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Montalti R, Pepe F, Cassese G, Russo G, Malapelle U, Carlomagno C, Giglio MC, Falco G, Alagia M, De Simone G, Geboes K, Troncone G, Troisi RI, Rompianesi G. Prognostic role of postoperative persistence of ctDNA molecular signature after liver resection for colorectal liver metastases: Preliminary results from a prospective study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109706. [PMID: 40009912 DOI: 10.1016/j.ejso.2025.109706] [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: 06/06/2024] [Revised: 02/06/2025] [Accepted: 02/14/2025] [Indexed: 02/28/2025]
Abstract
INTRODUCTION Liver resection represents the cornerstone treatment for Colo-Rectal Liver Metastases (CRLM), but it is still followed by a high recurrence rate. The identification of a valid and reproducible predictor of recurrence can play a key role in correct and timely management of the disease. In this scenario, liquid biopsy may represent an integrative, less invasive, and easily manageable tool to clinically stratify colorectal cancer patients.We aimed to investigate the prognostic role of persistent circulating tumor DNA (ctDNA) signature on CRLM recurrence after liver resection. METHODS A series of 51 consecutive patients undergoing liver resection for CRLM were prospectively enrolled between January 2020 and March 2023. Patients underwent liquid biopsy from peripheral blood samples before and after surgery. Other risk factors for disease recurrence were also investigated. RESULTS Twenty-nine patients were found to be positive for one of the clinically relevant molecular alterations detected by NGS, at preoperative (T0) ctDNA analysis. At univariate analysis, total tumor size bigger than 60 mm (p = 0.046, HR 2.486) and postoperative persistence of ctDNA molecular signature (p = 0.024, HR 2.831) were significantly associated with recurrence. Multivariable Cox Regression analysis showed that only postoperative persistence of ctDNA molecular signature was associated with recurrence (p = 0.027, HR 2.766). Similarly, 1-3 yr DFS was significantly lower in the subgroup with persistence of molecular signature at liquid biopsy (100-49.5 % vs 57.1-21.4 %, p = 0.018). CONCLUSION Postoperative persistence of ctDNA molecular signature could represent a useful tool to predict recurrence after liver resection for CRLM patients.
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Affiliation(s)
- Roberto Montalti
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy; Department of Public Health, Federico II University, 80131, Naples, Italy.
| | - Francesco Pepe
- Department of Public Health, Federico II University, 80131, Naples, Italy
| | - Gianluca Cassese
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
| | - Gianluca Russo
- Department of Public Health, Federico II University, 80131, Naples, Italy
| | - Umberto Malapelle
- Department of Public Health, Federico II University, 80131, Naples, Italy
| | - Chiara Carlomagno
- Department of Clinical Medicine and Surgery, Division of Oncology, University Federico II, Naples, Italy
| | - Mariano Cesare Giglio
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
| | - Giacinto Falco
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
| | - Mariantonietta Alagia
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
| | - Giuseppe De Simone
- Department of Anesthesiology, Federico II University Hospital, Naples, Italy
| | - Karen Geboes
- Oncology Centrum, Ghent University Hospital, Belgium
| | - Giancarlo Troncone
- Department of Public Health, Federico II University, 80131, Naples, Italy
| | - Roberto Ivan Troisi
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
| | - Gianluca Rompianesi
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, 80131, Naples, Italy
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Zhang Y, Li J, Guan X, Wang S, Jiang N, Jiao S, Liu Y, Zhang W, Hu H, Wang G, Liu H, Wang X, Bai W, Zhou H, Jin S. Impact of lymph node metastasis on prognosis in colorectal cancer patients with liver metastasis and staging systems Refinement: An international multicenter retrospective cohort study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:110124. [PMID: 40393144 DOI: 10.1016/j.ejso.2025.110124] [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: 01/15/2025] [Revised: 04/10/2025] [Accepted: 05/04/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND The current AJCC staging for colorectal cancer liver metastasis (CRLM) classifies stages IVA, IVB, and IVC based on organ metastasis, disregarding lymph node metastasis (LNM). We evaluated the prognostic impact of LNM in CRLM and proposed incorporating LNM into staging criteria. METHODS Data were extracted from the SEER database (2010-2017) and a Chinese cohort (2009-2018), including 11,266 CRLM patients (9648 SEER; 1618 Chinese cohort). Kaplan-Meier and Cox regression analyses assessed cancer-specific survival (CSS) between LNM and non-LNM groups. Inverse probability treatment weighting (IPTW) was used for primary analysis, with subgroup analyses exploring LNM's prognostic impact. RESULTS In both the SEER and Chinese cohorts, patients with LNM were significantly associated with worse CSS than patients without LNM before and after IPTW/sIPTW (all p < 0.001). Furthermore, LNM in the M1a subgroup still led to poorer prognosis (all log-rank p < 0.001). In contrast, in the M1b subgroup, the prognostic difference between those with and without LNM was not significant (log-rank p = 0.031 and 0.037, respectively, in the SEER and Chinese cohorts) because the PFDR was set at 0.025. Additionally, in both cohorts, the 5-year CSS rates of M1a stage CRLM patients decreased with advancing N staging, regardless of the resectability of liver metastasis (all log-rank P < 0.001). CONCLUSION LNM has significant association with worse survival outcomes in CRLM patients, although this prognostic impact exhibits progressive attenuation with increasing liver metastatic burden. For patients with M1a stage CRLM, we suggest that incorporating N staging into their prognostic evaluation can further refine the AJCC TNM staging system.
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Affiliation(s)
- Yueyang Zhang
- 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
| | - Jiale Li
- Department of Colorectal Surgery, Shanxi Province Cancer Hospital/Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Xu Guan
- 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; Department of Colorectal Surgery, Shanxi Province Cancer Hospital/Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Siyuan Wang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Nan Jiang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Shuai Jiao
- Department of Colorectal Surgery, Shanxi Province Cancer Hospital/Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Yunxiao Liu
- Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Weiyuan Zhang
- Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hanqing Hu
- Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Guiyu Wang
- Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Haiyi Liu
- Department of Colorectal Surgery, Shanxi Province Cancer Hospital/Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 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; Department of Colorectal Surgery, Shanxi Province Cancer Hospital/Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Wenqi Bai
- Department of Colorectal Surgery, Shanxi Province Cancer Hospital/Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
| | - Haitao Zhou
- 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.
| | - Shuo Jin
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Key Laboratory of Digital Intelligence Hepatology, Ministry of Education, School of Clinical Medicine, Tsinghua University, Beijing, China; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China.
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Lindgren M, Ljuslinder I, Jonsson P, Nyström H. Type IV collagen, carcinoembryonic antigen, osteopontin, and hepatocyte growth factor as biomarkers for liver metastatic colorectal cancer. Int J Biol Markers 2025:3936155251329590. [PMID: 40289465 DOI: 10.1177/03936155251329590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
IntroductionDiagnosis and monitoring of metastatic colorectal cancer (mCRC) depend on diagnostic imaging. Circulating carcinoembryonic antigen (CEA) can be analyzed but no optimal, non-invasive biomarker exists. Circulating collagen IV (COL IV) is a promising biomarker in patients with colorectal liver metastases (CLM). This study aimed to evaluate COL IV and other cancer-related and stroma-derived proteins as biomarkers for mCRC.Materials & methodsPlasma COL IV and 10 other proteins were analyzed with ELISA and Luminex multiplex assays.ResultsmCRC patients have elevated levels of circulating COL IV, CEA, interleukin-8 (IL-8), hepatocyte growth factor (HGF), cytokeratin-19 fragments (CYFRA 21-1), osteopontin (OPN), and migration inhibitory factor (MIF) compared to primary CRC (pCRC) patients. COL IV is elevated in mCRC patients compared to healthy individuals. Levels of COL IV, CEA, OPN, CYFRA 21-1, IL-8, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were dependent on the metastatic site. OPN, CEA, and HGF are very good at discriminating between mCRC patients and pCRC controls. COL IV is very good at distinguishing between mCRC patients and healthy controls. The combination of OPN + CEA is superior at detecting mCRC than CEA alone. High HGF and COL IV levels correlate to poor prognosis.ConclusionOPN, CEA, and HGF are potential biomarkers for mCRC. COL IV is a potential biomarker for CLM. The combination of OPN with CEA is superior to CEA alone in detecting mCRC. Levels of circulating proteins depend on metastatic localization, implying that a combination of markers is better than single markers in detecting mCRC disease. High levels of COL IV and HGF have potential prognostic value.
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Affiliation(s)
- Moa Lindgren
- Department of Diagnostics and Intervention/Surgery, Umeå University, SE-901 85, Sweden
| | - Ingrid Ljuslinder
- Department of Diagnostics and Intervention/Oncology, Umeå University, SE-901 87, Sweden
| | - Pär Jonsson
- Department of Chemistry, Umeå University, SE-907 36, Sweden
| | - Hanna Nyström
- Department of Diagnostics and Intervention/Surgery, Umeå University, SE-901 85, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, SE-901 87, Sweden
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Zhang Y, Wu D, Zhang Z, Ma J, Jiao S, Ma X, Li J, Meng Y, Zhao Z, Chen H, Jiang Z, Wang G, Liu H, Xi Y, Zhou H, Wang X, Guan X. Impact of lymph node metastasis on immune microenvironment and prognosis in colorectal cancer liver metastasis: insights from multiomics profiling. Br J Cancer 2025; 132:513-524. [PMID: 39753715 PMCID: PMC11920064 DOI: 10.1038/s41416-024-02921-2] [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: 08/13/2024] [Revised: 11/15/2024] [Accepted: 11/26/2024] [Indexed: 02/19/2025] Open
Abstract
BACKGROUND This study aimed to investigate the prognostic impact of lymph node metastasis (LNM) on patients with colorectal cancer liver metastasis (CRLM) and elucidate the underlying immune mechanisms using multiomics profiling. METHODS We enrolled patients with CRLM from the US Surveillance, Epidemiology, and End Results (SEER) cohort and a multicenter Chinese cohort, integrating bulk RNA sequencing, single-cell RNA sequencing and proteomics data. The cancer-specific survival (CSS) and immune profiles of the tumor-draining lymph nodes (TDLNs), primary tumors and liver metastasis were compared between patients with and without LNM. Pathological evaluations were used to assess immune cell infiltration and histological features. RESULTS The CRLM patients with LNM had significantly shorter CSS than patients without LNM in two large cohorts. Our results showed that nonmetastatic TDLNs exhibited a greater abundance of immune cells, including CD4+ T cells, CD8+ T cells, and CD19+ B cells, whereas metastatic TDLNs were enriched with fibroblasts, endothelial cells, and macrophages. Immunohistochemical analysis confirmed elevated levels of CD3+ T cells, CD8+ T cells, and CD19+ B cells in nonmetastatic TDLNs. The presence of nonmetastatic TDLNs was associated with enhanced antitumor immune responses in primary tumors, characterized by a higher Klintrup-Makinen (KM) grade and the presence of tertiary lymphoid structures. Furthermore, liver metastasis in patients with nonmetastatic TDLNs were predominantly of the desmoplastic growth pattern (dHGP), while those with metastatic TDLNs were predominantly of the replacement growth pattern (rHGP). CONCLUSIONS This research highlights the adverse prognostic impact of LNM on patients with CRLM and reveals potential related mechanisms through multiomics analysis. Our research paves the way for further refinement of the AJCC TNM staging system for CRLM in clinical practice.
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Affiliation(s)
- Yueyang Zhang
- 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
| | - Deng Wu
- College of Biomedical Information and Engineering, Hainan Medical University, Haikou, China
| | - Zhen Zhang
- Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Jian Ma
- 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
| | - Shuai Jiao
- Department of Colorectal Surgery, Shanxi Province Cancer Hospital/Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Xiaolong Ma
- Department of Colorectal Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jiangtao Li
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongsheng Meng
- Department of Tumor Biobank, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/ Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Zhixun Zhao
- 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
| | - Haipeng Chen
- 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
| | - Zheng Jiang
- 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
| | - Guiyu Wang
- Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, China
| | - Haiyi Liu
- Department of Colorectal Surgery, Shanxi Province Cancer Hospital/Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Yanfeng Xi
- Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
| | - Haitao Zhou
- 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.
| | - 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.
- Department of Colorectal Surgery, Shanxi Province Cancer Hospital/Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
| | - Xu Guan
- 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.
- Department of Colorectal Surgery, Shanxi Province Cancer Hospital/Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
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Furukawa K, Tsunematsu M, Haruki K, Onda S, Abe K, Matsumoto M, Taniai T, Yanagaki M, Toyama Y, Ikegami T. Simple definition of biologically borderline resectable colorectal liver metastases based on early surgical failure. Int J Clin Oncol 2025:10.1007/s10147-025-02752-y. [PMID: 40159356 DOI: 10.1007/s10147-025-02752-y] [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: 08/08/2024] [Accepted: 03/14/2025] [Indexed: 04/02/2025]
Abstract
BACKGROUND The benefit of neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastasis (CRLM) is debatable. This study aimed to establish a definition of biologically borderline resectable CRLM based on early surgical failure. METHODS One hundred forty-two patients who underwent upfront surgery for resectable CRLM were examined. Potential predictors of early surgical failure were investigated to establish a definition of biologically borderline resectable CRLM. The impact of NAC on overall survival (OS) in patients with borderline resectable CRLM was examined, as were predictors of OS. RESULTS Extrahepatic lesions (p < 0.01) and tumor ≥ 30 mm with carcinoembryonic antigen (CEA) concentration ≥ 20 ng/mL (p = 0.02) were independent predictors of early surgical failure. Borderline resectable CRLM was defined as extrahepatic lesions or tumor size ≥ 30 mm with CEA concentration ≥ 20 ng/mL. Fifty-eight patients had borderline resectable CRLM. Three-year OS was significantly higher in borderline resectable CRLM patients who received NAC than in those who did not (71.8% vs. 52.7%) and 5-year survival was also significantly higher in this group (62.8% vs. 25.5%). CONCLUSION We have proposed a simple definition of biologically borderline resectable CRLM based on early surgical failure. NAC could be a good indication for patients who met the definition.
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Affiliation(s)
- Kenei Furukawa
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan.
| | - Masashi Tsunematsu
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Koichiro Haruki
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Shinji Onda
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Kyohei Abe
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Michinori Matsumoto
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Tomohiko Taniai
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Mitsuru Yanagaki
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Yoichi Toyama
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Toru Ikegami
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
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6
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Yohanathan L, Chopra A, Simo K, Clancy TE, Khithani A, Anaya DA, Maegawa FA, Sheikh M, Raoof M, Jacobs M, Aleassa E, Boff M, Ferguson B, Tan-Tam C, Winslow E, Qadan M, D’Angelica MI. Assessment and treatment considerations for patients with colorectal liver metastases: AHPBA consensus guideline and update for surgeons. HPB (Oxford) 2025; 27:263-278. [PMID: 39828468 DOI: 10.1016/j.hpb.2024.12.006] [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: 10/15/2024] [Revised: 11/20/2024] [Accepted: 12/09/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND Colorectal cancer most commonly metastasizes to the liver. While various treatment strategies have been developed, surgical management of these patients has vital implications on the prognosis and survival of this group of patients. There remains a need for a consensus guideline regarding the surgical evaluation and management of patients with colorectal liver metastases (CRLM). METHODS This review article is a consensus guideline established by the members of the AHPBA Professional Standards Committee, as an amalgamation of existent literature and a guide to surgeons managing this complex disease. RESULTS These guidelines reports the benefits and shortcomings of various diagnostic modalities including imaging and next-generation sequencing in the management of patients with CRLM. While surgery has established survival benefits in patients with resectable disease, this report notes the importance of treatment sequencing with non-surgical modalities as well as between colon and liver resection. Finally, the guidelines address the various treatment modalities for patients with unresectable disease, that may have significant impact on survival. CONCLUSION CRLM is a complex diagnosis which warrants multidisciplinary approach with early surgical involvement in both assessment and management of the disease, to optimize patient outcomes and survival.
