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Kawashima J, Akabane M, Endo Y, Woldesenbet S, Altaf A, Ruzzenente A, Popescu I, Kitago M, Poultsides G, Sasaki K, Aucejo F, Sahara K, Endo I, Pawlik TM. Recurrence Timing and Risk Following Curative Resection of Colorectal Liver Metastases: Insights From a Hazard Function Analysis. J Surg Oncol 2025; 131:857-864. [PMID: 39574215 PMCID: PMC12120377 DOI: 10.1002/jso.28007] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 10/29/2024] [Indexed: 05/31/2025]
Abstract
INTRODUCTION There is no consensus on the optimal surveillance interval for patients undergoing resection of colorectal liver metastases (CRLM). We sought to assess the timing and intensity of recurrence following curative-intent resection of CRLM utilizing a recurrence-free survival (RFS) hazard function analysis. METHODS Patients with CRLM who underwent curative-intent resection were identified from a multi-institutional database. The RFS hazard function was used to plot hazard rates and identify the peak of recurrence over time. RESULTS Among 1804 patients, the median RFS was 19.9 months. In the analytic cohort, the RFS hazard curve peaked at 5.9 months (peak hazard rate: 0.054) and gradually declined, indicative of early recurrence. In subgroup analyses, patients with high and medium tumor burden scores (TBS) had RFS hazard peaks at 4.9 months (peak hazard rate: 0.060) and 5.8 months (peak hazard rate: 0.054), respectively. In contrast, patients with low TBS had a later peak at 7.5 months, with the lowest peak hazard rate of 0.047. CONCLUSIONS The recurrence peak for CRLM patients occurred approximately 6 months postsurgery, highlighting the need for intensified early postoperative surveillance. Patients with high TBS experienced earlier recurrence, underscoring the importance of close monitoring, particularly during the first 6 months after surgery.
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Affiliation(s)
- Jun Kawashima
- Department of SurgeryThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbusOhioUSA
- Department of Gastroenterological SurgeryYokohama City University School of MedicineYokohamaJapan
| | - Miho Akabane
- Department of SurgeryThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbusOhioUSA
| | - Yutaka Endo
- Department of Transplant SurgeryUniversity of Rochester Medical CenterRochesterNew YorkUSA
| | - Selamawit Woldesenbet
- Department of SurgeryThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbusOhioUSA
| | - Abdullah Altaf
- Department of SurgeryThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbusOhioUSA
| | | | - Irinel Popescu
- Department of SurgeryFundeni Clinical InstituteBucharestRomania
| | | | | | - Kazunari Sasaki
- Department of SurgeryStanford UniversityStanfordCaliforniaUSA
| | - Federico Aucejo
- Department of General SurgeryCleveland Clinic FoundationClevelandOhioUSA
| | - Kota Sahara
- Department of Gastroenterological SurgeryYokohama City University School of MedicineYokohamaJapan
| | - Itaru Endo
- Department of Gastroenterological SurgeryYokohama City University School of MedicineYokohamaJapan
| | - Timothy M. Pawlik
- Department of SurgeryThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbusOhioUSA
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Li Y, Liu F, Cai Q, Deng L, Ouyang Q, Zhang XHF, Zheng J. Invasion and metastasis in cancer: molecular insights and therapeutic targets. Signal Transduct Target Ther 2025; 10:57. [PMID: 39979279 PMCID: PMC11842613 DOI: 10.1038/s41392-025-02148-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 12/24/2024] [Accepted: 01/16/2025] [Indexed: 02/22/2025] Open
Abstract
The progression of malignant tumors leads to the development of secondary tumors in various organs, including bones, the brain, liver, and lungs. This metastatic process severely impacts the prognosis of patients, significantly affecting their quality of life and survival rates. Research efforts have consistently focused on the intricate mechanisms underlying this process and the corresponding clinical management strategies. Consequently, a comprehensive understanding of the biological foundations of tumor metastasis, identification of pivotal signaling pathways, and systematic evaluation of existing and emerging therapeutic strategies are paramount to enhancing the overall diagnostic and treatment capabilities for metastatic tumors. However, current research is primarily focused on metastasis within specific cancer types, leaving significant gaps in our understanding of the complex metastatic cascade, organ-specific tropism mechanisms, and the development of targeted treatments. In this study, we examine the sequential processes of tumor metastasis, elucidate the underlying mechanisms driving organ-tropic metastasis, and systematically analyze therapeutic strategies for metastatic tumors, including those tailored to specific organ involvement. Subsequently, we synthesize the most recent advances in emerging therapeutic technologies for tumor metastasis and analyze the challenges and opportunities encountered in clinical research pertaining to bone metastasis. Our objective is to offer insights that can inform future research and clinical practice in this crucial field.
