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Peng K, Li Y, Su H, Lan C, Huang Z, Wei Y, Liao X, Peng M, Peng T, Zhu G. Case report: hepatic arterial infusion chemotherapy combined with sintilimab and lenvatinib for conversion therapy of colorectal cancer liver metastases. Front Immunol 2023; 14:1325445. [PMID: 38173715 PMCID: PMC10762641 DOI: 10.3389/fimmu.2023.1325445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 11/28/2023] [Indexed: 01/05/2024] Open
Abstract
Background Liver metastasis is one of the most common causes of death in patients with colorectal cancer. Therefore, improving the treatment effect of liver metastatic carcinoma of colorectal cancer is also one of the effective ways to improve the survival time of patients with colorectal cancer. The main treatment method for liver metastasis of colorectal cancer is preoperative neoadjuvant chemotherapy through intravenous administration. However, no one has reported a conversion therapy approach for the treatment of colorectal cancer liver metastases patients through arterial infusion chemotherapy combined with targeted agents and PD-1 monoclonal antibody. This case reports a conversion therapy method of liver metastases of colorectal cancer by hepatic arterial infusion chemotherapy (HAIC), sintilimab injection combined with lenvatinib to achieve radical resection of liver metastatic carcinoma after treatment. Case presentation The patient was a 69-year-old man who had previously undergone laparoscopic left hemicolectomy for descending colorectal cancer and multiple interventional and surgical treatments for hepatocellular carcinoma. During this treatment, the patient underwent radiological and serological tests, and primary liver cancer was considered at the initial diagnosis stage. Therefore, this liver malignant tumor lesion was treated according to the primary liver cancer treatment protocol before surgical resection. Therefore, the patient received HAIC combined with sintilimab injection and lenvatinib. After three treatment cycles, radiological examination showed no obvious tumor activity, alpha-fetoprotein (AFP) decreased to normal, protein induced by vitamin K absence or antagonist II (PIVKA II) decreased significantly, and the curative effect was evaluated as complete remission. Subsequently, we performed surgical resection of this liver lesion. The pathological response of left lobe tumor was partial remission (PR). Most of the tumors were necrotic and the necrosis rate was greater than 95%. A small amount of live tumor tissue remains (<5%). The pathological classification of this tumor was confirmed as moderately differentiated adenocarcinoma by immunohistochemical staining of multiple tumor indicators in the pathology department. No significant adverse drug events were observed in this patient during treatment. Conclusion Hepatic arterial infusion chemotherapy combined with sintilimab injection and lenvatinib conversion therapy provides the opportunity for radical surgical resection of colorectal cancer liver metastases.
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Affiliation(s)
- Kai Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yuhua Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Hao Su
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Chenlu Lan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zaida Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yongguang Wei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiwen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Minhao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
- Key Laboratory of Early Prevention & Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, China
| | - Guangzhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
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Chen Y, Zhu D, Chen M, Xu Y, Ye Q, Wang X, Xu P, Feng Q, Ji M, Wei Y, Fan J, Xu J. Impact of Surgical Management for Relapse After Conversion Hepatectomy for Initially Unresectable Colorectal Liver Metastasis: A Retrospective Cohort Study. Clin Colorectal Cancer 2023; 22:464-473.e5. [PMID: 37730473 DOI: 10.1016/j.clcc.2023.08.007] [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: 07/15/2023] [Revised: 08/26/2023] [Accepted: 08/29/2023] [Indexed: 09/22/2023]
Abstract
BACKGROUND For patients with initially unresectable colorectal liver metastasis (IU-CRLM) receiving conversion therapy, disease relapse after conversion hepatectomy is common. However, few studies have focused on the assessment and management of relapse following conversion hepatectomy for IU-CRLM. METHODS In the retrospective cohort study, 255 patients with IU-CRLM received conversion therapy and underwent subsequent R0 resection. The treatment effects of repeated liver-directed treatment (RLDT) versus non-RLDT for liver relapse were examined. Survival analysis was evaluated with the use of Cox proportional hazards methods. The importance of RLDT was further confirmed in the propensity score matching (PSM) and subgroup analyses. RESULTS The 5-year overall survival (OS) rate after conversion hepatectomy was 34.9%. Liver relapse was observed in 208 patients. Of these patients, 106 underwent RLDT (65 underwent repeated hepatectomy and the remainder underwent ablation treatment), while 102 received only palliative chemotherapy. The relapse patients who underwent RLDT had a significantly longer OS than those who did not (hazard ratio (HR): 0.382, 95% CI: 0.259-0.563; P<0.001). In a multivariable analysis, RLDT was independently associated to prolonged survival (HR: 0.309, 95%CI: 0.181-0.529; P<0.001). In the PSM and subgroup analyses, RLDT consistently showed evidence of prolonging OS significantly. CONCLUSION For IU-CRLM patients with liver relapse following conversion hepatectomy, the RLDT is essential for cure and prolonged survival. To avoid missing the opportunity for RLDT, intensive disease surveillance should be proposed.
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Affiliation(s)
- Yijiao Chen
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dexiang Zhu
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Miao Chen
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuqiu Xu
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qinghai Ye
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaoying Wang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Pingping Xu
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive
| | - Qingyang Feng
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Meiling Ji
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive
| | - Ye Wei
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Jianmin Xu
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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Yu W, Xie Q, Li J, Tang J, Yang W, Tao Y. Salvage 125I brachytherapy for liver metastases of colorectal cancer in anatomically challenging locations after failure of systemic chemotherapy-A retrospective study. Brachytherapy 2022; 21:592-598. [PMID: 35750620 DOI: 10.1016/j.brachy.2022.05.006] [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: 02/09/2022] [Revised: 04/28/2022] [Accepted: 05/20/2022] [Indexed: 11/02/2022]
Abstract
PURPSOE Colorectal cancer liver metastasis (CCLM) in anatomically challenging locations is difficult to treat. This retrospective study aimed to evaluate the effectiveness and safety of permanent 125I seeds implantation (ISI) for treatment of CCLM in anatomically challenging locations after failure of systemic chemotherapy. METHODS AND MATERIALS A total of 31 liver metastases (in 25 patients) were treated by ISI under computerized tomography guidance from January 2011 to December 2017. Post-treatment follow-up was for 40 months. Adverse events were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events. Tumor response was evaluated by the mRECIST criteria. Objective response rate, overall survival rate, and complications were retrospectively analyzed. RESULTS All ISI procedures were performed successfully. Most patients only complained of fatigue and mild pain after ISI. Only one patient had liver rupture during the procedure. Serum alanine aminotransferase and aspartate aminotransferase levels at 1 month after ISI were not significantly different from pre-procedure levels (p > 0.05). Computed tomography at 6 months after ISI treatment showed completed response in 11 (11/31, 35.5%) lesions, partial response in 14 (14/31, 45.2%) lesions, stable disease in 4 (4/31, 12.9%) lesions, and disease progression in 2 (2/31, 6.5%) lesions; thus, the objective response rate was 80.6%. Median survival was for 12 months. The 1 and 2 year overall survival rates were 52.0% and 20.0%, respectively. CONCLUSIONS 125I seeds implantation for CCLM in anatomically challenging locations is safe and effective. Survival benefit is limited in the salvage setting where patients have high intrahepatic tumor load after failed systemic chemotherapy.
