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Zhou J, Qin S, Cui R, Chen Y, Wang Y, Liu G. Outcomes of ultrasound-guided percutaneous ablation of >5 versus ≤ 5 colorectal liver metastases: a propensity score matching study. Int J Hyperthermia 2025; 42:2488128. [PMID: 40255153 DOI: 10.1080/02656736.2025.2488128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 03/28/2025] [Accepted: 03/30/2025] [Indexed: 04/22/2025] Open
Abstract
OBJECTIVES To investigate the effectiveness and safety of microwave ablation (MWA) in patients with 1-5 colorectal liver metastases (CRLM) versus those with 6-9 CRLM. METHODS Data from patients with 1-9 CRLM, who underwent ultrasound (US)-guided percutaneous MWA between January 2018 and May 2023, were retrospectively analyzed. Propensity score matching (PSM) at a ratio of 1:2 was used to balance potential bias between the groups. RESULTS Data from 264 patients were included in the analysis. After PSM, there were 43 and 75 patients in the CRLM >5 and ≤5 groups, respectively. Even with higher tumor burden and technical difficulty, there was no statistical difference in the local tumor progression (LTP)-free survival (LTPFS) between the groups (p > 0.05). Patients with an ablation margin (AM) ≤5 mm exhibited a significantly higher rate of LTP than those with AM >5 mm in both groups(p < 0.05). Patients with 6-9 CRLM experienced a higher incidence of intrahepatic recurrence (iHR) (p = 0.041) and shorter progression-free survival (PFS) at any site (p < 0.05). CRLM > 5 is an independent risk factor for poor PFS (p = 0.008). The minor complication rate was lower in the CRLM ≤ 5 group (p < 0.05) and the major complication rate showed no difference (p > 0.05). CONCLUSIONS When the number of CRLM was limited to 9, single-session MWA was feasible and safe for radical local treatment. An AM >5 mm was critical for local tumor control. Compared with patients with 1-5 CRLM, those with 6-9 CRLM experienced inferior PFS at any site, which mainly lies in more iHR.
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Affiliation(s)
- Jingwen Zhou
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Si Qin
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Rui Cui
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yao Chen
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yimin Wang
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Guangjian Liu
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Ocuin LM, Stitzel H, Chung M, Tirumani SH, Elshami M, Tomaro M, Miller-Ocuin JL, Deitz DW, Steinhagen E, Charles R, Costedio M, Liu M, Lumish M, Selfridge JE. Initial outcomes of a single-institution hepatic artery infusion pump program for colorectal liver metastases and intrahepatic cholangiocarcinoma: Safety, feasibility, and circulating tumor DNA tracking. Surgery 2025; 182:109325. [PMID: 40088540 DOI: 10.1016/j.surg.2025.109325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 01/27/2025] [Accepted: 02/18/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Hepatic artery infusion with floxuridine is a treatment option for patients with colorectal liver metastases or intrahepatic cholangiocarcinoma. Outcomes from newer centers are understudied. Predictive markers are needed, and quantitative circulating tumor DNA is an emerging candidate method for predicting response in patients receiving hepatic artery infusion. We aimed to describe safety, feasibility, early oncologic outcomes, and quantitative circulating tumor DNA dynamics in patients treated with hepatic artery infusion at a newly established program. METHODS Single-institution analysis of patients who underwent hepatic artery infusion pump placement (April 2022-April 2024) was conducted. Primary outcomes included safety and feasibility (receiving ≥1 cycle of floxuridine). Secondary outcomes included radiographic response (Response Evaluation Criteria in Solid Tumors 1.1), relative dose intensity of floxuridine received, and quantitative circulating tumor DNA response. RESULTS A total of 36 patients underwent hepatic artery infusion pump placement (colorectal liver metastases: 32; cholangiocarcinoma: 4). Technical success was 100%. Feasibility was 97%. One patient experienced mortality at 90 days from disease progression. Three patients (8%) experienced a total of 5 hepatic artery infusion pump-specific complications (pump pocket [n = 3], hemorrhage [n = 1], biliary sclerosis [n = 1]). Median relative dose intensity was 68.5% (colorectal liver metastases: 68.3%; cholangiocarcinoma 72.5.0%). For the 27 patients who underwent floxuridine therapy with available postoperative imaging, disease control rate was 97% (partial response: n = 15; stable disease: n = 11). Quantitative circulating tumor DNA was obtained from 16 patients (44%). Circulating tumor DNA dynamics appeared to correlate with and precede radiographic response. CONCLUSIONS Implementation of a new hepatic artery infusion program is safe and feasible with promising early oncologic outcomes. Circulating tumor DNA tracking is achievable and dynamic changes in circulating tumor DNA may correlate with radiographic response to treatment.
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Affiliation(s)
- Lee M Ocuin
- Division of Surgical Oncology, Lehigh Valley Topper Cancer Institute, Allentown, PA.
| | - Henry Stitzel
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH
| | - Michelle Chung
- Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Sree Harsha Tirumani
- Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Mohamedraed Elshami
- Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Maria Tomaro
- Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH
| | | | - David W Deitz
- Division of Colorectal Surgery, New York University Langone Medical Center, New York, NY
| | - Emily Steinhagen
- Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Ronald Charles
- Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Meagan Costedio
- Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Michael Liu
- Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Melissa Lumish
- Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - J Eva Selfridge
- Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH
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Sengar D, Pathan NS, Gajbhiye V. D-bait: A siDNA for regulation of DNA-protein kinases against DNA damage and its implications in cancer. Int J Pharm 2025; 673:125416. [PMID: 40024452 DOI: 10.1016/j.ijpharm.2025.125416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 01/31/2025] [Accepted: 02/26/2025] [Indexed: 03/04/2025]
Abstract
siDNA fragments, also called Dbait and Pbait, are small DNA oligonucleotides of 30-32 base pairs that cause impairment in DNA repair pathways. Like siRNA and miRNA molecules, which lead to the degradation of mRNA molecules through the Argonaute and Drosha machinery, respectively, Dbait molecules act as false DNA damage signals and trigger and exhaust the DNA repair machinery. In normal cells with no significant DNA damage, the influence of these molecules is negligible. However, in cancer, when there is heavy DNA damage due to replication and anticancer therapies, the cancer cell is heavily dependent on DNA repair proteins to keep the genome intact and limit breaks. This phenomenon primarily occurs during radiation therapy, as significant DNA damage surpasses several DNA repair mechanisms, causing an accumulation of unrepaired lesions and ultimately leading to cell death. This review explores the therapeutic capacity of siDNA molecules in cancer treatment by stimulating the repair mechanisms in cells that depend on DNA repair pathways. For aggressive malignancies such as glioblastoma, prostate cancer, and colorectal cancer, the use of siDNA as a radiosensitizer, especially when combined with other treatments, increases the vulnerability of tumor cells to radiation-induced DNA damage, hence potentially enhancing therapy results.
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Affiliation(s)
- Devyani Sengar
- Nanobioscience Group, Agharkar Research Institute, Pune 411004, India; Savitribai Phule Pune University, Pune 411007, India
| | - Nida Sayed Pathan
- Nanobioscience Group, Agharkar Research Institute, Pune 411004, India; Savitribai Phule Pune University, Pune 411007, India
| | - Virendra Gajbhiye
- Nanobioscience Group, Agharkar Research Institute, Pune 411004, India; Savitribai Phule Pune University, Pune 411007, India.
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Liu L, Cui WC, Sun Y, Wang H, Liang ZN, Wu W, Yan K, Ji YL, Dong L, Yang W. Classification of Neoadjuvant Therapy Response in Patients With Colorectal Liver Metastases Using Contrast-Enhanced Ultrasound-With Histological Pathology as the Gold Standard. ULTRASOUND IN MEDICINE & BIOLOGY 2025; 51:102-111. [PMID: 39414406 DOI: 10.1016/j.ultrasmedbio.2024.09.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 08/29/2024] [Accepted: 09/16/2024] [Indexed: 10/18/2024]
Abstract
OBJECTIVE To evaluate the response to neoadjuvant therapy in patients with colorectal liver metastases (CRLMs) using ultrasound(US) and contrast-enhanced ultrasound(CEUS), with correction to the tumor regression grade (TRG) of pathological results. METHODS This study included patients with resectable CRLMs admitted from February to December 2022. After at least 4 cycles neoadjuvant therapy, all the patients received US and CEUS examinations within two weeks before hepatectomy. CEUS clips were postprocessed with color parameter imaging (CPI) and microflow imaging (MFI) analysis. Logistic regression analyses were used to develop an evaluation Nomogram. Ultrasound-based model was constructed to discriminate between the response (TRG1/2/3) and nonresponse (TRG4/5) groups at the lesion level. The model's predictive ability was evaluated using the C index and calibration curve, with decision curve analysis assessing the Nomogram's added value. RESULTS The study analyzed 105 CRLM lesions (the lesion with the highest diameter analyzed for each patient), with 43.8% showing a response to therapy. Univariate analysis identified calcification on US (p = 0.039), CEUS enhancement degree (p < 0.001), CEUS enhancement pattern (p<0.001), CEUS washout type (p < 0.001), CEUS necrosis (p < 0.001), CPI feeding artery (p = 0.003) and MFI pattern (p < 0.001) were significantly associated with TRG. The multivariate analysis showed CEUS enhancement pattern (p = 0.026), CEUS washout type (p = 0.018) and CEUS necrosis (p = 0.005) were independently associated with the neoadjuvant therapy response. A Nomogram with the three independent predictors was developed, with an AUC of 0.898. CONCLUSION The ultrasound-based model provided accurate evaluation of pathological tumor response to preoperative chemotherapy in patients with CRLM, and may help to decide the individualized treatment strategy.
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Affiliation(s)
- Li Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wen-Chao Cui
- Department of Ultrasonography, Shengli Oil Field Center Hospital, Dongying, Shandong Province, China
| | - Yu Sun
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hong Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zi-Nan Liang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, 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
| | - Kun Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yong-Li Ji
- Department of Ultrasonography, Shengli Oil Field Center Hospital, Dongying, Shandong Province, China
| | - Liang Dong
- Department of Ultrasonography, Shengli Oil Field Center Hospital, Dongying, Shandong Province, China
| | - Wei Yang
- 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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Zheng J, Wang T, Wang H, Yan B, Lai J, Qiu K, Zhou X, Tan J, Wang S, Ji H, Feng M, Jiang W, Wang H, Yan J. Use of a Pathomics Nomogram to Predict Postoperative Liver Metastasis in Patients with Stage III Colorectal Cancer. Ann Surg Oncol 2024:10.1245/s10434-024-16519-8. [PMID: 39614006 DOI: 10.1245/s10434-024-16519-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 10/30/2024] [Indexed: 12/01/2024]
Abstract
BACKGROUND Approximately 25% of patients with stage III colorectal cancer experience liver metastasis after radical resection; however, there is currently a lack of methods to predict liver metastasis. This study aims to develop and validate a pathomics nomogram to predict liver metastasis in patients with stage III colorectal cancer. METHODS A total of 318 enrolled patients were divided into three cohorts: a training cohort (n = 139), a validation cohort (n = 69), and an external cohort (n = 110). A competitive risk nomogram was established by the pathomics signature and clinicopathological characteristics and assessed by calibration, discrimination, and clinical usefulness. RESULTS A significant correlation between the pathomics signature and liver metastasis in stage III colorectal cancer was found. Multivariate Fine-Gray analysis indicated that preoperative carcinoembryonic antigen level, postoperative chemotherapy, and pathomics signature were independent predictors of liver metastasis. A competitive risk nomogram was developed to predict liver metastasis in patients with stage III colorectal cancer. The predicting nomogram shows good discrimination and calibration, with C-indexes of 0.811 (95% confidence interval [CI] 0.651-0.971), 0.759 (95% CI 0.531-0.987), and 0.845 (95% CI 0.641-0.999), with area under the receiver operating characteristic (AUROC) curves at 5 years of 0.833 (95% CI 0.742-0.925), 0.760 (95% CI 0.652-0.893), and 0.812 (95% CI 0.692-0.931) in the training, validation, and external cohorts, respectively. Compared with the clinicopathological nomogram, the nomogram combined with the pathomics signature had better performance (AUROC 0.823 [95% CI 0.764-0.881] vs. 0.678 [95% CI 0.606-0.751]; p < 0.001). CONCLUSIONS The pathomics signature is a predictive indicator for liver metastasis in patients with stage III colorectal cancer, and the integrated nomogram can be used to predict liver metastasis better than the clinicopathological nomogram alone.
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Affiliation(s)
- Jixiang Zheng
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Ting Wang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Huaiming Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People's Republic of China
| | - Botao Yan
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Jianbo Lai
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Kemao Qiu
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Xinyi Zhou
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Jie Tan
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Shijie Wang
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Hongli Ji
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Mingyuan Feng
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Wei Jiang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China.
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
| | - Hui Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People's Republic of China.
| | - Jun Yan
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China.
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
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Zheng J, Wang T, Wang S, Ji H, Yan J. ASO Author Reflections: Use of a Pathomics Nomogram to Predict Postoperative Liver Metastasis in Patients with Stage III Colorectal Cancer. Ann Surg Oncol 2024:10.1245/s10434-024-16576-z. [PMID: 39565491 DOI: 10.1245/s10434-024-16576-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 11/06/2024] [Indexed: 11/21/2024]
Affiliation(s)
- Jixiang Zheng
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Ting Wang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Shijie Wang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Hongli Ji
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Jun Yan
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China.