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Affiliation(s)
- Yongxing Li
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, China
| | - Fengshuo Liu
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
- McNair Medical Institute, Baylor College of Medicine, Houston, TX, USA
- Graduate School of Biomedical Science, Cancer and Cell Biology Program, Baylor College of Medicine, Houston, TX, USA
| | - Qingjin Cai
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, China
| | - Lijun Deng
- Department of Medicinal Chemistry, Third Military Medical University (Army Medical University), Chongqing, China
| | - Qin Ouyang
- Department of Medicinal Chemistry, Third Military Medical University (Army Medical University), Chongqing, China.
| | - Xiang H-F Zhang
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
- McNair Medical Institute, Baylor College of Medicine, Houston, TX, USA.
| | - Ji Zheng
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
- State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing, China.
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Liu J, Tang W, Ye L, Miao G, Zeng M, Liu L. Estimating Efficacy of Conversion Therapy on Patients with Initially Unresectable Colorectal Cancer Liver Metastases by using MRI: Development of a Predictive Score. Acad Radiol 2024; 31:4478-4487. [PMID: 38734578 DOI: 10.1016/j.acra.2024.04.038] [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: 03/09/2024] [Revised: 04/15/2024] [Accepted: 04/22/2024] [Indexed: 05/13/2024]
Abstract
RATIONALE AND OBJECTIVES The conversion success rate (CSR) has crucial implication for clinical outcomes of initially unresectable colorectal liver metastases (CRLM) following conversion therapy. This study aimed to develop a simple predictive scoring model for identifying CSR according to baseline magnetic resonance imaging (MRI) features, and confirm its performance and prognostic significance in a validation cohort. METHODS A total of 155 consecutive patients with initially unresectable CRLM were retrospectively reviewed in the study. A simple MRI-based predictive scoring model for identifying CSR was developed in the development cohort (n = 104) by using multivariable logistic regression analyzes. The diagnostic performance was evaluated for the predictive score. Thereafter, patients in the validation cohort (n = 51) were stratified into groups with predicted high CSR or low CSR according to the score. The progression-free survival (PFS) and overall survival (OS) were compared between two groups using the log-rank test. RESULTS The predictive score of CSR, named mrNISE, incorporated the number of CRLM ≥ 10, the largest size ≥ 50 mm, poorly defined tumor-liver interface, and peritumoral enhancement. The AUC of the mrNISE score was 0.845 for the development cohort and 0.776 for the validation cohort. According to the score, patients with predicted high CSR had better PFS and OS than those with low CSR in both development and validation cohorts. CONCLUSION The predictive score demonstrated great performance for identifying CSR of initially unresectable CRLM. Stratifying patients by the score, personalized treatment goals can be formulated before conversion therapy to improve clinical prognosis and reduce adverse events caused by ineffective treatment.
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Affiliation(s)
- Jingjing Liu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China
| | - Wentao Tang
- Department of General Surgery, Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lechi Ye
- Department of General Surgery, Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Gengyun Miao
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China
| | - Liheng Liu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China.