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Affiliation(s)
- Wenhui Yu
- Department of Interventional Radiology, Hospital of Jiangnan University, Jiangsu Province, Wuxi, China.
| | - Qigen Xie
- Department of Interventional Radiology, Hospital of Jiangnan University, Jiangsu Province, Wuxi, China
| | - Jie Li
- Department of Interventional Radiology, Hospital of Jiangnan University, Jiangsu Province, Wuxi, China
| | - Jie Tang
- Department of Interventional Radiology, Hospital of Jiangnan University, Jiangsu Province, Wuxi, China
| | - Wenge Yang
- Department of Interventional Radiology, Hospital of Jiangnan University, Jiangsu Province, Wuxi, China
| | - Yun Tao
- Department of Interventional Radiology, Hospital of Jiangnan University, Jiangsu Province, Wuxi, China
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Shen HY, Wei FZ, Liu Q. Differential analysis revealing APOC1 to be a diagnostic and prognostic marker for liver metastases of colorectal cancer. World J Clin Cases 2021; 9:3880-3894. [PMID: 34141744 PMCID: PMC8180235 DOI: 10.12998/wjcc.v9.i16.3880] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/10/2021] [Accepted: 03/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most malignant gastrointestinal cancers worldwide. The liver is the most important metastatic target organ, and liver metastasis is the leading cause of death in patients with CRC. Owing to the lack of sensitive biomarkers and unclear molecular mechanism, the occurrence of liver metastases cannot be predicted and the clinical outcomes are bad for liver metastases. Therefore, it is very important to identify the diagnostic or prognostic markers for liver metastases of CRC.
AIM To investigate the highly differentially expressed genes (HDEGs) and prognostic marker for liver metastases of CRC.
METHODS Data from three NCBI Gene Expression Omnibus (GEO) datasets were used to show HDEGs between liver metastases of CRC and tumour or normal samples. These significantly HDEGs of the three GEO datasets take the interactions. And these genes were screened through an online tool to explore the prognostic value. Then, TIMER and R package were utilized to investigate the immunity functions of the HDEGs and gene set enrichment analysis was used to explore their potential functions.
RESULTS Based on the selection criteria, three CRC datasets for exploration (GSE14297, GSE41258, and GSE49355) were chosen. Venn diagrams were used to show HDEGs common to the six groups and 47 HDEGs were obtained. The HDEGs were shown by using STRING and Cytoscape software. Based on the TCGA database, APOC1 showed significantly different expression between N2 and N0, and N2 and N1. And there was also a significant difference in expression between T2 and T4, and between T2 and T3. In 20 paired CRC and normal tissues, quantitative real-time polymerase chain reaction illustrated that the APOC1 mRNA was strongly upregulated in CRC tissues (P = 0.014). PrognoScan and GEPIA2 revealed the prognostic value of APOC1 for overall survival and disease-free survival in CRC (P < 0.05). TIMER showed that APOC1 has a close relationship with immune infiltration (P < 0.05).
CONCLUSION APOC1 is a biomarker that is associated with both the diagnosis and prognosis of liver metastases of CRC.
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Affiliation(s)
- Hai-Yu Shen
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Fang-Ze Wei
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Qian Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Zhou SN, Pan WT, Pan MX, Luo QY, Zhang L, Lin JZ, Zhao YJ, Yan XL, Yuan LP, Zhang YX, Yang DJ, Qiu MZ. Comparison of Immune Microenvironment Between Colon and Liver Metastatic Tissue in Colon Cancer Patients with Liver Metastasis. Dig Dis Sci 2021; 66:474-482. [PMID: 32193860 DOI: 10.1007/s10620-020-06203-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 03/10/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND Liver metastasis is an indicator of unfavorable responses to immunotherapy in colorectal cancer patients. However, the difference of immune microenvironment between primary tumors and liver metastases has not been well understood. PATIENTS AND METHODS Fifty-four colon cancer with liver metastasis patients who received resection of both primary and metastasis lesions have been analyzed. The immune score is based on the density of infiltrating immune cells (CD3+ cell, CD8+ cell, CD11b+ cell, CD11c+ cell, and CD33+ cell) in the center and margin of the tumor. The expression of immune markers between the primary tumor and hepatic metastases was analyzed using Wilcoxon's signed rank test. RESULTS All the five markers had higher expression in tumor margins than center tumor in both primary tumor and hepatic metastases lesions. The expression of CD11c and CD11b had no difference between metastatic lesions and primary tumor. In tumor margins, except CD11b, all the other 4 markers expressed significantly higher in hepatic metastases than in primary tumor. Intra-tumor, CD3 had higher expression in primary tumor than in hepatic metastases, while CD33 had higher expression in hepatic metastases than in primary tumor. CD8+ CD3+ cells of the total CD8+ cell population in primary tumor was significantly higher than in hepatic metastases (36.42% vs. 24.88%, p = 0.0069). CONCLUSIONS The immune microenvironment between primary tumor and hepatic metastasis is different. More immunosuppressing cells in liver may partially explain why immunotherapy in colon cancer is less effective with liver metastatic disease.
