (hazard ratio (HR) 0.83 (0.47−8.43), p = 0.005 in group A and HR 1.02 (0.56−7.39), p = 0.003 in group B). There was no significant difference in the number of prominent complications between group A (7 complications) and group B (6 complications), p = 0.663. Conclusions: Previous therapy with anti-EGFR antibodies before treatment with irinotecan chemoembolization of liver metastatic lesions did not have a significant effect on radiological response to treatment or post-treatment progression. However, higher baseline levels of CEA (>10 ng/mL) were correlated with worse OS (p = 0.039).
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Affiliation(s)
- Marcin Szemitko
- Department of Interventional Radiology, Pomeranian Medical University, 70-111 Szczecin, Poland
- Correspondence: ; Tel./Fax: +48-91-4661169
| | | | - Jerzy Sienko
- Department of General and Transplant Surgery, Pomeranian Medical University, 70-111 Szczecin, Poland
| | - Aleksander Falkowski
- Department of Interventional Radiology, Pomeranian Medical University, 70-111 Szczecin, Poland
| | - Ireneusz Wiernicki
- Department of Vascular Surgery, General Surgery and Angiology, Pomeranian Medical University, 70-111 Szczecin, Poland
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The Correlation between 18F-FDG PET/CT Imaging SUVmax of Preoperative Colon Cancer Primary Lesions and Clinicopathological Factors. JOURNAL OF ONCOLOGY 2021; 2021:4312296. [PMID: 34567115 PMCID: PMC8463203 DOI: 10.1155/2021/4312296] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 08/25/2021] [Indexed: 11/17/2022]
Abstract
Background The purpose of this study is to explore the correlation between the 18F-FDG PET/CT imaging maximum standardized uptake value (SUVmax) of preoperative colon cancer primary lesions and clinicopathological factors. Methods 88 colon cancer patients diagnosed by histopathology were collected from January 2014 to December 2015. 18F-FDG PET/CT imaging was performed before surgery. Kaplan–Meier survival analysis was used to assess the prognosis of colon cancer patients. Results The 18F-FDG PET/CT imaging SUVmax value of preoperative colon cancer primary lesion was significantly correlated with the length of the lesion, clinical stage, histopathological type, and the degree of tumor differentiation. The SUVmax value of tumors with long-diameter, ≥ 3 cm, clinically high-stage, adenocarcinoma, and poorly differentiated lesions was significantly high. In addition, the consistency between PET/CT and surgical pathological results at stage I and IV was higher. Stage II and III PET/CT are basically consistent with the pathological results of surgery. Kaplan–Meier survival analysis showed that the 5-year event-free survival rate of the SUVmax > 18.26 group was significantly lower than that of the SUVmax ≤ 18.26 group. Conclusion 18F-FDG PET/CT imaging SUVmax of preoperative colon cancer primary lesions can not only reflect the proliferation and invasion ability but also monitor the recurrence and metastasis of colon cancer.
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Fan H, Wang X, Qu J, Lu W, Pang Z, Shao T, Xia J, Wang H, Li G, Zhang Y, Sun J, Yang X. Periprocedural risk factors for incomplete radiofrequency ablation of liver metastases from colorectal cancer: a single-center retrospective analysis. Int J Hyperthermia 2021; 38:985-994. [PMID: 34167430 DOI: 10.1080/02656736.2021.1942564] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE To explore independent risk factors for incomplete radiofrequency ablation (iRFA) of colorectal cancer liver metastases (CRLM) and evaluate adverse outcomes following iRFA. MATERIALS AND METHODS Magnetic resonance imaging data of CRLM patients who received percutaneous RFA were randomized into training (70%) and validation set 1 (30%) data sets. An independent validation set 2 was derived from computed tomography scans. Uni- and multivariate analyses identified independent risk factors for iRFA. Area under the curve (AUC) values were used to evaluate the predictive model performance. Risk points were assigned to independent predictors, and iRFA was predicted according to the total risk score. Kaplan-Meier curves were used to assess new intrahepatic metastases (NIHM), unablated tumor progression, and overall survival (OS). RESULTS Multivariate regression determined as independent iRFA risk factors perivascular tumor location, subcapsular tumor location, tumor size ≥20 mm, and minimal ablative margin ≤5 mm. The AUC values of the model in the training set, validation set 1, and validation set 2 were 0.867, 0.772, and 0.820, respectively. The respective AUC values of the total risk score were 0.864, 0.768, and 0.817. During the 6-year follow-up, the cumulative OS was significantly shorter in the iRFA than in the complete RFA group, and NIHM (hazard ratio [HR] = 2.79; 95% confidence interval [CI]: 1.725, 4.513) and unablated tumor progression (HR = 3.473; 95% CI: 1.506, 8.007) were more severe. CONCLUSIONS Perivascular tumor location, subcapsular tumor location, tumor size ≥20 mm, and minimal ablative margin ≤5 mm were independent risk factors for iRFA. iRFA may be a potential predictor of NIHM, unablated tumor progression, and OS.
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Affiliation(s)
- Hongjie Fan
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xiaoyan Wang
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jiali Qu
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Wei Lu
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zhenzhu Pang
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Tingting Shao
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jingya Xia
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Huiyang Wang
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Guangyao Li
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yanhua Zhang
- Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jihong Sun
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xiaoming Yang
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.,Department of Radiology, Image-Guided Bio-Molecular Intervention Research, University of Washington School of Medicine, Seattle, WA, USA
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Complications Following Irinotecan-Loaded Microsphere Chemoembolization of Colorectal Metastatic Liver Lesions Associated with Hepatic-Artery Branch Temporary Stasis. ACTA ACUST UNITED AC 2021; 28:2296-2307. [PMID: 34203031 PMCID: PMC8293090 DOI: 10.3390/curroncol28030211] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/04/2021] [Accepted: 06/14/2021] [Indexed: 01/01/2023]
Abstract
Chemoembolization with irinotecan-loaded microspheres has proven effective in the treatment of unresectable liver metastases in the course of colorectal cancer (CRC). Most researchers recommend slowly administering the embolizate at the level of the lobar arteries, without obtaining visible stasis. However, there are reports of a relationship between postoperative embolizate retention in metastatic lesions and the response to treatment. To retain residual embolizate throughout the entire neoplastic lesion requires a temporary flow stop (stasis) within all supply vessels, which may cause temporary stasis in subsegmental or even segmental vessels. Objective: To assess the risk of complications and post-embolization syndrome severity following chemoembolization of CRC metastatic liver lesions with microspheres loaded with Irinotecan, with regard to hepatic-artery branch level of temporary stasis. Patients and methods: The study included 52 patients (29 female, 23 male) with liver metastases from CRC, who underwent 202 chemoembolization treatments (mean: 3.88 per patient) with microspheres loaded with 100 mg irinotecan. Postembolization syndrome (PES) severity and complication occurrence were assessed with regard to the hepatic-artery branch level of temporary stasis. Adverse events were assessed according to Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events. Results: Median survival from the start of chemoembolization was 13 months. From 202 chemoembolization sessions, 15 (7.4%) significant complications were found. The study found a significant relationship between the branch level of temporary stasis and the presence of complications (p < 0.001), with the highest number of complications observed with temporary stasis in segmental vessels. PES was diagnosed after 103 (51%) chemoembolization treatments. A significant association was found between PES severity and the branch level of temporary stasis (p < 0.001). Conclusions: The branch level of temporary stasis affected the severity of post-embolization syndrome. A significant association was found between the branch level of temporary stasis obtained in chemoembolization procedures and the presence of complications. The apparent lack of change in numbers of complications when stasis was applied at tumor supply vessels or subsegmental arteries may indicate the safe use of temporary stasis in some cases where colorectal cancer metastases are treated. Further research is needed to determine the most effective chemoembolization technique.
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Majlesara A, Krause J, Khajeh E, Ghamarnejad O, Gharabaghi N, Tinoush P, Mohammadi S, Al-Saeedi M, Mehrabi A, Golriz M. A fast and easy-to-learn technique for liver resection in a porcine model. J Int Med Res 2021; 49:300060521990219. [PMID: 33557642 PMCID: PMC7876770 DOI: 10.1177/0300060521990219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Objective Despite the recent advances in surgical techniques and perioperative care,
liver resection (especially extended hepatectomy) is still a high-risk
procedure with considerable morbidity and mortality. Experimental large
animal models are the best option for studies in this regard. The present
study was performed to present an easy-to-learn, fast, and multipurpose
model of liver resection in a porcine model. Method Stepwise liver resections (resection of segments II/III, IVa/IVb, and
VIII/IV) were performed in eight pigs with intraoperative monitoring of
hemodynamic parameters. The technical aspects, tips, and tricks of this
method are explained in detail. Results Based on the specific anatomical characteristics of the porcine liver, all
resection types including segmental resection, hemihepatectomy, and extended
hepatectomy could be performed in one animal in an easy-to-learn and fast
technique. All animals were hemodynamically stable following stepwise liver
resection. Conclusion Stepwise liver resection using stapler in a porcine model is a fast and
easy-to-learn method with which junior staff and research fellows can
perform liver resection up to extended hepatectomy under stable
conditions.
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Affiliation(s)
- Ali Majlesara
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Jürgen Krause
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Elias Khajeh
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Omid Ghamarnejad
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Negin Gharabaghi
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Parham Tinoush
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Sara Mohammadi
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Mohammed Al-Saeedi
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Mohammad Golriz
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
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Yoshikawa M, Morine Y, Yamada S, Miyazaki K, Tokuda K, Saito Y, Arakawa Y, Ikemoto T, Imura S, Shimada M. Prognostic prediction of resectable colorectal liver metastasis using the apparent diffusion coefficient from diffusion-weighted magnetic resonance imaging. Ann Gastroenterol Surg 2021; 5:252-258. [PMID: 33860146 PMCID: PMC8034686 DOI: 10.1002/ags3.12404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 08/01/2020] [Accepted: 09/09/2020] [Indexed: 11/09/2022] Open
Abstract
AIM Diffusion-weighted magnetic resonance imaging (DWI-MRI) is used to predict tumor malignancy. Here we explored the role of apparent diffusion coefficient (ADC) values in the treatment of patients with resectable colorectal liver metastasis (CRLM). METHODS Magnetic resonance imaging (MRI) scans were conducted using a Signa HDe or Signa Explorer 1.5-T scanner (GE Healthcare). ADC maps were calculated using DWI with b values of 0, 20, and 800 s/mm2. We enrolled 60 patients who underwent upfront hepatic resection for CRLM and divided them into ADC-high (n = 30) and ADC-low (n = 30) groups. Clinicopathological variables of the groups were compared. Immunohistochemical analysis of HIF-1α expression in tumor tissues was performed, and the relationship between the ADC value and HIF-1α expression was evaluated. RESULTS The disease-free survival rate of the ADC-low group was significantly lower than that of the ADC-high group (P < .05). Univariate analysis revealed that tumor number (more than five), synchronous metastasis, and low ADC were prognostic factors. Multivariate analysis identified low ADC as an independent prognostic factor. Furthermore, the ADC-low group more frequently expressed high levels of HIF-1α than the ADC-high group. CONCLUSION Low ADC values were an independent prognostic factor of resectable CRLM and correlated with HIF-1α expression.
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Affiliation(s)
- Masato Yoshikawa
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Yuji Morine
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Shinichiro Yamada
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Katsuki Miyazaki
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Kazunori Tokuda
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Yu Saito
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Yusuke Arakawa
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Tetsuya Ikemoto
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Satoru Imura
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
| | - Mitsuo Shimada
- Department of SurgeryInstitute of Biomedical SciencesUniversity of TokushimaTokushimaJapan
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Rostirolla R, Fontes P, Pinho M, Pedroso M, Masuko T, Novelli P, Lima R, Sampaio J. The impact of laparoscopic surgery in colorectal cancer resection with respect to the development of liver metastasis in the long-term. JOURNAL OF COLOPROCTOLOGY 2021. [DOI: 10.1016/j.jcol.2015.12.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AbstractIntroduction Colorectal cancer (CRC) shows high incidence and mortality worldwide, particularly in Western and developed countries. The objective of this study is to evaluate the oncologic results during a minimum follow-up of 2 years of curable CRC patients submitted to laparoscopic resection in our environment, regarding to the development of hepatic metastases.Methods Medical records of 189 colon and rectal patients with potentially curable adenocarcinoma who have been submitted to laparoscopic resection have been reviewed through a retrospective cohort between January 2005 and March 2012 at a single institution regarded as reference to this type of treatment. Pearson's χ 2 and Long-rank tests have been used for statistical analysis and data was analyzed by statistic package STATA version 11.0.Results The eligible population for the study was 146 patients, 91 women (62%), with a mean age of 61 ± 13 years. Minimum follow-up was 24 months, having an mean follow-up of 60 ± 27 months and an mean follow-up of global disease recurrence of 27 ± 11 months. Hepatic metastases occurred in 7.5% of the population, most from stage III, and the mean recurrence period was 25 ± 16 months.Conclusions Laparoscopic resection for potentially curable CRC in this cohort did not change the long-term incidence of hepatic metastases, considering that our results are comparable to large randomized clinical trial results. Laparoscopic resection was effective and safe for analyzed patients, regarding long-term oncologic results.