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Wehrle CJ, Sarioglu AG, Akgun E, Berber E. The impact of Kirsten rat sarcoma (KRAS) status on local tumor progression after surgical ablation of colorectal liver metastases. Surgery 2025; 179:108807. [PMID: 39322485 DOI: 10.1016/j.surg.2024.07.070] [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: 03/17/2024] [Revised: 06/17/2024] [Accepted: 07/08/2024] [Indexed: 09/27/2024]
Abstract
BACKGROUND Kirsten rat sarcoma mutation was reported to adversely affect local tumor control after percutaneous ablation of colorectal liver metastasis. Nevertheless, the effect of Kirsten rat sarcoma mutation on surgical ablation has not been investigated in the literature. The aim of this study is to analyze the impact of Kirsten rat sarcoma mutation on local recurrence after surgical ablation of colorectal liver metastasis. METHODS This was an institutional review board-approved study of patients who underwent surgical ablation of colorectal liver metastasis between 2005 and 2023 at a single center and underwent Kirsten rat sarcoma testing with ≥1 year follow-up. Local recurrence was analyzed using univariate Kaplan-Meier and multivariate Cox hazard models. RESULTS A total of 163 patients with 424 lesions fulfilled inclusion criteria. Fifty (30.7%) patients received radiofrequency ablation and 113 (69.3%) patients received microwave ablation. Fifty-seven patients (32.2%) with 177 lesions were found to have a Kirsten rat sarcoma mutation. Patients with Kirsten rat sarcoma mutation had a larger number of tumors, percentage of posteriorly located tumors, and tumor burden score compared with those with wild-type Kirsten rat sarcoma. Nevertheless, there was no difference between the groups regarding local recurrence per lesion (15% vs 17%, respectively, P = not significant). Independent predictors of local recurrence included tumor size, ablation margin, and blood vessel proximity for radiofrequency ablation compared with tumor size and ablation margin for microwave ablation. CONCLUSION There was no effect of Kirsten rat sarcoma mutations on local recurrence after surgical radiofrequency ablation or microwave ablation of colorectal liver metastasis in this study. Tumor size and ablation margin remained as independent predictors.
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Affiliation(s)
- Chase J Wehrle
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland, OH. https://twitter.com/ChaseWehrle
| | - Ali Gunduz Sarioglu
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland, OH
| | - Ege Akgun
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland, OH
| | - Eren Berber
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland, OH.
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8
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Wehrle CJ, Chávez-Villa M, Byrne M, Kusakabe J, Gross A, Mahajan P, Ruffolo L, Whitsett Linganna M, Sobotka A, Naffouje S, Khalil M, Pita A, Fujiki M, Tomiyama K, Schlegel A, Kwon DCH, Line PD, Miller C, Hashimoto K, Hernandez-Alejandro R, Aucejo F. Pretransplant metabolic tumor volume predicts recurrence following liver transplantation for colorectal metastasis: A multicenter study. Liver Transpl 2025; 31:298-310. [PMID: 39526884 DOI: 10.1097/lvt.0000000000000535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 10/14/2024] [Indexed: 11/16/2024]
Abstract
Liver transplant (LT) for colorectal cancer liver metastases (CRLM) is increasingly popular, yet the ideal selection criteria remain unknown. Pretransplant positron emission tomography (PET) metabolic tumor volume (MTV) has been described as predicting recurrence, with a proposed cutoff of MTV ≥70 cm 3 . This approach has not been validated. Patients undergoing LT for CRLM at 2 academic transplant centers (January 1, 2017, to December 1, 2023) were included. PET-MTV was calculated by a staff radiologist from the most recent PET-scan before LT using the published protocol. Twenty-six patients were included. Median follow-up was 609 days (IQR 320-1069) and from PET to LT was 1.9 months (1.3-2.6). Nearly all (n=24, 92.3%) received living donor transplantation. Absolute recurrence rate was 30.8% (n=8). Actuarial unadjusted 1- and 2-year recurrence-free survival (RFS) were 83% (n=15/18) and 62% (n=8/13); 1- and 2-year overall survival were 100% (n=18/18) and 85% (n=11/13). The incidence of recurrence-per-year follow-up was 0.35 when MTV ≥70 cm 3 versus 0.10 if MTV <70 cm 3 ( P <0.001). Median RFS using Kaplan-Meier product-estimate was 0.83 years (95% CI: 0.43-1.23) in MTV≥70 cm 3 versus 4.1 years (95% CI: 2.90-5.22) when MTV<70 cm 3 ( p <0.001); this was also associated with improved overall survival ( p =0.003). MTV>70 cm 3 demonstrated HR=2.42 (95% CI: 2.2-62.2, p =0.006) for association with RFS on univariate Cox-proportional hazards analysis, and an AUC=0.771 (95% CI: 0.560-0.981) for predicting recurrence ( p =0.030). Nineteen patients (69.2%) had histologically viable tumors, which were associated with recurrence (43% vs. 0%, p =0.039) and reduced RFS (log-rank p =0.019). PET-MTV was associated with the presence of histologically viable tumor (AUC=0.763, 95% CI: 0.583-0.944). PET-MTV ≥70 cm 3 was associated with reduced RFS and overall survival after LT for CRLM, confirming findings from the Norway group. This is likely due to its ability to identify residual viable tumors, which are independently associated with recurrence. PET-MTV should be a key selection criterion prior to LT for CRLM.
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Affiliation(s)
- Chase J Wehrle
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Mariana Chávez-Villa
- Department of Surgery, Division of Transplantation, University of Rochester Medical Center, Rochester, New York, USA
| | - Matthew Byrne
- Department of Surgery, Division of Transplantation, University of Rochester Medical Center, Rochester, New York, USA
| | - Jiro Kusakabe
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Abby Gross
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
- Department of Quantitative Health Sciences Affiliation, Cleveland Clinic, Cleveland, Ohio, USA
| | - Paresh Mahajan
- Department of Nuclear Medicine, Cleveland Clinic, Imaging Institute, Cleveland, Ohio, USA
| | - Luis Ruffolo
- Department of Surgery, Division of Transplantation, University of Rochester Medical Center, Rochester, New York, USA
| | - Maureen Whitsett Linganna
- Department of Surgery, Division of Transplantation, University of Rochester Medical Center, Rochester, New York, USA
| | - Annie Sobotka
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Samer Naffouje
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Mazhar Khalil
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Alejandro Pita
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Masato Fujiki
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Koji Tomiyama
- Department of Surgery, Division of Transplantation, University of Rochester Medical Center, Rochester, New York, USA
| | - Andrea Schlegel
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - David C H Kwon
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Pal-Dag Line
- Department of Transplantation, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Charles Miller
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Koji Hashimoto
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Roberto Hernandez-Alejandro
- Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Federico Aucejo
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
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9
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Zeng X, Li X, Lin W, Wang J, Fang C, Pan M, Tao H, Yang J. Efficacy of laparoscopic parenchyma-sparing hepatectomy using augmented reality navigation combined with fluorescence imaging for colorectal liver metastases: a retrospective cohort study using inverse probability treatment weighting analysis. Int J Surg 2025; 111:1749-1759. [PMID: 39715148 DOI: 10.1097/js9.0000000000002193] [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: 05/16/2024] [Accepted: 11/15/2024] [Indexed: 12/25/2024]
Abstract
BACKGROUND Laparoscopic parenchyma-sparing hepatectomy (PSH) is an effective treatment for colorectal liver metastases (CRLMs), but ensuring the safety and radicality of the procedure, particularly for deep-seated tumors, remains challenging. Surgical navigation technologies such as augmented reality navigation (ARN) and indocyanine green fluorescence imaging (ICG-FI) are increasingly utilized to guide surgery, yet their efficacy for CRLMs is unclear. This study aims to evaluate the short-term and long-term outcomes of ARN combined with ICG-FI-guided (ARN-FI) laparoscopic PSH for CRLMs. METHODS Between January 2020 and December 2022, 89 consecutive patients who underwent laparoscopic PSH for CRLMs were included in the study. Patients were divided into an ARN-FI group ( n = 38) and a non-ARN-FI group ( n = 51) based on the use of ARN-FI. Inverse probability treatment weighting (IPTW) was used to balance baseline characteristics and minimize potential selection bias. Short-term and long-term outcomes were compared between the two groups. Cox regression analysis was conducted to identify risk factors associated with recurrence-free survival (RFS) and hepatic RFS. RESULTS After IPTW, there were 87 patients in the ARN-FI group and 89 patients in the non-ARN-FI group. Shorter parenchymal transection time, postoperative hospital stays, and wider margins were observed in the ARN-FI group. There was no significant difference in RFS or hepatic RFS between the groups. Mutant KRAS status was an independent risk factor for both RFS and hepatic RFS, while tumor diameter ≥ 5 cm and deep-seated location were risk factors for hepatic RFS. In the subgroup analysis of deep-seated tumors, the ARN-FI group also showed less intraoperative blood loss, a lower rate of strategy change, shorter postoperative recovery times, a higher R0 resection rate, and improved RFS and hepatic RFS. CONCLUSIONS In laparoscopic PSH for CRLMs, ARN-FI may improve surgical efficiency and accuracy. Especially for deep-seated tumors, it has the potential to reduce blood loss and attain higher R0 resection rates.
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Affiliation(s)
- Xiaojun Zeng
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Xinci Li
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Wenjun Lin
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Junfeng Wang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Chihua Fang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Mingxin Pan
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Haisu Tao
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Jian Yang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
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10
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Connell LC, Kemeny NE. Intraarterial Chemotherapy for Liver Metastases. Hematol Oncol Clin North Am 2025; 39:143-159. [PMID: 39510670 DOI: 10.1016/j.hoc.2024.08.005] [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] [Indexed: 11/15/2024]
Abstract
Colorectal cancer (CRC) is one of the leading cancers globally in terms of both incidence and cancer-related mortality. Liver metastatic disease is the main prognostic driver for patients with CRC. The management options for liver metastatic CRC continue to evolve, particularly with the incorporation of locoregional therapies into the treatment paradigm. Hepatic arterial infusion (HAI) chemotherapy is one such liver directed approach used with the goal of converting patients to liver resection, reducing the risk of recurrence, treating recurrent disease, and most importantly improving overall survival. This article summarizes the role of HAI chemotherapy in the treatment of liver metastatic CRC.
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Affiliation(s)
- Louise C Connell
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, 10th floor, New York, NY 10065, USA
| | - Nancy E Kemeny
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, 10th floor, New York, NY 10065, USA.
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11
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Trehub Y, Malovanna A, Zemskov S. The Current State of Perioperative Chemotherapy in Resectable Colorectal Liver Metastases: A Narrative Review. J Surg Oncol 2025. [PMID: 39866030 DOI: 10.1002/jso.28101] [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: 01/01/2025] [Accepted: 01/06/2025] [Indexed: 01/28/2025]
Abstract
Perioperative chemotherapy has emerged as a critical component in managing resectable colorectal liver metastases (CRLM), aiming to improve long-term survival, although data supporting its use remains controversial. This narrative review explores the current state of perioperative chemotherapy in patients with resectable CRLM, focusing on its role in different oncological risk categories. The review highlights ongoing controversies, such as optimal patient selection and the role of post- versus preoperative treatment in specific scenarios.
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Affiliation(s)
- Yevhenii Trehub
- The Center of Organ and Anatomical Tissues Transplantation, Feofaniya Clinical Hospital, Kyiv, Ukraine
| | - Anna Malovanna
- Department of Surgery and Transplantation, Kyiv City Center of Nephrology and Dialysis, Kyiv, Ukraine
| | - Sergii Zemskov
- Department of General Surgery N1, Bogomolets National Medical University, Kyiv, Ukraine
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12
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Choi S, Kang M, Kim JW, Kim JW, Jeon JH, Oh HK, Lee HW, Cho JY, Kim DW, Cho S, Kim JH, Kim K, Kang SB, Jheon S, Lee KW. Long-term clinical outcomes after the second metastasectomy in patients with resected metastatic colorectal cancer. Curr Probl Cancer 2024; 53:101151. [PMID: 39442487 DOI: 10.1016/j.currproblcancer.2024.101151] [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: 05/21/2024] [Revised: 09/19/2024] [Accepted: 09/20/2024] [Indexed: 10/25/2024]
Abstract
PURPOSE Primary tumor resection and metastasectomy are curative for metastatic colorectal cancer. However, there is still a paucity of data regarding the clinical outcomes and risk factors after disease recurrence and second metastasectomy. MATERIALS AND METHODS We retrospectively evaluated the clinical outcomes of patients who underwent the second metastasectomy. In addition, risk factors for the outcomes were analyzed. RESULTS A total of 94 patients (39 females and 55 males) received a second metastasectomy after the recurrence. Recurrent sites included the lung (47 patients), liver (36 patients), both lung and liver (four patients), and non-lung/non-liver (seven patients). Among them, 89 (94.7 %) patients achieved R0 resection, while three (3.2 %) and two (2.1 %) patients achieved R1 and R2 resections, respectively. The 5-year disease-free survival (DFS) and overall survival (OS) were 42.8±5.3 % and 67.2±4.9 %, respectively. Multivariable analysis for DFS identified that primary rectal cancer (hazard ratio [HR] 0.45, P=0.033) and disease-free interval after the first metastasectomy of ≥12 months (HR 0.39, P=0.002) were good predictive factors; in contrast, non-lung/non-liver metastasis (HR 3.32, P=0.020) was a poor predictive factor. Multivariable analysis for OS showed that age ≥70 years (HR 3.27, P=0.011), non-lung/non-liver metastasis (HR 4.04, P=0.024), and lesion number ≥2 (HR 2.25, P=0.023) were poor prognostic factors. CONCLUSION Patients who underwent a second metastasectomy had a long-term disease-free state and good OS. Our data suggest that a second metastasectomy should be considered if a patient has a limited number of metastases confined to the liver and/or lung and long DFS after the first metastasectomy.
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Affiliation(s)
- Songji Choi
- Department of Genomic Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Minsu Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Ji-Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
| | - Jin Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Jae Hyun Jeon
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Heung-Kwon Oh
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Duck-Woo Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Sukki Cho
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Jee Hyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Kwhanmien Kim
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Sung-Bum Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Sanghoon Jheon
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Keun-Wook Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
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13
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Wehrle CJ, Fujiki M, Schlegel A, Uysal M, Sobotka A, Whitsett Linganna M, Modaresi Esfeh J, Kamath S, Khalil M, Pita A, Kim JK, Kwon DCH, Miller C, Hashimoto K, Aucejo F. Intensive locoregional therapy before liver transplantation for colorectal cancer liver metastasis: A novel pretransplant protocol. Liver Transpl 2024; 30:1238-1249. [PMID: 38833301 DOI: 10.1097/lvt.0000000000000417] [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: 02/17/2024] [Accepted: 05/30/2024] [Indexed: 06/06/2024]
Abstract
We describe a novel pre-liver transplant (LT) approach in colorectal liver metastasis, allowing for improved monitoring of tumor biology and reduction of disease burden before committing a patient to transplantation. Patients undergoing LT for colorectal liver metastasis at Cleveland Clinic were included. The described protocol involves intensive locoregional therapy with systemic chemotherapy, aiming to reach minimal disease burden revealed by positron emission tomography scan and carcinoembryonic Ag. Patients with no detectable disease or irreversible treatment-induced liver injury undergo transplant. Nine patients received liver transplant out of 27 who were evaluated (33.3%). The median follow-up was 700 days. Seven patients (77.8%) received a living donor LT. Five had no detectable disease, and 4 had treatment-induced cirrhosis. Pretransplant management included chemotherapy (n = 9) +/- bevacizumab (n = 6) and/or anti-EGFR (n = 6). The median number of pre-LT cycles of chemotherapy was 16 (range 10-40). Liver-directed therapy included Yttrium-90 (n = 5), ablation (n = 4), resection (n = 4), and hepatic artery infusion pump (n = 3). Three patients recurred after LT. Actuarial 1- and 2-year recurrence-free survival were 75% (n = 6/8) and 60% (n = 3/5). Recurrence occurred in the lungs (n = 1), liver graft (n = 1), and lungs+para-aortic nodes (n = 1). Patients with pre-LT detectable disease had reduced RFS ( p = 0.04). All patients with recurrence had histologically viable tumors in the liver explant. Patients treated in our protocol (n = 16) demonstrated improved survival versus those who were not candidates (n = 11) regardless of transplant status ( p = 0.01). A protocol defined by aggressive pretransplant liver-directed treatment and transplant for patients with the undetectable disease or treatment-induced liver injury may help prevent tumor recurrence.