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Dawood ZS, Brown ZJ, Munir MM, Waqar U, Rawicz-Pruszynski K, Endo Y, Gajjar A, Schenk A, Pawlik TM. Outcomes of liver transplant for colorectal liver metastasis: a systematic review and meta-analysis. J Gastrointest Surg 2024; 28:1943-1950. [PMID: 39271001 DOI: 10.1016/j.gassur.2024.09.006] [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: 07/20/2024] [Revised: 08/31/2024] [Accepted: 09/07/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND Liver transplantation (LT) for nonresectable colorectal liver metastasis (NRCRLM) has become accepted for select patients meeting strict inclusion criteria. Advancements in patient selection and understanding of cancer biology may expand benefits to patients with colorectal liver metastasis (CRLM). In this meta-analysis, we sought to assess survival outcomes, recurrence patterns, and quality of life (QoL) after LT for CRLM. METHODS PubMed, Embase, and Scopus databases were searched. A random-effect meta-analysis was conducted to obtain pooled overall survival (OS) and disease-free survival (DFS) rates and to compare QoL from baseline. Continuous data were analyzed, and standardized mean differences were reported. RESULTS Overall, 16 studies (403 patients, 58.8% male sex) were included. The pooled 1-, 3-, and 5-year OS after LT for NRCRLM was 96% (95% CI: 92%-99%), 77% (95% CI: 62%-89%), and 53% (95% CI: 45%-61%), respectively. Moreover, the pooled 1-, 3-, and 5-year DFS was 58% (95% CI: 43%-72%), 33% (95% CI: 9%-61%), and 13% (95% CI: 4%-27%), respectively. Overall, 201 patients (49.8%) experienced recurrence during the follow-up period with the lungs being the most common site (45.8%). There was no significant differences in physical and emotional functioning, fatigue, and pain components of QoL at 6 months after LT compared with baseline (all P > .05). CONCLUSION LT for NRCRLM demonstrated good OS outcomes with no differences in the QoL at 6 months after transplantation. Transplantation may represent a viable treatment option for NRCRLM.
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Affiliation(s)
| | - Zachary J Brown
- Department of Surgery, Long Island School of Medicine, New York University, Mineola, NY, United States
| | - Muhammad Musaab Munir
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Usama Waqar
- Medical College, The Aga Khan University Hospital, Karachi, Pakistan
| | - Karol Rawicz-Pruszynski
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Yutaka Endo
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Aryan Gajjar
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Austin Schenk
- Division of Transplant, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States.
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Mazzotta AD, Usdin N, Samer D, Tribillon E, Gayet B, Fuks D, Louvet C, Soubrane O. Debulking hepatectomy for colorectal liver metastasis: Analysis of risk factors for progression free survival. Surg Oncol 2024; 55:102056. [PMID: 38531729 DOI: 10.1016/j.suronc.2024.102056] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 02/04/2024] [Accepted: 02/28/2024] [Indexed: 03/28/2024]
Abstract
BACKGROUND The study explores the role of liver debulking surgery in cases of unresectable colorectal liver metastases (CRLM), challenging the traditional notion that surgery is not a valid option in such scenarios. MATERIALS AND METHODS Patients with advanced but resectable disease who underwent surgery with a curative intent (Group I) and those with advanced incompletely resectable disease who underwent a "debulking" hepatectomy (Group II) were compared. RESULTS There was no difference in the intra-operative and post-operative results between the two groups. The 3-year and 5-year OS rates were 69% and 47% for group 1 vs 64% and 35% for group 2 respectively (p = 0.14). The 3-year and 5-year PFS rates were 32% and 21% for group 1 vs 12% and 8% for group 2 respectively (p = 0.009). Independent predictors of PFS in the debulking group were bilobar metastases (HR = 2.70; p = 0.02); the presence of extrahepatic metastasis (HR = 2.65, p = 0.03) and the presence of more than 9 metastases (HR = 2.37; p = 0.04). Iterative liver surgery for CRLM was a significant protective factor (HR = 0.34, p = 0.04). CONCLUSION An aggressive palliative surgical approach may offer a survival benefit for selected patients with unresectable CRLM, without increasing the morbidity. The decision for surgery should be made on a case-by-case basis.