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
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Okuyan D. Epidermal Growth Factor Downregulates Carbon Anhydrase III (CAIII) in Colon Cancer. Curr Issues Mol Biol 2024; 46:12994-13002. [PMID: 39590368 PMCID: PMC11593170 DOI: 10.3390/cimb46110774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 11/07/2024] [Accepted: 11/08/2024] [Indexed: 11/28/2024] Open
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related death in the world. Dysregulations in the EGF signaling pathway have been associated with colon cancer. Some members of the carbonic anhydrase family serve as biomarkers in cancer. Carbonic anhydrase III (CAIII), a member of this family, shows different activities than the other members of its family and has been associated with cancer. However, there are no studies on the effective regulation of EGF. In this study, we investigated the EGF-influenced regulation of CAIII in the HT29, SW480, and HUVEC cell lines and showed that CAIII regulation decreased with the effect of EGF. We aimed to investigate the EGF-affected mRNA and protein regulation of the CAIII gene in HT29, SW480, and HUVEC cell lines. For this purpose, we determined time-dependent CAIII mRNA and protein expression by applying EGF to HT29, SW480, and HUVEC cells. Time-dependent EGF-induced mRNA and protein level regulation of the CAIII gene decreased in the HT29, SW480, and HUVEC cell lines. EGF regulates the motility, adhesion, and metastasis of cancer cells. CAIII prevents cells from metastasizing through cell acidification. Therefore, our findings explained why the EGF-effective regulation of CAIII decreased. We suggest that the CAIII gene is promising as a targeted therapy due to the decrease in EGF-effected CAIII gene regulation in colon carcinoma.
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Affiliation(s)
- Derya Okuyan
- Department of Veterinary Medicine, Susurluk Agriculture and Forestry Vocational School, Bandırma Onyedi Eylül University, Susurluk 10600, Balıkesir, Türkiye
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Li Z, Yan T, Cai X. Comparative efficacy of microwave ablation and radiofrequency ablation for treating metastatic liver cancer: a systematic review and meta-analysis. Front Oncol 2024; 14:1473780. [PMID: 39540156 PMCID: PMC11557459 DOI: 10.3389/fonc.2024.1473780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 09/30/2024] [Indexed: 11/16/2024] Open
Abstract
Objective This study aims at evaluating and juxtaposing the efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) for hepatic metastases treatment. Methods We undertook an extensive literature search across the Cochrane Library, Web of Science, Embase, PubMed, CNKI, and databases for studies published up to December 2023, assessing the outcomes of RFA versus MWA in hepatic metastases treatment. Studies were included or excluded based on established criteria. Continuous variables were analyzed with the aid of the weighted mean difference (WMD) and its 95% confidence interval (CI), while the odds ratio (OR) with its 95% CI was utilized for dichotomous variables. Data were processed by use of STATA 17.0 software. Key outcomes assessed included ablation time, post-operative local tumor progression (LTP), disease-free survival (DFS), and post-operative complications (POCs). Results Seven studies, comprising 357 patients undergoing MWA and 452 patients undergoing RFA, fulfilled the inclusion criteria. As unveiled by the meta-analysis, RFA and MWA did not significantly differ in ablation time, DFS, and POCs. Nonetheless, MWA resulted in a strikingly reduced rate of post-operative LTP versus RFA. Conclusion MWA offers superior control over post-operative LTP, suggesting better overall efficacy in hepatic metastases treatment compared with RFA. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD42023385201.
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Affiliation(s)
- Zheng Li
- Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tingting Yan
- Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiujun Cai
- Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou, China
- Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Hangzhou, China
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Fadlallah H, El Masri J, Fakhereddine H, Youssef J, Chemaly C, Doughan S, Abou-Kheir W. Colorectal cancer: Recent advances in management and treatment. World J Clin Oncol 2024; 15:1136-1156. [PMID: 39351451 PMCID: PMC11438855 DOI: 10.5306/wjco.v15.i9.1136] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 06/11/2024] [Accepted: 07/29/2024] [Indexed: 08/29/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000, accounting for 10% of all cancer deaths worldwide. Accordingly, there is a vast amount of ongoing research aiming to find new and improved treatment modalities for CRC that can potentially increase survival and decrease overall morbidity and mortality. Current management strategies for CRC include surgical procedures for resectable cases, and radiotherapy, chemotherapy, and immunotherapy, in addition to their combination, for non-resectable tumors. Despite these options, CRC remains incurable in 50% of cases. Nonetheless, significant improvements in research techniques have allowed for treatment approaches for CRC to be frequently updated, leading to the availability of new drugs and therapeutic strategies. This review summarizes the most recent therapeutic approaches for CRC, with special emphasis on new strategies that are currently being studied and have great potential to improve the prognosis and lifespan of patients with CRC.
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Affiliation(s)
- Hiba Fadlallah
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Jad El Masri
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Hiam Fakhereddine
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Joe Youssef
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Chrystelle Chemaly
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Samer Doughan
- Department of Surgery, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Wassim Abou-Kheir
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
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Vogl TJ, Freichel J, Gruber-Rouh T, Nour-Eldin NEA, Bechstein WO, Zeuzem S, Naguib NNN, Stefenelli U, Adwan H. Interventional Treatments of Colorectal Liver Metastases Using Thermal Ablation and Transarterial Chemoembolization: A Single-Center Experience over 26 Years. Cancers (Basel) 2024; 16:1756. [PMID: 38730708 PMCID: PMC11083408 DOI: 10.3390/cancers16091756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 04/27/2024] [Indexed: 05/13/2024] Open
Abstract
The aim of this study was to analyze the long-term results of different locoregional treatments for colorectal cancer liver metastases (CRLM), including transarterial chemoembolization (TACE), laser-induced thermotherapy (LITT) and microwave ablation (MWA). A total of 2140 patients with CRLM treated at our department between 1993 and 2020 were included in this retrospective study. The patients were divided into the following groups: LITT (573 patients; median age: 62 years), TACE + LITT (346 patients; median age: 62 years), MWA (67 patients; median age: 59 years), TACE + MWA (152 patients; median age: 65 years), and TACE (1002 patients; median age: 62 years). Median survival was 1.9 years in the LITT group and 1.7 years in the TACE + LITT group. The median survival times in the MWA group and TACE + MWA group were 3.1 years and 2.1 years, respectively. The median survival in the TACE group was 0.8 years. The 1-, 3-, and 5-year survival rates were 77%, 27%, and 9% in the LITT group and 74%, 18%, and 5% in the TACE + LITT group, respectively. The corresponding survival rates were 80%, 55%, and 33% in the MWA group, 74%, 36%, and 20% in the TACE + MWA group and 37%, 3%, and 0% in the TACE group, respectively. The long-term results of this study demonstrate the efficacy of locoregional treatments in treating patients with CRLM. The longest survival was found in the MWA group, followed by the combination therapy of TACE and MWA.
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Affiliation(s)
- Thomas J. Vogl
- Clinic for Radiology and Nuclear Medicine, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Jason Freichel
- Clinic for Radiology and Nuclear Medicine, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Tatjana Gruber-Rouh
- Clinic for Radiology and Nuclear Medicine, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Nour-Eldin Abdelrehim Nour-Eldin
- Clinic for Radiology and Nuclear Medicine, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
- Department of Diagnostic and Interventional Radiology, Faculty of Medicine, Cairo University, Cairo 12613, Egypt
| | - Wolf-Otto Bechstein
- Department of General and Visceral Surgery, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Department of Internal Medicine I, University Hospital Frankfurt, Goethe University-Frankfurt am Main, 60590 Frankfurt am Main, Germany
| | - Nagy N. N. Naguib
- Radiology Department, AMEOS Hospital Halberstadt, 38820 Halberstadt, Germany
- Department of Diagnostic and Interventional Radiology, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt
| | - Ulrich Stefenelli
- Statistical Analysis Dr. Stefenelli, Untere Bockgasse 5, 97070 Würzburg, Germany
| | - Hamzah Adwan
- Clinic for Radiology and Nuclear Medicine, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
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11
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Meier J, Murimwa G, Nehrubabu M, DiMartino L, Singal AG, Karagkounis G, Yopp A, Zeh HJ, Polanco PM. Effect of Hospital Cancer Designation on use of Multimodal Therapy and Survival of Metastatic Colorectal Cancer: A State-Wide Analysis. Ann Surg Oncol 2024; 31:2591-2597. [PMID: 38245645 DOI: 10.1245/s10434-023-14859-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 12/17/2023] [Indexed: 01/22/2024]
Abstract
BACKGROUND Stage IV colorectal cancer (CRC) often requires multidisciplinary approach. However, multimodal treatment options (receipt of > 1 type of treatment) may not be uniformly delivered across health systems. We characterized the association between center-level cancer center designation and receipt of multimodal treatment and survival. METHODS The Texas Cancer Registry was used to identify patients diagnosed with stage IV CRC from 2004-2017. We identified those who received care at either: a National Cancer Institute-designated (NCI-D), an American College of Surgeons-Commission on Cancer-designated (ACS-D), or an undesignated facility. We used multivariable logistic regression and Cox regression for analysis to assess receipt of one or more treatment modality and 5-year overall survival. RESULTS Of 19,355 patients with stage IV CRC, 2955 (15%) received care at an NCI-D facility and 5871 (30%) received multimodal therapy. Both NCI-D (odds ratio [OR] 1.64; 95% confidence interval [CI] 1.49-1.81) and ACS-D (OR 1.37; 95% CI 1.27-1.48) were associated with increased likelihood of multimodal therapy compared with undesignated centers. NCI-D also was associated with significantly improved survival (hazard ratio [HR] 0.74; 95% CI 0.70-0.78), although ACS-D was associated with a modest improvement in survival (HR 0.95; 95% CI 0.92-0.99). Receipt of multimodal therapy was strongly associated with improved survival (HR 0.61; 95% CI 0.59-0.63). CONCLUSIONS In patients with stage IV CRC, treatment at ACS-D and NCI-D facilities was associated with increased use of multimodality therapy and improved survival. However, only a small proportion of patients have access to these specialized centers, highlighting a need for expanded access to multimodal therapies at other centers.
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Affiliation(s)
- Jennie Meier
- Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Gilbert Murimwa
- Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Mithin Nehrubabu
- Department of Mathematics, University of Texas at Dallas, Dallas, TX, USA
| | - Lisa DiMartino
- Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern, Dallas, TX, USA
| | - Amit G Singal
- Division of Digestive & Liver Diseases, University of Texas Southwestern, Dallas, TX, USA
| | | | - Adam Yopp
- Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Herbert J Zeh
- Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Patricio M Polanco
- Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
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12
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Wach MM, Washburn LA, Alvikas J, Qu LT, Zhang M, Etherington MS, Rieser C, Haykal T, Pingpank JF, Zureikat AH, Geller DA, Hoehn RS, Tohme S. Combined hepatic resection and ablation for high burden of colorectal liver metastases demonstrates safety and durable survival. HPB (Oxford) 2024; 26:362-369. [PMID: 38008683 DOI: 10.1016/j.hpb.2023.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 09/15/2023] [Accepted: 11/03/2023] [Indexed: 11/28/2023]
Abstract
BACKGROUND Hepatic resection (HR) and thermal ablation of Colorectal Liver Metastases (CRLM) have each individually demonstrated safety and survival benefit. We sought to provide our experience with the combination of HR + ablation within one operation for patients with multiple CRLM. METHODS Review of a single institution database of patients who underwent HR + ablation between 2010 and 2019. RESULTS 161 patients were identified who underwent HR + ablation for isolated CRLM (mean age: 59, male 63.4%). 125 (77.6%) patients had bilobar disease and 92 (57.1%) patients had ≥5 tumors. 28 (17.4%) patients experienced minor (grade 1 or 2) complications while 20 (12.4%) had grade 3-5 complications. Patients who underwent simultaneous colon resection with HR + ablation had a higher complication rate (22 of 47, 46.8%) than those undergoing HR + ablation only (26 of 114, 22.8%, p = 0.002). Median and 5-year OS for all patients undergoing HR + ablation was 38.2 months and 33.2%, respectively. 5-year hepatic recurrence free survival was 23.5%. Patients with 5 or more tumors demonstrated no difference in median survival compared to those with fewer than 5 tumors (37.0 months vs 38.4 months, p = 0.326). CONCLUSIONS In this population of CRLM patients with a relatively high burden of disease, HR + ablation demonstrated an acceptable safety profile as well as durable long-term survival.