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Affiliation(s)
- Su-Na Zhou
- Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Wen-Tao Pan
- Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Meng-Xian Pan
- Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Qiu-Yun Luo
- Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Lin Zhang
- Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
- Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Jun-Zhong Lin
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Yu-Jie Zhao
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Xiang-Lei Yan
- Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Lu-Ping Yuan
- Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Yu-Xin Zhang
- Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Da-Jun Yang
- Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Miao-Zhen Qiu
- Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China.
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China.
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Ren L, Zhu D, Benson AB, Nordlinger B, Koehne CH, Delaney CP, Kerr D, Lenz HJ, Fan J, Wang J, Gu J, Li J, Shen L, Tsarkov P, Tejpar S, Zheng S, Zhang S, Gruenberger T, Qin X, Wang X, Zhang Z, Poston GJ, Xu J. Shanghai international consensus on diagnosis and comprehensive treatment of colorectal liver metastases (version 2019). Eur J Surg Oncol 2020; 46:955-966. [PMID: 32147426 DOI: 10.1016/j.ejso.2020.02.019] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Accepted: 02/17/2020] [Indexed: 12/17/2022] Open
Abstract
The liver is the most common anatomical site for hematogenous metastases from colorectal cancer. Therefore effective treatment of liver metastases is one of the most challenging elements in the management of colorectal cancer. However, there is rare available clinical consensus or guideline only focusing on colorectal liver metastases. After six rounds of discussion by 195 clinical experts of the Shanghai International Consensus Expert Group on Colorectal Liver Metastases (SINCE) from 29 countries or regions, the Shanghai Consensus has been finally completed, based on current research and expert experience. The consensus emphasized the principle of multidisciplinary team, provided detailed diagnosis approaches, and guided precise local and systemic treatments. This Shanghai Consensus might be of great significance to standardized diagnosis and treatment of colorectal liver metastases all over the world.
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Affiliation(s)
- Li Ren
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dexiang Zhu
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Al B Benson
- Division of Hematology/Oncology, Northwestern Medical Group, Chicago, USA
| | - Bernard Nordlinger
- Surgery Department, Hospital Ambroise-Pare, Boulogne-Billancourt, France
| | | | - Conor P Delaney
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - David Kerr
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Heinz-Josef Lenz
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, China
| | - Jianping Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jin Gu
- Department of Colorectal Surgery, Peking University Cancer Hospital, Beijing, China; Department of Colorectal Surgery, Peking University Shougang Hospital, Beijing, China
| | - Jin Li
- Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China
| | - Petrv Tsarkov
- Clinic of Colorectal and Minimally Invasive Surgery, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Sabine Tejpar
- Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium
| | - Shu Zheng
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Suzhan Zhang
- Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | | | - Xinyu Qin
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xishan Wang
- Department of Colorectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Graeme John Poston
- Surgery Department, Aintree University Hospital, School of Translational Studies, University of Liverpool, Liverpool, UK.
| | - Jianmin Xu
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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Li Y, Huang N, Wang C, Ma H, Zhou M, Lin L, Huang Z, Sun L, Shi M, Liao W. Impact of liver tumor percutaneous radiofrequency ablation on circulating tumor cells. Oncol Lett 2018; 16:2839-2850. [PMID: 30127870 PMCID: PMC6096180 DOI: 10.3892/ol.2018.9019] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 04/13/2018] [Indexed: 12/13/2022] Open
Abstract
Radiofrequency ablation has become an increasingly common therapeutic technique for patients with hepatocellular carcinoma or metastatic liver tumors. However, reports on the effect of percutaneous radiofrequency ablation (PRFA) on circulating tumor cells (CTCs) are limited. The present study aimed to further investigate the impacts of PRFA on the numbers and phenotypes of CTCs in patients with hepatocellular carcinoma or metastatic liver tumors. A total of 43 patients with hepatocellular carcinoma or 7 types of metastatic liver tumors were treated with PRFA. A total of 5 ml blood per sample were collected from the peripheral circulation 30 min before and 3 days after PRFA. The total number of CTCs significantly increased 3 days after PRFA, and the mesenchymal phenotype CTCs, which also increased significantly, significantly contributed to the overall increase in CTCs. Furthermore, the lymphocyte levels were significantly decreased following PRFA, and the CTC level was significantly higher in patients with decreased lymphocyte levels compared with those with increased lymphocyte levels. Liver tumor PRFA may increase the level of mesenchymal phenotype CTCs, which is significantly associated with the lymphocyte count. Factors pertaining to the performance of PRFA were also investigated in the present research, but no significant results were identified.
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Affiliation(s)
- Yang Li
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Na Huang
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Chunlin Wang
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Huanrong Ma
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Minyu Zhou
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Li Lin
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Zhenhua Huang
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Li Sun
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Min Shi
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Wangjun Liao
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
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Marfà S, Marti J, Reyes A, Casals G, Fernández-Varo G, Carvajal S, García-Valdecasas JC, Fuster J, Jiménez W. Metastatic Tissue Proteomic Profiling Predicts 5-Year Outcomes in Patients with Colorectal Liver Metastases. Transl Oncol 2016; 9:445-452. [PMID: 27751349 PMCID: PMC5067925 DOI: 10.1016/j.tranon.2016.08.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 08/03/2016] [Accepted: 08/08/2016] [Indexed: 01/05/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers in the developed countries, and nearly 70% of patients with CRC develop colorectal liver metastases (CRLMs). During the last decades, several scores have been proposed to predict recurrence after CRLM resection. However, these risk scoring systems do not accurately reflect the prognosis of these patients. Therefore, this investigation was designed to identify a proteomic profile in human hepatic tumor samples to classify patients with CRLM as “mild” or “severe” based on the 5-year survival. The study was performed on 85 CRLM tumor samples. Firstly, to evaluate any distinct tumor proteomic signatures between mild and severe CRLM patients, a training group of 57 CRLM tumor samples was characterized by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, and a classification and regression tree (CART) analysis was subsequently performed. Finally, 28 CRLM tumor samples were used to confirm and validate the results obtained. Based on all the protein peaks detected in the training group, the CART analysis was generated, and four peaks were considered to be the most relevant to construct a diagnostic algorithm. Indeed, the multivariate model yielded a sensitivity of 85.7% and a specificity of 86.1%, respectively. In addition, the receiver operating characteristic (ROC) curve showed an excellent diagnostic accuracy to discriminate mild from severe CRLM patients (area under the ROC: 0.903). Finally, the validation process yielded a sensitivity and specificity of 68.8% and 83.3%, respectively. We identified a proteomic profile potentially useful to determine the prognosis of CRLM patients based on the 5-year survival.