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Affiliation(s)
- Chase J Wehrle
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Masato Fujiki
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Andrea Schlegel
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Melis Uysal
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Anastasia Sobotka
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Maureen Whitsett Linganna
- Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Jamak Modaresi Esfeh
- Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Suneel Kamath
- Department of Gastrointestinal Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, Ohio, USA
| | - Mazhar Khalil
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Alejandro Pita
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Jae-Keun Kim
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - David C H Kwon
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Charles Miller
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Koji Hashimoto
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Federico Aucejo
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
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14
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Kato T, Imamura M, Kyuno D, Kimura Y, Kukita K, Murakami T, Yoshida E, Mizuguchi T, Takemasa I. Impact of Infrared Indocyanine Green Fluorescence Imaging-guided Laparoscopic Hepatectomy on Securing the Resection Margin for Colorectal Liver Metastasis. Surg Laparosc Endosc Percutan Tech 2024; 34:551-558. [PMID: 39183534 DOI: 10.1097/sle.0000000000001320] [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: 04/30/2024] [Accepted: 08/01/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND Laparoscopic hepatectomy for colorectal liver metastases (CRLM) is performed worldwide. However, owing to a lack of palpatory information and difficulties associated with accurate intraoperative ultrasonographic diagnosis, the tumor may be exposed at the hepatic transection margin. This study aimed to investigate the pathological significance of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG)-guided laparoscopic hepatectomy and determine its usefulness in securing the resection margin for CRLMs. METHODS Fifty-nine patients who underwent laparoscopic hepatectomy for CRLM using NIR fluorescence imaging between February 2017 and June 2021 at Sapporo Medical University Hospital were included. Generally, all patients received intravenous ICG (2.5 mg/body) as a fluorescence agent 1 to 2 days before surgery. During the surgical procedure, real-time NIR fluorescence imaging was repeatedly performed to assess the surgical margins. RESULTS Of the 94 tumors in 59 patients, laparoscopic NIR fluorescence imaging identified 56 tumors (59.6%) on the liver surface. Pathological analysis indicated clear margins in 96.6% (57/59) of patients. Examination of paraffin-embedded sections, which were successful in only 20 of 94 cases (21.3%), revealed that there were no tumor cells positive for NIR fluorescence, and the median distance of the continuous fluorescent signal from the tumor margin was 1.074 mm. CONCLUSIONS We demonstrated a high R0 rate using NIR fluorescence-guided hepatectomy. This technique has the potential to improve intraoperative tumor identification and tumor margin assurance and reduce the rate of positive resection margins in patients with CRLMs.
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Affiliation(s)
- Toru Kato
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Hokkaido, Japan
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15
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Morawska I, Pasicz K, Cieszanowski A. Biomarkers of systemic treatment response: MR images of intratumoral fat deposition in colorectal liver metastases (CRLM) after chemotherapy. Int J Colorectal Dis 2024; 39:185. [PMID: 39562379 DOI: 10.1007/s00384-024-04762-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/11/2024] [Indexed: 11/21/2024]
Abstract
PURPOSE Colorectal cancer cells containing mobile lipids are said to be an early indicator of chemotherapy effects. The objective of the study was to examine the frequency and clinical relevance of intratumoral fat deposition in colorectal liver metastases (CRLM) post-chemotherapy using dual-echo chemical shift gradient-echo magnetic resonance imaging (MRI). METHODS A retrospective analysis of 98 patients with CRLM diagnosed between 2017 and 2022 (69 M, mean age 62.87 ± 10.73 years old) who had an MRI after chemotherapy was performed. On dual-echo chemical shift gradient-echo MRI, intratumoral fat deposition of CRLM was evaluated. A signal intensity drop of ≥ 12% in opposed-phase images vs. in-phase images indicated intratumoral fat. After chemotherapy, the presence of fat deposition was correlated with patients' overall survival. RESULTS Before and after chemotherapy, 0 (0%) and 29 (29.59%) patients exhibited intratumoral fat. The number of CRLM ranged from 1 to 25 with a median of 3 and a mean size of 32.58 ± 22.95 mm. The groups had statistically different survival times. Overall survival was shorter for patients with intratumoral fat deposition in CRLM (32 months (24-60, 95% CI)) than for patients without fat deposition in CRLM (48 months (36-NA, 95% CI)). CONCLUSION In our group, nearly 30% of CRLM patients exhibited intratumoral fat after chemotherapy. Patients with intratumoral fat deposition in CRLM have a shorter overall survival time. The presence of fat in CRLM correlates with a poor long-term prognosis.
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Affiliation(s)
- Irmina Morawska
- Department of Radiology I, The Maria Sklodowska-Curie National Research Institute of Oncology, 5 Wilhelm Conrad Roentgen St, 02-781, Warsaw, Poland.
| | - Katarzyna Pasicz
- Department of Medical Physics, The Maria Sklodowska-Curie National Research Institute of Oncology, 5 Wilhelm Conrad Roentgen St, 02-781, Warsaw, Poland
| | - Andrzej Cieszanowski
- Department of Clinical Radiology II, Faculty of Medicine, Medical University of Warsaw, 1A Stefan Banach St, 02-097, Warsaw, Poland
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16
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Liu X, Li D, Zhang Y, Liu H, Chen P, Zhao Y, Sun G, Zhao W, Dong G. Multi-Algorithm-Integrated Tertiary Lymphoid Structure Gene Signature for Immune Landscape Characterization and Prognosis in Colorectal Cancer Patients. Biomedicines 2024; 12:2644. [PMID: 39595209 PMCID: PMC11592260 DOI: 10.3390/biomedicines12112644] [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: 09/27/2024] [Revised: 11/12/2024] [Accepted: 11/15/2024] [Indexed: 11/28/2024] Open
Abstract
PURPOSE Colorectal cancer (CRC) is a common malignancy with a low survival rate as well as a low response rate to immunotherapy. This study aims to develop a risk model based on tertiary lymphoid structure (TLS)-associated gene signatures to enhance predictions of prognosis and immunotherapy response. METHODS TLS-associated gene data were obtained from TCGA-CRC and GEO cohorts. A comprehensive analysis using univariate Cox regression identified TLS-associated genes with significant prognostic implications. Subsequently, multiple algorithms were employed to select the most influential genes, and a stepwise Cox regression model was constructed. The model's predictive performance was validated using independent datasets (GSE39582, GSE17536, and GSE38832). To further investigate the immune microenvironment, immune cell infiltration in high-risk (HRG) and low-risk (LRG) groups was assessed using the CIBERSORT and ssGSEA algorithms. Additionally, we evaluated the model's potential to predict immune checkpoint blockade therapy response using data from The Cancer Imaging Archive, the TIDE algorithm, and external immunotherapy cohorts (GSE35640, GSE78200, and PRJEB23709). Immunohistochemistry (IHC) was employed to characterize TLS presence and CCL2 gene expression. RESULTS A three-gene (CCL2, PDCD1, and ICOS) TLS-associated model was identified as strongly associated with prognosis and demonstrated predictive power for CRC patient outcomes and immunotherapy efficacy. Notably, patients in the low-risk group (LRG) had a higher overall survival rate as well as a higher re-response rate to immunotherapy compared to the high-risk group (HRG). Finally, IHC results confirmed significantly elevated CCL2 expression in the TLS regions. CONCLUSIONS The multi-algorithm-integrated model demonstrated robust performance in predicting patient prognosis and immunotherapy response, offering a novel perspective for assessing immunotherapy efficacy. CCL2 may function as a TLS modulator and holds potential as a therapeutic target in CRC.
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Affiliation(s)
- Xianqiang Liu
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Dingchang Li
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Yue Zhang
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
| | - Hao Liu
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Peng Chen
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Yingjie Zhao
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Guanchao Sun
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
| | - Wen Zhao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Guanglong Dong
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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17
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Chlorogiannis DD, Charalampopoulos G, Kontopyrgou D, Gkayfillia A, Nikolakea M, Iezzi R, Filippiadis D. Emerging Indications for Interventional Oncology: A Comprehensive Systematic Review of Image-Guided Thermal Ablation for Metastatic Non-cervical Lymph Node Disease. Curr Oncol Rep 2024; 26:1543-1552. [PMID: 39466479 DOI: 10.1007/s11912-024-01616-4] [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] [Accepted: 10/14/2024] [Indexed: 10/30/2024]
Abstract
INTRODUCTION Lymphatic node metastatic disease encompasses a distinct oncological entity which has been associated with poor prognosis. Image-guided thermal ablation has recently been proposed as a safe and alternative treatment for these lesions. The aim of this systematic review is to evaluate the pooled safety and efficacy of thermal ablation techniques for the treatment of oligometastatic non-cervical lymph nodal disease. RECENT FINDINGS A systematic search of the three major databases (MEDLINE, EMBASE, and CENTRAL) from inception to 30 December 2023 was conducted according to the PRISMA Guidelines. Observational studies reporting technical success, complications and oncologic outcomes were included. Meta- analysis was performed by estimating the pooled incidence rates and risk ratios by fitting random-effect models. Overall, 8 studies were included, comprising of 225 patients and 305 ablated LNMs and a median follow-up of 12 months. The combined data analysis showed that technical success after thermal ablation was 98% (CI: 95%-99%), major complication rate was 1% (CI: 95%-99%), pooled overall response rate was 72% (CI: 54%-87%), local tumor progression rate was 18% (CI: 8%-33%) and disease-free survival rate was 68% (CI: 51%-81%). No difference between radiofrequency ablation and cryoablation was found for every outcome during subgroup analysis. Image-guided percutaneous thermal ablation (with either radiofrequency ablation or cryoablation) is safe and effective for the treatment of oligometastatic LMN disease, however further studies to confirm these findings are still needed.
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Affiliation(s)
- David-Dimitris Chlorogiannis
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 St Francis Str, Boston, MA, 02215, USA
| | - Georgios Charalampopoulos
- 2nd Department of Radiology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, Rimini 1124 62, Athens, Greece
| | - Dimitra Kontopyrgou
- Department If Hygiene, Social-Preventive Medicine and Statistics, Medical School, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece
| | | | - Melina Nikolakea
- Department of Internal Medicine, Hippokrateion General Hospital, 115 27, Athens, Greece
| | - Roberto Iezzi
- Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Lazio, Italy
- Facoltà Di Medicina E Chirurgia, Università Cattolica del Sacro Cuore, Roma, Lazio, Italy
| | - Dimitrios Filippiadis
- 2nd Department of Radiology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, Rimini 1124 62, Athens, Greece.
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18
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Shimizu T, Aoki T, Ishizuka M, Sakamoto K, Beppu T, Honda G, Kotake K, Yamamoto M, Takahashi K, Endo I, Hasegawa K, Itabashi M, Hashiguchi Y, Kotera Y, Kobayashi S, Yamaguchi T, Natsume S, Tabuchi K, Kobayashi H, Yamaguchi K, Tani K, Morita S, Miyazaki M, Sugihara K, Ajioka Y. Evaluation of two-stage hepatectomy using portal vein embolization for colorectal liver metastasis: a retrospective nationwide cohort survey in Japan. Int J Surg 2024; 110:6691-6701. [PMID: 38869986 PMCID: PMC11486952 DOI: 10.1097/js9.0000000000001811] [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: 01/24/2024] [Accepted: 05/28/2024] [Indexed: 06/15/2024]
Abstract
INTRODUCTION Two-stage hepatectomy (TSH) enables patients to undergo surgery for colorectal liver metastasis (CRLM), which one-stage hepatectomy cannot remove. Although the outcome of TSH has been reported, there is no original report from Japan. The aim of this retrospective study was to evaluate the outcome of TSH in Japanese patients with CRLM. METHODS The authors conducted a retrospective cohort study using the nationwide database that included clinical information of 12 519 patients treated with CRLM between 2005 and 2017 in Japan. The primary outcome measure was overall survival. The second outcome measure was progression-free survival. Fisher's exact test, χ 2 test and Mann-Whitney U test were conducted to examine an intergroup difference. Univariate and multivariate analyses were performed using Cox regression model. Survival analysis was performed by Kaplan-Meier method and log-rank test. RESULTS Of the database, 53 patients undergoing TSH using portal vein embolization (PVE) were identified and analyzed. Their morbidity and in-hospital mortality rates at the second hepatectomy were 26.4% and 0.0%. The mean observation period was 21.8 months. The estimated 1-, 3- and 5-year overall survival rate were 92.5%, 70.8% and 34.7%. Multivariate analyses showed that more than 10 liver nodules significantly increased the mortality risk by 4.2-fold (95% CI 1.224-14.99, P = 0.023). Survival analysis revealed that repeat hepatectomy for disease progression after TSH was superior to chemotherapy in overall survival (mean: 49.6 vs. 18.7, months, P = 0.004). CONCLUSION In the Japanese cohort, TSH was confirmed to be a safety procedure with an acceptable survival outcome. More than 10 liver nodules may be a predictor for unfavorable outcomes of patients with CRLM undergoing TSH. Furthermore, repeat hepatectomy can be a salvage treatment for resectable intrahepatic recurrence after TSH.
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Affiliation(s)
- Takayuki Shimizu
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi
| | - Taku Aoki
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi
| | - Mitsuru Ishizuka
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi
| | - Katsunori Sakamoto
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Ehime
| | - Toru Beppu
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Yamaga City Medical Center, Kumamoto
| | - Goro Honda
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical, Tochigi
| | - Kenjiro Kotake
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Sano City Hospital, Sano, Tochigi
| | - Masakazu Yamamoto
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Utsunomiya Memorial Hospital, Utsunomiya, Tochigi
| | - Keiichi Takahashi
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Tokyo Metropolitan Health and Hospitals Corporation Ohkubo Hospital, Tokyo
| | - Itaru Endo
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Kanagawa
| | - Kiyoshi Hasegawa
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Hepato-Biliary-Pancreatic Surgery Division, Graduate School of Medicine, The University of Tokyo
| | - Michio Itabashi
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical, Tochigi
| | - Yojiro Hashiguchi
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Teikyo University School of Medicine Tokyo
| | - Yoshihito Kotera
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical, Tochigi
| | - Shin Kobayashi
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Chiba
| | - Tatsuro Yamaguchi
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo
| | - Soichiro Natsume
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo
| | - Ken Tabuchi
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Pediatrics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo
| | - Hirotoshi Kobayashi
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Teikyo University Hospital, Kanagawa
| | - Kensei Yamaguchi
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Gastrointestinal Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo
| | - Kimitaka Tani
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical, Tochigi
| | - Satoshi Morita
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto
| | - Masaru Miyazaki
- International University of Health and Welfare, Narita Hospital, Tokyo
| | | | - Yoichi Ajioka
- Joint Committee for National Survey on Colorectal Liver Metastasis, Tokyo
- Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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19
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Wells AB, Butano VW, Phillips MC, Mckillop IH, Martinie JB, Baker EH, Iannitti DA. Outcomes after Surgical Microwave Ablation for the Treatment of Colorectal Liver Metastasis. J Am Coll Surg 2024; 239:276-285. [PMID: 38651746 DOI: 10.1097/xcs.0000000000001097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2024]
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide. Of these, approximately 25% will have liver metastasis. We performed 394 microwave ablations (MWAs) and analyzed outcomes for survival and ablation failure. STUDY DESIGN We conducted a retrospective review of patients who underwent a surgical MWA at a single-center high-volume institution from October 2006 to September 2022 using a prospectively maintained database. The primary outcome was overall survival. RESULTS A total of 394 operations were performed on 328 patients with 842 tumors undergoing MWA. Median tumor size was 1.5 cm (range 0.4 to 7.0 cm), with the median number of tumors ablated per operation being 1 (range 1 to 11). A laparoscopic approach was used 77.9% of the time. Concomitant procedures were performed 63% of the time, most commonly hepatectomy (22.3%), cholecystectomy (17.5%), and colectomy (6.6%). Clavien-Dindo grade III or IV complication occurred in 12 patients (3.6%), and all of these patients had undergone concomitant procedures. Mortality within 30 days occurred in 4 patients (1.2%). The rate of incomplete ablation was 1.5% per tumor. Local recurrence occurred at a rate of 6.3% per tumor. Black patients were found to have a higher incidence of incomplete ablation and local recurrence. One-year survival probability was 91% (95% CI 87.9 to 94.3), with a mean overall survival of 57.6 months (95% CI 49.9 to 65.4 months). CONCLUSIONS Surgical MWA offers a low-morbidity approach to treatment of colorectal liver metastasis, with low rate of failure. This large series reviews the outcomes of MWA as definitive treatment for colorectal liver metastasis.