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Affiliation(s)
- Michael M Wach
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Laura A Washburn
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Jurgis Alvikas
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Linda T Qu
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Michelle Zhang
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mark S Etherington
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Caroline Rieser
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Tony Haykal
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - James F Pingpank
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - David A Geller
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Richard S Hoehn
- Department of Surgery, University Hospitals, Cleveland, OH, USA
| | - Samer Tohme
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
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13
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Chandra P, Sacks GD. Contemporary Surgical Management of Colorectal Liver Metastases. Cancers (Basel) 2024; 16:941. [PMID: 38473303 DOI: 10.3390/cancers16050941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 02/13/2024] [Accepted: 02/19/2024] [Indexed: 03/14/2024] Open
Abstract
Colorectal cancer is the third most common cancer in the United States and the second most common cause of cancer-related death. Approximately 20-30% of patients will develop hepatic metastasis in the form of synchronous or metachronous disease. The treatment of colorectal liver metastasis (CRLM) has evolved into a multidisciplinary approach, with chemotherapy and a variety of locoregional treatments, such as ablation and portal vein embolization, playing a crucial role. However, resection remains a core tenet of management, serving as the gold standard for a curative-intent therapy. As such, the input of a dedicated hepatobiliary surgeon is paramount for appropriate patient selection and choice of surgical approach, as significant advances in the field have made management decisions extremely nuanced and complex. We herein aim to review the contemporary surgical management of colorectal liver metastasis with respect to both perioperative and operative considerations.
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Affiliation(s)
- Pratik Chandra
- Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA
| | - Greg D Sacks
- Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA
- VA New York Harbor Healthcare System, New York, NY 10010, USA
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14
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Filoni E, Musci V, Di Rito A, Inchingolo R, Memeo R, Mannavola F. Multimodal Management of Colorectal Liver Metastases: State of the Art. Oncol Rev 2024; 17:11799. [PMID: 38239856 PMCID: PMC10794467 DOI: 10.3389/or.2023.11799] [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: 07/13/2023] [Accepted: 12/13/2023] [Indexed: 01/22/2024] Open
Abstract
Liver is the most common site of colorectal cancer (CRC) metastases. Treatment of CRC liver metastases (CRLM) includes different strategies, prevalently based on the clinical and oncological intent. Valid approaches in liver-limited or liver-prevalent disease include surgery, percutaneous ablative procedures (radiofrequency ablation, microwave ablation), intra-arterial perfusional techniques (chemo-embolization, radio-embolization) as well as stereotactic radiotherapy. Systemic treatments, including chemotherapy, immunotherapy and other biological agents, are the only options for patients with no chance of locoregional approaches. The use of chemotherapy in other settings, such as neoadjuvant, adjuvant or conversion therapy of CRLM, is commonly accepted in the clinical practice, although data from several clinical trials have been mostly inconclusive. The optimal integration of all these strategies, when applicable and clinically indicated, should be ever considered in patients affected by CRLM based on clinical evidence and multidisciplinary experience. Here we revised in detail all the possible therapeutic approaches of CRLM focusing on the current evidences, the studies still in progress and the often contradictory data.
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Affiliation(s)
- Elisabetta Filoni
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Bari, Italy
- Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
| | - Vittoria Musci
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Bari, Italy
- Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
| | - Alessia Di Rito
- Radiotherapy Unit, P.O. “Mons A.R. Dimiccoli”, Barletta, Italy
| | - Riccardo Inchingolo
- Unit of Interventional Radiology, “F. Miulli” General Regional Hospital, Acquaviva delle Fonti, Italy
| | - Riccardo Memeo
- Unit of Hepato-Pancreatic-Biliary Surgery, “F. Miulli” General Regional Hospital, Acquaviva delle Fonti, Italy
| | - Francesco Mannavola
- Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
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15
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Ni Y, Wang W, Liu Y, Jiang Y. Causal associations between liver traits and Colorectal cancer: a Mendelian randomization study. BMC Med Genomics 2023; 16:316. [PMID: 38057864 PMCID: PMC10699049 DOI: 10.1186/s12920-023-01755-w] [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: 06/22/2023] [Accepted: 11/27/2023] [Indexed: 12/08/2023] Open
Abstract
OBJECTIVE This study aimed to investigate the causal associations between several liver traits (liver iron content, percent liver fat, alanine transaminase levels, and liver volume) and colorectal cancer (CRC) risk using a Mendelian randomization (MR) approach to improve our understanding of the disease and its management. METHODS Genetic variants were used as instrumental variables, extracted from genome-wide association studies (GWAS) datasets of liver traits and CRC. The Two-Sample MR package in R was used to conduct inverse variance weighted (IVW), MR Egger, Maximum likelihood, Weighted median, and Inverse variance weighted (multiplicative random effects) MR approaches to generate overall estimates of the effect. MR analysis was conducted with Benjamini-Hochberg method-corrected P values to account for multiple testing (P < 0.013). MR-PRESSO was used to identify and remove outlier genetic variants in Mendelian randomization (MR) analysis. The MR Steiger test was used to assess the validity of the assumption that exposure causes outcomes. Leave-one-out validation, pleiotropy, and heterogeneity testing were also conducted to ensure the reliability of the results. Multivariable MR was utilized for validation of our findings using the IVW method while also adjusting for potential confounding or pleiotropy bias. RESULTS The MR analysis suggested a causal effect between liver volume and a reduced risk of CRC (OR 0.60; 95% CI, 0.44-0.82; P = 0.0010) but did not provide evidence for causal effects of liver iron content, percent liver fat, or liver alanine transaminase levels. The MR-PRESSO method did not identify any outliers, and the MR Steiger test confirmed that the causal direction of the analysis results was correct in the Mendelian randomization analysis. MR results were consistent with heterogeneity and pleiotropy analyses, and leave-one-out analysis demonstrated the overall values obtained were consistent with estimates obtained when all available SNPs were included in the analysis. Multivariable MR was utilized for validation of our findings using the IVW method while also adjusting for potential confounding or pleiotropy bias. CONCLUSION The study provides tentative evidence for a causal role of liver volume in CRC, while genetically predicted levels of liver iron content, percent liver fat, and liver alanine transaminase levels were not associated with CRC risk. The findings may inform the development of targeted therapeutic interventions for colorectal liver metastasis (CRLM) patients, and the study highlights the importance of MR as a powerful epidemiological tool for investigating causal associations between exposures and outcomes.
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Affiliation(s)
- Ying Ni
- Beijing Normal University, 100875, Beijing, China
| | - Wenkai Wang
- Department of Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 200021, Shanghai, China
| | - Yongming Liu
- Shi's Center of Orthopedics and Traumatology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 200021, Shanghai, China
- Institute of Traumatology & Orthopedics, Shanghai Academy of Traditional Chinese Medicine, 200021, Shanghai, China
| | - Yun Jiang
- Beijing Normal University, 100875, Beijing, China.
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16
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Miller ED, Hitchcock KE, Romesser PB. Oligometastatic Colorectal Cancer: A Review of Definitions and Patient Selection for Local Therapies. J Gastrointest Cancer 2023; 54:1116-1127. [PMID: 36652155 PMCID: PMC10352468 DOI: 10.1007/s12029-022-00900-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2022] [Indexed: 01/19/2023]
Abstract
PURPOSE Nearly one-third of patients diagnosed with colorectal cancer (CRC) will ultimately develop metastatic disease. While a small percentage of patients can be considered for curative resection, more patients have limited disease that can be considered for local therapy. Challenges remain in defining oligometastatic CRC as well as developing treatment strategies guided by high level evidence. METHODS In this review, we present the challenges in defining oligometastatic CRC and summarize the current literature on treatment and outcomes of local therapy in patients with metastatic CRC. RESULTS For patients with liver- and/or lung-confined CRC metastases, surgical resection is the standard of care given the potential for long-term progression-free and overall survival. For patients with liver- or lung-confined disease not amenable to surgical resection, non-surgical local therapies, such as thermal ablation, hepatic arterial infusion pump (HAIP), or stereotactic body radiation therapy (SBRT), should be considered. For patients with more advanced disease, such as lymph node or bony metastases, the role of metastasis-directed therapy is controversial. Emerging data suggests that SBRT to ablate all metastases can improve progression-free and overall survival. CONCLUSION Multidisciplinary management is critical for patients with metastatic CRC due to the complexity of their cases and the nuanced patient, tumor, biological, and anatomical factors that must be weighed when considering local therapy. High-quality prospective randomized data in CRC are needed to further clarify the role of local ablative therapy in patients with unresectable oligometastatic CRC with ongoing studies including the RESOLUTE trial (ACTRN12621001198819) and the upcoming NCTN ERASur trial (NCT05673148).
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Affiliation(s)
- Eric D Miller
- Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center, 460 W. 10Th Ave., Room A209, Columbus, OH, 43210, USA.
| | - Kathryn E Hitchcock
- Department of Radiation Oncology, University of Florida Health, Gainesville, FL, USA
| | - Paul B Romesser
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Early Drug Development Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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17
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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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18
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Chen D, Li Q, Yu H. Prognosis of resectable colorectal liver metastases after surgery associated with pathological features of primary tumor. Front Oncol 2023; 13:1181522. [PMID: 37305574 PMCID: PMC10250016 DOI: 10.3389/fonc.2023.1181522] [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: 03/07/2023] [Accepted: 05/11/2023] [Indexed: 06/13/2023] Open
Abstract
Background Surgery is an important means for patients with colorectal liver metastases (CRLM) to improve their long-term survival, and accurate screening of high-risk factors is crucial to guiding postoperative monitoring and treatment. With this in mind, the aim of this study was to investigate the expression levels and prognostic roles of Mismatch Repair (MMR), Ki67, and Lymphovascular invasion(LVI) in the tumor tissues of colorectal of CRLM. Methods 85 Patients with CRLM who received surgical treatment for liver metastases after colorectal cancer resection from June, 2017 and Jan, 2020 were included in this study. Independent risk factors affecting the survival of patients with CRLM were investigated using a Cox regression model and the Kaplan-Meier method, and a nomogram for predicting the OS of patients with CRLM was established according to a Cox multivariate regression model. Calibration plots and Kaplan-Meier curves were used to assess the performance of the nomogram. Results The median survival time was 39 months (95% CI: 32.05-45.950), and MMR, Ki67 and LVI were significantly correlated with prognosis. Univariate analysis indicated that larger metastasis size (p=0.028), more than one liver metastases (p=0.001),higher serum CA199 (p<0.001), N1-2 stage (p<0.001), the presence of LVI (p=0.001), higher Ki67 (p<0.001), and pMMR predicted worse OS. In addition, synchronous liver metastasis (p = 0.008), larger metastasis size (p=0.02), more than one liver metastases (p<0.001),higher serum CA199 (p<0.001), the presence of LVI (p=0.001), nerve invasion (p=0.042) higher Ki67 (p=0.014), and pMMR (p=0.038) were each associated with worse DFS. Multivariate analysis indicated that higher serum CA199 (HR = 2.275, 95%CI: 1.302-3.975 p=0.004), N1-2 stage(HR = 2.232, 95%CI: 1.239-4.020 p=0.008), the presence of LVI (HR = 1.793, 95%CI: 1.030-3.121 p=0.039), higher Ki67 (HR = 2.700, 95%CI: 1.388-5.253\ p=0.003), and pMMR (HR = 2.213, 95%CI: 1.181-4.993 p=0.046) all predicted worse OS. Finally, synchronous liver metastasis (HR = 2.059, 95%CI: 1.087-3.901 p=0.027), more than one liver metastases ((HR =2.025, 95%CI: 1.120-3.662 p=0.020),higher serum CA199 (HR =2.914, 95%CI: 1.497-5.674 p=0.002), present LVI (HR = 2.055, 95%CI: 1.183-4.299 p=0.001), higher Ki67 (HR = 3.190, 95%CI: 1.648-6.175 p=0.001) and pMMR(HR = 1.676, 95%CI: 1.772-3.637 p=0.047) predicted worse DFS, and the nomogram achieved an effective level of predictive ability. Conclusion This study showed that MMR, Ki67, and Lymphovascular invasion were independent risk factors for the postoperative survival of CRLM patients, and a nomogram model was constructed to predict the OS of these patients after liver metastasis surgery. These results can help surgeons and patients to develop more accurate and individualized follow-up strategies and treatment plans after this surgery.
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Affiliation(s)
- Dawei Chen
- Department of Hepatobiliary Surgery, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Qingshan Li
- Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Haibo Yu
- Department of Hepatobiliary Surgery, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, Zhengzhou, China
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19
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Karam E, Tabutin M, Mastier C, Crignis LD, Peyrat P, Martin V, Badon F, Muller X, Meeus P, Rivoire M, Dupré A. Curative-intent treatment of pulmonary metastases from colorectal cancer: A comparison between imaging-guided thermal ablation and surgery. J Surg Oncol 2023; 127:183-191. [PMID: 36169242 DOI: 10.1002/jso.27108] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 08/19/2022] [Accepted: 09/16/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Pulmonary metastases (PM) are the most frequent extra-abdominal metastases from colorectal cancer. Lung resection and imaging-guided thermal ablation (IGTA) are used as curative-intent treatment. We compared the outcomes of patients with PM, treated with resection or ablation. METHODS We retrospectively analyzed data from patients who underwent surgery or IGTA for colorectal PM between April 2011 and November 2020. Surgery was performed for peripheral PM and IGTA for deep-located PM not in contact with major vessels. Patients who had both procedures were excluded. Patients were compared using propensity score matching (PSM) analysis, stratified according to number, size, and unilaterality of PM. RESULTS One hundred and fourty-six patients were included, 65 (44.5%) underwent surgery and 81 (55.5%) underwent IGTA. After PSM analysis, each group contained 46 patients. IGTA patients had a lower morbidity rate (13.1% vs. 15.2%, p = 0.028) and a shorter length of stay (5.13 vs. 2.63 days, p < 0.001). Oncological outcomes were similar in both groups with 5-year OS of 80% and 5-year progression-free survival (PFS) of 30% (p = 0.657 and p = 0.504, respectively) with similar recurrence patterns. CONCLUSION Lung resection and IGTA seem to have similar oncologic outcomes for both OS and PFS. IGTA could be an alternative effective treatment for small PM, whenever technically feasible.