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Affiliation(s)
- Alessandro D Mazzotta
- Department of Digestive, Oncological and Metabolic Surgery, Institut Mutualiste Montsouris, 42, Boulevard Jourdan, 75014, Paris, France.
| | - Nita Usdin
- Département d'oncologie Médicale, Institut Mutualiste Montsouris, 42, Boulevard Jourdan, 75014, Paris, France
| | - Diab Samer
- Department of Digestive, Oncological and Metabolic Surgery, Institut Mutualiste Montsouris, 42, Boulevard Jourdan, 75014, Paris, France
| | - Ecoline Tribillon
- Department of Digestive, Oncological and Metabolic Surgery, Institut Mutualiste Montsouris, 42, Boulevard Jourdan, 75014, Paris, France
| | - Brice Gayet
- Department of Digestive, Oncological and Metabolic Surgery, Institut Mutualiste Montsouris, 42, Boulevard Jourdan, 75014, Paris, France
| | - David Fuks
- Department of Hepato-Pancreatic-Biliary and Endocrine Surgery, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 75014, Paris, France; Université de Paris, Faculté de Médecine, 75006, Paris, France
| | - Christophe Louvet
- Département d'oncologie Médicale, Institut Mutualiste Montsouris, 42, Boulevard Jourdan, 75014, Paris, France
| | - Olivier Soubrane
- Department of Digestive, Oncological and Metabolic Surgery, Institut Mutualiste Montsouris, 42, Boulevard Jourdan, 75014, Paris, France
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Endo Y, Alaimo L, Moazzam Z, Woldesenbet S, Lima HA, Munir MM, Shaikh CF, Yang J, Azap L, Katayama E, Guglielmi A, Ruzzenente A, Aldrighetti L, Alexandrescu S, Kitago M, Poultsides G, Sasaki K, Aucejo F, Pawlik TM. Postoperative morbidity after simultaneous versus staged resection of synchronous colorectal liver metastases: Impact of hepatic tumor burden. Surgery 2024; 175:432-440. [PMID: 38001013 DOI: 10.1016/j.surg.2023.10.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 10/09/2023] [Accepted: 10/25/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND We sought to characterize the risk of postoperative complications relative to the surgical approach and overall synchronous colorectal liver metastases tumor burden score. METHODS Patients with synchronous colorectal liver metastases who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. Propensity score matching was employed to control for heterogeneity between the 2 groups. A virtual twins analysis was performed to identify potential subgroups of patients who might benefit more from staged versus simultaneous resection. RESULTS Among 976 patients who underwent liver resection for synchronous colorectal liver metastases, 589 patients (60.3%) had a staged approach, whereas 387 (39.7%) patients underwent simultaneous resection of the primary tumor and synchronous colorectal liver metastases. After propensity score matching, 295 patients who underwent each surgical approach were analyzed. Overall, the incidence of postoperative complications was 34.1% (n = 201). Among patients with high tumor burden scores, the surgical approach was associated with a higher incidence of postoperative complications; in contrast, among patients with low or medium tumor burden scores, the likelihood of complications did not differ based on the surgical approach. Virtual twins analysis demonstrated that preoperative tumor burden score was important to identify which subgroup of patients benefited most from staged versus simultaneous resection. Simultaneous resection was associated with better outcomes among patients with a tumor burden score <9 and a node-negative right-sided primary tumor; in contrast, staged resection was associated with better outcomes among patients with node-positive left-sided primary tumors and higher tumor burden score. CONCLUSION Among patients with high tumor burden scores, simultaneous resection of the primary tumor and liver metastases was associated with an increased incidence of postoperative complications.
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Affiliation(s)
- Yutaka Endo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Laura Alaimo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH; Department of Surgery, University of Verona, Italy
| | - Zorays Moazzam
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Selamawit Woldesenbet
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Henrique A Lima
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Muhammad Musaab Munir
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Chanza F Shaikh
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Jason Yang
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Lovette Azap
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Erryk Katayama
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | | | | | | | | | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | | | | | - Federico Aucejo
- Department of General Surgery, Cleveland Clinic Foundation, OH
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH.