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Affiliation(s)
- Alexandra B Wells
- From the Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC
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20
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Han F, Xu Y, Li X, Song Z, Xie J, Yao J. Clinicopathological features and prognosis analysis of proximal colonic mucinous adenocarcinoma. Sci Rep 2024; 14:18682. [PMID: 39134655 PMCID: PMC11319726 DOI: 10.1038/s41598-024-69916-0] [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: 11/14/2023] [Accepted: 08/09/2024] [Indexed: 08/15/2024] Open
Abstract
Mucinous adenocarcinoma (MAC) is a distinct subtype of colorectal cancer. Previous studies have confirmed the poor prognosis of rectal or left-sided colon MAC, while the prognosis and response to chemotherapy in proximal colon MAC remains controversial. The aim of this study was to investigate the clinicopathological characteristics, prognosis, response to chemotherapy, and risk prediction factors of proximal colon MAC. Patients with proximal colon MAC and non-mucinous adenocarcinoma (NMAC) were retrospectively analyzed in this study. The analyzed variables included gender, age, smoking, drinking, chemotherapy, metastasis, pathological stage, and tumor size. Overall survival (OS) was the primary outcome. Kaplan-Meier analysis was used to assess the impact of mucinous subtype and chemotherapy on OS. We conducted univariate and multivariate Cox regression analyses to determine prognosis factors for proximal colon MAC and NMAC. A total of 284 cases of proximal colon MAC and 1384 cases of NMAC were included in the study. Compared to NMAC, proximal colon MAC was diagnosed at a younger age. The proportion of synchronous and metachronous metastasis was also higher, as well as the pathological stage and tumor size. Proximal colon MAC had a worse prognosis than NMAC, especially in stage 3. Moreover, the prognosis of proximal colon NMAC improved after chemotherapy, while MAC showed no improvement in prognosis after chemotherapy. Advanced age, N1 and N2 stage were independent prognostic factors for adverse outcomes in MAC. For proximal colon adenocarcinoma, the independent predictors of adverse outcomes included mucinous subtype, order age, N1 and N2 stages, and pathological stage 4. Proximal colon MAC had a worse prognosis compared to NMAC. Chemotherapy did not improve the prognosis of proximal colon mucinous adenocarcinoma.
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Affiliation(s)
- Fei Han
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road of Erqi District, Zhengzhou, 450052, China
| | - Yue Xu
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Xiangyu Li
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road of Erqi District, Zhengzhou, 450052, China
| | - Zhaoxiang Song
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road of Erqi District, Zhengzhou, 450052, China
| | - Jinlin Xie
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road of Erqi District, Zhengzhou, 450052, China
| | - Jianning Yao
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road of Erqi District, Zhengzhou, 450052, China.
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21
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Michiel Zeeuw J, Wesdorp NJ, Ali M, Bakker AJJJ, Voigt KR, Starmans MPA, Roor J, Kemna R, van Waesberghe JHTM, van den Bergh JE, Nota IMGC, Moos SI, van Dieren S, van Amerongen MJ, Bond MJG, Chapelle T, van Dam RM, Engelbrecht MRW, Gerhards MF, van Gulik TM, Hermans JJ, de Jong KP, Klaase JM, Kok NFM, Leclercq WKG, Liem MSL, van Lienden KP, Quintus Molenaar I, Patijn GA, Rijken AM, Ruers TM, de Wilt JHW, Verpalen IM, Stoker J, Grunhagen DJ, Swijnenburg RJ, Punt CJA, Huiskens J, Verhoef C, Kazemier G. Prognostic value of total tumor volume in patients with colorectal liver metastases: A secondary analysis of the randomized CAIRO5 trial with external cohort validation. Eur J Cancer 2024; 207:114185. [PMID: 38924855 DOI: 10.1016/j.ejca.2024.114185] [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: 04/09/2024] [Revised: 05/30/2024] [Accepted: 06/16/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment. METHODS Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center. RESULTS In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P < 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008). CONCLUSION Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.
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Affiliation(s)
- J Michiel Zeeuw
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, the Netherlands.
| | - Nina J Wesdorp
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, the Netherlands
| | - Mahsoem Ali
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, the Netherlands
| | - Anne-Joëlle J J Bakker
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, the Netherlands
| | - Kelly R Voigt
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Martijn P A Starmans
- Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands; Department of Pathology, Erasmus MC, Rotterdam, the Netherlands
| | - Joran Roor
- Department of Health, SAS Institute B.V., Huizen, the Netherlands
| | - Ruby Kemna
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, the Netherlands
| | - Jan Hein T M van Waesberghe
- Cancer Center Amsterdam, the Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands
| | - Janneke E van den Bergh
- Cancer Center Amsterdam, the Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands
| | - Irene M G C Nota
- Cancer Center Amsterdam, the Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands
| | - Shira I Moos
- Cancer Center Amsterdam, the Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands
| | - Susan van Dieren
- Cancer Center Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
| | | | - Marinde J G Bond
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Thiery Chapelle
- Department of Hepatobiliary, Transplantation, and Endocrine Surgery, Antwerp University Hospital, Antwerp, Belgium
| | - Ronald M van Dam
- Department of Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Marc R W Engelbrecht
- Amsterdam UMC, University of Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands
| | | | - Thomas M van Gulik
- Cancer Center Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
| | - John J Hermans
- Department of Medical Imaging, Radboud University Medical Center, Radboud University Nijmegen, Nijmegen, the Netherlands
| | - Koert P de Jong
- Department of HPB Surgery and Liver Transplantation, University of Groningen, University Medical Center, Groningen, the Netherlands
| | - Joost M Klaase
- Department of HPB Surgery and Liver Transplantation, University of Groningen, University Medical Center, Groningen, the Netherlands
| | - Niels F M Kok
- Department of Surgery, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | | | - Mike S L Liem
- Department of Surgery, Medical Spectrum Twente, Enschede, the Netherlands
| | - Krijn P van Lienden
- Department of Interventional Radiology, St Antonius Hospital, Nieuwegein, the Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St Antonius Hospital, Nieuwegein, the Netherlands
| | - Gijs A Patijn
- Department of Surgery, Isala Hospital, Zwolle, the Netherlands
| | - Arjen M Rijken
- Department of Surgery, Amphia Hospital, Breda, the Netherlands
| | - Theo M Ruers
- Department of Surgery, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Center, Radboud University Nijmegen, Nijmegen, the Netherlands
| | - Inez M Verpalen
- Cancer Center Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands
| | - Jaap Stoker
- Cancer Center Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands
| | - Dirk J Grunhagen
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Rutger-Jan Swijnenburg
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
| | - Cornelis J A Punt
- Cancer Center Amsterdam, the Netherlands; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands
| | - Joost Huiskens
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Geert Kazemier
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, the Netherlands
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22
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Leiphrakpam PD, Newton R, Anaya DA, Are C. Evolution and current trends in the management of colorectal cancer liver metastasis. Minerva Surg 2024; 79:455-469. [PMID: 38953758 DOI: 10.23736/s2724-5691.24.10363-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/04/2024]
Abstract
Metastatic colorectal cancer (mCRC) is a major cause of cancer-related death, with a 5-year relative overall survival of up to 20%. The liver is the most common site of distant metastasis in colorectal cancer (CRC), with about 50% of CRC patients metastasizing to their liver over the course of their disease. Complete liver resection is the primary modality of treatment for resectable colorectal cancer liver metastasis (CRLM), with an overall 5-year survival rate of up to 58%. However, only 15% to 20% of patients with CRLM are deemed suitable for resection at presentation. For unresectable diseases, the median survival of patients remains low even with the best chemotherapy. In recent decades, the management of CRLM has continued to evolve with the expansion of resection criteria, novel targeted systemic therapies, and improved locoregional therapies. However, due to the heterogeneity of the CRC patient population, the optimal evaluation of treatment options for CRLM remains complex. Therefore, effective management requires a multidisciplinary team to help define resectability and devise a personalized treatment approach, from the initial diagnosis to the final treatment.
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Affiliation(s)
- Premila D Leiphrakpam
- Graduate Medical Education, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
- Division of Surgical Oncology, Department of Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Rachael Newton
- Department of Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Daniel A Anaya
- Section of Hepatobiliary Tumors, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Chandrakanth Are
- Graduate Medical Education, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA -
- Division of Surgical Oncology, Department of Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
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23
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Wiedeman C, Lorraine P, Wang G, Do R, Simpson A, Peoples J, De Man B. Simulated deep CT characterization of liver metastases with high-resolution filtered back projection reconstruction. Vis Comput Ind Biomed Art 2024; 7:13. [PMID: 38861067 PMCID: PMC11166620 DOI: 10.1186/s42492-024-00161-y] [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: 12/02/2023] [Accepted: 04/14/2024] [Indexed: 06/12/2024] Open
Abstract
Early diagnosis and accurate prognosis of colorectal cancer is critical for determining optimal treatment plans and maximizing patient outcomes, especially as the disease progresses into liver metastases. Computed tomography (CT) is a frontline tool for this task; however, the preservation of predictive radiomic features is highly dependent on the scanning protocol and reconstruction algorithm. We hypothesized that image reconstruction with a high-frequency kernel could result in a better characterization of liver metastases features via deep neural networks. This kernel produces images that appear noisier but preserve more sinogram information. A simulation pipeline was developed to study the effects of imaging parameters on the ability to characterize the features of liver metastases. This pipeline utilizes a fractal approach to generate a diverse population of shapes representing virtual metastases, and then it superimposes them on a realistic CT liver region to perform a virtual CT scan using CatSim. Datasets of 10,000 liver metastases were generated, scanned, and reconstructed using either standard or high-frequency kernels. These data were used to train and validate deep neural networks to recover crafted metastases characteristics, such as internal heterogeneity, edge sharpness, and edge fractal dimension. In the absence of noise, models scored, on average, 12.2% ( α = 0.012 ) and 7.5% ( α = 0.049 ) lower squared error for characterizing edge sharpness and fractal dimension, respectively, when using high-frequency reconstructions compared to standard. However, the differences in performance were statistically insignificant when a typical level of CT noise was simulated in the clinical scan. Our results suggest that high-frequency reconstruction kernels can better preserve information for downstream artificial intelligence-based radiomic characterization, provided that noise is limited. Future work should investigate the information-preserving kernels in datasets with clinical labels.
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Affiliation(s)
- Christopher Wiedeman
- Department of Electrical and Computer Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA
| | | | - Ge Wang
- Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA
| | - Richard Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Amber Simpson
- Biomedical Computing and Informatics, Queen's University, Kingston, ON, K7L 3N6, Canada
| | - Jacob Peoples
- Biomedical Computing and Informatics, Queen's University, Kingston, ON, K7L 3N6, Canada
| | - Bruno De Man
- GE Research - Healthcare, Niskayuna, NY, 12309, USA.
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24
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Kokkinakis S, Ziogas IA, Llaque Salazar JD, Moris DP, Tsoulfas G. Clinical Prediction Models for Prognosis of Colorectal Liver Metastases: A Comprehensive Review of Regression-Based and Machine Learning Models. Cancers (Basel) 2024; 16:1645. [PMID: 38730597 PMCID: PMC11083016 DOI: 10.3390/cancers16091645] [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: 04/07/2024] [Revised: 04/22/2024] [Accepted: 04/23/2024] [Indexed: 05/13/2024] Open
Abstract
Colorectal liver metastasis (CRLM) is a disease entity that warrants special attention due to its high frequency and potential curability. Identification of "high-risk" patients is increasingly popular for risk stratification and personalization of the management pathway. Traditional regression-based methods have been used to derive prediction models for these patients, and lately, focus has shifted to artificial intelligence-based models, with employment of variable supervised and unsupervised techniques. Multiple endpoints, like overall survival (OS), disease-free survival (DFS) and development or recurrence of postoperative complications have all been used as outcomes in these studies. This review provides an extensive overview of available clinical prediction models focusing on the prognosis of CRLM and highlights the different predictor types incorporated in each model. An overview of the modelling strategies and the outcomes chosen is provided. Specific patient and treatment characteristics included in the models are discussed in detail. Model development and validation methods are presented and critically appraised, and model performance is assessed within a proposed framework.
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Affiliation(s)
- Stamatios Kokkinakis
- Department of General Surgery, School of Medicine, University Hospital of Heraklion, University of Crete, 71500 Heraklion, Greece;
| | - Ioannis A. Ziogas
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (I.A.Z.); (J.D.L.S.)
| | - Jose D. Llaque Salazar
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (I.A.Z.); (J.D.L.S.)
| | - Dimitrios P. Moris
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA;
| | - Georgios Tsoulfas
- Department of Transplantation Surgery, Centre for Research and Innovation in Solid Organ Transplantation, Aristotle University School of Medicine, 54124 Thessaloniki, Greece
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Wang J, Botvinov J, Bhatt AJ, Beyer K, Kreis ME, Adam M, Alseidi A, Margonis GA. Somatic Mutations in Surgically Treated Colorectal Liver Metastases: An Overview. Cells 2024; 13:679. [PMID: 38667294 PMCID: PMC11049420 DOI: 10.3390/cells13080679] [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: 02/17/2024] [Revised: 03/31/2024] [Accepted: 04/08/2024] [Indexed: 04/28/2024] Open
Abstract
Colorectal cancer is the second most common cause of cancer death in the United States, and up to half of patients develop colorectal liver metastases (CRLMs). Notably, somatic genetic mutations, such as mutations in RAS, BRAF, mismatch repair (MMR) genes, TP53, and SMAD4, have been shown to play a prognostic role in patients with CRLM. This review summarizes and appraises the current literature regarding the most relevant somatic mutations in surgically treated CRLM by not only reviewing representative studies, but also providing recommendations for areas of future research. In addition, advancements in genetic testing and an increasing emphasis on precision medicine have led to a more nuanced understanding of these mutations; thus, more granular data for each mutation are reviewed when available. Importantly, such knowledge can pave the way for precision medicine with the ultimate goal of improving patient outcomes.
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Affiliation(s)
- Jane Wang
- Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA; (M.A.); (A.A.)
| | - Julia Botvinov
- Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA;
| | - Aarshvi Jahnvi Bhatt
- University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA;
| | - Katharina Beyer
- Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, 12203 Berlin, Germany; (K.B.); (M.E.K.)
| | - Martin E. Kreis
- Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, 12203 Berlin, Germany; (K.B.); (M.E.K.)
| | - Mohamed Adam
- Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA; (M.A.); (A.A.)
| | - Adnan Alseidi
- Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA; (M.A.); (A.A.)