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Affiliation(s)
- Elias Karam
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Mayeul Tabutin
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | | | - Lucas De Crignis
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Patrice Peyrat
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Valentine Martin
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Floriane Badon
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Xavier Muller
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Pierre Meeus
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Michel Rivoire
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France.,Univ Lyon, Université Lyon 1, Centre Léon Bérard, INSERM, LabTAU, Lyon, France
| | - Aurélien Dupré
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France.,Univ Lyon, Université Lyon 1, Centre Léon Bérard, INSERM, LabTAU, Lyon, France
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20
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Casabianca AS, Tsagkalidis V, Burchard PR, Chacon A, Melucci A, Reitz A, Swift DA, McCook AA, Switchenko JM, Shah MM, Carpizo DR. Surgery in combination with systemic chemotherapy is associated with improved survival in stage IV gallbladder cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:2448-2454. [PMID: 35773092 PMCID: PMC10993821 DOI: 10.1016/j.ejso.2022.06.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/14/2022] [Accepted: 06/20/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Gallbladder cancer (GBC) is the most common biliary malignancy frequently metastatic at diagnosis with poor prognosis. While surgery remains the standard for early-stage GBC, the role of surgery in patients with metastatic gastrointestinal cancers is expanding due to improvements in systemic therapies. We sought to evaluate the survival of patients with stage IV GBC undergoing surgery in an era of improved multi-agent systemic therapy. METHODS A retrospective review of the National Cancer Database was performed. Patients with stage IV GBC who underwent systemic therapy were included. Patients who received radiation therapy, palliative therapy or had missing survival data were excluded. Univariable and multivariable analysis was performed. RESULTS 4,145 patients were identified between 2004 and 2016. Mean age was 69. Surgery combined with systemic therapy predicted improved median survival compared with chemotherapy alone (11.1mo versus 6.8mo, HR 0.65, p < 0.001). Additionally, receipt of treatment after 2011 predicted improved survival (HR 0.86, p < 0.001). Patients treated with multi-agent chemotherapy in combination with surgery were associated with the greatest hazard ratio benefit (0.40, p < 0.001) versus single agent therapy alone. CONCLUSION Patients with stage IV gallbladder cancer treated with a combination of surgery and chemotherapy are associated with an improved overall survival compared to chemotherapy alone. Patients receiving care during the more recent era demonstrated improved survival. These results support a role for surgery in selected patients with stage IV gallbladder cancer receiving chemotherapy.
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Affiliation(s)
- Anthony S Casabianca
- Department of Surgery, Division of General Surgery, University of Rochester, Rochester, NY, USA
| | - Vasileios Tsagkalidis
- Department of Surgery, Division of General Surgery, University of Rochester, Rochester, NY, USA
| | - Paul R Burchard
- Department of Surgery, Division of General Surgery, University of Rochester, Rochester, NY, USA
| | - Alexander Chacon
- Department of Surgery, Division of General Surgery, University of Rochester, Rochester, NY, USA
| | - Alexa Melucci
- Department of Surgery, Division of General Surgery, University of Rochester, Rochester, NY, USA
| | - Alexandra Reitz
- Department of General Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - David A Swift
- Department of General Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Ashley A McCook
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Jeffrey M Switchenko
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Mihir M Shah
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
| | - Darren R Carpizo
- Department of Surgery, Division of Surgical Oncology, University of Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
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21
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The Prognostic Value of Serum Apolipoprotein A-I Level and Neutrophil-to-Lymphocyte Ratio in Colorectal Cancer Liver Metastasis. JOURNAL OF ONCOLOGY 2022; 2022:9149788. [PMID: 36204177 PMCID: PMC9532097 DOI: 10.1155/2022/9149788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 09/08/2022] [Indexed: 12/24/2022]
Abstract
Background Colorectal cancer liver metastasis (CRLM) is a high degree of malignancy with rapid disease progression and has a poor prognosis. Both serum apolipoprotein A-I (ApoA-I) and neutrophil-to-lymphocyte ratio (NLR) play key roles in anti-inflammation and antitumor. This study is aimed at evaluating the implication of serum ApoA-I level in combination with NLR in the prognosis of CRLM. Methods We retrospectively analyzed the serum ApoA-I level and NLR in 237 patients with CRLM. Cox regression analyses were used to identify the independent prognostic significance of these indicators. Kaplan-Meier method and Log-rank test were applied to compute overall survival (OS). Both the ApoA-I and NLR were divided into three levels, according to their medians. A risk-stratified prediction model was established to evaluate the prognosis of patients with CRLM. The ROC curve AUC values were applied to evaluate the capability of the model. Results Higher levels of ApoA-I and lower NLR were strongly associated with prolonged OS (Log-rank test, P < 0.05). The patients were then grouped into three queues according to the ApoA-I level and NLR. There was a crucial diversity in the OS (P < 0.001) between the high-risk (ApoA − I ≤ 1.03 g/L and NLR > 3.24), medium-risk (ApoA − I > 1.03 g/L or NLR ≤ 3.24) and low-risk groups (ApoA − I > 1.03 g/L and NLR ≤ 3.24). The AUC value of the prediction model (AUC = 0.623, 95% CI: 0.557-0.639, P = 0.001) was higher than other individual indicators (including ApoA-I, NLR, cT classification, and cN classification). Additionally, the association of the prediction model and cTN classification (AUC = 0.715, 95% CI: 0.606-0.708, P < 0.001) was better than the model and cTN classification alone. Conclusion The combination of ApoA-I level and NLR could be a prognostic indicator for CRLM.
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22
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Stavrovski T, Pereira P. Role of interventional oncology for treatment of liver metastases: evidence based best practice. Br J Radiol 2022; 95:20211376. [PMID: 35976260 PMCID: PMC9815747 DOI: 10.1259/bjr.20211376] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 07/17/2022] [Accepted: 07/28/2022] [Indexed: 01/13/2023] Open
Abstract
The presence of liver metastases is associated with a poor prognosis in many cancer diseases. Multiple studies during the last decades aimed to find out the best multimodal therapy to achieve an ideal, safe and highly effective treatment. In addition to established therapies such as systemic therapy, surgery and radiation therapy, interventional oncology with thermal ablation, transarterial chemoembolisation and radioembolisation, is becoming the fourth pillar of cancer therapies and is part of a personalised treatments' strategy. This review informs about the most popular currently performed interventional oncological treatments in patients with liver metastases.
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Affiliation(s)
- Tomislav Stavrovski
- Zentrum für Radiologie, Minimal-Invasive Therapien und Nuklearmedizin, SLK-Kliniken Heilbronn GmbH, Am Gesundbrunnen, Heilbronn, Germany
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-Invasive Therapien und Nuklearmedizin, SLK-Kliniken Heilbronn GmbH, Am Gesundbrunnen, Heilbronn, Germany
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23
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Maruyama K, Tominaga T, Nonaka T, Moriyama M, Oyama S, Ishii M, Sawai T, Nagayasu T. Efficacy of risk-stratified indicators for adjuvant chemotherapy with fluorouracil and oxaliplatin after hepatectomy for colorectal cancer liver metastasis. Int J Colorectal Dis 2022; 37:1545-1552. [PMID: 35624174 DOI: 10.1007/s00384-022-04189-5] [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] [Accepted: 05/21/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND The recurrence rate after hepatectomy for colorectal cancer liver metastasis (CRLM) is high, and there is no consensus regarding the effect of adjuvant chemotherapy (AC) using oxaliplatin (doublet AC) in these patients. METHODS The present study included 91 patients who underwent hepatectomy for complete resection at our hospitals between 2008 and 2018. Based on whether or not they had undergone doublet AC, patients were divided into AC (n = 35) and non-AC (n = 56) groups. The recurrent risk was evaluated by the Memorial Sloan Kettering Cancer Center clinical risk score (MSKCC-CRS). RESULTS The number of females and median age were higher in the AC group (51.4% vs 25.0%, p = 0.010 and 67 vs 61 years, p = 0.012, respectively). The median follow-up period was 45 months (range, 6-101 months). Doublet AC was an independent prognostic factor for 5-year relapse-free survival (hazard ratio, 0.225; 95%CI, 0.097-0.522; p < 0.001) and for 5-year overall survival (hazard ratio, 0.165; 95%CI, 0.057-0.476; p < 0.001) in multivariate analysis. In patients with a high risk of recurrence (MSKCC-CRS 3-5), 5-year relapse-free survival and 5-year overall survival was higher in the doublet AC group than in the non-AC group (p < 0.01). In low-risk patients (MSKCC-CRS 0-2), 5-year relapse-free survival and 5-year overall survival were similar between the groups. CONCLUSIONS Doublet AC could have a positive effect on prognosis after curative resection of CRLM, especially in high-risk patients. The selection of patients and AC regimen should take into consideration the risk of recurrence.
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Affiliation(s)
- Keizaburo Maruyama
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Tetsuro Tominaga
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
| | - Takashi Nonaka
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Masaaki Moriyama
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Shosaburo Oyama
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Mitsutoshi Ishii
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Terumitsu Sawai
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Takeshi Nagayasu
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
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24
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Aquina CT, Eskander MF, Pawlik TM. Liver-Directed Treatment Options Following Liver Tumor Recurrence: A Review of the Literature. Front Oncol 2022; 12:832405. [PMID: 35174097 PMCID: PMC8841620 DOI: 10.3389/fonc.2022.832405] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/11/2022] [Indexed: 01/27/2023] Open
Abstract
Recurrence following curative-intent hepatectomy for colorectal cancer liver metastasis, hepatocellular carcinoma, or cholangiocarcinoma is unfortunately common with a reported incidence as high as 75%. Various treatment modalities can improve survival following disease recurrence. A review of the literature was performed using PubMed. In addition to systemic therapy, liver-directed treatment options for recurrent liver disease include repeat hepatectomy, salvage liver transplantation, radiofrequency or microwave ablation, intra-arterial therapy, and stereotactic body radiation therapy. Repeat resection can be consider for patients with limited recurrent disease that meets resection criteria, as this therapeutic approach can provide a survival benefit and is potentially curative in a subset of patients. Salvage liver transplantation for recurrent hepatocellular carcinoma is another option, which has been associated with a 5-year survival of 50%. Salvage transplantation may be an option in particular for patients who are not candidates for resection due to underlying liver dysfunction but meet criteria for transplantation. Ablation is another modality to treat patients who recur with smaller tumors and are not surgical candidates due to comorbidity, liver dysfunction, or tumor location. For patients with inoperable disease, transarterial chemoembolization, or radioembolization with Yttrium-90 are liver-directed intra-arterial therapy modalities with relatively low risks that can be utilized. Stereotactic body radiation therapy is another palliative treatment option that can provide a response and local tumor control for smaller tumors.
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Affiliation(s)
- Christopher T. Aquina
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, United States
- Digestive Health and Surgery Institute, AdventHealth Orlando, Orlando, FL, United States
| | - Mariam F. Eskander
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, United States
- Division of Surgical Oncology, Department of Surgery, Robert Wood Johnson Medical School and Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
| | - Timothy M. Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, United States
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25
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The evolution of surgery for colorectal liver metastases: A persistent challenge to improve survival. Surgery 2021; 170:1732-1740. [PMID: 34304889 DOI: 10.1016/j.surg.2021.06.033] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/01/2021] [Accepted: 06/21/2021] [Indexed: 02/07/2023]
Abstract
Only a few decades ago, the opinion that colorectal liver metastases were a palliative diagnosis changed. In fact, previously, the prevailing view was strongly resistant against resecting colorectal liver metastases. Constant technical improvement of liver surgery and, much later, effective chemotherapy allowed for a successful wider application of surgery. The clinical use of portal vein embolization was the starting signal of regenerative liver surgery, where insufficient liver volume can be expanded to an extent where safe resection is possible. Today, a number of these techniques including portal vein ligation, associating liver partition and portal vein ligation for staged hepatectomy, and bi-embolization (portal and hepatic vein) can be successfully used to address an insufficient future liver remnant in staged resections. It turned out that the road to success is embedding surgery in a well-orchestrated oncological concept of controlling systemic disease. This concept was the prerequisite that meant liver transplantation could enter the treatment strategy for colorectal liver metastases, ending up with a 5-year overall survival of 80% in highly selected cases. In particular, techniques combining principles of 2-stage hepatectomy and liver transplantation, such as "resection and partial liver segment 2-3 transplantation with delayed total hepatectomy" (RAPID) are on the rise. These techniques enable the use of partial liver grafts with primarily insufficient liver volume. All this progress also prompted a number of innovative local therapies to address recurrences ultimately transferring colorectal liver metastases from instantly deadly into a chronic disease in some cases.