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Affiliation(s)
- Santiago Marfà
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Josep Marti
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Adalgiza Reyes
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Gregori Casals
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Guillermo Fernández-Varo
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biomedicine, University of Barcelona, Barcelona, Spain
| | - Silvia Carvajal
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - J C García-Valdecasas
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Josep Fuster
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Wladimiro Jiménez
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biomedicine, University of Barcelona, Barcelona, Spain.
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Kuo IM, Huang SF, Chiang JM, Yeh CY, Chan KM, Chen JS, Yu MC. Clinical features and prognosis in hepatectomy for colorectal cancer with centrally located liver metastasis. World J Surg Oncol 2015; 13:92. [PMID: 25889950 PMCID: PMC4354756 DOI: 10.1186/s12957-015-0497-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 02/01/2015] [Indexed: 12/24/2022] Open
Abstract
Background Hepatic metastasectomy for patients with primary colorectal cancer offers better long-term outcome, and chemotherapy can increase the rate of hepatic resectability for patients with initially inoperable disease. The pattern of liver metastasis and status of the primary tumor are rarely discussed in the analysis of long-term outcome. In this report, we evaluate the influence of the pattern of metastasis on clinical features and prognosis. Methods One hundred and fifty-nine patients who underwent hepatic metastasectomy with curative intent for liver metastasis of colorectal cancer between October 1991 and December 2006 were enrolled. Patients were grouped according to whether liver metastasis was centrally or peripherally located, based on imaging and operative findings. Patient demographics, characteristics of the primary and metastatic tumors, and surgical outcomes were analyzed for long-term survival. Results A greater proportion of patients with centrally located metastases were male, as compared with those with peripherally located metastases. Compared with patients with peripherally located metastases, patients with centrally located metastases were more likely to have multiple lesions (P = 0.016), involvement of multiple segments (P = 0.006), large metastases (P < 0.001), and bilobar distribution of metastases (P < 0.001). The estimated 5-year recurrence-free and overall survival rates were 22.4% and 34.2%, respectively. Univariate analysis revealed that centrally located metastasis, primary tumor in the transverse colon, metastasis in regional lymph nodes, initial extrahepatic metastasis, synchronous liver metastasis, multiple lesions, poorly differentiated tumor, and resection margin <10 mm were significant poor prognostic factors for recurrence-free survival and overall survival. Cox regression analysis showed that inadequate resection margin and centrally located liver metastasis were significant predictors of shorter overall survival. Conclusions In colorectal cancer, centrally located liver metastasis represents a poor prognostic factor after hepatectomy, and is associated with early recurrence. Neoadjuvant chemotherapy may be used to downstage centrally located liver metastases to improve outcome.
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Affiliation(s)
- I-Ming Kuo
- Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, 5, Fu-Shin Street, Kweishan, Taoyuan, 333, Taiwan.
| | - Song-Fong Huang
- Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, 5, Fu-Shin Street, Kweishan, Taoyuan, 333, Taiwan.
| | - Jy-Ming Chiang
- Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, 5, Fu-Shin Street, Kweishan, Taoyuan, 333, Taiwan.
| | - Chien-Yuh Yeh
- Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, 5, Fu-Shin Street, Kweishan, Taoyuan, 333, Taiwan.
| | - Kun-Ming Chan
- Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, 5, Fu-Shin Street, Kweishan, Taoyuan, 333, Taiwan.
| | - Jinn-Shiun Chen
- Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, 5, Fu-Shin Street, Kweishan, Taoyuan, 333, Taiwan.
| | - Ming-Chin Yu
- Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University, 5, Fu-Shin Street, Kweishan, Taoyuan, 333, Taiwan.
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10
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Giakoustidis A, Neofytou K, Khan A, Mudan S. Addition of bevacizumab to preoperative chemotherapy for colorectal liver metastases does not increase perioperative morbidity and mortality. Hepat Oncol 2014; 1:363-375. [PMID: 30190972 PMCID: PMC6095412 DOI: 10.2217/hep.14.17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
AIM Patients with colorectal liver metastases (CRLM) benefit from liver resection. Bevacizumab is commonly used in these patients resulting in a greater number of patients receiving an operation for a potentially curative liver resection, with initially unresectable liver metastases. Our purpose was to evaluate the effect of preoperative bevacizumab administration on perioperative complications in patients undergoing hepatic resection for CRLM. METHODS A retrospective analysis of patients undergoing hepatic resection for CRLM who received only neoadjuvant chemotherapy (chemotherapy group, n = 133), or neoadjuvant chemotherapy and bevacizumab (chemotherapy and bevacizumab group, n = 103). We compared surgical characteristics, perioperative complications and postoperative liver function. RESULTS The type of liver resection (minor vs major liver resection) was comparable in the two groups (major liver resection 52.6 vs 62.1%, p = 0.144). The addition of bevacizumab to preoperative chemotherapy does not affect the frequency (chemotherapy group vs chemotherapy and bevacizumab group, 35.3 vs 38.8%, p = 0.581), severity (major complications, 20.3 vs 19.4%, p = 0.487) and type of perioperative complications. Preoperative administration of bevacizumab was associated with a higher peak of postoperative alanine aminotransferase levels but did not affect functional recovery of the liver. CONCLUSION Neoadjuvant administration of bevacizumab was not associated with an increased risk of postoperative complications after hepatic resection and did not affect the liver's functional recovery. Patients receiving more than eight cycles of bevacizumab are at an increased risk to develop perioperative complications.