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26
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Tian Y, Wang Y, Wen N, Wang S, Li B, Liu G. Prognostic factors associated with early recurrence following liver resection for colorectal liver metastases: a systematic review and meta-analysis. BMC Cancer 2024; 24:426. [PMID: 38584263 PMCID: PMC11000331 DOI: 10.1186/s12885-024-12162-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 03/21/2024] [Indexed: 04/09/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the 3rd most common malignancy with the liver being the most common site of metastases. The recurrence rate of colorectal liver metastases (CRLM) after liver resection (LR) is notably high, with an estimated 40% of patients experiencing recurrence within 6 months. In this context, we conducted a meta-analysis to synthesize and evaluate the reliability of evidence pertaining to prognostic factors associated with early recurrence (ER) in CRLM following LR. METHODS Systematic searches were conducted from the inception of databases to July 14, 2023, to identify studies reporting prognostic factors associated with ER. The Quality in Prognostic Factor Studies (QUIPS) tool was employed to assess risk-of-bias for included studies. Meta-analysis was then performed on these prognostic factors, summarized by forest plots. The grading of evidence was based on sample size, heterogeneity, and Egger's P value. RESULTS The study included 24 investigations, comprising 12705 individuals, during an accrual period that extended from 2007 to 2023. In the evaluation of risk-of-bias, 22 studies were rated as low/moderate risk, while two studies were excluded because of high risk. Most of the studies used a postoperative interval of 6 months to define ER, with 30.2% (95% confidence interval [CI], 24.1-36.4%) of the patients experiencing ER following LR. 21 studies were pooled for meta-analysis. High-quality evidence showed that poor differentiation of CRC, larger and bilobar-distributed liver metastases, major hepatectomy, positive surgical margins, and postoperative complications were associated with an elevated risk of ER. Additionally, moderate-quality evidence suggested that elevated levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA199), lymph node metastases (LNM) of CRC, and a higher number of liver metastases were risk factors for ER. CONCLUSION This review has the potential to enhance the efficacy of surveillance strategies, refine prognostic assessments, and guide judicious treatment decisions for CRLM patients with high risk of ER. Additionally, it is essential to undertake well-designed prospective investigations to examine additional prognostic factors and develop salvage therapeutic approaches for ER of CRLM.
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Affiliation(s)
- Yuan Tian
- Department of General Surgery, Division of Biliary Surgery, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China
| | - Yaoqun Wang
- Department of General Surgery, Division of Biliary Surgery, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China
| | - Ningyuan Wen
- Department of General Surgery, Division of Biliary Surgery, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China
| | - Shaofeng Wang
- Department of General Surgery, Division of Biliary Surgery, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China
| | - Bei Li
- Department of General Surgery, Division of Biliary Surgery, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China.
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China.
| | - Geng Liu
- Department of General Surgery, Division of Biliary Surgery, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China.
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Sichuan, Chengdu, 610041, China.
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Iwata M, Haraguchi R, Kitazawa R, Ito C, Ogawa K, Takada Y, Kitazawa S. Reduced chemokine C-C motif ligand 1 expression may negatively regulate colorectal cancer progression at liver metastatic sites. J Cell Mol Med 2024; 28:e18193. [PMID: 38506205 PMCID: PMC10952021 DOI: 10.1111/jcmm.18193] [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: 08/13/2023] [Revised: 01/02/2024] [Accepted: 01/09/2024] [Indexed: 03/21/2024] Open
Abstract
Colorectal cancer (CRC) liver metastasis, albeit a stage-IV disease, is completely curable by surgical resection in selected patients. In addressing the molecular basics of this phenomenon, differentially expressed genes at primary and liver metastatic sites were screened by RNA sequencing with the use of paraffin-embedded surgical specimens. Chemokine C-C motif ligand 1 (CCL1), a chemotactic factor for a ligand of the chemokine C-C motif receptor 8 (CCR8), was isolated as one of the differentially expressed genes. Histological analysis revealed that the number of CCL1-positive cells, mainly tumour associated macrophages (TAMs) located in the stroma of CRC, decreased significantly at liver metastatic sites, while the expression level of CCR8 on CRC remained unchanged. To explore the biological significance of the CCL1-CCR8 axis in CRC, CCR8-positive CRC cell line Colo320DM was used to assess the effect of the CCL1-CCR8 axis on major signalling pathways, epithelial mesenchymal transition induction and cell motility. Upon stimulation of recombinant CCL1 (rCCL1), phosphorylation of AKT was observed in Colo320DM cells; on the other hand, the corresponding significant increase in MMP-2 levels demonstrated by RT-qPCR was nullified by siRNA (siCCR8). In the scratch test, rCCL1 treatment significantly increased the motility of Colo320DM cells, which was similarly nullified by siCCR8. Thus, the activation of the CCL1-CCR8 axis is a positive regulator of CRC tumour progression. Reduced CCL1 expression of TAMs at liver metastatic sites may partly explain the unique slow tumour progression of CRC, thus providing for a grace period for radical resection of metastatic lesions.
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Affiliation(s)
- Miku Iwata
- Department of Molecular PathologyEhime University Graduate School of MedicineToon CityEhimeJapan
- Department of Hepato‐Biliary‐Pancreatic and Breast SurgeryEhime University Graduate School of MedicineToon CityEhimeJapan
| | - Ryuma Haraguchi
- Department of Molecular PathologyEhime University Graduate School of MedicineToon CityEhimeJapan
| | - Riko Kitazawa
- Division of Diagnostic PathologyEhime University HospitalToon CityEhimeJapan
| | - Chihiro Ito
- Department of Molecular PathologyEhime University Graduate School of MedicineToon CityEhimeJapan
- Department of Hepato‐Biliary‐Pancreatic and Breast SurgeryEhime University Graduate School of MedicineToon CityEhimeJapan
| | - Kohei Ogawa
- Department of Hepato‐Biliary‐Pancreatic and Breast SurgeryEhime University Graduate School of MedicineToon CityEhimeJapan
| | - Yasutsugu Takada
- Department of Hepato‐Biliary‐Pancreatic and Breast SurgeryEhime University Graduate School of MedicineToon CityEhimeJapan
| | - Sohei Kitazawa
- Department of Molecular PathologyEhime University Graduate School of MedicineToon CityEhimeJapan
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28
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Asai M, Dobesh KD. Combined Resection Approaches: Decision Making for Synchronous Resection, Timing of Staged Intervention to Optimize Outcome. Clin Colon Rectal Surg 2024; 37:96-101. [PMID: 38322604 PMCID: PMC10843888 DOI: 10.1055/s-0043-1761475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2024]
Abstract
Advancement in systemic and regional radiation therapy, surgical technique, and anesthesia has provided a path for increased long-term survival and potential cure for more patients with stage IV rectal cancer in recent years. When patients have resectable disease, the sequence for surgical resection is classified in three strategies: classic, simultaneous, or combined, and reversed. The classic approach consists of rectal cancer resection followed by metastatic disease at a subsequent operation. Simultaneous resection addresses both rectal and metastatic disease in a single surgery. The reversed approach treats metastatic disease first, followed by the primary tumor in several months. Simultaneous resection is appropriate for selected patients to avoid delay of definitive surgery, and reduce number of surgeries, hospital stay, and cost to the health care system. It may also improve patients' psychological effect. Multidisciplinary discussions including colorectal and liver surgeons to review patients' baseline medical conditions, tumor biology and behavior, and disease burden and distribution is imperative to guide proper patient selection for simultaneous resection and perioperative treatments.
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Affiliation(s)
- Megumi Asai
- Division of Colon and Rectal Surgery, Henry Ford Hospital, Detroit, Michigan
| | - Kaitlyn D. Dobesh
- Division of Colon and Rectal Surgery, Henry Ford Hospital, Detroit, Michigan
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29
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Ilyas MIM. Epidemiology of Stage IV Colorectal Cancer: Trends in the Incidence, Prevalence, Age Distribution, and Impact on Life Span. Clin Colon Rectal Surg 2024; 37:57-61. [PMID: 38322602 PMCID: PMC10843881 DOI: 10.1055/s-0043-1761447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2024]
Abstract
Colorectal cancer is a common malignancy in men and women. Historically, stage IV colorectal cancer has 10 to 15% five-year survival. Developments in the management of colorectal metastatic disease have helped improve the overall survival of stage IV colorectal cancers from 12 to 30 months with some patients achieving disease-free survival.
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30
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Wehrle CJ, Perlmutter B, Hong H, Chang J, Stackhouse KA, Naples R, Shanaz Hossain M, Joyce D, Simon R, Kim J, Naffouje SA, Aucejo F, Kwon DCH, Walsh RM, Augustin T. Impact of autotransfusion on recurrence of colorectal cancer liver metastasis: Long-term follow-up of patients undergoing curative intent hepatectomy. J Surg Oncol 2024; 129:793-801. [PMID: 38151831 DOI: 10.1002/jso.27569] [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: 10/25/2023] [Revised: 11/30/2023] [Accepted: 12/10/2023] [Indexed: 12/29/2023]
Abstract
INTRODUCTION Colorectal cancer liver metastasis (CRLM) occurs in upto 50% of cases and drives patient outcomes. Up-front liver resection is the treatment of choice in resectable cases. There is no consensus yet established as to the safety of intraoperative autotransfusion in liver resection for CRLM. METHODS Patients undergoing curative-intent hepatectomy for CRLM at a single quaternary-care institution from 1999 to 2016 were included. Demographics, surgical variables, Fong Clinical Risk Score (FCRS), use of intraoperative auto and/or allotransfusion, and survival data were analyzed. Propensity score matching (PSM) was performed accounting for allotransfusion, extent of hepatectomy, FCRS, and systemic treatment regimens. RESULTS Three-hundred sixteen patients were included. The median follow-up was 10.4 years (7.8-14.1 years). The median recurrence-free survival (RFS) and overall survival (OS) in all patients were 1.6 years (interquartile range: 0.63-6.6 years) and 4.4 years (2.1-8.7), respectively. Before PSM, there was a significantly reduced RFS in the autotransfusion group (0.96 vs. 1.73 years, p = 0.20). There was no difference in OS (4.11 vs. 4.44 years, p = 0.118). Patients in groups of FCRS 0-2 and 3-5 both had reduced RFS when autotransfusion was used (p = 0.005). This reduction in RFS was further found when comparing autotransfusion versus no autotransfusion within the FCRS 0-2 group and within the FCRS 3-5 group (p = 0.027). On Cox-regression analysis, autotransfusion (hazard ratio = 1.423, 1.028-2.182, p = 0.015) remained predictive of RFS. After PSM, there were no differences in FCRS (p = 0.601), preoperative hemoglobin (p = 0.880), allotransfusion (p = 0.130), adjuvant chemotherapy (p = 1.000), immunotherapy (p = 0.172), tumor grade (p = 1.000), use of platinum-based chemotherapy (p = 0.548), or type of hepatic resection (p = 0.967). After matching, there was a higher rate of recurrence with autotransfusion (69.0% vs. 47.6%, p = 0.046). There was also a reduced time to recurrence in the autotransfusion group compared with the group without (p = 0.006). There was no difference in OS after PSM (p = 0.262). CONCLUSION Autotransfusion may adversely affect recurrence in liver resection for CRLM. Until further studies clarify this risk profile, the use of intraoperative autotransfusion should be critically assessed on a case-by-case basis only when other resuscitation options are not available.
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Affiliation(s)
- Chase J Wehrle
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Breanna Perlmutter
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Hanna Hong
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Jenny Chang
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Kathryn A Stackhouse
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Rob Naples
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - M Shanaz Hossain
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Daniel Joyce
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Robert Simon
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Jaekeun Kim
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Samer A Naffouje
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Federico Aucejo
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - David C H Kwon
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - R Matthew Walsh
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Toms Augustin
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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Cheng F, Li P, Xu S, Zhang C, Liang H, Ding Z. A pair of primary colorectal cancer-derived and corresponding synchronous liver metastasis-derived organoid cell lines. Aging (Albany NY) 2024; 16:4396-4422. [PMID: 38407980 PMCID: PMC10968669 DOI: 10.18632/aging.205595] [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: 10/27/2023] [Accepted: 01/29/2024] [Indexed: 02/28/2024]
Abstract
Proper preclinical models for the research of colorectal cancer (CRC) and CRC liver metastases (CLM) are a clear and unmet need. Patient-derived organoids have recently emerged as a robust preclinical model, but are not available to all scientific researchers. Here, we present paired 3D organoid cell lines of CWH22 (CRC-derived) and CLM22 (CLM-derived) with sound background information and the short tandem repeats are identical to those of the normal tissue. Morphological and immunohistochemical staining, along with whole-exome sequencing (WES), confirmed that the organoids exhibited the same differentiation, molecular expression, and mutation status as the corresponding tumor tissue. Both organoids possessed mutated APC/KRAS/SMAD4/CDKN1B/KMT2C genes and wild-type TP53 and PIK3CA; stably secreted the tumor markers CEA and CA19-9, and possessed sound proliferation rates in vitro, as well as subcutaneous tumorigenicity and liver metastatic abilities in vivo. IC50 assays confirmed that both cell lines were sensitive to 5-fluorouracil, oxaliplatin, SN-38, and sotorasib. WES and karyotype analyses revealed the genomic instability status as chromosome instability. The corresponding adherent cultured CWH22-2D/CLM22-2D cells were established and compared with commonly used CRC cell lines from the ATCC. Both organoids are publicly available to all researchers and will be useful tools for specific human CRC/CLM studies both in vitro and in vivo.
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Affiliation(s)
- Fangling Cheng
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, China
| | - Pengcheng Li
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, China
| | - Sanpeng Xu
- Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Chao Zhang
- Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Huifang Liang
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, China
| | - Zeyang Ding
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, China
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Mahootiha M, Qadir HA, Aghayan D, Fretland ÅA, von Gohren Edwin B, Balasingham I. Deep learning-assisted survival prognosis in renal cancer: A CT scan-based personalized approach. Heliyon 2024; 10:e24374. [PMID: 38298725 PMCID: PMC10828686 DOI: 10.1016/j.heliyon.2024.e24374] [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: 07/17/2023] [Revised: 12/19/2023] [Accepted: 01/08/2024] [Indexed: 02/02/2024] Open
Abstract
This paper presents a deep learning (DL) approach for predicting survival probabilities of renal cancer patients based solely on preoperative CT imaging. The proposed approach consists of two networks: a classifier- and a survival- network. The classifier attempts to extract features from 3D CT scans to predict the ISUP grade of Renal cell carcinoma (RCC) tumors, as defined by the International Society of Urological Pathology (ISUP). Our classifier is a 3D convolutional neural network to avoid losing crucial information on the interconnection of slides in 3D images. We employ multiple procedures, including image augmentation, preprocessing, and concatenation, to improve the performance of the classifier. Given the strong correlation between ISUP grading and renal cancer prognosis in the clinical context, we use the ISUP grading features extracted by the classifier as the input to the survival network. By leveraging this clinical association and the classifier network, we are able to model our survival analysis using a simple DL-based network. We adopt a discrete LogisticHazard-based loss to extract intrinsic survival characteristics of RCC tumors from CT images. This allows us to build a completely parametric survival model that varies with patients' tumor characteristics and predicts non-proportional survival probability curves for different patients. Our results demonstrated that the proposed method could predict the future course of renal cancer with reasonable accuracy from the CT scans. The proposed method obtained an average concordance index of 0.72, an integrated Brier score of 0.15, and an area under the curve value of 0.71 on the test cohorts.