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26
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Kelm M, Schollbach J, Anger F, Wiegering A, Klein I, Germer CT, Schlegel N, Kunzmann V, Löb S. Prognostic impact of additive chemotherapy after curative resection of metachronous colorectal liver metastasis: a single-centre retrospective study. BMC Cancer 2021; 21:490. [PMID: 33941104 PMCID: PMC8091534 DOI: 10.1186/s12885-021-07941-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 02/21/2021] [Indexed: 01/05/2023] Open
Abstract
Background A prognostic benefit of additive chemotherapy in patients following resection of metachronous colorectal liver metastases (CRLM) remains controversial. Therefore, the goal of this retrospective study was to investigate the impact of perioperative chemotherapy on disease-free survival (DFS) and overall survival (OS) of patients after curative resection of metachronous CRLM. Methods In a retrospective single-centre study, patients after curative resection of metachronous CRLM were included and analysed for DFS and OS with regard to the administration of additive chemotherapy. The Kaplan-Meier method was applied to compare DFS and OS while Cox regression models were used to identify independent prognostic variables. Results Thirty-four of 75 patients were treated with additive 5-FU based chemotherapy. OS was significantly prolonged in this patient subgroup (62 vs 57 months; p = 0.032). Additive chemotherapy significantly improved 10-year survival rates (42% vs 0%, p = 0.023), but not 5-year survival (58% vs 42%, p = 0.24). Multivariate analysis identified additive chemotherapy (p = 0.016, HR 0.44, 95% CI 0.23–0.86), more than five CRLM (p = 0.026, HR 2.46, 95% CI 1.16–10.32) and disease recurrence (0.009, HR 2.70, 95% CI 1.29–5.65) as independent risk factors for OS. Conclusion Additive chemotherapy significantly prolonged OS and 10-year survival in patients after curative resection of metachronous CRLM. Randomized clinical trials are needed in the future to identify optimal chemotherapy regimens for those patients.
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Affiliation(s)
- Matthias Kelm
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.
| | - Julia Schollbach
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany
| | - Friedrich Anger
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany
| | - Armin Wiegering
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.,Theodor-Boveri-Institute, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany.,Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str. 6, 97080, Würzburg, Germany
| | - Ingo Klein
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.,Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str. 6, 97080, Würzburg, Germany
| | - Christoph-Thomas Germer
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.,Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str. 6, 97080, Würzburg, Germany
| | - Nicolas Schlegel
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany
| | - Volker Kunzmann
- Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str. 6, 97080, Würzburg, Germany.,Department of Internal Medicine II, University of Würzburg, Würzburg, Germany
| | - Stefan Löb
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.,Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str. 6, 97080, Würzburg, Germany
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27
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Kanikarla Marie P, Haymaker C, Parra ER, Kim YU, Lazcano R, Gite S, Lorenzini D, Wistuba II, Tidwell RSS, Song X, Foo WC, Maru DM, Chun YS, Futreal A, Kee B, Menter D, Solis L, Tzeng CW, Parseghian C, Raghav K, Morris V, Chang CC, Jenq R, Tam A, Bernatchez C, Kopetz S, Vauthey JN, Overman MJ. Pilot Clinical Trial of Perioperative Durvalumab and Tremelimumab in the Treatment of Resectable Colorectal Cancer Liver Metastases. Clin Cancer Res 2021; 27:3039-3049. [PMID: 33811152 DOI: 10.1158/1078-0432.ccr-21-0163] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 03/11/2021] [Accepted: 03/30/2021] [Indexed: 12/13/2022]
Abstract
PURPOSE Despite the prognostic importance of immune infiltrate in colorectal cancer, immunotherapy has demonstrated limited clinical activity in refractory metastatic proficient mismatch-repair (pMMR) colorectal cancer. This study explores combining anti-CTLA-4 and an anti-PD-L1 therapy in the preoperative management of resectable colorectal cancer liver metastases with the intent to improve immune responses in this disease setting. PATIENTS AND METHODS Patients with resectable colorectal cancer liver-only metastases received one dose of tremelimumab and durvalumab preoperatively followed by single-agent durvalumab postoperatively. Primary objectives were to determine feasibility and safety. RESULTS A total of 24 patients were enrolled between November 2016 and November 2019. Twenty-three patients received treatment [21 pMMR and 2 deficient mismatch-repair (dMMR)] and subsequently 17 (74%; 95% CI: 53%-88%) underwent surgical resection. Grade 3/4 treatment-related immune toxicity and postoperative grade 3/4 toxicity were seen in 5/23 (22%; 95% CI: 10%-44%) and 2/17 (12%; 95% CI: 2%-38%) patients. The median relapse-free survival (RFS) was 9.7 (95% CI: 8.1-17.8) months, and overall survival was 24.5 (95% CI: 16.5-28.4) months. Four patients demonstrated complete pathologic response, two dMMR patients and two POLE mutation patients. Pre- and post-tumor tissue analysis by flow cytometry, immunofluorescence, and RNA sequencing revealed similar levels of T-cell infiltration, but did demonstrate evidence of CD8+ and CD4+ activation posttreatment. An increase in B-cell transcriptome signature and B-cell density was present in posttreatment samples from patients with prolonged RFS. CONCLUSIONS This study demonstrates the safety of neoadjuvant combination tremelimumab and durvalumab prior to colorectal cancer liver resection. Evidence for T- and B-cell activation following this therapy was seen in pMMR metastatic colorectal cancer.
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Affiliation(s)
- Preeti Kanikarla Marie
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Cara Haymaker
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Edwin Roger Parra
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Young Uk Kim
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Rossana Lazcano
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Swati Gite
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Daniele Lorenzini
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ignacio I Wistuba
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Rebecca S Slack Tidwell
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Xiaofei Song
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Wai Chin Foo
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Dipen M Maru
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Andy Futreal
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Bryan Kee
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - David Menter
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Luisa Solis
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ching-Wei Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Christine Parseghian
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Kanwal Raghav
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Van Morris
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Chia-Chi Chang
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Robert Jenq
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Alda Tam
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Chantale Bernatchez
- Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Uhlig J, Lukovic J, Dawson LA, Patel RA, Cavnar MJ, Kim HS. Locoregional Therapies for Colorectal Cancer Liver Metastases: Options Beyond Resection. Am Soc Clin Oncol Educ Book 2021; 41:133-146. [PMID: 34010047 DOI: 10.1200/edbk_320519] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Colorectal cancer was the third most common malignancy worldwide in 2018, and most patients present with or develop distant metastases. Colorectal liver metastases are most commonly observed because of the vascular drainage of the colon and superior rectum. Current guidelines recommend surgical resection as first-line treatment; however, 80% to 90% of patients with colorectal liver metastases are ineligible for primary resection. For patients with unresectable disease, a multidisciplinary treatment approach is favored, incorporating systemic therapy and a toolbox of local ablative therapies. These treatments either aim at cytoreduction to enable a conversion to surgical resectability or control of disease progression and spread. Each of these treatments carries unique outcomes and risk profiles, thereby contributing to an individualized treatment strategy for patients with colorectal liver metastases. This review summarizes evidence on hepatic artery infusion, stereotactic body radiation therapy, thermal ablation, transarterial chemoembolization with drug-eluding beads, and transarterial radioembolization for treatment of colorectal liver metastases. Results of large-scale prospective and retrospective studies and international guidelines are discussed to provide detailed background on the current and prospective use of local ablative techniques in management of colorectal liver metastases.
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Affiliation(s)
- Johannes Uhlig
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD
- Department of Diagnostic and Interventional Radiology, University Medical Center Goettingen, Goettingen, Germany
| | - Jelena Lukovic
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Laura A Dawson
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Reema A Patel
- Department of Internal Medicine, Division of Medical Oncology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY
| | - Michael J Cavnar
- Department of Surgery, Division of Surgical Oncology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY
| | - Hyun S Kim
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD
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Joharatnam-Hogan N, Wilson W, Shiu KK, Fusai GK, Davidson B, Hochhauser D, Bridgewater J, Khan K. Multimodal Treatment in Metastatic Colorectal Cancer (mCRC) Improves Outcomes-The University College London Hospital (UCLH) Experience. Cancers (Basel) 2020; 12:cancers12123545. [PMID: 33261002 PMCID: PMC7760146 DOI: 10.3390/cancers12123545] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/21/2020] [Accepted: 11/25/2020] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Despite notable advances in the management of metastatic colorectal cancer (mCRC) over the last two decades, treatment intent in the vast majority of patients remains palliative due to technically unresectable disease, extensive disease, or co-morbidities precluding major surgery. Up to 30% of individuals with mCRC are considered potentially suitable for primary or metastasis-directed multimodal therapy, including surgical resection, ablative techniques, or stereotactic radiotherapy (RT), with the aim of improving survival outcomes. We reviewed the potential benefits of multimodal therapy on the survival of patients with mCRC treated at the UCLH. METHODS Clinical data on baseline characteristics, multimodal treatments, and survival outcomes were retrospectively collected from all patients with mCRC receiving systemic chemotherapy between January 2013 and April 2017. Primary outcome was the impact of multimodal therapy on overall survival, compared to systemic therapy alone, and the effect of different types of multimodal therapy on survival outcome, and was assessed using the Kaplan-Meier approach. All analyses were adjusted for age, gender, and side of primary tumour. RESULTS One-hundred and twenty-five patients with mCRC were treated during the study period (median age: 62 years (range 19-89). The liver was the most frequent metastatic site (78%; 97/125). A total of 52% (65/125) had ≥2 lines of systemic chemotherapy. Of the 125 patients having systemic chemotherapy, 74 (59%) underwent multimodal treatment to the primary tumour or metastasis. Median overall survival (OS) was 25.7 months [95% Confidence Interval (CI) 21.5-29.0], and 3-year survival, 26%. Univariate analysis demonstrated that patients who had additional procedures (surgery/ablation/RT) were significantly less likely to die (Hazard Ratio (HR) 0.18, 95% CI 0.12-0.29, p < 0.0001) compared to those receiving systemic chemotherapy alone. Increasing number of multimodal procedures was associated with an incremental increase in survival-with median OS 28.4 m, 35.7 m, and 64.8 m, respectively, for 1, 2, or ≥3 procedures (log-rank p < 0.0001). After exclusion of those who received systemic chemotherapy only (n = 51), metastatic resections were associated with improved survival (adjusted HR 0.36, 95% CI 0.20-0.63, p < 0.0001), confirmed in multivariate analysis. Multiple single-organ procedures did not improve survival. CONCLUSION Multimodal therapy for metastatic bowel cancer is associated with significant survival benefit. Resection/radical RT of the primary and resection of metastatic disease should be considered to improve survival outcomes following multidisciplinary team (MDT) discussion and individual assessment of fitness.
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Affiliation(s)
- Nalinie Joharatnam-Hogan
- Department of Gastrointestinal Oncology, University College London Hospital NHS Foundation Trust, London NW1 2PG, UK; (N.J.-H.); (K.K.S.); (D.H.); (J.B.)
| | - William Wilson
- Department of Statistics, Cancer Research UK and UCL Cancer Trials Centre, London W1T 4TJ, UK;
| | - Kai Keen Shiu
- Department of Gastrointestinal Oncology, University College London Hospital NHS Foundation Trust, London NW1 2PG, UK; (N.J.-H.); (K.K.S.); (D.H.); (J.B.)
| | - Giuseppe Kito Fusai
- HPB and Liver Transplant Unit, Royal Free London NHS Foundation Trust, London NW13 1QG, UK; (G.K.F.); (B.D.)
| | - Brian Davidson
- HPB and Liver Transplant Unit, Royal Free London NHS Foundation Trust, London NW13 1QG, UK; (G.K.F.); (B.D.)
| | - Daniel Hochhauser
- Department of Gastrointestinal Oncology, University College London Hospital NHS Foundation Trust, London NW1 2PG, UK; (N.J.-H.); (K.K.S.); (D.H.); (J.B.)
| | - John Bridgewater
- Department of Gastrointestinal Oncology, University College London Hospital NHS Foundation Trust, London NW1 2PG, UK; (N.J.-H.); (K.K.S.); (D.H.); (J.B.)
| | - Khurum Khan
- Department of Gastrointestinal Oncology, University College London Hospital NHS Foundation Trust, London NW1 2PG, UK; (N.J.-H.); (K.K.S.); (D.H.); (J.B.)
- Research Department of Oncology, UCL Cancer Institute, London WC1E 6BT, UK
- Department of Medical Oncology, North Middlesex University Hospital, London N18 1QX, UK
- Department of Oncology, GI Cancer Lead North London & Oncology Research Lead North Middlesex University Hospital, London N18 1QX, UK
- Correspondence: or
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Hamm A, Hidding S, Mokry T, Radeleff B, Mehrabi A, Büchler MW, Schneider M, Schmidt T. Postoperative liver regeneration does not elicit recurrence of colorectal cancer liver metastases after major hepatectomy. Surg Oncol 2020; 35:24-33. [PMID: 32818879 DOI: 10.1016/j.suronc.2020.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/06/2020] [Accepted: 07/21/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVES Recurrence is a frequent concern in curatively resected CRC liver metastases. Translational research suggests that regeneration upon hepatectomy may also alleviate metastatic recurrence; however, the significance in patients is unclear. We therefore sought to study the effect of liver regeneration on tumor recurrence in patients. METHODS In this retrospective cohort study, we included 58 out of 186 potentially eligible patients from our prospectively maintained database of CRC liver metastasis patients between 2001 and 2012 with a median follow-up of 42 months who underwent a formal right or left hemihepatectomy. Liver regeneration in CT volumetry was correlated with recurrence of CRC liver metastases and overall survival. RESULTS Liver regeneration increased up to 14 months to 21.0% for left and 122.6% for right hemihepatectomy, respectively, with comparable final volumes. Regeneration was independent of initial tumor stage, number of metastases, and preoperative chemotherapy. Patients with lower liver regeneration showed earlier recurrence of CRC liver metastases (p = 0.006). Overall survival did not differ in patients with weak versus strong liver regeneration. CONCLUSIONS The extent of liver regeneration after major hepatectomy does not impede overall survival. Therefore, our data encourage aggressive therapeutical regimes for CRC liver metastases involving major hepatectomies as part of a curative approach.