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Affiliation(s)
- Renata Rostirolla
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Paulo Fontes
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Mauro Pinho
- Universidade da Região de Joinville (Univille), Joinville, SC, Brazil
| | - Miguel Pedroso
- General Surgery Service Department, Hospital do Servidor Publico Estadual de São Paulo (HSPESP), São Paulo, SP, Brazil
| | - Tatiana Masuko
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Paula Novelli
- Lubeck Institute of Research and Education, Lübeck, Germany
| | - Renato Lima
- Lubeck Institute of Research and Education, Lübeck, Germany
| | - José Sampaio
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
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MC38 Tumors Induce Musculoskeletal Defects in Colorectal Cancer. Int J Mol Sci 2021; 22:ijms22031486. [PMID: 33540821 PMCID: PMC7867345 DOI: 10.3390/ijms22031486] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 01/27/2021] [Accepted: 01/29/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related death, and the prevalence of CRC in young adults is on the rise, making this a largescale clinical concern. Advanced CRC patients often present with liver metastases (LM) and an increased incidence of cachexia, i.e., musculoskeletal wasting. Despite its high incidence in CRC patients, cachexia remains an unresolved issue, and animal models for the study of CRC cachexia, in particular, metastatic CRC cachexia, remain limited; therefore, we aimed to establish a new model of metastatic CRC cachexia. C57BL/6 male mice (8 weeks old) were subcutaneously (MC38) or intrasplenically injected (mMC38) with MC38 murine CRC cells to disseminate LM, while experimental controls received saline (n = 5-8/group). The growth of subcutaneous MC38 tumors was accompanied by a reduction in skeletal muscle mass (-16%; quadriceps muscle), plantarflexion force (-22%) and extensor digitorum longus (EDL) contractility (-20%) compared to experimental controls. Meanwhile, the formation of MC38 LM (mMC38) led to heighted reductions in skeletal muscle mass (-30%; quadriceps), plantarflexion force (-28%) and EDL contractility (-35%) compared to sham-operated controls, suggesting exacerbated cachexia associated with LM. Moreover, both MC38 and mMC38 tumor hosts demonstrated a marked loss of bone indicated by reductions in trabecular (Tb.BV/TV: -49% in MC38, and -46% in mMC38) and cortical (C.BV/TV: -12% in MC38, and -8% in mMC38) bone. Cell culture experiments revealed that MC38 tumor-derived factors directly promote myotube wasting (-18%) and STAT3 phosphorylation (+5-fold), while the pharmacologic blockade of STAT3 signaling was sufficient to preserve myotube atrophy in the presence of MC38 cells (+21%). Overall, these results reinforce the notion that the formation of LM heightens cachexia in an experimental model of CRC.
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Shi Y, Wang Z, Chi J, Shi D, Wang T, Cui D, Lin Y, Zhai B. Long-term results of percutaneous microwave ablation for colorectal liver metastases. HPB (Oxford) 2021; 23:37-45. [PMID: 32561175 DOI: 10.1016/j.hpb.2020.04.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 03/23/2020] [Accepted: 04/13/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Radiofrequency ablation (RFA) has been used for therapy of colorectal liver metastases (CRLMs) several years, with considerable data confirming its safety and efficacy. However, there are few studies focusing on the long-term results of percrtaneous microwave ablation (PMWA) for CRLMs. The aim of this study was to evaluate the long-term survival and prognostic factors in patients with CRLMs undergoing PMWA. METHODS We retrospectively analyzed treatment and survival parameters of 210 patients with CRLMs who had received PMWA in a single center from January 2010 to December 2017. Prognostic factors for survival were evaluated by means of univariate and multivariate analyses. RESULTS The median follow-up time after PMWA was 48 months. The median overall survival (OS) time were 40.0 months (95% CI, 31.4 to 48.5 months), with 1-, 2, 3-, 4, and 5-year cumulative survival rates of 98.6%, 73.3%, 53.3%, 42.2%, and 32.9%, respectively. Tumor number (P = 0.004; HR: 1.838; CI: 1.213- 2.784), main tumor size (P = 0.017; HR: 1.631; CI: 1.093- 2.436), and serum CEA level (P = 0.032; HR: 1.559; CI: 1.039-2.340) were found as independent predictors of OS. The median OS time for patients with resectable lesions was 60.91 months (95% CI, 51.36 to 70.47 months), with 5-year cumulative survival rates of 53.5%. CONCLUSION PMWA is a safe and effective treatment for CRLMs, with a favorable long-term outcome. Multiple lesions, main tumor diameter>3 cm, and serum CEA >30 ng/ml have a significant negative effect on OS.
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Affiliation(s)
- Yaoping Shi
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao-tong University, 160 Pujian Road, Shanghai, 200120, China
| | - Zhenyu Wang
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao-tong University, 160 Pujian Road, Shanghai, 200120, China
| | - Jiachang Chi
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao-tong University, 160 Pujian Road, Shanghai, 200120, China
| | - Donghua Shi
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao-tong University, 160 Pujian Road, Shanghai, 200120, China
| | - Tao Wang
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao-tong University, 160 Pujian Road, Shanghai, 200120, China
| | - Dan Cui
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao-tong University, 160 Pujian Road, Shanghai, 200120, China
| | - Yan Lin
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao-tong University, 160 Pujian Road, Shanghai, 200120, China
| | - Bo Zhai
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao-tong University, 160 Pujian Road, Shanghai, 200120, China.
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Han K, Kim JH, Yang SG, Park SH, Choi HK, Chun SY, Kim PN, Park J, Lee M. A Single-Center Retrospective Analysis of Periprocedural Variables Affecting Local Tumor Progression after Radiofrequency Ablation of Colorectal Cancer Liver Metastases. Radiology 2021; 298:212-218. [PMID: 33170105 DOI: 10.1148/radiol.2020200109] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background Local tumor progression (LTP) is associated with poorer survival in patients undergoing radiofrequency ablation (RFA) for colorectal liver metastasis (CLM). An algorithmic strategy to predict LTP may help in selection of patients who would benefit most from RFA for CLM. Purpose To estimate local tumor progression-free survival (LTPFS) following RFA of CLM and develop an algorithmic strategy based on clinical variables. Materials and Methods In this retrospective study, between March 2000 and December 2014, patients who underwent percutaneous RFA for CLM were randomly split into development (60%) and internal validation (40%) data sets. Kaplan-Meier method was used to estimate LTPFS and overall survival (OS) rates. Independent factors affecting LTPFS in the development data set were investigated by using multivariable Cox proportional hazard regression analysis. Risk scores were assigned to the risk factors and applied to the validation data set. Results A total of 365 patients (mean age, 60 years ± 11 [standard deviation]; 259 men) with 512 CLMs were evaluated. LTPFS and OS rates were 85% and 92% at 1 year, 73% and 41% at 5 years, 72% and 30% at 10 years, and 72% and 28% at 15 years, respectively. Independent risk factors for LTP included tumor size of 2 cm or greater (hazard ratio [HR], 3.8; 95% CI: 2.3, 6.2; P < .001), subcapsular tumor location (HR, 1.9; 95% CI: 1.1, 3.1; P = .02), and minimal ablative margin of 5 mm or less (HR, 11.7; 95% CI: 4.7, 29.2; P < .001). A prediction model that used the risk factors had areas under the curve of 0.89, 0.92, and 0.90 at 1, 5, and 10 years, respectively, and it showed significantly better areas under the curve when compared with the model using the minimal ablative margin of 5 mm or less alone. Conclusion Radiofrequency ablation provided long-term control of colorectal liver metastases. Although minimal ablative margin of 5 mm or less was the most dominant factor, the multifactorial approach including tumor size and subcapsular location better predicted local tumor progression-free survival. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Soulen and Sofocleous in this issue.
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Affiliation(s)
- Kichang Han
- From the Department of Radiology, Severance Hospital, Research Institute of Radiological Science (K.H.), and Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics (M.L.), Yonsei University College of Medicine, Seoul, Korea; and Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 138-736, Korea (J.H.K., S.G.Y., S.H.P., H.K.C., S.Y.C., P.N.K., J.P.)
| | - Jin Hyoung Kim
- From the Department of Radiology, Severance Hospital, Research Institute of Radiological Science (K.H.), and Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics (M.L.), Yonsei University College of Medicine, Seoul, Korea; and Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 138-736, Korea (J.H.K., S.G.Y., S.H.P., H.K.C., S.Y.C., P.N.K., J.P.)
| | - Seul Gi Yang
- From the Department of Radiology, Severance Hospital, Research Institute of Radiological Science (K.H.), and Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics (M.L.), Yonsei University College of Medicine, Seoul, Korea; and Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 138-736, Korea (J.H.K., S.G.Y., S.H.P., H.K.C., S.Y.C., P.N.K., J.P.)
| | - Seong Ho Park
- From the Department of Radiology, Severance Hospital, Research Institute of Radiological Science (K.H.), and Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics (M.L.), Yonsei University College of Medicine, Seoul, Korea; and Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 138-736, Korea (J.H.K., S.G.Y., S.H.P., H.K.C., S.Y.C., P.N.K., J.P.)
| | - Hyun-Kyung Choi
- From the Department of Radiology, Severance Hospital, Research Institute of Radiological Science (K.H.), and Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics (M.L.), Yonsei University College of Medicine, Seoul, Korea; and Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 138-736, Korea (J.H.K., S.G.Y., S.H.P., H.K.C., S.Y.C., P.N.K., J.P.)
| | - Seng-Yong Chun
- From the Department of Radiology, Severance Hospital, Research Institute of Radiological Science (K.H.), and Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics (M.L.), Yonsei University College of Medicine, Seoul, Korea; and Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 138-736, Korea (J.H.K., S.G.Y., S.H.P., H.K.C., S.Y.C., P.N.K., J.P.)
| | - Pyo Nyun Kim
- From the Department of Radiology, Severance Hospital, Research Institute of Radiological Science (K.H.), and Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics (M.L.), Yonsei University College of Medicine, Seoul, Korea; and Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 138-736, Korea (J.H.K., S.G.Y., S.H.P., H.K.C., S.Y.C., P.N.K., J.P.)
| | - Jihong Park
- From the Department of Radiology, Severance Hospital, Research Institute of Radiological Science (K.H.), and Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics (M.L.), Yonsei University College of Medicine, Seoul, Korea; and Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 138-736, Korea (J.H.K., S.G.Y., S.H.P., H.K.C., S.Y.C., P.N.K., J.P.)
| | - Myeongjee Lee
- From the Department of Radiology, Severance Hospital, Research Institute of Radiological Science (K.H.), and Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics (M.L.), Yonsei University College of Medicine, Seoul, Korea; and Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, 138-736, Korea (J.H.K., S.G.Y., S.H.P., H.K.C., S.Y.C., P.N.K., J.P.)