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Amygdalos I, Hitpass L, Schmidt F, Josephs G, Bednarsch J, Berres ML, Lüdde T, Olde Damink SWM, Ulmer TF, Neumann UP, Bruners P, Lang SA. Survival after combined resection and ablation is not inferior to that after resection alone, in patients with four or more colorectal liver metastases. Langenbecks Arch Surg 2023; 408:343. [PMID: 37642753 PMCID: PMC10465667 DOI: 10.1007/s00423-023-03082-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 08/19/2023] [Indexed: 08/31/2023]
Abstract
PURPOSE Colorectal liver metastases (CRLM) are the predominant factor limiting survival in patients with colorectal cancer. Multimodal treatment strategies are frequently necessary to achieve total tumor elimination. This study examines the efficacy of liver resection combined with local ablative therapy in comparison to liver resection only, in the treatment of patients with ≥ 4 CRLM. METHODS This retrospective cohort study was conducted at the University Hospital RWTH Aachen, Germany. Patients with ≥ 4 CRLM in preoperative imaging, who underwent curative resection between 2010-2021, were included. Recurrent resections and deaths in the early postoperative phase were excluded. Ablation modalities included radiofrequency or microwave ablation, and irreversible electroporation. Differences in overall- (OS) and recurrence-free-survival (RFS) between patients undergoing combined resection-ablation vs. resection only, were examined. RESULTS Of 178 included patients, 46 (27%) underwent combined resection-ablation and 132 (73%) resection only. Apart from increased rates of adjuvant chemotherapy in the first group (44% vs. 25%, p = 0.014), there were no differences in perioperative systemic therapy. Kaplan-Meier and log-rank test analyses showed no statistically significant differences in median OS (36 months for both, p = 0.638) or RFS (9 months for combined resection-ablation vs. 8 months, p = 0.921). Cox regression analysis showed a hazard ratio of 0.891 (p = 0.642) for OS and 0.981 (p = 0.924) for RFS, for patients undergoing resection only. CONCLUSION For patients with ≥ 4 CRLM, combined resection-ablation is a viable option in terms of OS and RFS. Therefore, combined resection-ablation should be considered for complete tumor clearance, in patients with multifocal disease.
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Affiliation(s)
- Iakovos Amygdalos
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany.
| | - Lea Hitpass
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen, Germany
| | - Felix Schmidt
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
| | - Gerrit Josephs
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
| | - Jan Bednarsch
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
| | - Marie-Luise Berres
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Tom Lüdde
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Steven W M Olde Damink
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Tom Florian Ulmer
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
| | - Ulf P Neumann
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Philipp Bruners
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen, Germany
| | - Sven Arke Lang
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
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van der Ven RGFM, Westra D, van Erning FN, de Hingh IH, Olde Damink SWM, Paulus A, Leclercq WKG, den Dulk M. The impact of a multi-hospital network on the inequality in odds of receiving resection or ablation for synchronous colorectal liver metastases. Acta Oncol 2023; 62:842-852. [PMID: 37548150 DOI: 10.1080/0284186x.2023.2238545] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 07/04/2023] [Indexed: 08/08/2023]
Abstract
BACKGROUND This study investigates whether inequalities in the utilization of resection and/or ablation for synchronous colorectal liver metastases (SCLM) between patients diagnosed in expert and non-expert hospitals changed since a multi-hospital network started. MATERIALS AND METHODS Patients diagnosed with SCLM between 2009 and 2020 were included. The likelihood of receiving ablation and/or resection was analyzed in the prenetwork (2009-2012), startup (2013-2016), and matured-network (2017-2020) periods. RESULTS Nationwide, 13.981patients were diagnosed between 2009 and 2020, of whom 1.624 were diagnosed in the network. Of patients diagnosed in the network's expert hospitals, 36.7% received ablation and/or resection versus 28.3% in nonexpert hospitals (p < 0.01). The odds ratio (OR) of receiving ablation and/or resection for patients diagnosed in expert versus nonexpert hospitals increased from 1.38 (p = 0.581, pre-network), to 1.66 (p = 0.108, startup), to 2.48 (p = 0.090, matured-network). Nationwide, the same trend occurred (respectively OR 1.41, p = 0.011; OR 2.23, p < 0.001; OR 3.20, p < 0.001). CONCLUSIONS Patients diagnosed in expert hospitals were more likely to receive ablation and/or resection for SCLM than patients diagnosed in non-expert hospitals. This difference increased over time despite the startup of a multi-hospital network. Establishing a multi-hospital network did not have an effect on reducing the existing unequal odds of receiving specialized treatment. SYNOPSIS Specialized oncology treatments are increasingly provided through multi-hospital networks. However, scant empirical evidence on the effectiveness of these networks exists. This study analyzes whether a regional multi-hospital network was able to improve equal access to specialized oncology treatments.