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Affiliation(s)
| | - Kyriakos Neofytou
- Department of Academic Surgery, The Royal Marsden NHS Trust, Fulham Road, London, SW3 6JJ, UK
| | - Aamir Khan
- Department of Academic Surgery, The Royal Marsden NHS Trust, Fulham Road, London, SW3 6JJ, UK
| | - Satvinder Mudan
- Department of Surgery, The London Clinic, 116 Harley Street, London, W1G 7JL, UK
- Department of Academic Surgery, The Royal Marsden NHS Trust, Fulham Road, London, SW3 6JJ, UK
- Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London, W2 1PG, UK
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Safety of redo hepatectomy for colorectal liver metastases after selective interarterial radiation therapy: a case report. Case Rep Surg 2014; 2014:712572. [PMID: 24716079 PMCID: PMC3971541 DOI: 10.1155/2014/712572] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Accepted: 01/19/2014] [Indexed: 11/30/2022] Open
Abstract
Surgical resection is the only potentially curative strategy in the treatment of patients with colorectal liver metastases (CLM). Unfortunately, only about 10%–15% of patients are candidates for resection. Preoperative chemotherapy aims to increase the number of patients that may be eligible for liver resection by downsizing liver metastases. For patients with unresectable, chemotherapy refractory CLM the available treatment options are limited. Selective interarterial radiation therapy (SIRT) is one of the most promising treatment options for this group of patients. Although only a small number of these patients have been reported as becoming candidates for potentially curative hepatic resection following sufficient reduction in the volume of liver metastases, the question arises regarding the safety of liver resection in these patients. We report a case of a patient who presented unresectable liver relapse of CLM after previous right hepatectomy. He underwent SIRT which resulted in downsizing of the liver metastases making the patient candidate for left lateral sectionectomy. He underwent the redo hepatectomy without any complications. To the best of our knowledge, this is the first reported case of redo hepatectomy after SIRT for CLM.
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Cooper AB, Aloia TA, Vauthey JN, Curley SA. Controversies in Advanced Disease - Surgical Approaches for Metastatic Resection. COLORECTAL CANCER 2014. [DOI: 10.1002/9781118337929.ch13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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13
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Petitguillaume A, Bernardini M, Hadid L, de Labriolle-Vaylet C, Franck D, Desbrée A. Three-dimensional personalized Monte Carlo dosimetry in 90Y resin microspheres therapy of hepatic metastases: nontumoral liver and lungs radiation protection considerations and treatment planning optimization. J Nucl Med 2014; 55:405-13. [PMID: 24504053 DOI: 10.2967/jnumed.113.120444] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
UNLABELLED In the last decades, selective internal radiation therapy (SIRT) has become a real alternative in the treatment of unresectable hepatic cancers. In practice, the activity prescription is limited by the irradiation of organs at risk (OAR), such as the lungs and nontumoral liver (NTL). Its clinical implementation is therefore highly dependent on dosimetry. In that context, a 3-dimensional personalized dosimetry technique--personalized Monte Carlo dosimetry (PMCD)-based on patient-specific data and Monte Carlo calculations was developed and evaluated retrospectively on clinical data. METHODS The PMCD method was evaluated with data from technetium human albumin macroaggregates ((99m)Tc-MAA) evaluations of 10 patients treated for hepatic metastases. Region-of-interest outlines were drawn on CT images to create patient-specific voxel phantoms using the OEDIPE software. Normalized 3-dimensional matrices of cumulated activity were generated from (99m)Tc-SPECT data. Absorbed doses at the voxel scale were then obtained with the MCNPX Monte Carlo code. The maximum-injectable activity (MIA) for tolerance criteria based on either OAR mean absorbed doses (D(mean)) or OAR dose-volume histograms (DVHs) was determined using OEDIPE. Those MIAs were compared with the one recommended by the partition model (PM) with D(mean) tolerance criteria. Finally, OEDIPE was used to evaluate the absorbed doses delivered if those activities were injected to the patient and to generate the corresponding isodose curves and DVHs. RESULTS The MIA recommended using D(mean) tolerance criteria is, in average, 27% higher with the PMCD method than with the PM. If tolerance criteria based on DVHs are used along with the PMCD, an increase of at least 40% of the MIA is conceivable, compared with the PM. For MIAs calculated with the PMCD, D(mean) delivered to tumoral liver (TL) ranged from 19.5 to 118 Gy for D(mean) tolerance criteria whereas they ranged from 26.6 to 918 Gy with DVH tolerance criteria. Thus, using the PMCD method, which accounts for fixation heterogeneities, higher doses can be delivered to TL. Finally, absorbed doses to the lungs are not the limiting criterion for activity prescription. However, D(mean) to the lungs can reach 15.0 Gy. CONCLUSION Besides its feasibility and applicability in clinical routine, the interest for treatment optimization of a personalized Monte Carlo dosimetry in the context of SIRT was confirmed in this study.
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Affiliation(s)
- Alice Petitguillaume
- Laboratoire d'Evaluation de la Dose Interne (LEDI), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Fontenay-Aux-Roses, France
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14
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Yttrium-90 microsphere-selective internal radiation therapy with chemotherapy (chemo-SIRT) for colorectal cancer liver metastases: an in vivo double-arm-controlled phase II trial. Am J Clin Oncol 2013; 36:455-60. [PMID: 22643569 DOI: 10.1097/coc.0b013e3182546c50] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
OBJECTIVES Selective internal radiation therapy (SIRT) with yttrium-90 (Y) microspheres has emerged as an effective liver-directed therapy with a favorable therapeutic ratio for treatment of colorectal cancer liver metastases. The aim of this study was to investigate the objective responses obtained by Y microsphere treatment when combined with contemporary chemotherapy in the front-line (first or second line) setting in patients with CRCLM. METHODS This study used an in vivo comparison between the right and left liver lobes; systemic chemotherapy was supplied to both liver lobes by virtue of systemic administration, whereas SIRT was administered selectively to the target liver lobe only. Response to treatment was evaluated by serial fludeoxyglucose positron emission tomography computed tomography performed at 4 weeks, 2 to 4 months, and 6 to 8 months. Standard uptake value, anatomic volume, functional tumor volume, and total lesion glycolysis (TLG) calculations were obtained at each time point. RESULTS A decrease in TLG on fludeoxyglucose positron emission tomography computed tomography imaging was seen in 19 of the 20 patients. The mean decrease in TLG values in the tumors receiving chemo-SIRT and chemo-only treatment were 86.26%±18.57% and 31.74%±80.99% (P<0.01), 93.13%±11.81% and 40.80%±73.32% (P=0.01), and 90.55%±19.75% and 54.91%±38.55% (P<0.01) at 4 weeks, 2 to 4 months, 6 to 8 months posttreatment, respectively. Functional and anatomic tumor volume changes were in concordance with the TLG changes. CONCLUSIONS The study demonstrated that, under near identical conditions in terms of patient and tumor characteristics, the chemo-SIRT combination produced superior objective responses compared with chemo-only treatment in a front-line treatment setting in patients with colorectal cancer liver metastases.