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Huot JR, Pin F, Narasimhan A, Novinger LJ, Keith AS, Zimmers TA, Willis MS, Bonetto A. ACVR2B antagonism as a countermeasure to multi-organ perturbations in metastatic colorectal cancer cachexia. J Cachexia Sarcopenia Muscle 2020; 11:1779-1798. [PMID: 33200567 PMCID: PMC7749603 DOI: 10.1002/jcsm.12642] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 09/11/2020] [Accepted: 10/12/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Advanced colorectal cancer (CRC) is often accompanied by the development of liver metastases, as well as cachexia, a multi-organ co-morbidity primarily affecting skeletal (SKM) and cardiac muscles. Activin receptor type 2B (ACVR2B) signalling is known to cause SKM wasting, and its inhibition restores SKM mass and prolongs survival in cancer. Using a recently generated mouse model, here we tested whether ACVR2B blockade could preserve multiple organs, including skeletal and cardiac muscle, in the presence of metastatic CRC. METHODS NSG male mice (8 weeks old) were injected intrasplenically with HCT116 human CRC cells (mHCT116), while sham-operated animals received saline (n = 5-10 per group). Sham and tumour-bearing mice received weekly injections of ACVR2B/Fc, a synthetic peptide inhibitor of ACVR2B. RESULTS mHCT116 hosts displayed losses in fat mass ( - 79%, P < 0.0001), bone mass ( - 39%, P < 0.05), and SKM mass (quadriceps: - 22%, P < 0.001), in line with reduced muscle cross-sectional area ( - 24%, P < 0.01) and plantarflexion force ( - 28%, P < 0.05). Further, despite only moderately affected heart size, cardiac function was significantly impaired (ejection fraction %: - 16%, P < 0.0001; fractional shortening %: - 25%, P < 0.0001) in the mHCT116 hosts. Conversely, ACVR2B/Fc preserved fat mass ( + 238%, P < 0.001), bone mass ( + 124%, P < 0.0001), SKM mass (quadriceps: + 31%, P < 0.0001), size (cross-sectional area: + 43%, P < 0.0001) and plantarflexion force ( + 28%, P < 0.05) in tumour hosts. Cardiac function was also completely preserved in tumour hosts receiving ACVR2B/Fc (ejection fraction %: + 19%, P < 0.0001), despite no effect on heart size. RNA sequencing analysis of heart muscle revealed rescue of genes related to cardiac development and contraction in tumour hosts treated with ACVR2B/Fc. CONCLUSIONS Our metastatic CRC model recapitulates the multi-systemic derangements of cachexia by displaying loss of fat, bone, and SKM along with decreased muscle strength in mHCT116 hosts. Additionally, with evidence of severe cardiac dysfunction, our data support the development of cardiac cachexia in the occurrence of metastatic CRC. Notably, ACVR2B antagonism preserved adipose tissue, bone, and SKM, whereas muscle and cardiac functions were completely maintained upon treatment. Altogether, our observations implicate ACVR2B signalling in the development of multi-organ perturbations in metastatic CRC and further dictate that ACVR2B represents a promising therapeutic target to preserve body composition and functionality in cancer cachexia.
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Affiliation(s)
- Joshua R Huot
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.,Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Fabrizio Pin
- Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Ashok Narasimhan
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Leah J Novinger
- Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | | | - Teresa A Zimmers
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.,Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.,Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.,Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, USA.,Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Monte S Willis
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.,Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, USA.,Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Andrea Bonetto
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.,Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.,Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.,Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, USA.,Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA
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Jiang B, Luo H, Yan K, Zhang Z, Li X, Wu W, Yang W, Chen M. Ten-Year Outcomes of Percutaneous Radiofrequency Ablation for Colorectal Cancer Liver Metastases in Perivascular vs. Non-Perivascular Locations: A Propensity-Score Matched Study. Front Oncol 2020; 10:553556. [PMID: 33178581 PMCID: PMC7596897 DOI: 10.3389/fonc.2020.553556] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 09/25/2020] [Indexed: 12/14/2022] Open
Abstract
Purpose To compare long-term outcomes of percutaneous radiofrequency ablation for colorectal liver metastases in perivascular versus non-perivascular locations. Methods This retrospective study included 388 consecutive patients with colorectal liver metastases (246 men, 142 women; age range 27–86 years) who underwent percutaneous radiofrequency ablation between January 2006 and December 2018. Propensity-score matching was performed for groups with perivascular and non-perivascular colorectal liver metastases. Rates of accumulative local tumor progression, overall survival, intra/extrahepatic recurrence, and complications were compared between the two groups. Results We successfully matched 104 patients each in the perivascular and non-perivascular groups (mean age: 60.1 ± 11.5 and 60.1 ± 11.3 years, respectively). Cumulative local tumor progression rates at 6 months, 1 years, 3 years, and 5 years, respectively, were 8.8%,14.8%, 18.9%, and 18.9% in the perivascular group and 8.8%, 13.1%, 15.5%, and 15.5% in the non-perivascular group. The 1-, 3-, 5-, and 10-year overall survival rates, respectively, were 91.3%, 45.6%, 23.9%, and 18.7% in the perivascular group and 88.0%, 47.2%, 27.2%, and 22.6% in the non-perivascular group. No significant between-group differences were detected in cumulative local tumor progression (p=0.567, hazard ratio: 1.224) or overall survival (p = 0.801, hazard ratio: 1.047). The major complication rate was 1.0% (1/104, p > 0.999) in both groups. Tumor size was the only independent prognostic factor for local tumor progression (hazard ratio: 2.314; p = 0.002). On multivariate analysis for overall colorectal liver metastases, tumor diameter >3 cm, tumor location in the right colon, multiple tumors, and extrahepatic metastases before radiofrequency ablation (hazard ratios: 2.046, 1.920, 1.706, and 1.892, respectively; all p < 0.001) and intrahepatic recurrence (hazard ratio: 1.564; p = 0.002) were associated with poor overall survival. Conclusion Cumulative local tumor progression, overall survival, and major complications rates did not differ significantly between perivascular and non-perivascular colorectal liver metastases after percutaneous radiofrequency ablation. For perivascular colorectal liver metastases, percutaneous radiofrequency ablation is a safe and effective treatment option.
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Affiliation(s)
- Binbin Jiang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hongjie Luo
- Department of Hepatobiliary, Pancreatic and Minimally Invasive Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
| | - Kun Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhongyi Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiaoting Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wei Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wei Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Minhua Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
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20
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van Roekel C, Jongen JMJ, Smits MLJ, Elias SG, Koopman M, Kranenburg O, Borel Rinkes IHM, Lam MGEH. Mode of progression after radioembolization in patients with colorectal cancer liver metastases. EJNMMI Res 2020; 10:107. [PMID: 32960390 PMCID: PMC7509032 DOI: 10.1186/s13550-020-00697-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 09/10/2020] [Indexed: 12/14/2022] Open
Abstract
Background Radioembolization is an established treatment modality in colorectal cancer patients with liver-dominant disease in a salvage setting. Selection of patients who will benefit most is of vital importance. The aim of this study was to assess response (and mode of progression) at 3 months after radioembolization and the impact of baseline characteristics. Methods Three months after radioembolization with either yttrium-90 resin/glass or holmium-166, anatomic response, according to RECIST 1.1, was evaluated in 90 patients. Correlations between baseline characteristics and efficacy were evaluated. For more detailed analysis of progressive disease as a dismal clinical entity, distinction was made between intra- and extrahepatic progression, and between progression of existing metastases and new metastases. Results Forty-two patients (47%) had extrahepatic disease (up to five ≥ 1 cm lung nodules, and ≤ 2 cm lymph nodes) at baseline. No patients showed complete response, 5 (5.5%) patients had partial response, 16 (17.8%) had stable disease, and 69 (76.7%) had progressive disease. Most progressive patients (67/69; 97%) had new metastases (intra-hepatic N = 11, extrahepatic N = 32; or both N = 24). Significantly fewer patients had progressive disease in the group of patients presenting without extrahepatic metastases at baseline (63% versus 93%; p = 0.0016). Median overall survival in patients with extrahepatic disease was 6.5 months, versus 10 months in patients without extrahepatic disease at baseline (hazard ratio 1.79, 95%CI 1.24–2.57). Conclusions Response at 3-month follow-up and survival were heavily influenced by new metastases. Patients with extrahepatic disease at baseline had a worse outcome compared to patients without.
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Affiliation(s)
- Caren van Roekel
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, University Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
| | - Jennifer M J Jongen
- Department of Surgical Oncology, Endocrine and GI Surgery, Cancer Center, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands
| | - Maarten L J Smits
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, University Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Sjoerd G Elias
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, Cancer Center, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands
| | - Onno Kranenburg
- Division of Biomedical Genetics, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands
| | - Inne H M Borel Rinkes
- Department of Surgical Oncology, Endocrine and GI Surgery, Cancer Center, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands
| | - Marnix G E H Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, University Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
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21
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Gillies DJ, Bax J, Barker K, Gardi L, Kakani N, Fenster A. Geometrically variable three-dimensional ultrasound for mechanically assisted image-guided therapy of focal liver cancer tumors. Med Phys 2020; 47:5135-5146. [PMID: 32686142 DOI: 10.1002/mp.14405] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 06/02/2020] [Accepted: 06/27/2020] [Indexed: 01/03/2023] Open
Abstract
PURPOSE Image-guided focal ablation procedures are first-line therapy options in the treatment of liver cancer tumors that provide advantageous reductions in patient recovery times and complication rates relative to open surgery. However, extensive physician training is required and image guidance variabilities during freehand therapy applicator placement limit the sufficiency of ablation volumes and the overall potential of these procedures. We propose the use of three-dimensional ultrasound (3D US) to provide guidance and localization of therapy applicators, augmenting current ablation therapies without the need for specialized procedure suites. We have developed a novel scanning mechanism for geometrically variable 3D US images, a mechanical tracking system, and a needle applicator insertion workflow using a custom needle applicator guide for targeted image-guided procedures. METHODS A three-motor scanner was designed to use any commercially available US probe to generate accurate, consistent, and geometrically variable 3D US images. The designed scanner was mounted on a counterbalanced stabilizing and mechanical tracking system for determining the US probe orientation, which was assessed using optical tracking. Further exploiting the utility of the motorized scanner, an image-guidance workflow was developed that moved the probe to any identified target within an acquired 3D US image. The complete 3D US guidance system was used to perform mock targeted interventional procedures on a phantom by selecting a target in a 3D US image, navigating to the target, and performing needle insertion using a custom 3D-printed needle applicator guide. Registered postinsertion 3D US images and cone-beam computed tomography (CBCT) images were used to evaluate tip targeting errors when using the motors, tracking system, or mixed navigation approaches. Two 3D US image geometries were investigated to assess the accuracy of a small-footprint tilt approach and a large field-of-view hybrid approach for a total of 48 targeted needle insertions. 3D US image quality was evaluated in a healthy volunteer and compared to a commercially available matrix array US probe. RESULTS A mean positioning error of 1.85 ± 1.33 mm was observed when performing compound joint manipulations with the mechanical tracking system. A combined approach for navigation that incorporated the motorized movement and the in-plane tracking system corrections performed the best with a mean tip error of 3.77 ± 2.27 mm and 4.27 ± 2.47 mm based on 3D US and CBCT images, respectively. No significant differences were observed between hybrid and tilt image acquisition geometries with all mean registration errors ≤1.2 mm. 3D US volunteer images resulted in clear reconstruction of clinically relevant anatomy. CONCLUSIONS A mechanically tracked system with geometrically variable 3D US provides a utility that enables enhanced applicator guidance, placement verification, and improved clinical workflow during focal liver tumor ablation procedures. Evaluations of the tracking accuracy, targeting capabilities, and clinical imaging feasibility of the proposed 3D US system, provided evidence for clinical translation. This system could provide a workflow for improving applicator placement and reducing local cancer recurrence during interventional procedures treating liver cancer and has the potential to be expanded to other abdominal interventions and procedures.
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Affiliation(s)
- Derek J Gillies
- Department of Medical Biophysics, Robarts Research Institute, Western University, London, ON, N6A 3K7, Canada.,Robarts Research Institute, Western University, London, ON, N6A 3K7, Canada
| | - Jeffery Bax
- Robarts Research Institute, Western University, London, ON, N6A 3K7, Canada
| | - Kevin Barker
- Robarts Research Institute, Western University, London, ON, N6A 3K7, Canada
| | - Lori Gardi
- Robarts Research Institute, Western University, London, ON, N6A 3K7, Canada
| | - Nirmal Kakani
- Department of Radiology, Manchester Royal Infirmary, Manchester, M13 9WL, UK
| | - Aaron Fenster
- Department of Medical Biophysics, Robarts Research Institute, Western University, London, ON, N6A 3K7, Canada.,Robarts Research Institute, Western University, London, ON, N6A 3K7, Canada
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22
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Huot JR, Novinger LJ, Pin F, Narasimhan A, Zimmers TA, O'Connell TM, Bonetto A. Formation of colorectal liver metastases induces musculoskeletal and metabolic abnormalities consistent with exacerbated cachexia. JCI Insight 2020; 5:136687. [PMID: 32298240 DOI: 10.1172/jci.insight.136687] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 04/08/2020] [Indexed: 12/18/2022] Open
Abstract
Advanced colorectal cancer (CRC) is often accompanied by development of liver metastases (LMs) and skeletal muscle wasting (i.e., cachexia). Despite plaguing the majority of CRC patients, cachexia remains unresolved. By using mice injected with Colon-26 mouse tumors, either subcutaneously (s.c.; C26) or intrasplenically to mimic hepatic dissemination of cancer cells (mC26), here we aimed to further characterize functional, molecular, and metabolic effects on skeletal muscle and examine whether LMs exacerbate CRC-induced cachexia. C26-derived LMs were associated with progressive loss of body weight, as well as with significant reductions in skeletal muscle size and strength, in line with reduced phosphorylation of markers of protein anabolism and enhanced protein catabolism. mC26 hosts showed prevalence of fibers with glycolytic metabolism and enhanced lipid accumulation, consistent with abnormalities of mitochondrial homeostasis and energy metabolism. In a comparison with mice bearing s.c. C26, cachexia appeared exacerbated in the mC26 hosts, as also supported by differentially expressed pathways within skeletal muscle. Overall, our model recapitulates the cachectic phenotype of metastatic CRC and reveals that formation of LMs resulting from CRC exacerbate cancer-induced skeletal muscle wasting by promoting differential gene expression signatures.