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Affiliation(s)
- Alexander Hamm
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Sarah Hidding
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Theresa Mokry
- Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Boris Radeleff
- Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Martin Schneider
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Thomas Schmidt
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.
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Lenga L, Lange M, Arendt CT, Booz C, Yel I, Bodelle B, D'Angelo T, Hammerstingl RM, Huizinga NA, Vogl TJ, Martin SS, Albrecht MH. Measurement Reliability and Diagnostic Accuracy of Virtual Monoenergetic Dual-Energy CT in Patients with Colorectal Liver Metastases. Acad Radiol 2020; 27:e168-e175. [PMID: 31727567 DOI: 10.1016/j.acra.2019.09.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 09/04/2019] [Accepted: 09/12/2019] [Indexed: 12/12/2022]
Abstract
RATIONALE AND OBJECTIVES To compare dual-energy CT virtual monoenergetic images (VMI) and standard reconstructions for reliability of quantitative size measurements and diagnostic accuracy for the detection of colorectal liver metastases (CRLM). MATERIALS AND METHODS We retrospectively included 98 patients (mean age, 61.1±11.5 years) with colorectal cancer, of whom 49 subjects had CRLM. All patients underwent a portal-venous phase dual-energy CT examination. Standard linearly-blended reformats and 40-keV VMI were reconstructed. For both reconstruction techniques, two blinded readers performed measurements of CRLM twice in a preset sequence. Three additional radiologists independently assessed all liver lesions in terms of dignity (benign vs. malignant). Sensitivity, specificity and diagnostic accuracy were calculated on a per-patient basis using MRI as reference standard. Readers scored the suitability for metric measurements and their diagnostic confidence using 5-point Likert scales. Inter-rater agreement was evaluated using intraclass correlation coefficient (ICC). RESULTS Inter-rater agreement for lesion size measurements was higher for 40-keV VMI (ICC, 0.88) compared to standard linearly-blended series (ICC, 0.80). Sensitivity and diagnostic accuracy for the detection of CRLM were significantly higher for VMI at 40-keV compared to standard reconstructions (90.6% vs. 80.6%, and 89.1% vs. 81.3%; p < 0.001). Reader scores indicated that 40-keV VMI were more suitable for metric lesion measurements and provided greater diagnostic confidence compared to standard reformats (median, 5 vs. 3, and 5 vs. 4; both p < 0.001). CONCLUSION Low-keV VMI reconstructions improve reliability of quantitative size measurements and diagnostic accuracy for the assessment of CRLM compared to standard linearly-blended images.
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Ghiasloo M, Pavlenko D, Verhaeghe M, Van Langenhove Z, Uyttebroek O, Berardi G, Troisi RI, Ceelen W. Surgical treatment of stage IV colorectal cancer with synchronous liver metastases: A systematic review and network meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:1203-1213. [PMID: 32178961 DOI: 10.1016/j.ejso.2020.02.040] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 12/13/2019] [Accepted: 02/29/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND The ideal treatment approach for colorectal cancer (CRC) with synchronous liver metastases (SCRLM) remains debated. We performed a network meta-analysis (NMA) comparing the 'bowel-first' approach (BFA), simultaneous resection (SIM), and the 'liver-first' approach (LFA). METHODS A systematic search of comparative studies in CRC with SCRLM was undertaken using the Embase, PubMed, Web of Science, and CENTRAL databases. Outcome measures included postoperative complications, 30- and 90-day mortality, chemotherapy use, treatment completion rate, 3- and 5-year recurrence-free survival, and 3- and 5-year overall survival (OS). Pairwise and network meta-analysis were performed to compare strategies. Heterogeneity was assessed using the Higgins I2 statistic. RESULTS One prospective and 43 retrospective studies reporting on 10 848 patients were included. Patients undergoing the LFA were more likely to have rectal primaries and a higher metastatic load. The SIM approach resulted in a higher risk of major morbidity and 30-day mortality. Compared to the BFA, the LFA more frequently resulted in failure to complete treatment as planned (34% versus 6%). Pairwise and network meta-analysis showed a similar 5-year OS between LFA and BFA and a more favorable 5-year OS after SIM compared to LFA (odds ratio 0.25-0.90, p = 0.02, I2 = 0%), but not compared to BFA. CONCLUSION Despite a higher tumor load in LFA compared to BFA patients, survival was similar. A lower rate of treatment completion was observed with LFA. Uncertainty remains substantial due to imprecise estimates of treatment effects. In the absence of prospective trials, treatment of stage IV CRC patients should be individually tailored.
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Affiliation(s)
- Mohammad Ghiasloo
- Department of Human Structure and Repair, Faculty of Medicine, Ghent University, Belgium; Department of Surgery, Division of GI Surgery, Ghent University Hospital, Belgium
| | - Diana Pavlenko
- Department of Human Structure and Repair, Faculty of Medicine, Ghent University, Belgium
| | - Marzia Verhaeghe
- Department of Human Structure and Repair, Faculty of Medicine, Ghent University, Belgium
| | - Zoé Van Langenhove
- Department of Human Structure and Repair, Faculty of Medicine, Ghent University, Belgium
| | - Ortwin Uyttebroek
- Department of Surgery, Division of General and HPB Surgery, Ghent University Hospital, Belgium
| | - Giammauro Berardi
- Department of Surgery, Division of General and HPB Surgery, Ghent University Hospital, Belgium
| | - Roberto I Troisi
- Department of Human Structure and Repair, Faculty of Medicine, Ghent University, Belgium; Department of Clinical Medicine and Surgery, Federico II University Naples, Italy
| | - Wim Ceelen
- Department of Human Structure and Repair, Faculty of Medicine, Ghent University, Belgium; Department of Surgery, Division of GI Surgery, Ghent University Hospital, Belgium; Cancer Research Institute Ghent (CRG), Ghent University, Belgium.
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Alabraba E, Ibrahim H, Olaru A, Cameron I, Gomez D, Group NHPBS. Retrospective cohort study of statin therapy effect on resected colorectal liver metastases. World J Gastrointest Surg 2020; 12:34-44. [PMID: 32128027 PMCID: PMC7044105 DOI: 10.4240/wjgs.v12.i2.34] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 11/24/2019] [Accepted: 12/15/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Above and beyond their role in cardiovascular risk reduction, statins appear to have a chemopreventive role in some gastro-intestinal cancers. In the quest for new chemopreventive agents, some existing established drugs such as statins have shown potential for re-purposing as chemoprevention. Probing existing drugs, whose pharmacodynamics are familiar, for novel beneficial effects offers a more cost-effective and less time-consuming strategy than establishing brand new drugs whose pharmacodynamic profile is unfamiliar. Observational studies show statins decrease the risk of developing colorectal cancer but there are no published studies exploring the potential impact of statins on carcinogenesis in colorectal liver metastases (CRLM).
AIM To evaluate impact of statins on outcomes of CRLM resection, and secondarily to assess if statins influence CRLM histo-pathology.
METHODS We conducted a retrospective cohort study of patients operated for CRLM over a 13-year period from 2005 to 2017. Patients were identified from a prospective database maintained in our Tertiary care hospital. All 586 patients included the study had undergone resection of CRLM following discussion at multidisclipinary team meeting, some patients requiring neoadjuvant chemotherapy to downstage CRLM prior to surgery. We analysed patient demographics, operative details, CRLM histopathology, Index of Deprivation, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and chemotherapy use in relation to clinical outcome. Statistics were performed using SPSS version 16.0; significance taken at 5%.
RESULTS Liver resection for CRLM was undertaken in 586 patients at a median age of 68 (range 19 to 88) years. Statin therapy was used by 181 patients. Median follow-up time was 23 (range 12-96) mo and further colorectal cancer metastases developed in 267 patients. A total of 131 patients died. Multi-variate analysis identified 6 independent predictors of poorer disease-free survival: Synchronous presentation, multiple tumours, tumour size ≥ 5 cm, moderate–severe steatosis, peri-neural invasion, and R1-resection margin. Poorer overall survival was significantly associated with neo-adjuvant chemotherapy, major hepatectomy, peri-neural invasion and R1-resection margin. Neither histo-pathological nor radiological traits of CRLM were affected by statins, and, there was no demonstrable effect of statin therapy on patient outcomes.
CONCLUSION Statin therapy does not affect patient survival following liver resection for CRLM. We postulate the reason for this key finding is that statins do not modulate tumour biology of CRLM.
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Affiliation(s)
- Edward Alabraba
- Department of Hepatobiliary Surgery and Pancreatic Surgery, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, United Kingdom
| | - Hussain Ibrahim
- Department of Hepatobiliary Surgery and Pancreatic Surgery, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, United Kingdom
| | - Adina Olaru
- Department of Hepatobiliary Surgery and Pancreatic Surgery, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, United Kingdom
| | - Iain Cameron
- Department of Hepatobiliary Surgery and Pancreatic Surgery, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, United Kingdom
| | - Dhanny Gomez
- Department of Hepatobiliary Surgery and Pancreatic Surgery, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, United Kingdom
- NIHR Nottingham Digestive Disease Biomedical Research Unit, University of Nottingham, Nottingham NG7 2UH, United Kingdom
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Kemeny N, Kurilova I, Li J, Camacho JC, Sofocleous CT. Liver-Directed and Systemic Therapies for Colorectal Cancer Liver Metastases. Cardiovasc Intervent Radiol 2019; 42:1240-1254. [PMID: 31312902 DOI: 10.1007/s00270-019-02284-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 07/03/2019] [Indexed: 02/07/2023]
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Xing X, Zou Z, He C, Hu Z, Liang K, Liang W, Wang Y, Du X. Enhanced antitumor effect of cytotoxic T lymphocytes induced by dendritic cells pulsed with colorectal cancer cell lysate expressing α-Gal epitopes. Oncol Lett 2019; 18:864-871. [PMID: 31289564 DOI: 10.3892/ol.2019.10376] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Accepted: 04/24/2019] [Indexed: 01/08/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common types of gastrointestinal malignancy. Traditional therapeutic options for CRC exhibit a limited effect. Adoptive cellular therapy has emerged as a new treatment strategy for CRC. Dendritic cells (DCs) are potent antigen-presenting cells. Specific cytotoxic T lymphocytes (CTLs) activated by DCs pulsed with tumor lysate have been reported to be a safe and promising treatment approach for CRC. However, the antitumor effect of specific CTLs remains limited. The low immunogenicity of tumor-associated antigens (TAAs) is the main reason for this limited therapeutic effect. In the present study, α-gal epitopes were synthesized on the CRC cell line SW620 to increase the immunogenicity of TAAs. DCs were pulsed with α-gal-expressing tumor lysate and CTLs were activated by these DCs. The cytotoxicity of CTLs was measured in vitro. The results demonstrated that DCs pulsed with α-gal-expressing tumor lysate can increase the frequency of CD3+CD8+ CTLs and natural killer T cells, increase the level of tumor necrosis factor-α produced by CTLs and enhance the cytotoxicity of CTLs against tumor cells. Therefore, this novel approach may be an effective treatment strategy for patients with CRC.
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Affiliation(s)
- Xiaowei Xing
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
| | - Zhenyu Zou
- Department of Hernia and Abdominal Wall Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100853, P.R. China
| | - Changzheng He
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
| | - Zilong Hu
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
| | - Kai Liang
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
| | - Wentao Liang
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
| | - Yufeng Wang
- Department of Patient Admission Management, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
| | - Xiaohui Du
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
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El-Said MM, Emile SH. Cellular therapy: A promising tool in the future of colorectal surgery. World J Gastroenterol 2019; 25:1560-1565. [PMID: 30983816 PMCID: PMC6452228 DOI: 10.3748/wjg.v25.i13.1560] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 02/28/2019] [Accepted: 03/01/2019] [Indexed: 02/06/2023] Open
Abstract
Cellular therapy may be the solution of challenging problems in colorectal surgery such as impaired healing leading to anastomotic leakage and metastatic colorectal cancer (CRC). This review aimed to illustrate the role of cellular therapy in promotion of wound healing and management of metastatic CRC. An organized literature search for the role of cellular therapy in promotion of wound healing and management of metastatic CRC was conducted. Electronic databases including PubMed/Medline, Scopus, and Embase were queried for the search process. Two types of cellular therapy have been recognized, the mesenchymal stem cells (MSCs) and bone marrow-mononuclear cells (BM-MNCs) therapy. These cells have been shown to accelerate and promote healing of various tissue injuries in animal and human studies. In addition, experimental studies have reported that MSCs may help suppress the progression of colon cancer in rat models. This article reviews the possible mechanisms of action and clinical utility of MSCs and BM-MNCs in promotion of healing and suppression of tumor growth in light of the published literature. Cellular therapy has a potentially important role in colorectal surgery, particularly in the promotion of wound healing and management of metastatic CRC. Future directions of cellular therapy in colorectal surgery were explored which may help stimulate futures studies on the role of cellular therapy in colorectal surgery.