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Constantinidou A, Cunningham D, Shurmahi F, Asghar U, Barbachano Y, Khan A, Mudan S, Rao S, Chau I. Perioperative chemotherapy with or without bevacizumab in patients with metastatic colorectal cancer undergoing liver resection. Clin Colorectal Cancer 2012; 12:15-22. [PMID: 23021126 DOI: 10.1016/j.clcc.2012.07.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 06/03/2012] [Accepted: 07/09/2012] [Indexed: 12/31/2022]
Abstract
UNLABELLED The impact of adding bevacizumab to perioperative chemotherapy in patients with colorectal cancer (CRC) undergoing liver resection is yet to be defined. A retrospective review of our patient records showed that the addition of bevacizumab did not increase morbidity or mortality related to liver resection. Pathologic complete response (CR) is associated with prolonged survival. BACKGROUND Patients with colorectal cancer (CRC) and liver metastases benefit from perioperative chemotherapy and liver resection. The potential benefit of adding bevacizumab is yet to be defined. The impact of bevacizumab on liver resection complications has been explored in a small number of retrospective studies. METHODS The records of patients with CRC and liver metastases who underwent liver resection and had received perioperative chemotherapy were reviewed. Complications were reported separately for 2 groups (chemotherapy alone vs chemotherapy and bevacizumab). Survival outcomes (progression-free survival [PFS] and overall survival [OS]) for responders and nonresponders were estimated using the Kaplan-Meier method. RESULTS Fifty-two patients received chemotherapy alone and 42 patients received chemotherapy and bevacizumab. The median time from the end of systemic treatment to liver resection was 59 days (33-181 days) for the chemotherapy group and 62 days (44-127 days) for the chemotherapy and bevacizumab group. Postoperative complications developed in 54% of the chemotherapy group and in 48% of the chemotherapy and bevacizumab group. Severe complications (grade III-V) occurred in only 13% and 12%, respectively (P = .822). Pathologic complete response (CR) was seen in 11/94 patients. Poor performance status (PS) before starting chemotherapy was associated with higher rates of complications (P = .002), and severe complications led to prolonged hospital admission (P = .001). Patients with pathologic CR had longer OS (P = .0275), but there was no difference in OS between responders and nonresponders (P = .778). CONCLUSION The addition of bevacizumab to chemotherapy does not increase liver resection complication rates. Pathologic CR is associated with prolonged survival.
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Adam R, De Gramont A, Figueras J, Guthrie A, Kokudo N, Kunstlinger F, Loyer E, Poston G, Rougier P, Rubbia-Brandt L, Sobrero A, Tabernero J, Teh C, Van Cutsem E. The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus. Oncologist 2012; 17:1225-39. [PMID: 22962059 DOI: 10.1634/theoncologist.2012-0121] [Citation(s) in RCA: 400] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
An international panel of multidisciplinary experts convened to develop recommendations for the management of patients with liver metastases from colorectal cancer (CRC). The aim was to address the main issues facing the CRC hepatobiliary multidisciplinary team (MDT) when managing such patients and to standardize the treatment patients receive in different centers. Based on current evidence, the group agreed on a number of issues including the following: (a) the primary aim of treatment is achieving a long disease-free survival (DFS) interval following resection; (b) assessment of resectability should be performed with high-quality cross-sectional imaging, staging the liver with magnetic resonance imaging and/or abdominal computed tomography (CT), depending on local expertise, staging extrahepatic disease with thoracic and pelvic CT, and, in selected cases, fluorodeoxyglucose positron emission tomography with ultrasound (preferably contrast-enhanced ultrasound) for intraoperative staging; (c) optimal first-line chemotherapy-doublet or triplet chemotherapy regimens combined with targeted therapy-is advisable in potentially resectable patients; (d) in this situation, at least four courses of first-line chemotherapy should be given, with assessment of tumor response every 2 months; (e) response assessed by the Response Evaluation Criteria in Solid Tumors (conventional chemotherapy) or nonsize-based morphological changes (antiangiogenic agents) is clearly correlated with outcome; no imaging technique is currently able to accurately diagnose complete pathological response but high-quality imaging is crucial for patient management; (f) the duration of chemotherapy should be as short as possible and resection achieved as soon as technically possible in the absence of tumor progression; (g) the number of metastases or patient age should not be an absolute contraindication to surgery combined with chemotherapy; (h) for synchronous metastases, it is not advisable to undertake major hepatic surgery during surgery for removal of the primary CRC; the reverse surgical approach (liver first) produces as good an outcome as the conventional approach in selected cases; (i) for patients with resectable liver metastases from CRC, perioperative chemotherapy may be associated with a modestly better DFS outcome; and (j) whether initially resectable or unresectable, cure or at least a long survival duration is possible after complete resection of the metastases, and MDT treatment is essential for improving clinical and survival outcomes. The group proposed a new system to classify initial unresectability based on technical and oncological contraindications.
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Affiliation(s)
- René Adam
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, UMR-S 776, Villejuf, France.