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Affiliation(s)
- Joshua R Huot
- Department of Surgery.,Department of Anatomy, Cell Biology and Physiology
| | | | - Fabrizio Pin
- Department of Anatomy, Cell Biology and Physiology
| | | | - Teresa A Zimmers
- Department of Surgery.,Department of Anatomy, Cell Biology and Physiology.,Simon Cancer Center, and.,Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Thomas M O'Connell
- Department of Anatomy, Cell Biology and Physiology.,Department of Otolaryngology-Head & Neck Surgery.,Simon Cancer Center, and.,Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Andrea Bonetto
- Department of Surgery.,Department of Anatomy, Cell Biology and Physiology.,Department of Otolaryngology-Head & Neck Surgery.,Simon Cancer Center, and.,Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Abstract
OBJECTIVE To determine the impact of radiofrequency (RF) and microwave (MW) energy compared to direct cautery on metatstatic colon cancer growth. BACKGROUND Hepatic ablation with MW and RF energy creates a temperature gradient around a target site with temperatures known to create tissue injury and cell death. In contrast, direct heat application (cautery) vaporizes tissue with a higher site temperature but reduced heat gradient on surrounding tissue. We hypothesize that different energy devices create variable zones of sublethal injury that may promote tumor recurrence. To test this hypothesis we applied MW, RF, and cautery to normal murine liver with a concomitant metastatic colon cancer challenge. METHODS C57/Bl6 mice received hepatic thermal injury with MW, RF, or cautery to create a superficial 3-mm lesion immediately after intrasplenic injection of 50K MC38 colon cancer cells. Thermal imaging recorded tissue temperature during ablation and for 10 seconds after energy cessation. Hepatic tumor location and volume was determined at day 7. RESULTS Cautery demonstrated the highest maximum tissue temperatures (129°C) with more rapid return to baseline compared to MW or RF energy. All mice had metastasis at the ablation site. Mean tumor volume was significantly greater in the MW (95.3 mm; P = 0.007) and RF (55.7 mm; P = 0.015) than cautery (7.13 mm). There was no difference in volume between MW and RF energy (P = 0.2). CONCLUSIONS Hepatic thermal ablation promotes colon cancer metastasis at the injury site. MV and RF energy result in greater metastatic volume than cautery. These data suggest that the method of energy delivery promotes local metastasis.
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Huot JR, Novinger LJ, Pin F, Bonetto A. HCT116 colorectal liver metastases exacerbate muscle wasting in a mouse model for the study of colorectal cancer cachexia. Dis Model Mech 2020; 13:dmm043166. [PMID: 31915140 PMCID: PMC6994937 DOI: 10.1242/dmm.043166] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 12/16/2019] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is often accompanied by formation of liver metastases (LM) and skeletal muscle wasting, i.e. cachexia. Despite affecting the majority of CRC patients, cachexia remains underserved, understudied and uncured. Animal models for the study of CRC-induced cachexia, in particular models containing LM, are sparse; therefore, we aimed to characterize two new models of CRC cachexia. Male NSG mice were injected subcutaneously (HCT116) or intrasplenically (mHCT116) with human HCT116 CRC tumor cells to disseminate LM, whereas experimental controls received saline (n=5-8/group). Tumor growth was accompanied by loss of skeletal muscle mass (HCT116: -20%; mHCT116: -31%; quadriceps muscle) and strength (HCT116: -20%; mHCT116: -27%), with worsened loss of skeletal muscle mass in mHCT116 compared with HCT116 (gastrocnemius: -19%; tibialis anterior: -22%; quadriceps: -21%). Molecular analyses revealed elevated protein ubiquitination in HCT116, whereas mHCT116 also displayed elevated Murf1 and atrogin-1 expression, along with reduced mitochondrial proteins PGC1α, OPA1, mitofusin 2 and cytochrome C. Further, elevated IL6 levels were found in the blood of mHCT116 hosts, which was associated with higher phosphorylation of STAT3 in skeletal muscle. To clarify whether STAT3 was a main player in muscle wasting in this model, HCT116 cells were co-cultured with C2C12 myotubes. Marked myotube atrophy (-53%) was observed, along with elevated phospho-STAT3 levels (+149%). Conversely, inhibition of STAT3 signaling by means of a JAK/STAT3 inhibitor was sufficient to rescue myotube atrophy induced by HCT116 cells (+55%). Overall, our results indicate that the formation of LM exacerbates cachectic phenotype and associated skeletal muscle molecular alterations in HCT116 tumor hosts.
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Affiliation(s)
- Joshua R Huot
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Leah J Novinger
- Department of Otolaryngology - Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Fabrizio Pin
- Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Andrea Bonetto
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
- Department of Otolaryngology - Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
- Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
- Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA
- IUPUI Center for Cachexia Research Innovation and Therapy, Indiana University School of Medicine, Indianapolis, IN 46202, USA
- Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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25
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Zhang C, Tan Y, Xu H. Does adjuvant chemotherapy improve the prognosis of patients after resection of pulmonary metastasis from colorectal cancer? A systematic review and meta-analysis. Int J Colorectal Dis 2019; 34:1661-1671. [PMID: 31446479 DOI: 10.1007/s00384-019-03362-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/06/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND It remains controversial whether patients benefit from adjuvant chemotherapy (ACT) after resection of pulmonary metastasis (PM) from colorectal cancer (CRC). This meta-analysis was intended to evaluate the efficacy of ACT in patients after resection of PM from CRC. METHODS We systematically retrieved articles from PMC, PubMed, Cochrane Library, and Embase (up to March 5, 2019). Survival data, including overall survival (OS) and disease-free survival (DFS), were tested by hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS We included 18 cohort studies with a total of 3885 patients. The meta-analysis showed that ACT had no significant effect on OS (HR = 0.78; 95% CI = 0.60-1.03; P = 0.077) and DFS (HR = 0.91; 95% CI = 0.74-1.11; P = 0.339) in patients after resection of PM from CRC. There was no significant difference in OS (HR = 0.79; 95% CI = 0.42-1.50; P = 0.474) in patients after resection of PM from CRC treated with bevacizumab (BV). Subgroup analysis showed that ACT did not improve OS (HR = 0.86; 95% CI = 0.57-1.29; P = 0.461) in patients who had undergone previous resection of extra PM. ACT did not improve OS in patients who had positive hilar/mediastinal lymph node metastasis (HR = 0.80; 95% CI = 0.57-1.14; P = 0.22). CONCLUSION In conclusion, ACT does not provide survival benefits for patients after resection of PM from CRC. ACT and targeted agents (BV) are not suggested for these patients.
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Affiliation(s)
- Chao Zhang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, China.,Key Laboratory of Gastric Cancer Molecular Pathology of Liaoning Province, 155 Nanjing North Street, Heping District, Shenyang, 110001, China
| | - Yuen Tan
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, China.,Key Laboratory of Gastric Cancer Molecular Pathology of Liaoning Province, 155 Nanjing North Street, Heping District, Shenyang, 110001, China
| | - Huimian Xu
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, China. .,Key Laboratory of Gastric Cancer Molecular Pathology of Liaoning Province, 155 Nanjing North Street, Heping District, Shenyang, 110001, China.
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26
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Giuliante F, Panettieri E, Ardito F, De Rose A, Pocino K, Autilio C, Paolillo C, Capoluongo ED. Circulating tumor cell-related transcripts in blood as prognostic biomarkers of early recurrence after liver resection for colorectal metastases. Int J Biol Markers 2019; 34:269-275. [PMID: 31213130 DOI: 10.1177/1724600819849438] [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: 11/17/2022]
Abstract
BACKGROUND Several prognostic factors were proposed to improve early detection of recurrence after liver resection of metastases of colorectal cancer. Circulating tumor cell-related transcripts were evaluated in colorectal cancer patients with conflicting results. The aim of this study was to investigate usefulness of carcinoembryonic antigen CAM5, epidermal growth factor receptor, and ERCC1 transcripts in the bloodstream as predictive factors of recurrence in patients who underwent liver resection for metastases of colorectal cancer. METHODS Peripheral blood was collected from 29 patients at the time of the colorectal cancer liver metastasis resection, and from 25 normal controls. Follow-up draws (FUDs) were also performed at 30 days, and 3 and 12 months since surgery. On each sample, carcinoembryonic antigen CAM5, ERCC1, and GAPDH mRNAs were examined by quantitative reverse transcription (qRT). RESULTS Carcinoembryonic antigen transcript levels were linearly correlated to the number of spiked cells (qRT analytical limit = five cells). Among 29 patients (20 M/9 F; mean age 63 years (range 32-79), highly significant levels of carcinoembryonic antigen, if compared to the baseline, were detected in those relapsing after surgery (P <0.05). The main differences were between the 1st- and 12th-month FUDs. Significantly higher levels of carcinoembryonic antigen were also detected in patients who died from disease progression during the follow-up (as evaluated at 30 days and 90 days FUDs). CONCLUSIONS Blood carcinoembryonic antigen-mRNA absolute copy number overtime variation can represent a valid early predictor of relapse after liver resection in colorectal liver metastases patients. Prospective studies, in the context of large clinical trials, will provide further data to also qualify ERCC1 as a predictive biomarker for decisions on therapeutic strategies.
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Affiliation(s)
- Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Elena Panettieri
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Francesco Ardito
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Agostino De Rose
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Krizia Pocino
- Laboratory of Molecular Diagnostics and Genomics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Chiara Autilio
- Laboratory of Molecular Diagnostics and Genomics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Carmela Paolillo
- Laboratory of Molecular Diagnostics and Genomics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Ettore Domenico Capoluongo
- Laboratory of Molecular Diagnostics and Genomics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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Rong G, Yang X, Wu H, Wu Y. miR-150-504-519d inhibits the growth of human colorectal cancer cell line SW48 and downregulates c-FLIP receptor. J Cell Biochem 2019; 120:7962-7969. [PMID: 30548660 DOI: 10.1002/jcb.28073] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 10/22/2018] [Indexed: 01/24/2023]
Abstract
microRNAs (miRNAs) are noncoding RNAs that regulates the expression of target messenger RNAs (mRNAs). c-FLIP is an inhibitor of cell apoptosis through inhibition of caspase 8. miR-150, miR-504, and miR-519d were related to cancer cell proliferation, invasion, and migration in colorectal cancer (CRC). However, the role of miR-150-504-519d in CRC has not been studied and the relationship between miR-150-504-519d and c-FLIP remains unclear. In this study, we found that c-FLIP was upregulated in CRC tissues, without detectable expression in normal CRC tissues. Using SW48 cell line, we further showed that miR-150-504-519d inhibited migration, invasion, and promoted apoptosis of SW48 cells. Moreover, in SW48 cell line transfected with miR-150-504-519d, the protein expression of c-FLIP was significantly lower compared with cells transfected with scramble. Our results demonstrated upregulation of c-FLIP in CRC, which was downregulated in SW48 cells after the transfection of miR-150-504-519d, suggesting that manipulation of miR-150-504-519d expression might be a novel approach for the treatment of colorectal cancer.