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Affiliation(s)
- Mohammed Mohammed El-Said
- Colorectal Surgery Unit, General Surgery Department, Mansoura University Hospitals, Mansoura University, Mansoura 35516, Egypt
| | - Sameh Hany Emile
- Colorectal Surgery Unit, General Surgery Department, Mansoura University Hospitals, Mansoura University, Mansoura 35516, Egypt
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Sotirchos VS, Fujisawa S, Vakiani E, Solomon SB, Manova-Todorova KO, Sofocleous CT. Fluorescent Tissue Assessment of Colorectal Cancer Liver Metastases Ablation Zone: A Potential Real-Time Biomarker of Complete Tumor Ablation. Ann Surg Oncol 2019; 26:1833-1840. [PMID: 30830537 DOI: 10.1245/s10434-018-07133-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND This study aimed to evaluate whether rapid fluorescent tissue examination immediately after colorectal cancer liver metastasis (CLM) ablation correlates with standard pathologic and immunohistochemical (IHC) assessments. METHODS This prospective, National Institutes of Health-supported study enrolled 34 consecutive patients with 53 CLMs ablated between January 2011 and December 2014. Immediately after ablation, core needle sampling of the ablation zone was performed. Tissue samples were evaluated with fluorescent viability (MitoTracker Red) and nuclear (Hoechst) stains. Confocal microscope imaging was performed within 30 min after ablation. The same samples were subsequently fixed and stained with hematoxylin and eosin (H&E). Identified tumor cells underwent IHC staining for proliferation (Ki67) and viability (OxPhos). The study pathologist, blinded to the H&E and IHC assessment, evaluated the fluorescent images separately to detect viable tumor cells. Sensitivity, specificity, and overall concordance of the fluorescent versus H&E and IHC assessments were calculated. RESULTS A total of 63 tissue samples were collected and processed. The overall concordance rate between the immediate fluorescent and the subsequent H&E and IHC assessments was 94% (59/63). The fluorescent assessment sensitivity and specificity for the identification of tumor cells were respectively 100% (18/18) and 91% (41/45). CONCLUSIONS The study showed a high concordance rate between the immediate fluorescent assessment and the standard H&E and IHC assessment of the ablation zone. Given the documented prognostic value of ablation zone tissue characteristics for outcomes after ablation of CLM, the fluorescent assessment offers a potential intra-procedural biomarker of complete tumor ablation.
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Affiliation(s)
- Vlasios S Sotirchos
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, USA
| | - Sho Fujisawa
- Molecular Cytology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Efsevia Vakiani
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Stephen B Solomon
- Interventional Radiology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Hu S, Hu Z, Li S, He C, Wu Y, Teng D, Yan Y, Li H, Xing X, Zou G, Li Y, Yang Y, Wang Y, Du X. Expression of CUEDC2 in colorectal cancer with different invasion and migration abilities. J Int Med Res 2019; 47:905-914. [PMID: 30651016 PMCID: PMC6381460 DOI: 10.1177/0300060518813072] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE To investigate CUE domain containing 2 ( CUEDC2) expression in colorectal cancer with different invasion and migration abilities. METHODS Fresh colon cancer tissues, obtained from patients with or without lymph node metastasis who were treated at the Department of General Surgery, Chinese People's Liberation Army General Hospital, and SW620 and HT29 colorectal cancer cell lines, were analysed for CUEDC2 expression. RESULTS Real-time polymerase chain reaction showed significantly higher CUEDC2 mRNA levels in colon cancer tissue from patients with ( n = 8) versus without ( n = 8) lymph node metastasis, and in SW620 versus HT29 cells. Western blots revealed significantly higher CUEDC2 protein levels in colon cancer tissues from patients with versus without lymph node metastasis, and in SW620 versus HT29 cells. Colorectal cancer tissues from patients with lymph node metastasis showed more intense immunohistochemical staining and moderate staining of cell nuclei and cytoplasm versus less intense/weak staining in tissues from patients without lymph node metastasis. CONCLUSIONS CUEDC2 is highly expressed in colorectal cancer tissues and colorectal cancer cell lines with high invasion and migration ability. CUEDC2 may be involved in promoting invasion and metastasis in colorectal cancer.
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Affiliation(s)
- Shidong Hu
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China.,*These authors contributed equally to this work
| | - Zilong Hu
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China.,*These authors contributed equally to this work
| | - Songyan Li
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China.,*These authors contributed equally to this work
| | - Changzheng He
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Youjun Wu
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Da Teng
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yang Yan
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Hao Li
- 2 Team of Aviation Medical Examination, Chinese People's Liberation Army Air Force General Hospital, Beijing, China
| | - Xiaowei Xing
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Guijun Zou
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yuxuan Li
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yu Yang
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yufeng Wang
- 3 Department of Hospital Management, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Xiaohui Du
- 1 Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
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Tsitskari M, Filippiadis D, Kostantos C, Palialexis K, Zavridis P, Kelekis N, Brountzos E. The role of interventional oncology in the treatment of colorectal cancer liver metastases. Ann Gastroenterol 2018; 32:147-155. [PMID: 30837787 PMCID: PMC6394269 DOI: 10.20524/aog.2018.0338] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 11/20/2018] [Indexed: 12/14/2022] Open
Abstract
Colorectal cancer is a leading cause of death both in Europe and worldwide. Unfortunately, 20-25% of patients with colorectal cancer already have metastases at the time of diagnosis, while 50-60% of the remainder will develop metastases later during the course of the disease. Although hepatic excision is the first-line treatment for patients with liver-limited colorectal metastases and is reported to prolong the survival of these patients, few patients are candidates. Locoregional therapy encompasses minimally invasive techniques practiced by interventional radiology. Most widely used locoregional therapies include ablative treatments (radiofrequency ablation, microwave ablation) and transcatheter intra-arterial therapies (transarterial chemoembolization, and radioembolization with yttrium-90).
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Affiliation(s)
- Maria Tsitskari
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Dimitris Filippiadis
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Chrysostomos Kostantos
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Kostantinos Palialexis
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Periklis Zavridis
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Nikolaos Kelekis
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Elias Brountzos
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
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Tsitskari M, Filippiadis D, Kostantos C, Palialexis K, Zavridis P, Kelekis N, Brountzos E. The role of interventional oncology in the treatment of colorectal cancer liver metastases. Ann Gastroenterol 2018. [PMID: 30837787 DOI: 10.20524/aog.2019.0338] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Colorectal cancer is a leading cause of death both in Europe and worldwide. Unfortunately, 20-25% of patients with colorectal cancer already have metastases at the time of diagnosis, while 50-60% of the remainder will develop metastases later during the course of the disease. Although hepatic excision is the first-line treatment for patients with liver-limited colorectal metastases and is reported to prolong the survival of these patients, few patients are candidates. Locoregional therapy encompasses minimally invasive techniques practiced by interventional radiology. Most widely used locoregional therapies include ablative treatments (radiofrequency ablation, microwave ablation) and transcatheter intra-arterial therapies (transarterial chemoembolization, and radioembolization with yttrium-90).
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Affiliation(s)
- Maria Tsitskari
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Dimitris Filippiadis
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Chrysostomos Kostantos
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Kostantinos Palialexis
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Periklis Zavridis
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Nikolaos Kelekis
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
| | - Elias Brountzos
- Second Department of Radiology, Unit of Vascular and Interventional Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Greece
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Li D, Zhao C, Ding H, Wu Q, Ren T, Wang J, Chen C, Zhao Q. A novel inhibitor of ADAM17 sensitizes colorectal cancer cells to 5-Fluorouracil by reversing Notch and epithelial-mesenchymal transition in vitro and in vivo. Cell Prolif 2018; 51:e12480. [PMID: 30069943 PMCID: PMC6528951 DOI: 10.1111/cpr.12480] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 05/04/2018] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVES Colorectal cancer is one of the most common malignancies both in men and women. Owing to metastasis and resistance, the prognosis of colorectal cancerCRC patients remains extremely poor with chemotherapy. A disintegrin and metalloproteinase 17 (ADAM17) induces the activation of Notch pathway and contributes to the chemoresistance. This study aimed to discover a novel ADAM17 inhibitor and investigate the chemosensitization effect. MATERIALS AND METHODS Pharmacophore model, western blot and enzymatic assay were used to discover ZLDI-8. Cell proliferation was determined by MTT and colony formation assay. Cell migratory and invasive ability were determined by wound healing scratch and transwell assay. Immunofluorescence images and western blot analysed the expression of Notch or epithelial-mesenchymal transition (EMT) pathway markers. Xenografts were employed to evaluate the chemosensitization effect of ZLDI-8 in vivo. RESULTS We found that ZLDI-8 cell-specifically inhibited the proliferation of CRC, and this effect was due to abrogation of ADAM17 and Notch pathway. Meanwhile, we reported for the first time that ZLDI-8 synergistically improved the anti-tumour and anti-metastasis activity of 5-fluorouracil or irinotecan by reversing Notch and EMT pathways. Interestingly, in vivo studies further demonstrated that ZLDI-8 promoted the anti-tumour effect of 5-fluorouracil through Notch and EMT reversal. CONCLUSIONS A novel ADAM17 inhibitor ZLDI-8 may be a potential chemosensitizer which sensitized CRC cells to 5-fluorouracil or irinotecan by reversing Notch and EMT pathways.
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Affiliation(s)
- Dan‐Dan Li
- Department of PharmacyGeneral Hospital of Shenyang Military Area CommandShenyangChina
- Department of Traditional Chinese MedicineShenyang Pharmaceutical UniversityShenyangChina
| | - Chang‐Hao Zhao
- College of PharmacyThe Heilongjiang University of Traditional Chinese MedicineHeilongjiangChina
| | - Huai‐Wei Ding
- Key Laboratory of Structure‐Based Drug Design and Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyangChina
| | - Qiong Wu
- Department of PharmacyGeneral Hospital of Shenyang Military Area CommandShenyangChina
| | - Tian‐Shu Ren
- Department of PharmacyGeneral Hospital of Shenyang Military Area CommandShenyangChina
| | - Jian Wang
- Key Laboratory of Structure‐Based Drug Design and Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyangChina
| | - Cong‐Qin Chen
- Department of PharmacyGeneral Hospital of Shenyang Military Area CommandShenyangChina
- Department of PharmacyLongyan First HospitalFujian Medical UniversityLongyanChina
| | - Qing‐Chun Zhao
- Department of PharmacyGeneral Hospital of Shenyang Military Area CommandShenyangChina
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Park SH, Kim H, Kim EK, Kim H, Choi DK, Chung YE, Kim MJ, Choi JY. Aberrant expression of OATP1B3 in colorectal cancer liver metastases and its clinical implication on gadoxetic acid-enhanced MRI. Oncotarget 2017; 8:71012-71023. [PMID: 29050339 PMCID: PMC5642614 DOI: 10.18632/oncotarget.20295] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Accepted: 07/11/2017] [Indexed: 12/29/2022] Open
Abstract
Purpose To investigate the factors associated with hepatobiliary phase (HBP) enhancement at gadoxetic acid-enhanced magnetic resonance imaging (MRI) and to determine whether HBP images could be used to predict prognosis in patients with colorectal cancer liver metastasis (CRLM). Results Of the 96 total nodules, 65 and 31 nodules were in the mixed and clearly hypointense groups, respectively. In the 55 nodules without preoperative chemotherapy, organic anionic transporting polypeptide 1B3 (OATP1B3) expression was a significant factor regarding the HBP enhancement (P=0.042). In this subgroup, nodules with OATP1B3 expression displayed a significantly higher relative intensity ratio on the HBP image (RIRpost) and relative enhancement ratio (RER) than those lacking this marker (P=0.024, 0.003, respectively). No significant factor was associated with the enhancement pattern in the chemotherapy group. The mixed hypointense group displayed worse survival rates (P=0.002). Materials and Methods Ninety-six patients who underwent pre-operative liver MRI and surgical resection for CRLM from January 2010 to June 2012 were retrospectively analyzed. We qualitatively evaluated the HBP enhancement pattern of CRLMs and classified them into mixed and clearly hypointense groups. For quantitative measurement, the RIRpost and RER were analyzed. To investigate factors associated with HBP enhancement, tumor components (fibrosis, necrosis, and cellularity) and OATP1B3 expression were scored on a 4-point scale. Univariate and multivariate analyses were done to determine significant factors for visual enhancement and quantitative parameters. Conclusions OATP1B3 expression is associated with mixed hypointense CRLMs without chemotherapy. Signal intensity on HBP has potential usefulness to predict prognosis in CRLMs.