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Affiliation(s)
- Maryamalsadat Mahootiha
- The Intervention Centre, Oslo University Hospital, Oslo, 0372, Norway
- Faculty of Medicine, University of Oslo, Oslo, 0372, Norway
| | - Hemin Ali Qadir
- The Intervention Centre, Oslo University Hospital, Oslo, 0372, Norway
| | - Davit Aghayan
- The Intervention Centre, Oslo University Hospital, Oslo, 0372, Norway
| | | | - Bjørn von Gohren Edwin
- The Intervention Centre, Oslo University Hospital, Oslo, 0372, Norway
- Faculty of Medicine, University of Oslo, Oslo, 0372, Norway
| | - Ilangko Balasingham
- The Intervention Centre, Oslo University Hospital, Oslo, 0372, Norway
- Department of Electronic Systems, Norwegian University of Science and Technology, Trondheim, Norway
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33
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Pecqueux M, Brückner F, Oehme F, Hempel S, Baenke F, Riediger C, Distler M, Weitz J, Kahlert C. Preoperative IL-8 levels as prognostic indicators of overall survival: an extended follow-up in a prospective cohort with colorectal liver metastases. BMC Cancer 2024; 24:90. [PMID: 38233759 PMCID: PMC10792859 DOI: 10.1186/s12885-023-11787-1] [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: 10/14/2023] [Accepted: 12/21/2023] [Indexed: 01/19/2024] Open
Abstract
INTRODUCTION CRC with liver metastases is a major contributor to cancer-related mortality. Despite advancements in liver resection techniques, patient survival remains a concern due to high recurrence rates. This study seeks to uncover prognostic biomarkers that predict overall survival in patients undergoing curative hepatic resection for CRC liver metastases. METHODS Prospectively collected serum samples from a cohort of 49 patients who received curative hepatic resection for CRC liver metastases were studied. The patients are part of a cohort, previously analyzed for perioperative complications (see methods). Various preoperative serum markers, clinical characteristics, and factors were analyzed. Univariate and multivariate Cox regression analyses were conducted to determine associations between these variables and disease-free survival as well as overall survival. RESULTS For disease-free survival, univariate analysis highlighted the correlation between poor outcomes and advanced primary tumor stage, high ASA score, and synchronous liver metastases. Multivariate analysis identified nodal-positive primary tumors and synchronous metastases as independent risk factors for disease-free survival. Regarding overall survival, univariate analysis demonstrated significant links between poor survival and high preoperative IL-8 levels, elevated neutrophil-lymphocyte ratio (NLR), and presence of metastases in other organs. Multivariate analysis confirmed preoperative IL-8 and having three or more liver metastases as independent risk factors for overall survival. The impact of IL-8 on survival was particularly noteworthy, surpassing the influence of established clinical factors. CONCLUSION This study establishes preoperative IL-8 levels as a potential prognostic biomarker for overall survival in patients undergoing curative liver resection for CRC liver metastases. This study underscores the importance of incorporating IL-8 and other biomarkers into clinical decision-making, facilitating improved patient stratification and tailored treatment approaches. Further research and validation studies are needed to solidify the clinical utility of IL-8 as a prognostic marker.
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Affiliation(s)
- Mathieu Pecqueux
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.
| | - Frederik Brückner
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
| | - Florian Oehme
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
| | - Sebastian Hempel
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
| | - Franziska Baenke
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
| | - Carina Riediger
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
| | - Marius Distler
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
| | - Christoph Kahlert
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
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Libia A, Podda M, Di Martino M, Pata F, Pellino G, Di Saverio S, Anselmo A, Muttillo EM, De Pastena M, Campanile FC, Ielpo B, Spampinato MG. Current status of liver surgery for non-colorectal non-neuroendocrine liver metastases: the NON.LI.MET. Italian Society for Endoscopic Surgery and New Technologies (SICE) and Association of Italian Surgeons in Europe (ACIE) collaborative international survey. Updates Surg 2024; 76:43-55. [PMID: 37875725 DOI: 10.1007/s13304-023-01649-7] [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: 03/21/2023] [Accepted: 09/23/2023] [Indexed: 10/26/2023]
Abstract
Despite the increasing trend in liver resections for non-colorectal non-neuroendocrine liver metastases (NCNNLM), the role of surgery for these liver malignancies is still debated. Registries are an essential, reliable tool for assessing epidemiology, diagnosis, and therapeutic approach in a single hub, especially when data are dispersive and inconclusive, as in our case. The dissemination of this preliminary survey would allow us to understand if the creation of an International Registry is a viable option, while still offering a snapshot on this issue, investigating clinical practices worldwide. The steering committee designed an online questionnaire with Google Forms, which consisted of 37 questions, and was open from October 5th, 2022, to November 30th, 2022. It was disseminated using social media and mailing lists of the Italian Society of Endoscopic Surgery and New Technologies (SICE), the Association of Italian Surgeons in Europe (ACIE), and the Spanish Chapter of the American College of Surgeons (ACS). Overall, 141 surgeons (approximately 18% of the total invitations sent) from 27 countries on four continents participated in the survey. Most respondents worked in general surgery units (62%), performing less than 50 liver resections/year (57%). A multidisciplinary discussion was currently performed to validate surgical indications for NCNNLM in 96% of respondents. The most commonly adopted selection criteria were liver resectability, RECIST criteria, and absence of extrahepatic disease. Primary tumors were generally of gastrointestinal (42%), breast (31%), and pancreaticobiliary origin (13%). The most common interventions were parenchymal-sparing resections (51% of respondents) of metachronous metastases with an open approach. Major post-operative complications (Clavien-Dindo > 2) occurred in up to 20% of the procedures, according to 44% of respondents. A subset analysis of data from high-volume centers (> 100 cases/year) showed lower post-operative complications and better survival. The present survey shows that NCNNLM patients are frequently treated by surgeons in low-volume hospitals for liver surgery. Selection criteria are usually based on common sense. Liver resections are performed mainly with an open approach, possibly carrying a high burden of major post-operative complications. International guidelines and a specific consensus on this field are desirable, as well as strategies for collaboration between high-volume and low-volume centers. The present study can guide the elaboration of a multi-institutional document on the optimal pathway in the management of patients with NCNNLM.
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Affiliation(s)
- Annarita Libia
- General Surgery Unit, Hospital Vito Fazzi, Lecce, Italy.
| | - Mauro Podda
- Department of Surgical Science, Cagliari State University, Cagliari, Italy
| | - Marcello Di Martino
- Division of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, Naples, Italy
| | - Francesco Pata
- Department of Surgery, Nicola Giannettasio Hospital, Corigliano-Rossano, Italy
| | - Gianluca Pellino
- Department of Advanced Medical and Surgical Sciences, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy
| | - Salomone Di Saverio
- Unit of General Surgery, San Benedetto del Tronto Hospital, av5 Asur Marche, San Benedetto del Tronto, Italy
| | - Alessandro Anselmo
- Department of Surgical Science, University of Rome "Tor Vergata", 00133, Rome, Italy
| | | | - Matteo De Pastena
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Fabio Cesare Campanile
- Division of General Surgery, ASL Viterbo, San Giovanni Decollato-Andosilla Hospital, 01033, Civita Castellana, Italy
| | - Benedetto Ielpo
- Hepatobiliary and Pancreatic Surgery Unit, Hospital del Mar Medical Research Institute (IMIM), Universitat Pompeu Fabra, Barcelona, Spain
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Leonhardt CS, Stamm T, Hank T, Prager G, Strobel O. Defining oligometastatic pancreatic cancer: a systematic review and critical synthesis of consensus. ESMO Open 2023; 8:102067. [PMID: 37988953 PMCID: PMC10774968 DOI: 10.1016/j.esmoop.2023.102067] [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: 08/05/2023] [Accepted: 10/14/2023] [Indexed: 11/23/2023] Open
Abstract
BACKGROUND Small retrospective series suggest that local consolidative treatment (LCT) may improve survival in oligometastatic pancreatic ductal adenocarcinoma (PDAC). However, no uniform definition of oligometastatic disease (OMD) in PDAC exists; this impedes meaningful conclusions. PATIENTS AND METHODS A systematic literature search using PubMed, Web of Science, and Cochrane CENTRAL registries for studies and protocols reporting on definitions and/or LCT of OMD in PDAC was performed. The primary endpoint was the definition of OMD. Levels of agreement were categorized as consensus (≥75% agreement between studies), fair agreement (50%-74%), and absent/poor agreement (<50%). RESULTS After screening of 5374 abstracts, the full text of 218 studies was assessed, of which 76 were included in the qualitative synthesis. The majority of studies were retrospective (n = 66, 87%), two were prospective studies and eight were study protocols. Studies investigated mostly liver (n = 38, 51%) and lung metastases (n = 15, 20%). Across studies, less than one-half (n = 32, 42%) reported a definition of OMD, while 44 (58%) did not. Involvement was limited to a single organ (consensus). Additional criteria for defining OMD were the number of lesions (consensus), metastatic site (poor agreement), metastatic size (poor agreement), treatment possibilities (poor agreement), and biomarker response (poor agreement). Liver OMD could involve three or fewer lesions (consensus) and synchronous disease (fair agreement), while lung metastases could involve two or fewer lesions and metachronous disease (consensus). The large majority of studies were at a high risk of bias or did not include any control groups. CONCLUSION Definitions of OMD were not used or varied widely between studies hampering across-study comparability and highlighting an unmet need for a consensus. The present study is part of a multistep process that aims to develop an interdisciplinary consensus on OMD in pancreatic cancer.
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Affiliation(s)
- C-S Leonhardt
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna
| | - T Stamm
- Institute of Outcomes Research, Center for Medical Data Science, Medical University of Vienna; Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna
| | - T Hank
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna
| | - G Prager
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - O Strobel
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna.
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Jones A, Findlay A, Knight SR, Rees J, O'Reilly D, Jones RP, Pathak S. Follow up after surgery for colorectal liver metastases: A systematic review. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:107103. [PMID: 37890234 DOI: 10.1016/j.ejso.2023.107103] [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: 04/21/2023] [Revised: 09/04/2023] [Accepted: 09/27/2023] [Indexed: 10/29/2023]
Abstract
INTRODUCTION Recurrence post hepatectomy for colorectal liver metastases (CRLM) occurs in 70 % of patients within two years. No established guidance on the method or intensity of follow-up currently exists. The aim of this systematic review was to summarise literature and determine whether it is possible to identify an optimal follow up regime. To this date there are no randomised prospective studies investigating this. METHODS A systematic review was performed according to PRISMA guidelines. Outcomes included general demographics, method, frequency and duration of follow up, survival and recurrence data. Quality assessment of the papers was performed. RESULTS Twenty-five articles published between 1994 and 2022 were included, including 9945 patients. CT was the most common imaging modality (n = 14) and CEA most common blood test (n = 11). Intensity of follow up was higher in the first two years post resection and only two papers continued follow up post 5 years resection. There was wide variation in outcome measures - Overall survival (OS) was most commonly reported. Nine papers reported OS ranging between 39 and 78.1 %. CONCLUSIONS There is wide variation in follow up methods and outcome reporting. There is no strong evidence to support intensive follow up, and the benefits of long term follow up are also unknown due to the lack of patient centred data. High quality, prospective studies should be the focus of future research as further retrospective data is unlikely to resolve uncertainties around optimal follow up.
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Affiliation(s)
- Annabel Jones
- University Hospitals Bristol and Weston NHS Foundation Trust, Marlborough St, Bristol, BS1 3NU, UK
| | - Alasdair Findlay
- Department of Abdominal Medicine and Surgery, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK
| | - Stephen R Knight
- Centre for Medical Informatics, Usher Institute, Nine Edinburgh BioQuarter, 9 Little France Road, EH16 4UX, UK
| | - Jonathan Rees
- University Hospitals Bristol and Weston NHS Foundation Trust, Marlborough St, Bristol, BS1 3NU, UK
| | - David O'Reilly
- Cardiff Liver Unit, University Hospital of Wales, Cardiff, CF14 4XW, UK
| | - Robert P Jones
- Institute of Translational Medicine, University of Liverpool, Brownlow Hill, Liverpool, L69 3BX, UK
| | - Samir Pathak
- Department of Abdominal Medicine and Surgery, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK.
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Plahuta I, Mencinger M, Peruš I, Magdalenić T, Turk Š, Brumec A, Potrč S, Ivanecz A. Ranking as a Procedure for Selecting a Replacement Variable in the Score Predicting the Survival of Patients Treated with Curative Intent for Colorectal Liver Metastases. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:2003. [PMID: 38004052 PMCID: PMC10673064 DOI: 10.3390/medicina59112003] [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: 10/16/2023] [Revised: 11/04/2023] [Accepted: 11/13/2023] [Indexed: 11/26/2023]
Abstract
Background and Objectives: The issue of a missing variable precludes the external validation of many prognostic models. For example, the Liverpool score predicts the survival of patients undergoing surgical therapy for colorectal liver metastases, but it includes the neutrophil-lymphocyte ratio, which cannot be measured retrospectively. Materials and Methods: We aimed to find the most appropriate replacement for the neutrophil-lymphocyte ratio. Survival analysis was performed on data representing 632 liver resections for colorectal liver metastases from 2000 to 2020. Variables associated with the Liverpool score, C-reactive protein, albumins, and fibrinogen were ranked. The rankings were performed in four ways: The first two were based on the Kaplan-Meier method (log-rank statistics and the definite integral IS between two survival curves). The next method of ranking was based on univariate and multivariate Cox regression analyses. Results: The ranks were as follows: the radicality of liver resection (rank 1), lymph node infiltration of primary colorectal cancer (rank 2), elevated C-reactive protein (rank 3), the American Society of Anesthesiologists Classification grade (rank 4), the right-sidedness of primary colorectal cancer (rank 5), the multiplicity of colorectal liver metastases (rank 6), the size of colorectal liver metastases (rank 7), albumins (rank 8), and fibrinogen (rank 9). Conclusions: The ranking methodologies resulted in almost the same ranking order of the variables. Elevated C-reactive protein was ranked highly and can be considered a relevant replacement for the neutrophil-lymphocyte ratio in the Liverpool score. These methods are suitable for ranking variables in similar models for medical research.
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Affiliation(s)
- Irena Plahuta
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
| | - Matej Mencinger
- Faculty of Civil Engineering, Transportation Engineering, and Architecture, University of Maribor, Smetanova ulica 17, 2000 Maribor, Slovenia; (M.M.); (I.P.)
- Institute of Mathematics, Physics and Mechanics, Jadranska 19, 1000 Ljubljana, Slovenia
| | - Iztok Peruš
- Faculty of Civil Engineering, Transportation Engineering, and Architecture, University of Maribor, Smetanova ulica 17, 2000 Maribor, Slovenia; (M.M.); (I.P.)
- Faculty of Natural Science and Engineering, University of Ljubljana, Aškerčeva cesta 12, 1000 Ljubljana, Slovenia
| | - Tomislav Magdalenić
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Špela Turk
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Aleks Brumec
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Stojan Potrč
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
| | - Arpad Ivanecz
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
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Joechle K, Amygdalos I, Schmidt F, Bednarsch J, Chrysos A, Meister FA, Czigany Z, Heise D, Berres ML, Bruners P, Ulmer TF, Neumann UP, Lang SA. Value of prognostic scoring systems in the era of multimodal therapy for recurrent colorectal liver metastases. HPB (Oxford) 2023; 25:1354-1363. [PMID: 37438185 DOI: 10.1016/j.hpb.2023.06.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 05/12/2023] [Accepted: 06/22/2023] [Indexed: 07/14/2023]
Abstract
BACKGROUND Various predictive scoring systems have been developed to estimate outcomes of patients undergoing surgery for colorectal liver metastases (CRLM). However, data regarding their effectiveness in recurrent CRLM (recCRLM) are very limited. METHODS Patients who underwent repeat hepatectomy for recCRLM at the University Hospital RWTH Aachen, Germany from 2010 to 2021 were included. Nine predictive scoring systems (Fong's, Nordlinger, Nagashima, RAS mutation, Tumor Burden, GAME, CERR, and Glasgow Prognostic score, Basingstoke Index) were evaluated by likelihood ratio (LR) χ2, linear trend (LT) χ2 and Akaike Information Criterion (AIC) for their predictive value regarding overall survival (OS) and recurrence free survival (RFS). RESULTS Among 150 patients, median RFS was 9 (2-124) months with a 5-year RFS rate of 10%. Median OS was 39 (4-131) months with a 5-year OS rate of 32%. For RFS and OS, the Nagashima score showed the best prognostic ability (LT χ2 3.00, LR χ2 9.39, AIC 266.66 and LT χ2 2.91, LR χ2 20.91, 290.36). DISCUSSION The Nagashima score showed the best prognostic stratification to predict recurrence as well as survival, and therefore might be considered when evaluating patients with recCRLM for repeat hepatectomy.