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Affiliation(s)
- Guoqiang Rong
- Department of General Surgery, The Fifth People s Hospital of Changshu, Changshu, Jiangsu, P.R. China
| | - Xiaodong Yang
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China
| | - Haorong Wu
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China
| | - Yongyou Wu
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China
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Tan HL, Chia CS, Tan GHC, Choo SP, Tai DWM, Chua CWL, Ng MCH, Soo KC, Teo MCC. Metastatic gastric cancer: Does the site of metastasis make a difference? Asia Pac J Clin Oncol 2019; 15:10-17. [PMID: 29920947 DOI: 10.1111/ajco.13025] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 05/14/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Metastatic gastric cancer has a poor prognosis. We aim to study how clinical features and prognosis differs between different metastatic sites, and to identify prognostic factors for overall survival. METHODS We retrospectively reviewed patients with metastatic gastric adenocarcinoma managed at a tertiary referral cancer center over a 5-year period. We divided our cohort into three groups based on the site(s) of metastasis at presentation-peritoneal metastasis only (P), distant metastasis only (D), and peritoneal and distant metastases (PD). RESULTS We studied 470 patients with 175 (37.2%), 193 (41.1%) and 102 (21.7%) patients in the P, D and PD groups, respectively. Patients with peritoneal disease (both P and PD) had higher proportions of patients experiencing chemotherapy disruption due to unplanned hospitalizations, which were also of a longer average duration. The P group had the longest overall median survival of 8.9 months compared to the PD and D groups with 7.4 and 5.5 months, respectively (P < 0.001). On multivariate Cox regression analysis, the presence of ≥1 metastatic site (hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.23-2.28; P = 0.001) was significantly associated with increased overall mortality, whereas palliative systemic chemotherapy (HR 0.29; 95% CI, 0.22-0.37; P < 0.001) and palliative gastrectomy (HR 0.24; 95% CI, 0.15-0.39; P < 0.001) were significantly associated with decreased overall mortality. CONCLUSION Metastatic gastric cancer represents a heterogeneous disease, with specific disease complications and treatment outcomes unique to different metastatic sites. We can consider novel multimodality therapies for patient subgroups with isolated metastatic disease and good prognostic factors in a bid to improve long-term survival.
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Affiliation(s)
- Hwee Leong Tan
- Division of Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Claramae Shulyn Chia
- Division of Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Grace Hwei Ching Tan
- Division of Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Su Pin Choo
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - David Wai-Meng Tai
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | | | - Matthew Chau Hsien Ng
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Khee Chee Soo
- Division of Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
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Mendiratta-Lala M, Masch W, Shankar PR, Hartman HE, Davenport MS, Schipper MJ, Maurino C, Cuneo KC, Lawrence TS, Owen D. Magnetic Resonance Imaging Evaluation of Hepatocellular Carcinoma Treated With Stereotactic Body Radiation Therapy: Long Term Imaging Follow-Up. Int J Radiat Oncol Biol Phys 2018; 103:169-179. [PMID: 30213751 DOI: 10.1016/j.ijrobp.2018.09.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 08/28/2018] [Accepted: 09/04/2018] [Indexed: 12/14/2022]
Abstract
PURPOSE To determine the natural history of imaging findings seen on magnetic resonance imaging (MRI) of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT). Although arterial hyperenhancement is a key feature of untreated HCC, our clinical experience suggested that tumors that never progressed could still show hyperenhancement. Therefore, we undertook a systematic study to test the hypothesis that persistent arterial phase hyperenhancement (APHE) after SBRT is an expected finding that does not suggest failure of treatment. METHODS AND MATERIALS One hundred forty-six patients undergoing SBRT for HCC between January 1, 2007, and December 31, 2015, were screened retrospectively using an institutional review board-approved prospectively maintained registry. Inclusion criteria were (1) HCC treated with SBRT, (2) multiphasic MRI ≤3 months before SBRT, (3) up to 1 year of follow-up MRI post-SBRT, and (4) cirrhosis. The exclusion criterion was ≤3 months of locoregional therapy to the liver segment containing the SBRT-treated HCC. Pre- and post-SBRT MRI from up to 3 years were analyzed in consensus by independent pairs of subspecialty-trained radiologists to determine the temporal evolution of major features for HCC and imaging findings in off-target parenchyma. RESULTS Sixty-two patients with 67 HCCs (Organ Procurement and Transplantation Network imaging criteria [OPTN] 5a [n = 26], OPTN 5b [n = 28], OPTN 5x [n = 7]; Liver Imaging Reporting Data System [LI-RAD]-M [n = 4] and LiRADs-4 [n = 2]) were studied. Tumor size either decreased (66% [44 of 67]) or remained unchanged (34% [23 of 67]) within the first 12 months. Post-SBRT APHE was common (58% [39 of 67]). When graded using modified Response Evaluation Criteria in Solid Tumors at 3 to 6 months, 25% (17 of 67) met criteria for complete response and 75% (50 of 67) met criteria for stable disease. CONCLUSIONS SBRT is an effective locoregional treatment option for HCC. Persistent APHE is common and does not necessarily indicate viable neoplasm; thus, standard response assessment such as modified Response Evaluation Criteria should be used with caution, particularly in the early phases after SBRT therapy.
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Affiliation(s)
| | - William Masch
- Department of Radiology, University of Michigan, Ann Arbor, Michigan
| | - Prasad R Shankar
- Department of Radiology, University of Michigan, Ann Arbor, Michigan
| | - Holly E Hartman
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | | | - Matthew J Schipper
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - Chris Maurino
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Kyle C Cuneo
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Theodore S Lawrence
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Dawn Owen
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
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Liang HH, Huang CY, Chou CW, Makondi PT, Huang MT, Wei PL, Chang YJ. Heat shock protein 27 influences the anti-cancer effect of curcumin in colon cancer cells through ROS production and autophagy activation. Life Sci 2018; 209:43-51. [PMID: 30056019 DOI: 10.1016/j.lfs.2018.07.047] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Revised: 07/21/2018] [Accepted: 07/24/2018] [Indexed: 01/14/2023]
Abstract
The problem of therapeutic resistance and chemotherapeutic efficacy is tricky and critical in the management of colorectal cancer (CRC). Curcumin is a promising anti-cancer agent. Heat shock protein 27 (HSP27) is correlated with CRC progression and is said to affect CRC response to different therapies. However, the role of HSP27 on the therapeutic efficacy of curcumin remains unknown. HSP27 was silenced using small hairpin RNA (shRNA) technique. The cytotoxic and apoptotic effects of curcumin were assessed by sulforhodamine B (SRB) colorimetric assay, flow cytometric cell cycle analysis, and annexin V/propidium iodide (PI) double-labeling assays. Total reactive oxygen species (ROS)/superoxide and autophagy detection were performed, and the levels of apoptosis-related proteins were examined by Western blotting. It was found that the silencing of HSP27 (HSP27-KD) resulted in increased treatment resistance to curcumin in CRC cells. In addition, cell cycle analysis showed that the curcumin treatment caused cell cycle arrest at the G2/M phase in the control group, and apoptosis was reduced in the HSP27-KD group. Curcumin treatment also resulted in a decrease in anti-apoptotic proteins, p-Akt, Akt, Bcl-2 and p-Bad, and increase in pro-apoptotic proteins Bad and c-PARP levels in the control cells but not in the HSP27-KD cells. This was also followed by low reactive oxygen/nitrogen species (ROS/RNS), superoxide and autophagy induction levels in the HSP27-KD cells as compared to the control cells. Therefore, as silencing of HSP27 increases curcumin resistance by reducing apoptosis and reactive oxidative stress production, HSP27 is a potential selective target for curcumin treatment in CRC.
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Affiliation(s)
- Hung-Hua Liang
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
| | - Chien-Yu Huang
- Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
| | - Ching-Wen Chou
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
| | - Precious Takondwa Makondi
- International PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ming-Te Huang
- Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
| | - Po-Li Wei
- Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Colorectal Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Cancer Research Center and Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan; Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
| | - Yu-Jia Chang
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
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Greco C, Catalano G, Di Grazia A, Orecchia R. Radiotherapy of Liver Malignancies. From Whole Liver Irradiation to Stereotactic Hypofractionated Radiotherapy. TUMORI JOURNAL 2018; 90:73-9. [PMID: 15143976 DOI: 10.1177/030089160409000116] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Aims and background Until recently radiotherapy of hepatic malignancies has played a limited role due to the well-known limited radiotolerance of the liver. The aim of this paper is to review the available data on the risk of radiation-induced liver disease (RILD) and to define the modern role of radiotherapy in the management of patients with metastatic or primary liver malignancies. Methods The advent of three-dimensional conformal treatment planning with dose-volume histogram analysis has made the study of partial liver irradiation possible. Limited portions of the liver may withstand high doses of radiation with minimal risk of RILD. Patients with solitary unresectable liver tumors may be treated with high-dose radiotherapy with curative intent. Recently, the feasibility of stereotactically guided treatment techniques with a single fraction or few treatment sessions has been explored in numerous institutions. Results The radiation tolerance of the whole liver found by several investigations is in the order of approximately 30 Gy, which seriously restricts its clinical application. The role of whole liver irradiation therefore appears of limited benefit in the palliation of patients with multiple liver metastases. The use of three-dimensional conformal techniques has made partial liver irradiation possible to doses in the 70–80 Gy range with conventional fractionation. At least two published series have reported improved local control and survival rates with dose escalation with three-dimensional conformal radiotherapy in patients with unresectable liver metastases. Similar outcomes have been recently reported with single dose (or hypofractionated) stereotactic radiotherapy both in metastatic and primary hepatic malignancies with minimal morbidity. Accurate target delineation and treatment reproducibility are the key to the success of this novel treatment approach, and specific treatment planning techniques and patient setup procedures must be developed to implement it. Conclusions Stereotactic high-dose radiotherapy is technically feasible for the treatment of inoperable liver malignancies, with the potential of high local control and low morbidity. Definitive evidence on the clinical advantages of this technique over other more established treatments can only be gathered from well-designed clinical studies.
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Affiliation(s)
- Carlo Greco
- Division of Radiation Oncology, European Institute of Oncology, Milan, Italy.
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Ou-Yang GQ, Pan GD, Wu YR, Xu HL. Orthotopic mouse models of colorectal cancer liver metastases. Shijie Huaren Xiaohua Zazhi 2018; 26:512-517. [DOI: 10.11569/wcjd.v26.i8.512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a malignancy with high incidence and mortality, and its high mortality rate is mainly attributed to metastases, with liver metastasis being the main cause of death. Appropriate animal models can provide a basis for studying the metastatic mechanism of colorectal cancer and assessing pre-clinical therapeutic effects. Orthotopic transplantation models that simulate colorectal cancer with liver metastases can better reflect the characteristic of liver metastasis in colorectal cancer. In this article, we review orthotopic transplantation models of liver metastases of colorectal cancer.
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Binnebösel M, Bruners P, Klink CD, Kuhl C, Neumann UP. [Oligometastasized stage IV colorectal cancer : Surgical resection and local ablative procedures]. Chirurg 2018; 87:371-9. [PMID: 27146386 DOI: 10.1007/s00104-016-0187-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND By the intensified combination of systemic, surgical and local ablative therapies a significant improvement in therapy results for metastasized colorectal cancer has been achieved in the last decade. Downstaging with subsequent resection is nowadays a standard for oligometastasized primarily unresectable colorectal cancer. MATERIAL AND METHODS The value of combining resection and local ablation is unclear; therefore, this article gives an overview of the available literature dealing with the combination of surgery and local ablative methods for oligometastasized stage IV colorectal cancer. RESULTS The best results were obtained following surgical resection alone. Whereas nowadays cryoablation is of minor importance, the most successful results are achieved following local ablative methods by radiofrequency and microwave ablation. In the future irreversible electroporation will be the most promising local ablative method. A combination of surgical resection and local ablation appears to be rational in patients if an R0 resection can be achieved. CONCLUSION Surgical resection of colorectal liver metastases is the gold standard for oncological therapy whenever possible. The rational combination of non-curative surgical resection and local ablation should be considered in the context of a multimodal therapeutic strategy, particularly in patients with primarily resectable disease.
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Affiliation(s)
- M Binnebösel
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Uniklinik der RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland
| | - P Bruners
- Klinik für Diagnostische und Interventionelle Radiologie, Uniklinik der RWTH Aachen, Aachen, Deutschland
| | - C D Klink
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Uniklinik der RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland
| | - C Kuhl
- Klinik für Diagnostische und Interventionelle Radiologie, Uniklinik der RWTH Aachen, Aachen, Deutschland
| | - U P Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Uniklinik der RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland.