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Xu J, Qin X, Wang J, Zhang S, Zhong Y, Ren L, Wei Y, Zeng S, Wan D, Zheng S. Chinese guidelines for the diagnosis and comprehensive treatment of hepatic metastasis of colorectal cancer. J Cancer Res Clin Oncol 2011; 137:1379-96. [PMID: 21796415 DOI: 10.1007/s00432-011-0999-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2011] [Accepted: 06/16/2011] [Indexed: 12/14/2022]
Affiliation(s)
- Jianmin Xu
- Zhongshan Hospital, Fudan University, Shanghai, China
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Cui Y, Li H, Wu Q, Zhang T, Kong D, Song T, Ru T, Chen P, Li Q. Treatment of colorectal cancer with unresectable synchronous liver-only metastases with combined therapeutic modalities. J Gastrointest Surg 2011; 15:285-93. [PMID: 20922574 DOI: 10.1007/s11605-010-1357-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2010] [Accepted: 09/17/2010] [Indexed: 01/31/2023]
Abstract
BACKGROUND Resection + radiofrequency ablation (RFA) + hepatic artery infusion (HAI) + systemic chemotherapy for patients with unresectable synchronous liver-only metastases from colorectal cancer was rarely used previously. METHODS We compared the outcomes of 42 patients underwent resection + RFA + HAI + systemic chemotherapy (RRHS) with that of 43 patients underwent resection + RFA + systemic chemotherapy (RRS). RESULTS The overall survival, the survival free of hepatic recurrence and the median survival in the RRHS group were all significantly higher than those in RRS group at 4 years. While the rates of adverse effects were similar in the two groups. CONCLUSION For patients with unresectable synchronous liver-only metastases from colorectal cancer, RRHS not only decreases but also postpones hepatic recurrence and therefore improves overall survival at 4 years, as compared with RRS.
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Affiliation(s)
- Yunlong Cui
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin, China
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Abstract
BACKGROUND Despite major advances in therapies for liver metastases, colorectal cancer remains one of the commonest causes of cancer-related deaths in the UK. SOURCES OF DATA The international literature on the management of colorectal liver metastases (CLM) was reviewed. AREAS OF AGREEMENT Due to a combination of highly active systemic agents and low perioperative mortality achieved by high-volume centres, a growing number of patients are being offered liver resection with curative intent. Patients with bilobar and/or extrahepatic disease who would previously have received palliative treatment only, are undergoing major surgery with good results. This review focuses on preoperative evaluation, surgical planning and the role of adjuvant therapies in the management of patients with CLM. AREAS OF CONTROVERSY Can ablative therapies match the outcomes of surgical resection? How can even more patients be rendered resectable? GROWING POINTS The use of other therapies, such as radiofrequency ablation and selective internal radiation therapy. AREAS TIMELY FOR DEVELOPING RESEARCH New chemotherapy regimens for neo-adjuvant therapy and the development of new modalities of liver tumour ablation.
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Omed A, Lawrance JAL, Murphy G, Laasch HU, Wilson G, Illidge T, Tipping J, Zivanovic M, Jeans S. A retrospective analysis of selective internal radiation therapy (SIRT) with yttrium-90 microspheres in patients with unresectable hepatic malignancies. Clin Radiol 2010; 65:720-8. [PMID: 20696299 DOI: 10.1016/j.crad.2010.05.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2009] [Revised: 03/14/2010] [Accepted: 05/07/2010] [Indexed: 01/25/2023]
Abstract
AIM To evaluate the efficacy and safety of selective internal radiation therapy (SIRT). MATERIALS AND METHODS A retrospective analysis was undertaken of all patients who underwent SIRT at a single institution. Diagnostic and therapeutic angiograms, computed tomography (CT) images, positron-emission tomography (PET) images, and planar isotope images were analysed. The response to SIRT was analysed using radiological data and tumour markers. Overall survival, complications, and side effects of SIRT were also analysed. RESULTS The initial 12 patients were included on an intention-to-treat basis, between 21/09/2005 and 07/05/2008. All patients had advanced disease and multiple prior courses of chemotherapy. One patient did not receive yttrium-90 due to complex vascular anatomy; the remaining 11 patients underwent 13 SIRT treatment episodes following work-up angiography. A response was seen using PET in 80% of patients. Using CT, the response of the tumour to therapy in the treated hepatic segments demonstrated a 20% partial response, stable disease in 50%, and progressive disease in 30%. Estimated median survival was 229 days, with 64% of patients still alive at the time of writing. No major complications were observed, although 82% of patients experienced side-effects following SIRT, mainly nausea, vomiting, and abdominal pain. CONCLUSIONS There have been no complications in the 12 SIRT patients. Tumour response was seen in four out of five patients who underwent PET. Objective CT response rates were mixed and are perhaps partially explained by advanced disease and limitations of using measurements to assess response. This complex and potentially hazardous service has been successfully and safely established.
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Affiliation(s)
- A Omed
- Manchester Medical School, University of Manchester, Stopford Building, Manchester, UK.
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Bult W, Seevinck PR, Krijger GC, Visser T, Kroon-Batenburg LMJ, Bakker CJG, Hennink WE, van het Schip AD, Nijsen JFW. Microspheres with ultrahigh holmium content for radioablation of malignancies. Pharm Res 2009; 26:1371-8. [PMID: 19240985 DOI: 10.1007/s11095-009-9848-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2008] [Accepted: 02/05/2009] [Indexed: 01/04/2023]
Abstract
PURPOSE The aim of this study was to develop microspheres with an ultra high holmium content which can be neutron activated for radioablation of malignancies. These microspheres are proposed to be delivered selectively through either intratumoral injections into solid tumors or administered via an intravascularly placed catheter. METHODS Microspheres were prepared by solvent evaporation, using holmium acetylacetonate (HoAcAc) crystals as the sole ingredient. Microspheres were characterized using light and scanning electron microscopy, coulter counter, titrimetry, infrared and Raman spectroscopy, differential scanning calorimetry, X-ray powder diffraction, magnetic resonance imaging (MRI), and X-ray computed tomography (CT). RESULTS Microspheres, thus prepared displayed a smooth surface. The holmium content of the HoAcAc microspheres (44% (w/w)) was higher than the holmium content of the starting material, HoAcAc crystals (33% (w/w)). This was attributed to the loss of acetylacetonate from the HoAcAc complex, during rearrangement of acetylacetonate around the holmium ion. The increase of the holmium content allows for the detection of (sub)microgram amounts of microspheres using MRI and CT. CONCLUSIONS HoAcAc microspheres with an ultra-high holmium content were prepared. These microspheres are suitable for radioablation of tumors by intratumoral injections or treatment of liver tumors through transcatheter administration.