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Affiliation(s)
- Seung Hyun Park
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Honsoul Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Kyung Kim
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hogeun Kim
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Kyu Choi
- New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea
| | - Yong Eun Chung
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Myeong-Jin Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jin-Young Choi
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Napoleone M, Kielar AZ, Hibbert R, Saif S, Kwan BY. Local tumor progression patterns after radiofrequency ablation of colorectal cancer liver metastases. Diagn Interv Radiol 2017; 22:548-554. [PMID: 27705879 DOI: 10.5152/dir.2016.15543] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
PURPOSE We aimed to evaluate patterns of local tumor progression (LTP) after radiofrequency ablation (RF ablation) of colorectal cancer liver metastases (CRCLM) and to highlight the percentage of LTP not attributable to lesion size or RF ablation procedure-related factors (heat sink or insufficient ablation margin). METHODS CRCLM treated by RF ablation at a single tertiary care center from 2004-2012, with a minimum of six months of postprocedure follow-up, were included in this retrospective study. LTP morphology was classified as focal nodular (<90° of ablation margin), circumferential (>270°), or crescentic (90°-270°). Initial metastasis size, minimum ablation margin size, morphology of LTP, presence of a heat sink, and time to progression were recorded independently by two radiologists. RESULTS Thirty-two of 127 RF ablation treated metastases (25%) with a mean size of 23 mm (standard deviation 12 mm) exhibited LTP. Fifteen of 32 LTPs (47%) were classified as focal nodular, with seven having no procedure-related factor to explain recurrence. Ten of 32 LTPs (31%) were circumferential, with four having no procedure-related factor to explain recurrence. Seven of 32 LTPs (22%) were crescentic, with two having no procedure-related factor to explain recurrence. Of the 13 lesions without any obvious procedure-related reason for LTP, six (46%) were <3 cm in size. CONCLUSION Although LTP in RF ablation treated CRCLM can often be explained by procedure-related factors or size of the lesion, in this study up to six (5%) of the CRCLM we treated showed LTP without any reasonable cause.
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Affiliation(s)
- Marc Napoleone
- Department of Radiology, University of Ottawa, Canada and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
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Tinguely P, Fusaglia M, Freedman J, Banz V, Weber S, Candinas D, Nilsson H. Laparoscopic image-based navigation for microwave ablation of liver tumors-A multi-center study. Surg Endosc 2017; 31:4315-4324. [PMID: 28342124 DOI: 10.1007/s00464-017-5458-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Accepted: 02/03/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Stereotactic navigation technology has been proposed to augment accuracy in targeting intrahepatic lesions for local ablation therapy. This retrospective study evaluated accuracy, efficacy, and safety when using laparoscopic image-guided microwave ablation (LIMA) for malignant liver tumors. METHODS All patients treated for malignant liver lesions using LIMA at two European centers between 2013 and 2015 were included for analysis. A landmark-based registration technique was applied for intraoperative tumor localization and positioning of ablation probes. Intraoperative efficiency of the procedure was measured as number of registration attempts and time needed to achieve sufficient registration accuracy. Technical accuracy was assessed as Fiducial Registration Error (FRE). Outcome at 90 days including mortality, postoperative morbidity, rates of incomplete ablations, and early intrahepatic recurrences were reported. RESULTS In 34 months, 54 interventions were performed comprising a total of 346 lesions (median lesions per patient 3 (1-25)). Eleven patients had concomitant laparoscopic resections of the liver or the colorectal primary tumor. Median time for registration was 4:38 min (0:26-19:34). Average FRE was 8.1 ± 2.8 mm. Follow-up at 90 days showed one death, 24% grade I/II, and 4% grade IIIa complications. Median length of hospital stay was 2 days (1-11). Early local recurrence was 9% per lesion and 32% per patient. Of these, 63% were successfully re-ablated within 6 months. CONCLUSIONS LIMA does not interfere with the intraoperative workflow and results in low complication and early local recurrence rates, even when simultaneously targeting multiple lesions. LIMA may represent a valid therapy option for patients with extensive hepatic disease within a multimodal treatment approach.
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Affiliation(s)
- Pascale Tinguely
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, University of Bern, 3010, Bern, Switzerland.
| | - Matteo Fusaglia
- ARTORG Center for Biomedical Engineering Research, University of Bern, 3010, Bern, Switzerland
| | - Jacob Freedman
- Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88, Stockholm, Sweden
| | - Vanessa Banz
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, University of Bern, 3010, Bern, Switzerland
| | - Stefan Weber
- ARTORG Center for Biomedical Engineering Research, University of Bern, 3010, Bern, Switzerland
| | - Daniel Candinas
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, University of Bern, 3010, Bern, Switzerland
| | - Henrik Nilsson
- Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88, Stockholm, Sweden
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García R, Santa-Olalla I, Lopez Guerra JL, Sanchez S, Azinovic I. Robotic radiosurgery for the treatment of liver metastases. Rep Pract Oncol Radiother 2017; 22:111-117. [DOI: 10.1016/j.rpor.2016.10.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Revised: 08/05/2016] [Accepted: 10/09/2016] [Indexed: 12/31/2022] Open
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Periportal low attenuation associated with liver metastasis from colorectal cancer: evaluation using multi-detector-row CT with pathological correlation. Jpn J Radiol 2016; 35:10-15. [PMID: 27783272 DOI: 10.1007/s11604-016-0592-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 10/16/2016] [Indexed: 10/20/2022]
Abstract
OBJECTIVES Periportal low attenuation (PPLA) associated with metastatic liver cancer is occasionally seen on multi-detector-row CT (MDCT). The purpose of this study was to investigate the MDCT patterns of the PPLA and to correlate it with pathological findings. METHODS We retrospectively reviewed the MDCT images of 63 patients with metastatic liver cancers from colorectal adenocarcinoma. On MDCT scans, PPLA associated with liver metastasis was visualized in six patients with colorectal cancer. In these six patients who had undergone surgical resection, the radiologic-pathologic correlation was analyzed. All patients underwent a single contrast-enhanced MDCT within 1 month before surgical resection. The six liver cancers were pathologically proven to be moderately differentiated adenocarcinoma. We assessed the PPLA on MDCT concerning the distribution patterns and contrast enhancement with pathological correlation. RESULTS In five of the patients, the PPLA extended to the hilar side from metastatic liver cancer. Pathologically, there was no cancer invasion into the intra-hepatic periportal area; however, massive lymphedema and fibrosis occurred in all six cases. CONCLUSIONS PPLA on the hilar and peripheral sides of hepatic metastasis from colorectal cancer may be present suggesting lymphedema and fibrosis of portal tracts not always indicating cancer infiltration.
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The Preoperative Peripheral Blood Monocyte Count Is Associated with Liver Metastasis and Overall Survival in Colorectal Cancer Patients. PLoS One 2016; 11:e0157486. [PMID: 27355390 PMCID: PMC4927165 DOI: 10.1371/journal.pone.0157486] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 05/30/2016] [Indexed: 01/28/2023] Open
Abstract
Background Colorectal cancer (CRC) is the third most common malignancy in males and the second most common in females worldwide. Distant metastases have a strong negative impact on the prognosis of CRC patients. The most common site of CRC metastases is the liver. Both disease progression and metastasis have been related to the patient’s peripheral blood monocyte count. We therefore performed a case-control study to assess the relationship between the preoperative peripheral blood monocyte count and colorectal liver metastases (CRLM). Methods Clinical data from 117 patients with colon cancer and 93 with rectal cancer who were admitted to the Chinese People’s Liberation Army General Hospital (Beijing, China) between December 2003 and May 2015 were analysed retrospectively, with the permission of both the patients and the hospital. Results Preoperative peripheral blood monocyte counts, the T and N classifications of the primary tumour and its primary site differed significantly between the two groups (P < 0.001, P < 0.001, P = 0.002, P < 0.001), whereas there were no differences in the sex, age, degree of tumour differentiation or largest tumour diameter. Lymph node metastasis and a high preoperative peripheral blood monocyte count were independent risk factors for liver metastasis (OR: 2.178, 95%CI: 1.148~4.134, P = 0.017; OR: 12.422, 95%CI: 5.076~30.398, P < 0.001), although the risk was lower in patients with rectal versus colon cancer (OR: 0.078, 95%CI: 0.020~0.309, P < 0.001). Primary tumour site (P<0.001), degree of tumour differentiation (P = 0.009), T, N and M classifications, TNM staging and preoperative monocyte counts (P<0.001) were associated with the 5-year overall survival (OS) of CRC patients. A preoperative peripheral blood monocyte count > 0.505 × 109 cells/L, high T classification and liver metastasis were independent risk factors for 5-year OS (RR: 2.737, 95% CI: 1.573~ 4.764, P <0.001; RR: 2.687, 95%CI: 1.498~4.820, P = 0.001; RR: 4.928, 95%CI: 2.871~8.457, P < 0.001). Conclusions The demonstrated association between preoperative peripheral blood monocyte count and liver metastasis in patients with CRC recommends the former as a useful predictor of postoperative prognosis in CRC patients.
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Solomon SB, Sofocleous CT. The interventional radiologist role in treating liver metastases for colorectal cancer. Am Soc Clin Oncol Educ Book 2016:202-4. [PMID: 24451734 DOI: 10.14694/edbook_am.2012.32.115] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Interventional radiologists (IRs) have an expanding role in the treatment of liver metastases from colorectal cancer. Increasing data on the ability to treat liver metastases with locoregional therapies has solidified this position. Ablative approaches, such as radiofrequency ablation and microwave ablation, have shown durable eradication of tumors. Catheter-directed therapies-such as transarterial chemoembolization (TACE), drug-eluting beads (DEB), Y90 radioembolization, intra-arterial chemotherapy ports, and isolated hepatic perfusion (IHP)-are potential techniques for managing patients with unresectable liver metastases. Understanding the timing and role of these techniques in the multidisciplinary care of the patient is critical. Implementation of the IR clinic for consultation has enabled better integration of these therapies into the patient's overall care and has facilitated improved opportunities for clinical studies.
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Saif S, Z A, Kielar, McInnes M. Systematic review of 12 years of thermal ablative therapies of non-resectable colorectal cancer liver metastases. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2016. [DOI: 10.18528/gii150007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Sameh Saif
- Department of Medical Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
- Department of Radiology, Faculty of Medicine (Kasr Alainy), Cairo University, Cairo, Egypt
| | | | - Kielar
- Department of Medical Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
| | - Matthew McInnes
- Department of Medical Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
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Sotirchos VS, Petrovic LM, Gönen M, Klimstra DS, Do RKG, Petre EN, Garcia AR, Barlas A, Erinjeri JP, Brown KT, Covey AM, Alago W, Brody LA, DeMatteo RP, Kemeny NE, Solomon SB, Manova-Todorova KO, Sofocleous CT. Colorectal Cancer Liver Metastases: Biopsy of the Ablation Zone and Margins Can Be Used to Predict Oncologic Outcome. Radiology 2016; 280:949-59. [PMID: 27010254 DOI: 10.1148/radiol.2016151005] [Citation(s) in RCA: 101] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Purpose To establish the prognostic value of biopsy of the central and marginal ablation zones for time to local tumor progression (LTP) after radiofrequency (RF) ablation of colorectal cancer liver metastasis (CLM). Materials and Methods A total of 47 patients with 67 CLMs were enrolled in this prospective institutional review board-approved and HIPAA-compliant study between November 2009 and August 2012. Mean tumor size was 2.1 cm (range, 0.6-4.3 cm). Biopsy of the center and margin of the ablation zone was performed immediately after RF ablation (mean number of biopsy samples per ablation zone, 1.9) and was evaluated for the presence of viable tumor cells. Samples containing tumor cells at morphologic evaluation were further interrogated with immunohistochemistry and were classified as either positive, viable tumor (V) or negative, necrotic (N). Minimal ablation margin size was evaluated in the first postablation CT study performed 4-8 weeks after ablation. Variables were evaluated as predictors of time to LTP with the competing-risks model (uni- and multivariate analyses). Results Technical effectiveness was evident in 66 of 67 (98%) ablated lesions on the first contrast material-enhanced CT images at 4-8-week follow-up. The cumulative incidence of LTP at 12-month follow-up was 22% (95% confidence interval [CI]: 12, 32). Samples from 16 (24%) of 67 ablation zones were classified as viable tumor. At univariate analysis, tumor size, minimal margin size, and biopsy results were significant in predicting LTP. When these variables were subsequently entered in a multivariate model, margin size of less than 5 mm (P < .001; hazard ratio [HR], 6.7) and positive biopsy results (P = .008; HR, 3.4) were significant. LTP within 12 months after RF ablation was noted in 3% (95% CI: 0, 9) of necrotic CLMs with margins of at least 5 mm. Conclusion Biopsy proof of complete tumor ablation and minimal ablation margins of at least 5 mm are independent predictors of LTP and yield the best oncologic outcomes. (©) RSNA, 2016.
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Affiliation(s)
- Vlasios S Sotirchos
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Lydia M Petrovic
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Mithat Gönen
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - David S Klimstra
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Richard K G Do
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Elena N Petre
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Alessandra R Garcia
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Afsar Barlas
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Joseph P Erinjeri
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Karen T Brown
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Anne M Covey
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - William Alago
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Lynn A Brody
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Ronald P DeMatteo
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Nancy E Kemeny
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Stephen B Solomon
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Katia O Manova-Todorova
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
| | - Constantinos T Sofocleous
- From the Section of Interventional Radiology, Department of Radiology (V.S.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., L.A.B., S.B.S., C.T.S.), Departments of Epidemiology and Biostatistics (M.G.), Pathology (D.S.K.), Radiology (R.K.G.D., A.R.G.), Molecular Cytology (A.B., K.O.M.), Surgery (R.P.D.), and Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; and Department of Pathology, University of Southern California University Hospital, Los Angeles, Calif (L.M.P.)
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