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Abstract
BACKGROUND The clinical efficacy of gadoxetic acid-enhanced liver MRI as a routine preoperative procedure for all patients with colorectal cancer remains unclear. OBJECTIVE The purpose of this study was to evaluate the efficacy of preoperative gadoxetic acid-enhanced liver MRI for the diagnosis of liver metastasis in patients with colorectal cancer. DESIGN This was a retrospective analysis from a prospective cohort database. SETTINGS All of the patients were from a subspecialty practice at a tertiary referral hospital. PATIENTS Patients who received preoperative gadoxetic acid-enhanced liver MRI after CT and attempted curative surgery for colorectal cancer were included. MAIN OUTCOME MEASURES The number of equivocal hepatic lesions based on CT and gadoxetic acid-enhanced liver MRI and diagnostic use of the gadoxetic acid-enhanced liver MRI were measured. RESULTS We reviewed the records of 690 patients with colorectal cancer. Equivocal hepatic lesions were present in 17.2% of patients based on CT and in 4.5% based on gadoxetic acid-enhanced liver MRI. Among 496 patients with no liver metastasis based on CT, gadoxetic acid-enhanced liver MRI detected equivocal lesions in 15 patients and metastasis in 3 patients. Among 119 patients who had equivocal liver lesions on CT, gadoxetic acid-enhanced liver MRI indicated hepatic lesions in 103 patients (86.6%), including 90 with no metastasis and 13 with metastasis. Among 75 patients who had liver metastasis on CT, gadoxetic acid-enhanced liver MRI indicated that the hepatic lesions in 2 patients were benign, in contrast to CT findings. The initial surgical plans for hepatic lesions according to CT were changed in 17 patients (3%) after gadoxetic acid-enhanced liver MRI. LIMITATIONS This study was limited by its retrospective design. CONCLUSIONS The clinical efficacy of gadoxetic acid-enhanced liver MRI as a routine preoperative procedure for all patients with colorectal cancer is low, in spite of its high diagnostic value for detecting liver metastasis. However, this study showed gadoxetic acid-enhanced liver MRI was helpful in characterizing equivocal hepatic lesions identified in CT and could lead to change in treatment plans for some patients. See Video Abstract at http://links.lww.com/DCR/A420.
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McLoughlin JM, Jensen EH, Malafa M. Resection of Colorectal Liver Metastases: Current Perspectives. Cancer Control 2017; 13:32-41. [PMID: 16508624 DOI: 10.1177/107327480601300105] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Metastases to the liver is the leading cause of death in patients with colorectal cancer. METHODS The authors review the data on diagnosis and management of this clinical problem, and they discuss management options that can be considered. RESULTS Complete surgical resection of metastases from colorectal cancer that are localized to the liver results in 5-year survival rates ranging from 26% to 40%. CONCLUSIONS By adding modalities such as targeted systemic therapy and other "local" treatments for liver metastases, further gains in survival are anticipated.
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Affiliation(s)
- James M McLoughlin
- Gastrointestinal Tumor Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612-9497, USA
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Schmeel FC, Simon B, Luetkens JA, Träber F, Meyer C, Schmeel LC, Sabet A, Ezziddin S, Schild HH, Hadizadeh DR. Prognostic value of pretreatment diffusion-weighted magnetic resonance imaging for outcome prediction of colorectal cancer liver metastases undergoing 90Y-microsphere radioembolization. J Cancer Res Clin Oncol 2017; 143:1531-1541. [PMID: 28317063 DOI: 10.1007/s00432-017-2395-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 03/12/2017] [Indexed: 12/15/2022]
Abstract
PURPOSE To investigate the clinical potential of pretreatment apparent diffusion coefficient (ADC) on diffusion-weighted magnetic resonance imaging (DWI) for therapy response and outcome prediction in patients with liver-predominant metastatic colorectal cancer (CRC) undergoing radioembolization with 90Yttrium-microspheres (90Y-RE). METHODS Forty-six consecutive patients with unresectable CRC liver metastases underwent standardized clinical DWI on a 1.5 T MR scanner prior to and 4-6 weeks after 90Y-RE. Pretreatment clinical parameters, ADC values derived from region-of-interest analysis, and the corresponding tumor sizes of three treated liver metastases per subject were recorded. Long-term tumor response to radioembolization was categorized into response (partial remission) and nonresponse (stable disease, progressive disease) according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST) 3 months after treatment. Associations between long-term tumor response and the clinical and imaging parameters were evaluated. The impact of pretreatment clinical and imaging parameters on progression-free survival (PFS) and overall survival (OS) was further assessed by Kaplan-Meier and multivariate Cox-regression analyses. RESULTS Nonresponders had higher hepatic tumor burden (p = 0.021) and lower ADC values than patients responding to 90Y-RE, both pretreatment (986 ± 215 vs. 1162 ± 178; p = 0.036) and posttreatment (1180 ± 350 vs. 1598 ± 225; p = 0.002). ADC values higher than 935 × 10-6 mm2 (5 vs. 3 months; p = 0.022) and hepatic tumor burden ≤25% (6 vs. 3 months; p = 0.014) were associated with longer median PFS, whereas ADC >935 × 10-6 mm2 (14 vs. 6 months; p = 0.02), hepatic tumor burden ≤25% (14 vs. 6 months; p = 0.048), size of the largest metastasis <4.7 cm (18 vs. 7 months; p = 0.024), and Eastern Cooperative Oncology Group (ECOG) score <1 (8 vs. 5 months; p = 0.045) were associated with longer median OS. On multivariate analysis, ADC >935 × 10-6 mm2 and hepatic tumor burden ≤25% remained prognostic factors for PFS, and ADC >935 × 10-6 mm2 and size of the largest metastasis <4.7 cm were independent predictors of OS. CONCLUSION Pretreatment ADC on DWI represents a valuable prognostic biomarker for predicting both the therapeutic efficacy and survival prognosis in CRC liver metastases treated by 90Y-RE, allowing risk stratification and potentially optimizing further treatment strategies.
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Affiliation(s)
- Frederic Carsten Schmeel
- Department of Radiology and Radiation Oncology, University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany.
| | - Birgit Simon
- Department of Radiology and Radiation Oncology, University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany
| | - Julian Alexander Luetkens
- Department of Radiology and Radiation Oncology, University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany
| | - Frank Träber
- Department of Radiology and Radiation Oncology, University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany
| | - Carsten Meyer
- Department of Radiology and Radiation Oncology, University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany
| | - Leonard Christopher Schmeel
- Department of Radiology and Radiation Oncology, University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany
| | - Amir Sabet
- Department of Nuclear Medicine, University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
- Department of Nuclear Medicine, University Hospital Saarland, Universität des Saarlandes, Homburg, Germany
| | - Samer Ezziddin
- Department of Nuclear Medicine, University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
- Department of Nuclear Medicine, University Hospital Saarland, Universität des Saarlandes, Homburg, Germany
| | - Hans Heinz Schild
- Department of Radiology and Radiation Oncology, University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany
| | - Dariusch Reza Hadizadeh
- Department of Radiology and Radiation Oncology, University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany
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Prediction of novel target genes and pathways involved in irinotecan-resistant colorectal cancer. PLoS One 2017; 12:e0180616. [PMID: 28749961 PMCID: PMC5531462 DOI: 10.1371/journal.pone.0180616] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 06/14/2017] [Indexed: 01/02/2023] Open
Abstract
Background Acquired drug resistance to the chemotherapeutic drug irinotecan (the active metabolite of which is SN-38) is one of the significant obstacles in the treatment of advanced colorectal cancer (CRC). The molecular mechanism or targets mediating irinotecan resistance are still unclear. It is urgent to find the irinotecan response biomarkers to improve CRC patients’ therapy. Methods Genetic Omnibus Database GSE42387 which contained the gene expression profiles of parental and irinotecan-resistant HCT-116 cell lines was used. Differentially expressed genes (DEGs) between parental and irinotecan-resistant cells, protein-protein interactions (PPIs), gene ontologies (GOs) and pathway analysis were performed to identify the overall biological changes. The most common DEGs in the PPIs, GOs and pathways were identified and were validated clinically by their ability to predict overall survival and disease free survival. The gene-gene expression correlation and gene-resistance correlation was also evaluated in CRC patients using The Cancer Genomic Atlas data (TCGA). Results The 135 DEGs were identified of which 36 were upregulated and 99 were down regulated. After mapping the PPI networks, the GOs and the pathways, nine genes (GNAS, PRKACB, MECOM, PLA2G4C, BMP6, BDNF, DLG4, FGF2 and FGF9) were found to be commonly enriched. Signal transduction was the most significant GO and MAPK pathway was the most significant pathway. The five genes (FGF2, FGF9, PRKACB, MECOM and PLA2G4C) in the MAPK pathway were all contained in the signal transduction and the levels of those genes were upregulated. The FGF2, FGF9 and MECOM expression were highly associated with CRC patients’ survival rate but not PRKACB and PLA2G4C. In addition, FGF9 was also associated with irinotecan resistance and poor disease free survival. FGF2, FGF9 and PRKACB were positively correlated with each other while MECOM correlated positively with FGF9 and PLA2G4C, and correlated negatively with FGF2 and PRKACB after doing gene-gene expression correlation. Conclusion Targeting the MAPK signal transduction pathway through the targeting of the FGF2, FGF9, MECOM, PLA2G4C and PRKACB might increase tumor responsiveness to irinotecan treatment.
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Detection and Viability of Colorectal Liver Metastases After Neoadjuvant Chemotherapy: A Multiparametric PET/CT-MRI Study. Clin Nucl Med 2017; 42:258-263. [PMID: 28166142 DOI: 10.1097/rlu.0000000000001538] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE The aim of this study was to compare combined gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced and diffusion-weighted (DW) MRI with IV contrast-enhanced F-FDG PET/CT to detect and assess the viability of colorectal liver metastases (CLMs) after neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS After NAC, 45 patients with CLMs were prospectively enrolled and underwent combined Gd-EOB-DTPA-enhanced and DW-MRI and contrast-enhanced F-FDG PET/CT. Forty patients subsequently underwent surgery based on intraoperative ultrasound, which served as the reference standard for the presence of CLMs. The number of metastases detected by each technique was then compared. In 69 resected metastases, the SUVmean and SUVmax, mean and maximum target-to-background ratio (TBR), total lesion glycolysis, metabolic tumor volume, and mean and minimum apparent diffusion coefficient (ADC) were examined to identify correlations with the corresponding tumor viability (TV) determined from histological specimens. RESULTS Intraoperative ultrasound revealed 153 CLMs, 122 of which were resected. The detection rate of MRI and contrast-enhanced F-FDG PET/CT were similar (P = 0.61). The SUVmax and minimum ADC were negatively correlated (r = -0.34, P = 0.005) on preoperative imaging after NAC. However, TV was significantly correlated with the maximum TBR (r = 0.33, P = 0.006) and mean TBR (r = 0.37, P = 0.002), but not with the minimum ADC (r = -0.02, P = 0.9) or mean ADC (r = 0.01, P = 0.9). CONCLUSIONS Combined Gd-EOB-DTPA-enhanced and DW-MRI and contrast-enhanced F-FDG PET/CT allow confident detection of CLMs, but only F-FDG PET metrics are associated with TV after NAC.
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Yang Q, Wang X, Tang C, Chen X, He J. H19 promotes the migration and invasion of colon cancer by sponging miR-138 to upregulate the expression of HMGA1. Int J Oncol 2017; 50:1801-1809. [PMID: 28358427 DOI: 10.3892/ijo.2017.3941] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 03/09/2017] [Indexed: 11/06/2022] Open
Abstract
Colon cancer is the most common digestive system malignancy, along with high mortality rate, familial transmissibility and hepatic metastasis. Our study investigated the role of long non-coding RNA H19 in colon cancer. We found that H19 was overexpressed in colon cancer tissues and cell lines, the interference of H19 by short hairpin RNA (shRNA) effectively decreased the migration and invasion of colon cancer cells (HT-29 and RKO). Besides, miR-138 was predicted a target of H19, and low expression of miR-138 was found in colon cancer tissues and cells. The silence of H19 strongly increased the expression of miR-138. The decreased level of miR-138 was elevated adding miR-138 mimic in RKO cells transfected with lncRNA-H19. Similarly, the upregulated level of miR-138 was downregulated adding miR-138 inhibitor in RKO cells transfected with H19 shRNA. The luciferase reporter confirmed the targeting reaction between H19 and miR-138. Moreover, the high-mobility group A (HMGA1) protein was predicted as a target of miR-138. HMGA1 was suppressed by H19 shRNA and could be up-regulated by miR-138 inhibitor. The migration and invasion ability of colon cancer was restrained by H19 shRNA and promoted by miR-138 inhibitor. Finally, the in vivo experiment revealed that H19 shRNA strongly reduced the tumor growth and tumor volume. H19 shRNA also inhibited metastasis via suppressing hepatic metastases and the expression of metastasis-related proteins. Taken together, our research indicated an H19-miR138-HMGA1 pathway in regulating the migration and invasion of colon cancer, providing new insight for treatment of colon cancer.