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Affiliation(s)
- Roos G F M van der Ven
- Department of Health Services Research, Faculty of Health, Care and Public Health Research Institute (CAPHRI), Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, Maastricht, The Netherlands
- Department of Oncology and Developmental Biology (GROW), Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, Maastricht, The Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
| | - Daan Westra
- Department of Health Services Research, Faculty of Health, Care and Public Health Research Institute (CAPHRI), Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, Maastricht, The Netherlands
| | - Felice N van Erning
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Ignace H de Hingh
- Department of Oncology and Developmental Biology (GROW), Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, Maastricht, The Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Steven W M Olde Damink
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
- Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, Aachen, Germany
| | - Agnes Paulus
- Department of Health Services Research, Faculty of Health, Care and Public Health Research Institute (CAPHRI), Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, Maastricht, The Netherlands
- Faculty of Health, Medicine and Life Sciences (FHML), School of Health Professions Education (SHE), Maastricht University, Maastricht, The Netherlands
| | - Wouter K G Leclercq
- Department of Surgery, Máxima Medical Center, Eindhoven and Veldhoven, The Netherlands
| | - Marcel den Dulk
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
- Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, Aachen, Germany
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9
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Ruff SM, Pawlik TM. A Review of Translational Research for Targeted Therapy for Metastatic Colorectal Cancer. Cancers (Basel) 2023; 15:cancers15051395. [PMID: 36900187 PMCID: PMC10000872 DOI: 10.3390/cancers15051395] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/12/2023] [Accepted: 02/20/2023] [Indexed: 02/25/2023] Open
Abstract
Colorectal cancer is the third most common cause of cancer-related death in the United States, with 20% of patients presenting with metastatic disease at the time of diagnosis. Metastatic colon cancer is often treated with a combination of surgery, systemic therapy (chemotherapy, biologic therapy, immunotherapy), and/or regional therapy (hepatic artery infusion pumps). Utilizing the molecular and pathologic features of the primary tumor to tailor treatment for patients may improve overall survival. Rather than a "one size fits all" approach, a more nuanced treatment plan guided by the unique features of a patient's tumor and the tumor's microenvironment can more effectively treat the disease. Basic science work to elucidate new drug targets, understand mechanisms of evasion, and develop drugs and drug combinations is critical to inform clinical trials and identify novel, effective therapies for metastatic colorectal cancer. Through the lens of key targets for metastatic colorectal cancer, this review discusses how work in the basic science lab translates into clinical trials.