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Affiliation(s)
- Katharina Joechle
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Iakovos Amygdalos
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Felix Schmidt
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Jan Bednarsch
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Alexandros Chrysos
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Franziska A Meister
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Zoltan Czigany
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Daniel Heise
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Marie-Luise Berres
- Department of Internal Medicine III, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Philipp Bruners
- Department of Diagnostic und Interventional Radiology, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Tom F Ulmer
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Ulf P Neumann
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany
| | - Sven A Lang
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany; Center for Integrated Oncology Aachen, Boon, Cologne and Duesseldorf (CIO ABCD), Site, Aachen, Germany.
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Pham H, Dixon E. Integration of Next-Generation Sequencing in the Surgical Management of Colorectal Liver Metastasis. Ann Surg Oncol 2023; 30:6815-6823. [PMID: 37316745 DOI: 10.1245/s10434-023-13750-7] [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: 05/27/2022] [Accepted: 06/04/2023] [Indexed: 06/16/2023]
Abstract
Hepatic resection remains the treatment of choice for colorectal liver metastases. The advancement of surgical technique and use of perioperative systemic therapy has expanded the number and complexity of patients eligible for surgical resection. In recent years, investigation into gene mutations, such as RAS/RAF pathway, have led to targeted therapies that have significantly improved outcomes. Next-generation sequencing allows analysis of large number of genes that may have potential prognostic relevance in the clinical setting. This review summarizes the current applications of next-generation sequencing technology in metastatic colorectal cancer, focusing on its prognostic implications on patient management.
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Affiliation(s)
- Helen Pham
- Department of Surgery, Faculty of Medicine, University of Calgary, Foothills Medical Centre, Calgary, AB, Canada.
| | - Elijah Dixon
- Department of Surgery, Faculty of Medicine, University of Calgary, Foothills Medical Centre, Calgary, AB, Canada
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Liao L, Sun H, He J, Liu Y, Pan Z, Wu X, Fan W, Peng J, Li C. Neoadjuvant chemotherapy weakens the prognostic value of the pathological tumor burden score for colorectal cancer liver metastases. BMC Surg 2023; 23:271. [PMID: 37689651 PMCID: PMC10492270 DOI: 10.1186/s12893-023-02145-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: 02/13/2023] [Accepted: 08/09/2023] [Indexed: 09/11/2023] Open
Abstract
BACKGROUND The pathological tumor burden score (TBS) has been proven to be a better risk stratification tool for liver metastasis of colorectal cancer than the traditional clinical risk score (CRS). The aim of this study was to evaluate the prognostic value of the pathological tumor burden score in patients with or without neoadjuvant chemotherapy (NAC). METHODS A total of 348 patients with colorectal liver metastases (CRLM) who underwent curative hepatic resection were retrospectively enrolled from September 1999 to December 2016. Univariable and multivariable Cox regression analyses were conducted to identify the independent predictors of prognosis. Kaplan-Meier curves and log-rank tests were used to determine whether TBS has enough discriminatory ability under certain grouping. RESULTS Patients who received NAC had a higher median TBS than patients who did not receive NAC (4.07 vs. 2.69, P < 0.001). Among patients who did not receive NAC, those with TBS > 3 showed a significantly worse 3-year RFS (41.1% vs. 63.6%, P < 0.001) and 3-year OS rate (73.3% vs. 84.1%, P = 0.003) than those with TBS ≤ 3. Among the patients who received NAC, those with TBS ≤ 3 or TBS > 3 showed comparable 3-year RFS (33.3% vs. 26.4%, P = 0.400) and 3-year OS rates (76.5% vs. 58.2%, P = 0.064) to those who did not. Regardless of the regimen and response to NAC, there was no significant difference about 3-year RFS and 3-year OS rates between the TBS ≤ 3 and TBS > 3 groups. CONCLUSION Pathological TBS can be applied to predict the RFS and OS of patients suffering from CRLM who did not receive NAC. However, pathological TBS might not be regard as prognosis in patients who did receive NAC.
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Affiliation(s)
- Leen Liao
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Hui Sun
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510060, P. R. China
| | - Jiahua He
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Yujun Liu
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510060, P. R. China
| | - Zhizhong Pan
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Xiaojun Wu
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Wenhua Fan
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Jianhong Peng
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.
| | - Cong Li
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.
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Katipally RR, Martinez CA, Pugh SA, Bridgewater JA, Primrose JN, Domingo E, Maughan TS, Talamonti MS, Posner MC, Weichselbaum RR, Pitroda SP, with the S:CORT Consortium. Integrated Clinical-Molecular Classification of Colorectal Liver Metastases: A Biomarker Analysis of the Phase 3 New EPOC Randomized Clinical Trial. JAMA Oncol 2023; 9:1245-1254. [PMID: 37471075 PMCID: PMC10360005 DOI: 10.1001/jamaoncol.2023.2535] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 05/09/2023] [Indexed: 07/21/2023]
Abstract
Importance Personalized treatment approaches for patients with oligometastatic colorectal liver metastases are critically needed. We previously defined 3 biologically distinct molecular subtypes of colorectal liver metastases: (1) canonical, (2) immune, and (3) stromal. Objective To independently validate these molecular subtypes in the phase 3 New EPOC randomized clinical trial. Design, Setting, and Participants This retrospective secondary analysis of the phase 3 New EPOC randomized clinical trial included a bi-institutional discovery cohort and multi-institutional validation cohort. The discovery cohort comprised patients who underwent hepatic resection for limited colorectal liver metastases (98% received perioperative chemotherapy) from May 31, 1994, to August 14, 2012. The validation cohort comprised patients who underwent hepatic resection for liver metastases with perioperative chemotherapy (fluorouracil, oxaliplatin, and irinotecan based) with or without cetuximab from February 26, 2007, to November 1, 2012. Data were analyzed from January 18 to December 10, 2021. Interventions Resected metastases underwent RNA sequencing and microRNA (miRNA) profiling in the discovery cohort and messenger RNA and miRNA profiling with microarray in the validation cohort. Main Outcomes and Measures A 31-feature (24 messenger RNAs and 7 miRNAs) neural network classifier was trained to predict molecular subtypes in the discovery cohort and applied to the validation cohort. Integrated clinical-molecular risk groups were designated based on molecular subtypes and the clinical risk score. The unique biological phenotype of each molecular subtype was validated using gene set enrichment analyses and immune deconvolution. The primary clinical end points were progression-free survival (PFS) and overall survival (OS). Results A total of 240 patients were included (mean [range] age, 63.0 [56.3-68.0] years; 151 [63%] male), with 93 in the discovery cohort and 147 in the validation cohort. In the validation cohort, 73 (50%), 28 (19%), and 46 (31%) patients were classified as having canonical, immune, and stromal metastases, respectively. The biological phenotype of each subtype was concordant with the discovery cohort. The immune subtype (best prognosis) demonstrated 5-year PFS of 43% (95% CI, 25%-60%; hazard ratio [HR], 0.37; 95% CI, 0.20-0.68) and OS of 63% (95% CI, 40%-79%; HR, 0.38; 95% CI, 0.17-0.86), which was statistically significantly higher than the canonical subtype (worst prognosis) at 14% (95% CI, 7%-23%) and 43% (95% CI, 32%-55%), respectively. Adding molecular subtypes to the clinical risk score improved prediction (the Gönen and Heller K for discrimination) from 0.55 (95% CI, 0.49-0.61) to 0.62 (95% CI, 0.57-0.67) for PFS and 0.59 (95% CI, 0.52-0.66) to 0.63 (95% CI, 0.56-0.70) for OS. The low-risk integrated group demonstrated 5-year PFS of 44% (95% CI, 20%-66%; HR, 0.38; 95% CI, 0.19-0.76) and OS of 78% (95% CI, 44%-93%; HR, 0.26; 95% CI, 0.08-0.84), superior to the high-risk group at 16% (95% CI, 10%-24%) and 43% (95% CI, 32%-52%), respectively. Conclusions and Relevance In this prognostic study, biologically derived colorectal liver metastasis molecular subtypes and integrated clinical-molecular risk groups were highly prognostic. This novel molecular classification warrants further study as a possible predictive biomarker for personalized systemic treatment for colorectal liver metastases. Trial Registration isrctn.org Identifier: ISRCTN22944367.
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Affiliation(s)
- Rohan R. Katipally
- Department of Radiation and Cellular Oncology, The University of Chicago Medicine, Chicago, Illinois
| | - Carlos A. Martinez
- Department of Radiation and Cellular Oncology, The University of Chicago Medicine, Chicago, Illinois
| | - Siân A. Pugh
- Department of Oncology, Addenbrooke’s Hospital, Cambridge, England, United Kingdom
| | - John A. Bridgewater
- UCL Cancer Institute, University College London, London, England, United Kingdom
| | - John N. Primrose
- Department of Surgery, University of Southampton, Southampton, England, United Kingdom
| | - Enric Domingo
- Department of Oncology, University of Oxford, Oxford, England, United Kingdom
| | - Timothy S. Maughan
- MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, England, United Kingdom
| | - Mark S. Talamonti
- Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois
| | - Mitchell C. Posner
- Department of Surgery, The University of Chicago Medicine, Chicago, Illinois
| | - Ralph R. Weichselbaum
- Department of Radiation and Cellular Oncology, The University of Chicago Medicine, Chicago, Illinois
| | - Sean P. Pitroda
- Department of Radiation and Cellular Oncology, The University of Chicago Medicine, Chicago, Illinois
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Wehrle CJ, Raj R, Aykun N, Orabi D, Stackhouse K, Chang J, Estfan B, Kamath S, Krishnamurthi S, Walsh RM, Kwon DCH, Aucejo F. Circulating Tumor DNA in Colorectal Cancer Liver Metastasis: Analysis of Patients Receiving Liver Resection and Transplant. JCO Clin Cancer Inform 2023; 7:e2300111. [PMID: 37820293 DOI: 10.1200/cci.23.00111] [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: 06/14/2023] [Revised: 08/13/2023] [Accepted: 08/29/2023] [Indexed: 10/13/2023] Open
Abstract
PURPOSE Liver metastases occur in about 50% of colorectal cancer cases and drive patient outcomes. Circulating tumor DNA (ctDNA) is emerging as a diagnostic, surveillance, and tumor mutational information tool. METHODS Patients with colorectal cancer liver metastasis (CCLM) seen in a multidisciplinary liver tumor clinic from January to August 2022 received ctDNA testing on each visit. ctDNA was obtained using the Guardant360 platform. Tumor mutational burden (TMB) is defined as the number of identified mutations per megabase of genome analyzed. RESULTS Fifty-two patients had available ctDNA, with 34 (65%) tested preoperatively and 18 (35%) postoperatively; nine patients had sequential pre- and postoperative testing. The median time to test result was 12 days (IQR, 10-13.5). There were a greater number of somatic mutations identified preoperatively (n = 29 v n = 11) and a greater genomic heterogeneity (P = .0069). The mean TMB score was 12.77 in those without pathologic response to cytotoxic therapy and 6.0 in those with pathologic response (P = .10). All nine patients with sequential testing were positive preoperatively, compared with just three (33.3%) postoperatively (P = .0090). Positive postoperative ctDNA was associated with the increased likelihood of disease recurrence after resection (57%) versus negative ctDNA (0%, P = .0419). CONCLUSION Routine ctDNA screening in patients with CCLM is logistically feasible. Liver resection and/or transplant may be associated with clearance of detectable ctDNA and a reduction in TMB or genomic heterogeneity. Persistence of ctDNA alterations postresection appears predictive of disease recurrence. Further studies are necessary to confirm these findings, and longitudinal ctDNA testing is needed to monitor changing tumor biology.
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Affiliation(s)
- Chase J Wehrle
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland, OH
| | - Roma Raj
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland, OH
| | - Nihal Aykun
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland, OH
| | - Danny Orabi
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland, OH
| | - Kathryn Stackhouse
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland, OH
| | - Jenny Chang
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland, OH
| | - Bassam Estfan
- Cleveland Clinic Foundation, Taussig Cancer Institute, Department of Hematology and Oncology, Cleveland, OH
| | - Suneel Kamath
- Cleveland Clinic Foundation, Taussig Cancer Institute, Department of Hematology and Oncology, Cleveland, OH
| | - Smitha Krishnamurthi
- Cleveland Clinic Foundation, Taussig Cancer Institute, Department of Hematology and Oncology, Cleveland, OH
| | - R Matthew Walsh
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland, OH
| | - David Choon Hyuck Kwon
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland, OH
| | - Federico Aucejo
- Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland, OH
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Yue L, Xu X, Dai S, Xu F, Zhao W, Gu J, Dai X, Qian X. Orosomucoid 1 promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing macrophage M2 polarization. Sci Rep 2023; 13:14092. [PMID: 37640741 PMCID: PMC10462626 DOI: 10.1038/s41598-023-40404-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 08/09/2023] [Indexed: 08/31/2023] Open
Abstract
Approximately 25-30% of those affected by colorectal cancer (CRC), the most prevalent gastrointestinal malignancy, develop metastases. The survival rate of patients with liver metastasis of CRC (CRLM) remains low owing to its unpredictability and a lack of biomarkers that can be applied to distinguish groups at higher risk for CRLM among patients with CRC. Therefore, our study aimed to find biomarkers that can predict the risk of CRLM. Screening of the Gene Expression Omnibus database, supported by an analysis of clinically obtained tissue and serum data using qPCR and ELISA, in an attempt to identify relevant biomarkers, enabled us to determine that orosomucoid 1 (ORM1) was differentially expressed in liver metastases and primary tumors of patients with CRC. Functionally, overexpression of ORM1 promoted the epithelial-mesenchymal transition and the proliferative, migratory, and invasive activities of MC38 cells and activated the PI3K/AKT signaling pathway. Moreover, MC38 cells overexpressing ORM1 enhanced the tumor immune microenvironment by promoting macrophage M2 polarization and elevating interleukin-10 (IL-10) expression. In vivo experiments further confirmed in vitro results, indicating that liver metastases elevated by ORM1 were partially attenuated by the depletion of macrophages or IL-10. Considered together, ORM1 promotes CRC progression and liver metastasis by regulating tumor cell growth and inducing macrophage M2 polarization, which mediates tumor immune tolerance, and thus acts as a potential predictive marker and therapeutic target in CRLM.
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Affiliation(s)
- Lei Yue
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Xiaozhang Xu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, 210029, Jiangsu Province, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
| | - Shipeng Dai
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, 210029, Jiangsu Province, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
| | - Fan Xu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, 210029, Jiangsu Province, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
| | - Wenhu Zhao
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, 210029, Jiangsu Province, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
| | - Jian Gu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, 210029, Jiangsu Province, China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
| | - Xinzheng Dai
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China.
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, 210029, Jiangsu Province, China.
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China.
| | - Xiaofeng Qian
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China.
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, 210029, Jiangsu Province, China.
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China.