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Affiliation(s)
- Qingqiang Yang
- Department of General Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Xin Wang
- Department of General Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Chunyan Tang
- Department of Nursing, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Xuan Chen
- Department of General Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Jianjun He
- Department of General Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
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Rabinel P, Dousse D, Muscari F, Suc B. Management of liver cancer. The Surgeon's point of view. Rep Pract Oncol Radiother 2017; 22:176-180. [PMID: 28490990 DOI: 10.1016/j.rpor.2017.02.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 12/27/2016] [Accepted: 02/06/2017] [Indexed: 02/07/2023] Open
Abstract
During the last twenty years, a huge progress has been achieved in the treatment of liver cancer and recent strategies include interventional radiology, chemotherapy regimens and surgery. Meanwhile, Stereotactic Body Radiation Therapy (SRBT) has developed in the treatment of all organs with millimetre accuracy, very few side effects and a high control rate. So, SRBT has become a therapeutic weapon in his own right in liver tumour treatment. Many publications have reported encouraging results in colorectal liver metastasis, hepatocellular carcinoma on cirrhosis and peripheric cholangiocarcinoma. It is important that radiation therapists involve systematic multidisciplinary "liver tumour" meetings to discuss therapeutic indications and initiate treatments quickly.
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Affiliation(s)
- Pierre Rabinel
- Department of Digestive Surgery and Liver Transplantation, Rangueil Hospital, 1, Avenue du Pr Jean Poulhès TSA 50032, 31059 Toulouse Cedex, France
| | - Damien Dousse
- Department of Digestive Surgery and Liver Transplantation, Rangueil Hospital, 1, Avenue du Pr Jean Poulhès TSA 50032, 31059 Toulouse Cedex, France
| | - Fabrice Muscari
- Department of Digestive Surgery and Liver Transplantation, Rangueil Hospital, 1, Avenue du Pr Jean Poulhès TSA 50032, 31059 Toulouse Cedex, France
| | - Bertrand Suc
- Department of Digestive Surgery and Liver Transplantation, Rangueil Hospital, 1, Avenue du Pr Jean Poulhès TSA 50032, 31059 Toulouse Cedex, France
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Han Y, Yan D, Xu F, Li X, Cai JQ. Radiofrequency Ablation versus Liver Resection for Colorectal Cancer Liver Metastasis: An Updated Systematic Review and Meta-analysis. Chin Med J (Engl) 2017; 129:2983-2990. [PMID: 27958231 PMCID: PMC5198534 DOI: 10.4103/0366-6999.195470] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background: Controversial results about the therapeutic value of radiofrequency ablation (RFA) and liver resection (LR) in the treatment of colorectal cancer liver metastasis (CRCLM) have been reported. Thus, we performed the present meta-analysis to summarize the related clinical evidences. Methods: A systematic literature search was conducted using PubMed (Medline), EMBASE, Cochrane Library, and Web of Science, for all years up to April 2016. Pooled analyses of the overall survival (OS), progression-free survival (PFS), and morbidity rates were performed. Results: A total of 14 studies were finally enrolled in the meta-analysis. Patients treated by LR gained a longer OS and PFS than those of patients treated by RFA. Patients in the RFA group had lower morbidity rates than those of patients in the LR group. Publication bias analysis revealed that there was no significant publication bias in the meta-analysis. Conclusions: Patients with CRCLM gained much more survival benefits from LR than that from RFA. RFA rendered lower rates of morbidities. More well-designed randomized controlled trails comparing the therapeutic value of LR and RFA are warranted.
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Affiliation(s)
- Yue Han
- Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dong Yan
- Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Fei Xu
- Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiao Li
- Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jian-Qiang Cai
- Department of Abdominal Surgical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Jia Z, Liu W, Gong L, Xiao Z. Downregulation of RASAL2 promotes the proliferation, epithelial-mesenchymal transition and metastasis of colorectal cancer cells. Oncol Lett 2017; 13:1379-1385. [PMID: 28454265 DOI: 10.3892/ol.2017.5581] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Accepted: 11/03/2016] [Indexed: 12/13/2022] Open
Abstract
RAS protein activator like 2 (RASAL2) is a RAS-GTPase-activating protein and has recently been identified to be a tumor suppressor in various types of human cancer; however, the function of RASAL2 in colorectal carcinoma (CRC) remains unclear. In the present study, the function of RASAL2 in CRC cells was investigated using a RASAL2 loss-of-function cell model. RASAL2 short hairpin RNA was transfected into the human CRC cell lines LoVo, SW620 and HCT116, and the wild-type colon cell line NCM460. The subsequent downregulation of RASAL2 was evaluated using western blot and reverse transcription-quantitative polymerase chain reaction analyses. It was observed that RASAL2 expression was significantly decreased in human CRC tissues and cell lines (P<0.01). In the loss-of-function cell models, RASAL2 expression was decreased significantly, while cell proliferation, colony formation, migration and invasion were increased (all P<0.01). These effects were associated with the induction of epithelial-mesenchymal transition and Raf/mitogen-activated protein kinase hyperactivation. The results of the present study indicate that RASAL2 is a potential therapeutic target to inhibit CRC progression and metastasis.
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Affiliation(s)
- Zeming Jia
- Hepatobiliary and Enteric Surgery Research Center of Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Weidong Liu
- Hepatobiliary and Enteric Surgery Research Center of Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Liansheng Gong
- Hepatobiliary and Enteric Surgery Research Center of Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Zhongfu Xiao
- Hepatobiliary and Enteric Surgery Research Center of Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
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Marfà S, Marti J, Reyes A, Casals G, Fernández-Varo G, Carvajal S, García-Valdecasas JC, Fuster J, Jiménez W. Metastatic Tissue Proteomic Profiling Predicts 5-Year Outcomes in Patients with Colorectal Liver Metastases. Transl Oncol 2016; 9:445-452. [PMID: 27751349 PMCID: PMC5067925 DOI: 10.1016/j.tranon.2016.08.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 08/03/2016] [Accepted: 08/08/2016] [Indexed: 01/05/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers in the developed countries, and nearly 70% of patients with CRC develop colorectal liver metastases (CRLMs). During the last decades, several scores have been proposed to predict recurrence after CRLM resection. However, these risk scoring systems do not accurately reflect the prognosis of these patients. Therefore, this investigation was designed to identify a proteomic profile in human hepatic tumor samples to classify patients with CRLM as “mild” or “severe” based on the 5-year survival. The study was performed on 85 CRLM tumor samples. Firstly, to evaluate any distinct tumor proteomic signatures between mild and severe CRLM patients, a training group of 57 CRLM tumor samples was characterized by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, and a classification and regression tree (CART) analysis was subsequently performed. Finally, 28 CRLM tumor samples were used to confirm and validate the results obtained. Based on all the protein peaks detected in the training group, the CART analysis was generated, and four peaks were considered to be the most relevant to construct a diagnostic algorithm. Indeed, the multivariate model yielded a sensitivity of 85.7% and a specificity of 86.1%, respectively. In addition, the receiver operating characteristic (ROC) curve showed an excellent diagnostic accuracy to discriminate mild from severe CRLM patients (area under the ROC: 0.903). Finally, the validation process yielded a sensitivity and specificity of 68.8% and 83.3%, respectively. We identified a proteomic profile potentially useful to determine the prognosis of CRLM patients based on the 5-year survival.
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Affiliation(s)
- Santiago Marfà
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Josep Marti
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Adalgiza Reyes
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Gregori Casals
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Guillermo Fernández-Varo
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biomedicine, University of Barcelona, Barcelona, Spain
| | - Silvia Carvajal
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - J C García-Valdecasas
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Josep Fuster
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Wladimiro Jiménez
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biomedicine, University of Barcelona, Barcelona, Spain.
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Teraoku H, Morine Y, Ikemoto T, Saito Y, Yamada S, Yoshikawa M, Takasu C, Higashijima J, Imura S, Shimada M. Role of thrombospondin-1 expression in colorectal liver metastasis and its molecular mechanism. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2016; 23:565-73. [PMID: 27404020 DOI: 10.1002/jhbp.376] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Accepted: 07/08/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND Thrombospondin-1 (THBS-1), a glycoprotein, is an endogenous inhibitor of angiogenesis and tumor growth. In this study, we investigated the clinical role and mechanism of THBS-1 expression in colorectal liver metastases, focusing on the relationships between its expression and tumor growth, epithelial-mesenchymal transition (EMT), and expression of other relevant molecules. METHODS Ninety-four patients who initially underwent curative hepatic resection were enrolled in this study and correlations between expression of THBS-1 (THBS-1 high [n = 35] and THBS-1 low [n = 59]) and tumor growth, Ki-67 labeling index (Ki-67 LI), expression of other relevant molecules, and microvessel density (MVD) investigated. RESULTS THBS-1 low expression correlated with more advanced grade of liver and lymph node metastases and significantly worse overall survival than strong THBS-1 expression (3-year survival: 96.7% vs. 65.4%, P < 0.01). Multivariate analysis identified THBS-1 low expression as an independent prognostic factor (HR 2.82, 95% CI 1.21-7.71, P = 0.01). THBS-1 low expression correlated positively with high Ki-67 LI (P < 0.05) and inversely with E-cadherin (P < 0.05) and hypoxia inducible factor-1α (HIF-1α) expression (P < 0.05); THBS-1 expression and MVD were not significantly correlated. CONCLUSIONS Low THBS-1 expression may be an independent poor prognostic factor that affects tumor growth and EMT acquisition. Additionally, THBS-1 may be regulated by the HIF-1 pathway.
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Affiliation(s)
- Hiroki Teraoku
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yuji Morine
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Tetsuya Ikemoto
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yu Saito
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Shinichiro Yamada
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Masato Yoshikawa
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Chie Takasu
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Jun Higashijima
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Satoru Imura
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Mitsuo Shimada
- Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
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Chang YJ, Cheng YW, Lin RK, Huang CC, Chen WTL, Ke TW, Wei PL. Thrombomodulin Influences the Survival of Patients with Non-Metastatic Colorectal Cancer through Epithelial-To-Mesenchymal Transition (EMT). PLoS One 2016; 11:e0160550. [PMID: 27512995 PMCID: PMC4981396 DOI: 10.1371/journal.pone.0160550] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Accepted: 07/21/2016] [Indexed: 12/29/2022] Open
Abstract
Background Treatment resistance and metastasis are the major causes of death among patients with colorectal cancer (CRC). Approximately 20% of surgically treated patients ultimately develop metastases during the follow-up period. Currently, the TNM system is the only available prognostic test. Therefore, the identification of new markers for CRC remains important. Thrombomodulin (TM), a glycoprotein, is involved in angiogenesis and has been linked to many malignant diseases. However, the function of TM in CRC remains unclear. Methods A total of 170 patients with CRC participated in this study. TM expression was analyzed via immunohistochemistry. Univariate (Kaplan-Meier) analysis was used to analyze patient outcomes, including overall survival (OS) and disease-free survival (DFS). TM expression was manipulated using shRNA or an overexpression system. Transwell migration assays, wound healing migration assays, and the xCELLigence biosensor system were used to detect cell proliferative and migratory capacities. Results TM expression in the tumor tissues significantly and positively correlated with the DFS and OS of non-metastatic patients with CRC (ps = 0.036 and 0.0218, respectively). Suppression of TM expression increased the proliferation and migration of DLD-1 cells. TM overexpression reduced the cells’ proliferative and migratory capacities. Cyclooxygenase (COX)-2 expression was up-regulated following TM silencing. Furthermore, the association between the migration of colon cancer cells and the levels of TM and epithelial-to-mesenchymal transition (EMT) markers (fibronectin, vimentin and ezrin) was confirmed in HT29 and DLD-1 cells. Conclusions Our study demonstrates that patients with non-metastatic CRC display low TM expression in their tumors and exhibit reduced DFS and OS. The enhanced expression of mesenchymal markers and COX-2 may be involved in the mechanisms that underlie recurrence in patients with cancer displaying low TM expression.