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10
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Lin J, Sun H, Zhang W, Hong Z, Lu Z, Pan Z, Hou Z, Peng J. Conversion therapy with the intent to perform radical local treatment may not be suitable for patients with 10 or more liver metastases from colorectal cancer. Cancer Med 2022; 11:4225-4235. [PMID: 35466587 DOI: 10.1002/cam4.4775] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 02/18/2022] [Accepted: 04/01/2022] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The number of colorectal cancer liver metastases (CRLMs) is usually considered a contradictory indicator to surgical resection. However, some patients with initially unresectable CRLMs can receive radical local treatment after conversion therapy. This study aimed to evaluate the effect of radical local treatment after conversion therapy and the prognosis of patients with more than 10 initially unresectable CRLMs. METHODS Data for a total of 229 patients with initially unresectable CRLMs were retrospectively reviewed between December 2012 and January 2020. Among these patients, 107 had ≥10 CRLMs, and 122 had <10 CRLMs. Overall survival (OS) and progression-free survival (PFS) were used to reflect the prognosis of different groups of patients. Conversion therapy was defined as an initially unresectable liver metastasis converted into an R0 resectable lesion after systemic chemotherapy. Radical local treatment included hepatectomy and radiofrequency ablation (RFA). RESULTS Patients with ≥10 CRLMs had a lower conversion rate (42.7% vs. 56.6%, p = 0.001). Baseline clinical N stage 1-2, ≥8 first-line chemotherapy courses, and stable disease (SD) according to the Response Evaluation Criteria in Solid Tumours (RECIST) were independent factors predictive of conversion failure. Primary tumour location in the right colon, RECIST response of SD, and the absence of targeted therapy were independent factors predictive of unfavourable OS. The survival curves revealed that the OS of patients with or without conversion could be distinguished only among patients with <10 CRLMs (89.9% [95% CI, 82.5%-98.0%] vs. 58.9% [95% CI, 45.2%-76.7%], p < 0.001); this cut-off point could also distinguish patients with a successful conversion outcome according to OS (89.9% [95% CI, 82.5-98.0%] vs. 58.2% [95% CI, 42.2-80.4%], p = 0.008). CONCLUSION For CRLMs ≥ 10, patients with a successful conversion outcome cannot be distinguished from those without successful conversion outcome according to OS. Thus, conversion therapy with the intent to perform radical local treatment may not be suitable for patients with 10 or more liver metastases from colorectal cancer.
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Affiliation(s)
- Junzhong Lin
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
| | - Hui Sun
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P. R. China
| | - Weili Zhang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
| | - Zhigang Hong
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
| | - Zhenhai Lu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
| | - Zhizhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
| | - Zhenlin Hou
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
| | - Jianhong Peng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
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11
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Tsilimigras DI, Hyer JM, Bagante F, Guglielmi A, Ruzzenente A, Alexandrescu S, Poultsides G, Sasaki K, Aucejo F, Pawlik TM. Resection of Colorectal Liver Metastasis: Prognostic Impact of Tumor Burden vs KRAS Mutational Status. J Am Coll Surg 2020; 232:590-598. [PMID: 33383214 DOI: 10.1016/j.jamcollsurg.2020.11.023] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 11/30/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The prognostic impact of colorectal liver metastasis (CRLM) morphologic characteristics relative to KRAS mutational status after hepatic resection remains ill defined. STUDY DESIGN Patients undergoing hepatectomy for CRLM between 2001 and 2018 were identified using an international multi-institutional database. Tumor burden score (TBS) was defined as distance from origin on a Cartesian plane that incorporated maximum tumor size (x-axis) and number of lesions (y-axis). Impact of TBS on overall survival (OS) relative to KRAS status (wild type [wtKRAS] vs mutated [mutKRAS]) was assessed. RESULTS Among 1,361 patients, the median number of metastatic lesions was 2 (interquartile range [IQR] 1-3), and median size of the largest metastatic lesion was 3.0 cm (IQR 2.0-5.0 cm), resulting in a median TBS of 4.1 (IQR 2.8-6.1); KRAS status was wtKRAS (n = 420, 30.9%), mutKRAS (n = 251, 18.4%), and unknown (n = 690, 50.7%). Overall median and 5-year OS were 49.5 months (95%CI 45.2-53.8) and 43.2%, respectively. In examining the entire cohort, TBS was associated with long-term prognosis (5-year OS, low TBS: 49.4% vs high TBS: 36.7%), as was KRAS mutational status (5-year OS, wtKRAS: 48.2% vs mutKRAS: 31.1%; unknown KRAS: 44.0%)(both p < 0.01). Among patients with wtKRAS tumors, TBS was strongly associated with improved OS (5-year OS, low TBS: 59.1% vs high TBS: 38.4%, p = 0.002); however, TBS failed to discriminate long-term prognosis among patients with mutKRAS tumors (5-year OS, low TBS: 37.4% vs high TBS: 26.7%, p = 0.19). In fact, patients with high TBS/wtKRAS CRLM had comparable outcomes to patients with low TBS/mutKRAS tumors (5-year OS, 38.4% vs 37.4%, respectively; p = 0.59). On multivariable analysis, while TBS was associated with OS among patients with wtKRAS CRLM (hazard ratio 1.43, 95%CI 1.02-2.00; p = 0.03), TBS was not an independent predictor of survival among patients with mutKRAS CRLM (HR 1.36, 95%CI 0.92-1.99; p = 0.12). CONCLUSIONS While TBS was associated with survival among patients with wtKRAS tumors, CRLM morphology was not predictive of long-term outcomes among patients with mutKRAS CRLM.