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Affiliation(s)
- W Bult
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
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Sawai H, Yasuda A, Ochi N, Ma J, Matsuo Y, Wakasugi T, Takahashi H, Funahashi H, Sato M, Takeyama H. Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival. BMC Gastroenterol 2008; 8:56. [PMID: 19036165 PMCID: PMC2611992 DOI: 10.1186/1471-230x-8-56] [Citation(s) in RCA: 100] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2008] [Accepted: 11/26/2008] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. To evaluate the correlation between PTEN expression and clinicopathological characteristics of colorectal cancer patients with and without liver metastases, we investigated PTEN expression in primary colorectal cancer and colorectal cancer liver metastases. METHODS Sixty-nine pairs of primary colorectal cancer and corresponding liver metastasis specimens were analyzed immunohistochemically, and the correlation between immunohistochemical findings and clinicopathological factors was investigated. Seventy primary colorectal cancer specimens from patients without liver metastases were used as controls. RESULTS PTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases. In contrast, PTEN was weakly expressed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and was absent in liver metastases. Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05). PTEN expression was significantly stronger in primary colorectal cancer specimens from patients without liver metastases. Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012). CONCLUSION Our results suggest that loss of PTEN expression is involved with colorectal cancer aggressive capacity and that diagnostic evaluation of PTEN expression may provide valuable prognostic information to aid treatment strategies for colorectal cancer patients.
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Affiliation(s)
- Hirozumi Sawai
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 4678601, Japan.
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Abstract
Colorectal cancer (CRC) is a highly prevalent malignant disease in industrialized nations. The annual incidence of invasive CRC in the U.S. is among the highest in the world, and the liver is the only metastatic site in approximately one third of patients. Without treatment, patients with metastatic disease have a poor prognosis; however, long-term survival benefits and even cure have been reported in patients undergoing surgical resection of metastases. In addition, advances in chemotherapy, imaging, and surgical techniques have increased the proportion of patients who are eligible for resection. Combination therapy with fluorouracil and leucovorin has been the mainstay of treatment for metastatic CRC; however, the introduction of newer agents, such as oxaliplatin and irinotecan, and targeted agents, such as cetuximab and bevacizumab, has yielded improvements in response rates (RRs) and survival. Maximizing the exposure of hepatic metastases to high target concentrations of cytotoxic drugs using hepatic arterial infusion (HAI) increases RRs further than with systemic chemotherapy; however, the impact of HAI on survival is unclear. As the goals of chemotherapeutic treatment for metastatic CRC increasingly shift from palliation to prolongation of survival, improvement in RRs, and downsizing of tumors in order to enable or optimize resection, treatment in a multidisciplinary environment involving a medical oncologist, radiologist, and surgical oncologist with hepatobiliary expertise will become central to deciding the best course of therapy and timing of surgery.
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Denecke T, Rühl R, Hildebrandt B, Stelter L, Grieser C, Stiepani H, Werk M, Podrabsky P, Plotkin M, Amthauer H, Ricke J, Lopez Hänninen E. Planning transarterial radioembolization of colorectal liver metastases with Yttrium 90 microspheres: evaluation of a sequential diagnostic approach using radiologic and nuclear medicine imaging techniques. Eur Radiol 2008; 18:892-902. [PMID: 18175122 DOI: 10.1007/s00330-007-0836-2] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2007] [Revised: 10/22/2007] [Accepted: 11/26/2007] [Indexed: 12/20/2022]
Abstract
The purpose of the study was to establish a diagnostic approach to the preparation of patients with colorectal liver metastases considered for transarterial radioembolization (RE). Twenty-two patients sequentially underwent computed tomography (CT; thorax/abdomen), magnetic resonance imaging (MRI; liver; hepatocyte-specific contrast), positron emission tomography (PET/PET-CT; F18-fluoro-desoxy-glucose), and angiography with perfusion scintigraphy [planar imaging; tomography with integrated CT (SPECT-CT)]. The algorithm was continued when no contraindication or alternative treatment option was found. The impact of each test on the therapy decision and RE management was recorded. Patient evaluation using CT revealed contraindications for RE in 4/22 patients (18%). Of the remaining 18 patients, 2 were excluded and 3 were assigned to locally ablative treatment based on MRI and PET results (28%). The remaining 13 patients entered the planning algorithm: SPECT-CT revealed gastrointestinal tracer accumulations in 4 (31%) patients [SPECT, 2 (15%)], making a modified application necessary. In five patients (38%), planar scintigraphy revealed relevant hepatopulmonary shunting. Therapy was finally administered to all 13 patients without therapy-related pulmonary or gastrointestinal morbidity. Each part of the diagnostic algorithm showed a relevant impact on patient management. The sequential approach appears to be suitable and keeps the number of unnecessary treatments and therapy risks to a minimum.
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Affiliation(s)
- Timm Denecke
- Klinik für Strahlenheilkunde, Bereiche Radiologie und Nuklearmedizin, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
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Weitz J, Weigand MA, Kienle P, Jäger D, Büchler MW, Martin E. Stellenwert der Anästhesie in multimodalen onkologischen Therapiekonzepten. Anaesthesist 2006; 55:1299-306. [PMID: 16998657 DOI: 10.1007/s00101-006-1091-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Patients with malignant diseases are increasingly being treated with multimodal therapeutical concepts based on the three major modalities surgery, radiotherapy and chemotherapy. The perioperative period is crucial within this multimodal concept as the prognosis of patients may be directly influenced by perioperative measures. In addition, it is of major importance to avoid complications in the perioperative phase, as these might worsen the prognosis of the patient and in order to prevent a delay in the beginning of planned adjuvant therapies. These aspects demonstrate the important role of anesthesia in the treatment of patients with cancer. Further studies defining the relevance of anesthesiologic measures in oncologic patients are needed.
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Affiliation(s)
- J Weitz
- Abteilung für Allgemein-, Visceral- und Unfallchirurgie, Chirurgische Universitätsklinik, Im Neuenheimer Feld 110, 69120 Heidelberg.
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