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Affiliation(s)
- Yu-Jia Chang
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
| | - Ya-Wen Cheng
- Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology,Taipei Medical University, Taipei, Taiwan, ROC
| | - Ruo-Kai Lin
- Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan, ROC
| | - Chi-Chou Huang
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC
- Department of Surgery, Chung Shan Medical University, Taichung, Taiwan, ROC
| | - William Tzu-Liang Chen
- Division of Colorectal Surgery, Department of Surgery, China Medical University Hospital, Taichung, Taiwan, ROC
| | - Tao-Wei Ke
- Division of Colorectal Surgery, Department of Surgery, China Medical University Hospital, Taichung, Taiwan, ROC
- Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan, ROC
| | - Po-Li Wei
- Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology,Taipei Medical University, Taipei, Taiwan, ROC
- Department of Surgery, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
- Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan, ROC
- Cancer Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan, ROC
- * E-mail:
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Surrogate Imaging Biomarkers of Response of Colorectal Liver Metastases After Salvage Radioembolization Using 90Y-Loaded Resin Microspheres. AJR Am J Roentgenol 2016; 207:661-70. [PMID: 27384594 DOI: 10.2214/ajr.15.15202] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The purpose of the present study is to evaluate Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, tumor attenuation criteria, Choi criteria, and European Organization for Research and Treatment of Cancer (EORTC) PET criteria as measures of response and subsequent predictors of liver progression-free survival (PFS) after radioembolization (RE) of colorectal liver metastases (CLM). The study also assesses interobserver variability for measuring tumor attenuation using a single 2D ROI on a simple PACS workstation. MATERIALS AND METHODS We performed a retrospective review of the clinical RE database at our institution, to identify patients treated in the salvage setting for CLM between December 2009 and March 2013. Response was evaluated on FDG PET scans, with the use of EORTC PET criteria, and on portal venous phase CT scans, with the use of RECIST 1.1, tumor attenuation criteria, and Choi criteria. Two independent blinded observers measured tumor attenuation using a single 2D ROI. The intraclass correlation coefficient (ICC) for interobserver variability was assessed. Kaplan-Meier methodology was used to calculate liver PFS, and the log-rank test was used to assess the response criteria as predictors of liver PFS. RESULTS A total of 25 patients with 46 target tumors were enrolled in the study. The ICC was 0.95 at baseline and 0.98 at response evaluation. Among the 25 patients, more responders (i.e., partial response) were identified on the basis of EORTC PET criteria (n = 14), Choi criteria (n = 15), and tumor attenuation criteria (n = 13) than on the basis of RECIST 1.1 (n = 2). The median liver PFS was 3.0 months (95% CI, 2.1-4.0 months). Response identified on the basis of EORTC PET criteria (p < 0.001), Choi criteria (p < 0.001), or tumor attenuation criteria (p = 0.01) predicted liver PFS; however, response identified by RECIST 1.1 did not (p = 0.1). CONCLUSION RECIST 1.1 has poor sensitivity for detecting metabolic responses classified by EORTC PET criteria. EORTC PET criteria, Choi criteria, and tumor attenuation criteria appear to be equally reliable surrogate imaging biomarkers of liver PFS after RE in patients with CLM.
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Nardo B, Serafini S, Ruggiero M, Grande R, Fugetto F, Zullo A, Novello M, Rizzuto A, Bonaiuto E, Vaccarisi S, Cavallari G, Serra R, Cannistrà M, Sacco R. Liver resection for metastases from colorectal cancer in very elderly patients: New surgical horizons. Int J Surg 2016; 33 Suppl 1:S135-41. [PMID: 27353843 DOI: 10.1016/j.ijsu.2016.06.014] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION AND AIM Patients with colorectal cancer (CRC) may develop liver metastases. Surgical resection remains the best treatment of choice for colorectal liver metastases (CRLM) according to resectability criteria, with a long-term survival of 25% up to 41% after 5 years. Advanced age is associated with a higher incidence and co-morbidity, particularly cardiovascular disease, as well as deteriorating physiological reserves. The aim of this study was to analyse the overall and disease-free survival for patients with CRLM according to their chronological age. METHODS Patients with CRLM were enrolled in the study. Data on gender, age, co-morbidity, metastasis characteristics (number, size and total metastatic volume (TMV)), use of perioperative chemotherapy and operative and post-operative complications were collected. Then, according to recent World Health Organization (WHO) guidelines, the patients were grouped by age. Statistical analysis was performed using the software R (ver. 2.14.1). RESULTS Hepatic resection was performed in 149 patients (21 patients in the very elderly group, 79 in the elderly group and 49 in the younger group). The three groups were comparable in terms of operative duration, transfusion rate, length of high-dependency unit (HDU) stay and post-operative hospital stay. The very elderly group showed a non-significant increase in post-operative morbidity. The 30-day and 60-day/inpatient mortality rates increased with age without any significant statistically difference between the three groups (very elderly group 4.8% and 4.8%; elderly group: 2.5% and 3.8%; and younger group 0% and 2%). At 5 years, the overall survival was 28.6% for very elderly patients (≥75 years), 33.3% for elderly patients (≥65 to <75 years) and 43.5% for younger patients (≤65 years). The 1-, 3- and 5-year disease-free survival was similar across the groups. CONCLUSIONS Liver resection for CRLM in carefully selected patients above the age of 75 can be performed with acceptable morbidity and mortality rates, similar to those in younger patients. Moreover, the severity of CRLM in elderly patients is proven to be lesser than in younger patients. Thus, we can conclude that advanced chronological age cannot be considered a contraindication to hepatic resection for CRLM.
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Affiliation(s)
- Bruno Nardo
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Italy; Department of Surgery, Annunziata Hospital of Cosenza, Cosenza, Italy.
| | - Simone Serafini
- Department of Surgery, Annunziata Hospital of Cosenza, Cosenza, Italy.
| | - Michele Ruggiero
- Department of Surgery, Annunziata Hospital of Cosenza, Cosenza, Italy.
| | - Raffaele Grande
- Department of Medical and Surgical Sciences, University of Catanzaro, Italy.
| | - Francesco Fugetto
- Department of Medical and Surgical Science, University of Modena, Italy.
| | - Alessandra Zullo
- Department of Medical and Surgical Sciences, University of Catanzaro, Italy.
| | - Matteo Novello
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Italy.
| | - Antonia Rizzuto
- Department of Medical and Surgical Sciences, University of Catanzaro, Italy.
| | | | | | - Giuseppe Cavallari
- Department of Experimental Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, University of Bologna, Italy.
| | - Raffaele Serra
- Department of Experimental Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, University of Bologna, Italy.
| | - Marco Cannistrà
- Department of Surgery, Annunziata Hospital of Cosenza, Cosenza, Italy.
| | - Rosario Sacco
- Department of Medical and Surgical Sciences, University of Catanzaro, Italy.
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Shady W, Kishore S, Gavane S, Do RK, Osborne JR, Ulaner GA, Gonen M, Ziv E, Boas FE, Sofocleous CT. Metabolic tumor volume and total lesion glycolysis on FDG-PET/CT can predict overall survival after (90)Y radioembolization of colorectal liver metastases: A comparison with SUVmax, SUVpeak, and RECIST 1.0. Eur J Radiol 2016; 85:1224-31. [PMID: 27161074 DOI: 10.1016/j.ejrad.2016.03.029] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 03/23/2016] [Accepted: 03/30/2016] [Indexed: 12/12/2022]
Abstract
PURPOSE To compare the performance of 4 metrics of metabolic response on FDG-PET/CT against RECIST 1.0 for determining response and predicting overall survival (OS) following (90)Y resin microspheres radioembolization of colorectal liver metastases (CLM). METHODS We conducted an IRB-waived retrospective review of our radioembolization database to identify patients with unresectable CLM treated between December 2009 and December 2013. We included patients who had both PET/CT and contrast enhanced CT (CECT) available at baseline and on the first follow-up post-radioembolization. On baseline CECT up to five target tumors were chosen per patient according to RECIST 1.0. Four metrics of FDG-avidity (SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)) on PET/CT were measured for the same target tumors. Using RECIST 1.0, patients were classified as no progression (partial response or stable disease) and progression. For each PET metric, a cut-off point of ≥30% decrease was chosen to define response. OS was calculated from the time of radioembolization using Kaplan-Meier methodology. The log-rank test was used for univariate analysis to identify predictors of OS. RESULTS The study enrolled 49 patients with 119 target tumors; a median of 2 (range: 1-5) tumors were selected per patient. Median OS was 12.7 months (95%CI: 7.2-16.7). Response by MTV (P=0.035) and TLG (P=0.044) reached statistical significance in predicting OS. Response by SUVmax (P=0.21), SUVpeak (P=0.20) or no progression by RECIST 1.0 (P=0.44) did not predict OS. CONCLUSION Metabolic response based on changes in MTV and TLG can predict OS post-radioembolization of CLM.
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Affiliation(s)
- Waleed Shady
- Section of Interventional Radiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Sirish Kishore
- Department of Nuclear medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Somali Gavane
- Department of Nuclear medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Richard K Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Joseph R Osborne
- Department of Nuclear medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Gary A Ulaner
- Department of Nuclear medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Etay Ziv
- Section of Interventional Radiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Franz E Boas
- Section of Interventional Radiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Constantinos T Sofocleous
- Section of Interventional Radiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States.
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Shady W, Petre EN, Gonen M, Erinjeri JP, Brown KT, Covey AM, Alago W, Durack JC, Maybody M, Brody LA, Siegelbaum RH, D’Angelica MI, Jarnagin WR, Solomon SB, Kemeny NE, Sofocleous CT. Percutaneous Radiofrequency Ablation of Colorectal Cancer Liver Metastases: Factors Affecting Outcomes--A 10-year Experience at a Single Center. Radiology 2016; 278:601-11. [PMID: 26267832 PMCID: PMC4734163 DOI: 10.1148/radiol.2015142489] [Citation(s) in RCA: 279] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE To identify predictors of oncologic outcomes after percutaneous radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLMs) and to describe and evaluate a modified clinical risk score (CRS) adapted for ablation as a patient stratification and prognostic tool. MATERIALS AND METHODS This study consisted of a HIPAA-compliant institutional review board-approved retrospective review of data in 162 patients with 233 CLMs treated with percutaneous RFA between December 2002 and December 2012. Contrast material-enhanced CT was used to assess technique effectiveness 4-8 weeks after RFA. Patients were followed up with contrast-enhanced CT every 2-4 months. Overall survival (OS) and local tumor progression-free survival (LTPFS) were calculated from the time of RFA by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariate and multivariate analysis to identify predictors of outcomes. RESULTS Technique effectiveness was 94% (218 of 233). Median LTPFS was 26 months. At univariate analysis, predictors of shorter LTPFS were tumor size greater than 3 cm (P < .001), ablation margin size of 5 mm or less (P < .001), high modified CRS (P = .009), male sex (P = .03), and no history of prior hepatectomy (P = .04) or hepatic arterial infusion chemotherapy (P = .01). At multivariate analysis, only tumor size greater than 3 cm (P = .01) and margin size of 5 mm or less (P < .001) were independent predictors of shorter LTPFS. Median and 5-year OS were 36 months and 31%. At univariate analysis, predictors of shorter OS were tumor size larger than 3 cm (P = .005), carcinoembryonic antigen level greater than 30 ng/mL (P = .003), high modified CRS (P = .02), and extrahepatic disease (EHD) (P < .001). At multivariate analysis, tumor size greater than 3 cm (P = .006) and more than one site of EHD (P < .001) were independent predictors of shorter OS. CONCLUSION Tumor size of less than 3 cm and ablation margins greater than 5 mm are essential for satisfactory local tumor control. Tumor size of more than 3 cm and the presence of more than one site of EHD are associated with shorter OS.
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Affiliation(s)
- Waleed Shady
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Elena N. Petre
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Mithat Gonen
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Joseph P. Erinjeri
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Karen T. Brown
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Anne M. Covey
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - William Alago
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Jeremy C. Durack
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Majid Maybody
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Lynn A. Brody
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Robert H. Siegelbaum
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Michael I. D’Angelica
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - William R. Jarnagin
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Stephen B. Solomon
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Nancy E. Kemeny
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Constantinos T. Sofocleous
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
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Bhutiani N, Philips P, Martin RCG, Scoggins CR. Impact of surgical margin clearance for resection of secondary hepatic malignancies. J Surg Oncol 2015; 113:289-95. [PMID: 26662026 DOI: 10.1002/jso.24107] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 11/14/2015] [Indexed: 12/11/2022]
Abstract
Over the past several decades, there has been increasing discussion regarding the optimal management of secondary liver malignancies. Traditionally, resection has only been recommended if it could be accomplished with negative microscopic margins of at least 10 mm. However, many investigators have pushed this limit to offer resection to patients with narrower margins. We review the data regarding the impact of margin clearance on outcomes for patients undergoing hepatic metastasectomy.
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Affiliation(s)
- Neal Bhutiani
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky
| | - Prejesh Philips
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky
| | - Robert C G Martin
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky
| | - Charles R Scoggins
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky
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