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Kim S, Lee E. A deep attention LSTM embedded aggregation network for multiple histopathological images. PLoS One 2023; 18:e0287301. [PMID: 37384648 PMCID: PMC10310006 DOI: 10.1371/journal.pone.0287301] [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: 09/14/2022] [Accepted: 06/03/2023] [Indexed: 07/01/2023] Open
Abstract
Recent advancements in computer vision and neural networks have facilitated the medical imaging survival analysis for various medical applications. However, challenges arise when patients have multiple images from multiple lesions, as current deep learning methods provide multiple survival predictions for each patient, complicating result interpretation. To address this issue, we developed a deep learning survival model that can provide accurate predictions at the patient level. We propose a deep attention long short-term memory embedded aggregation network (DALAN) for histopathology images, designed to simultaneously perform feature extraction and aggregation of lesion images. This design enables the model to efficiently learn imaging features from lesions and aggregate lesion-level information to the patient level. DALAN comprises a weight-shared CNN, attention layers, and LSTM layers. The attention layer calculates the significance of each lesion image, while the LSTM layer combines the weighted information to produce an all-encompassing representation of the patient's lesion data. Our proposed method performed better on both simulated and real data than other competing methods in terms of prediction accuracy. We evaluated DALAN against several naive aggregation methods on simulated and real datasets. Our results showed that DALAN outperformed the competing methods in terms of c-index on the MNIST and Cancer dataset simulations. On the real TCGA dataset, DALAN also achieved a higher c-index of 0.803±0.006 compared to the naive methods and the competing models. Our DALAN effectively aggregates multiple histopathology images, demonstrating a comprehensive survival model using attention and LSTM mechanisms.
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Affiliation(s)
- Sunghun Kim
- Department of Information and Statistics, Chungnam National University, Daejeon, Republic of Korea
- Department of Artificial Intelligence, Sungkyunkwan University, Suwon, Republic of Korea
| | - Eunjee Lee
- Department of Information and Statistics, Chungnam National University, Daejeon, Republic of Korea
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Torén W, Sasor A, Ansari D, Andersson R. Histopathological investigation of colon liver metastases - which factors affect survival after surgery? Scand J Gastroenterol 2023; 58:627-633. [PMID: 36440692 DOI: 10.1080/00365521.2022.2151319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 11/17/2022] [Accepted: 11/20/2022] [Indexed: 11/29/2022]
Abstract
INTRODUCTION Novel therapeutic options have improved prognosis for patients with colonic liver metastases (CLM) over the last decades. Despite this, the challenge to select and stratify patients for optimal treatment regimen persists. This study aimed to evaluate established and novel histopathological features and investigate the impact on overall survival (OS) and recurrence in patients undergoing surgery for CLM. METHODS Two hundred and sixty patients who underwent resection of CLM with curative intent 2006-2017 were included in the study. Clinicopathological characteristics were retrieved from patient medical records. The following histopathological parameters were investigated: vascular/lymphatic invasion, perineural invasion, tumor regression grade (TRG), tumor growth pattern, pseudocapsule and acellular mucin. Histopathological traits were correlated to OS. RESULTS Vascular and lymphatic invasion, as well as perineural invasion, significantly correlated with an adverse prognosis hazard ratio (HR) = 1.7, 95% confidence interval (CI) 1.23-2.40 and HR = 1.7, 95% CI 1.20-2.51, respectively. Results retrieved from the study could not propose any novel explorative histopathological features (TRG, tumor growth pattern, pseudocapsule and acellular mucin) to be of significant value as comes correlation with patient OS. DISCUSSION Classical histopathological characteristics of previously reported influence on survival were confirmed, while more novel factors that has been proposed, like tumor growth pattern, tumor regression and grade and presence of a pseudocapsule, were not. Further studies are thus needed to identify better ways of understanding the impact of tumor microenvironment and tumor biology on patient outcome and not at least for stratification and improved treatment response.
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Affiliation(s)
- William Torén
- Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden
| | - Agata Sasor
- Department of Pathology, Skåne University Hospital, Lund, Sweden
| | - Daniel Ansari
- Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden
| | - Roland Andersson
- Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden
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Weixler B, Lobbes LA, Scheiner L, Lauscher JC, Staubli SM, Zuber M, Raptis DA. The Value of Indocyanine Green Image-Guided Surgery in Patients with Primary Liver Tumors and Liver Metastases. Life (Basel) 2023; 13:1290. [PMID: 37374073 DOI: 10.3390/life13061290] [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: 04/10/2023] [Revised: 05/13/2023] [Accepted: 05/30/2023] [Indexed: 06/29/2023] Open
Abstract
INTRODUCTION Successful R0 resection is crucial for the survival of patients with primary liver cancer (PLC) or liver metastases. Up to date, surgical resection lacks a sensitive, real-time intraoperative imaging modality to determine R0 resection. Real-time intraoperative visualization with near-infrared light fluorescence (NIRF) using indocyanine green (ICG) may have the potential to meet this demand. This study evaluates the value of ICG visualization in PLC and liver metastases surgery regarding R0 resection rates. MATERIALS AND METHODS Patients with PLC or liver metastases were included in this prospective cohort study. ICG 10 mg was administered intravenously 24 h before surgery. Real-time intraoperative NIRF visualization was created with the SpectrumTM fluorescence imaging camera system. First, all liver segments were inspected with the fluorescence imaging system and intraoperative ultrasound for identification of the known tumor, as well as additional lesions, and were compared to preoperative MRI images. PLC, liver metastases, and additional lesions were then resected according to oncological principles. In all resected specimens, the resection margins were analyzed with the fluorescence imaging system for ICG-positive spots immediately after resection. Histology of additional detected lesions, as well as ICG fluorescence compared to histological resection margins, were assessed. RESULTS Of the 66 included patients, median age was 65.5 years (IQR 58.7-73.9), 27 (40.9%) were female, and 18 (27.3%) were operated on laparoscopically. Additional ICG-positive lesions were detected in 23 (35.4%) patients, of which 9 (29%) were malignant. In patients with no fluorescent signal at the resection margin, R0 rate was 93.9%, R1 rate was 6.1%, and R2 rate was 0% compared to an ICG-positive resection margin with an R0 rate of 64.3%, R1 rate of 21.4%, and R2 rate of 14.3% (p = 0.005). One- and two-year overall survival rates were 95.2% and 88.4%, respectively. CONCLUSION The presented study provides significant evidence that ICG NIRF guidance helps to identify R0 resection intraoperatively. This offers true potential to verify radical resection and improve patient outcomes. Furthermore, implementation of NIRF-guided imaging in liver tumor surgery allows us to detect a considerable amount of additional malignant lesions.
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Affiliation(s)
- Benjamin Weixler
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Leonard A Lobbes
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Luis Scheiner
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Johannes C Lauscher
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Sebastian M Staubli
- Department of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Royal Free Hospital, London NW3 2QG, UK
| | - Markus Zuber
- Clarunis University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, 4058 Basel, Switzerland
| | - Dimitri A Raptis
- Department of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Royal Free Hospital, London NW3 2QG, UK
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Ali Deeb A, Rauchfuß F, Gaßler N, Dondorf F, Rohland O, Tannapfel A, Settmacher U. Liver regeneration after two-stage liver transplantation is more effective than after other preconditioning procedures in colorectal liver metastases. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023; 30:615-624. [PMID: 36349494 DOI: 10.1002/jhbp.1266] [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: 05/13/2022] [Revised: 09/08/2022] [Accepted: 10/04/2022] [Indexed: 11/10/2022]
Abstract
INTRODUCTION Induction of liver regeneration represents an option to expand the resectability in patients with expected small future liver remnant (FLR). The aim of this cohort-study is to compare the liver regeneration between different surgical procedures, including novel procedures such as two-stage living donor liver transplantation using small-for-size grafts. METHODS Forty-three patients with colorectal liver metastases were included between 2004 and 2020. They underwent one of the following three procedures: portal vein embolization (PVE), associated liver partition with portal vein ligation for staged hepatectomy (ALPPS), and living donor two-stage liver transplantation (LT). The volume gain of the future liver remnant was analyzed in comparison between the three mentioned procedures. RESULTS The type of surgery performed had a significant correlation with liver regeneration with a strong effect on the benefit of ALPPS and liver transplantation, respectively (r = .6, p = .00003). The type of surgery was the only independent co-factor in the multiple regression, which showed a significant influence on FLR-increase favoring two-stage transplantation compared to the other two related procedures (ß = .12, T = 3.9, p = .0004). The histological and immunohistochemical studies also showed a clear advantage of proliferation to the benefits of two-stage liver transplantation compared with ALPPS. CONCLUSION Two-stage liver transplantation using small-for-size grafts induces better FLR-increase than portal vein embolization or ALPPS in patients with colorectal liver metastases.
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Affiliation(s)
- Aladdin Ali Deeb
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany
| | - Falk Rauchfuß
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany
| | - Nikolaus Gaßler
- Institute of Pathology, Jena University Hospital, Jena, Germany
| | - Felix Dondorf
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany
| | - Oliver Rohland
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany
| | | | - Utz Settmacher
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany
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Sakamoto K, Beppu T, Honda G, Kotake K, Yamamoto M, Takahashi K, Endo I, Hasegawa K, Itabashi M, Hashiguchi Y, Kotera Y, Kobayashi S, Yamaguchi T, Natsume S, Tabuchi K, Kobayashi H, Yamaguchi K, Tani K, Morita S, Miyazaki M, Sugihara K. Comprehensive data of 4502 patients newly diagnosed with colorectal liver metastasis between 2015 and 2017, and prognostic data of 2427 patients newly diagnosed with colorectal liver metastasis in 2013 and 2014: Third report of a nationwide survey in Japan. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023; 30:570-590. [PMID: 36259160 DOI: 10.1002/jhbp.1252] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 08/18/2022] [Accepted: 09/14/2022] [Indexed: 02/20/2025]
Abstract
To improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. The aim of the study was to evaluate transition in the characteristics and treatment strategy in CRLM patients and analyze prognostic factors using large-scale data. The present study summarizes the data of patients newly diagnosed between 2015 and 2017 and presents prognostic data of patients newly diagnosed in 2013 and 2014. Survival curves were generated by the Kaplan-Meier method and compared by log-rank test. Multivariate analyses were carried out using Cox proportional hazard modeling. The data of 4502 patients newly diagnosed with CRLM between 2015 and 2017 and the prognostic data of 2427 patients diagnosed in 2013 and 2014 are included. Regarding the 2013 and 2014 prognostic data, the 5-year overall survival (OS) rates of patients who underwent hepatectomy alone was 59.8%. Multivariate analyses identified age at diagnosis of CRLM ≥70 years, concomitant extrahepatic metastasis at diagnosis of CRLM, tumor depth of primary lesion ≥subserosa/pericolic or perirectal tissue, mutant KRAS status, number of CRLM ≥5, maximum diameter of CRLM >5 cm, and surgical curability R1/R2 as independent predictors of OS. Analysis of the latest nationwide database of patients diagnosed with CRLM revealed changes in patients and oncological characteristics, a transition in treatment strategy, and different independent prognosticators to those reported previously.
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Affiliation(s)
- Katsunori Sakamoto
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Toru Beppu
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
| | - Goro Honda
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Kenjiro Kotake
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Sano City Hospital, Sano, Tochigi, Japan
| | - Masakazu Yamamoto
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Utsunomiya Memorial Hospital, Utsunomiya, Tochigi, Japan
| | - Keiichi Takahashi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Tokyo Metropolitan Health and Hospitals Corporation Ohkubo Hospital, Shinjuku-ku, Tokyo, Japan
| | - Itaru Endo
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
| | - Kiyoshi Hasegawa
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Hepato-Biliary-Pancreatic Surgery Division, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Michio Itabashi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Yojiro Hashiguchi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Yoshihito Kotera
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Shin Kobayashi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa-shi, Chiba, Japan
| | - Tatsuro Yamaguchi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan
| | - Soichiro Natsume
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan
| | - Ken Tabuchi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Pediatrics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan
| | - Hirotoshi Kobayashi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Teikyo University Hospital, Kawasaki, Kanagawa, Japan
| | - Kensei Yamaguchi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Gastrointestinal Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
| | - Kimitaka Tani
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Satoshi Morita
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan
| | - Masaru Miyazaki
- International University of Health and Welfare, Narita Hospital, Minato-ku, Tokyo, Japan
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49
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Huang Y, Jiang H, Xu L, Wu X, Wu J, Zhang Y. 2-4 weeks is the optimal time to operate on colorectal liver metastasis after neoadjuvant chemotherapy. Biosci Trends 2023; 17:160-167. [PMID: 37088556 DOI: 10.5582/bst.2022.01432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2023]
Abstract
Neoadjuvant chemotherapy (NAC) is generally accepted for treatment of liver metastasis of colorectal cancer (CRLM), but what is a reasonable interval between the latest NAC and surgery is still unknown. The aim of the current study was to investigate the proper timing of surgery after NAC. Subjects were 141 patients with CRLM who underwent NAC and then surgery were retrospectively identified from 2008 to 2020. They were divided into a short interval group (SIG, ≤ 4 weeks) and long interval group (LIG, > 4 weeks) using the software X-tile. The SIG was subclassified group into 3 time periods (1-2 weeks, 2-3 weeks, and 3-4 weeks) to assess the incidence of complications. Patients in the SIG were more likely to have significantly better recurrence-free survival (RFS) (3-year RFS of 47.4% vs. 20.5%, P = 0.043) and no difference in overall survival (OS) (3-year OS 76.1% vs. 79.9%, P = 0.635). The postoperative complication rate was 23.5% in the SIG and 14.0% in the LIG (P = 0.198). The postoperative complication rate in the 1-2 weeks subgroup was marginally higher than that in the > 4 weeks subgroup (35% vs. 14.3% P = 0.055). Multivariate analysis revealed that chemotherapy-free intervals of 1-2 weeks were an independent predictor of increased postoperative complications (OR = 0.263, 95% CI 0.7-0.985 P = 0.048). Patients who underwent surgery within 4 weeks of NAC had better RFS. In addition, 1-2 weeks was an independent factor influencing the development of more complications. For patients with CRLM, performing surgery within 2-4weeks of NAC was feasible and safe, and it did not increase the incidence of postoperative complications but it did prolong RFS.
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Affiliation(s)
- Yurun Huang
- Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences, Hangzhou, Zhejiang, China
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Hang Jiang
- Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences, Hangzhou, Zhejiang, China
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Linwei Xu
- Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Xitian Wu
- Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences, Hangzhou, Zhejiang, China
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jia Wu
- Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Yuhua Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences, Hangzhou, Zhejiang, China
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50
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Lee SL, Bassetti MF, Rusthoven CG. The Role of Stereotactic Body Radiation Therapy in the Management of Liver Metastases. Semin Radiat Oncol 2023; 33:181-192. [PMID: 36990635 DOI: 10.1016/j.semradonc.2022.11.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
Abstract
The liver is a common site for metastatic spread for various primary tumor histologies. Stereotactic body radiation therapy (SBRT) is a non-invasive treatment technique with broad patient candidacy for the ablation of tumors in the liver and other organs. SBRT involves focused, high-dose radiation therapy delivered in one to several treatments, resulting in high rates of local control. Use of SBRT for ablation of oligometastatic disease has increased in recent years and emerging prospective data have demonstrated improvements in progression free and overall survival in some settings. When delivering SBRT to liver metastases, clinicians must balance the priorities of delivering ablative tumor dosing while respecting dose constraints to surrounding organs at risk (OARs). Motion management techniques are crucial for meeting dose constraints, ensuring low rates of toxicity, maintaining quality of life, and can allow for dose escalation. Advanced radiotherapy delivery approaches including proton therapy, robotic radiotherapy, and real-time MR-guided radiotherapy may further improve the accuracy of liver SBRT. In this article, we review the rationale for oligometastases ablation, the clinical outcomes with liver SBRT, tumor dose and OAR considerations, and evolving strategies to improve liver SBRT delivery.
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Affiliation(s)
- Sangjune Laurence Lee
- Division of Radiation Oncology, University of Calgary, Tom Baker Cancer Centre, Calgary, AB, Canada.
| | - Michael F Bassetti
- Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison, WI
| | - Chad G Rusthoven
- Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO
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