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Affiliation(s)
| | - J Madison Hyer
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Fabio Bagante
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH; University of Verona, Verona, Italy
| | | | | | | | | | | | | | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH.
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12
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Morin C, Drolet S, Daigle C, Deshaies I, Ouellet JF, Ball CG, Dixon E, Marceau J, Ouellet JFB. Additional value of gadoxetic acid-enhanced MRI to conventional extracellular gadolinium-enhanced MRI for the surgical management of colorectal and neuroendocrine liver metastases. HPB (Oxford) 2020; 22:710-715. [PMID: 31640929 DOI: 10.1016/j.hpb.2019.09.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 07/04/2019] [Accepted: 09/14/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Liver resection being the only potentially curative treatment for patients with liver metastasis, it is critical to select the appropriate preoperative imaging modality. The aim of this study was to assess the impact of preoperative gadoxetic acid-enhanced MRI compared to a conventional extracellular gadolinium-enhanced MRI on the surgical management of colorectal and neuroendocrine liver metastasis. METHODS We included 110 patients who underwent both a gadoxetic acid-enhanced MRI (hepatospecific contrast) and conventional extracellular gadolinium for the evaluation of colorectal or neuroendocrine liver metastases, from January 2012 to December 2015 at the CHU de Québec - Université Laval. When the number of lesions differed, a hepatobiliary surgeon evaluated if the gadoxetic acid-enhanced MRI modified the surgical management. RESULTS Gadoxetic acid-enhanced MRI found new lesions in 25 patients (22.7%), excluded lesions in 18 patients (16.4%) and identified the same number in 67 patients (60.9%). The addition of the gadoxetic acid-enhanced MRI directly altered the surgical management in 19 patients overall (17.3% (95% CI [10.73-25.65])). CONCLUSION Despite the additional cost associated with gadoxetic acid-enhanced MRI compared to conventional extracellular gadolinium-enhanced MRI, the use of this contrast agent has a significant impact on the surgical management of patients with liver metastases.
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Affiliation(s)
- Claudya Morin
- CHU de Québec - Université Laval, 11 Côte du Palais, Quebec, G1R 2J6 QC, Canada.
| | - Sebastien Drolet
- CHU de Québec - Université Laval, 11 Côte du Palais, Quebec, G1R 2J6 QC, Canada
| | - Carl Daigle
- CHU de Québec - Université Laval, 11 Côte du Palais, Quebec, G1R 2J6 QC, Canada
| | - Isabelle Deshaies
- CHU de Québec - Université Laval, 11 Côte du Palais, Quebec, G1R 2J6 QC, Canada
| | | | - Chad G Ball
- Foothills Medical Centre - University of Calgary, 1403 29 St NW, Calgary, T2N 2T9 Alberta, Canada
| | - Elijah Dixon
- Foothills Medical Centre - University of Calgary, 1403 29 St NW, Calgary, T2N 2T9 Alberta, Canada
| | - Julie Marceau
- CHU de Québec - Université Laval, 11 Côte du Palais, Quebec, G1R 2J6 QC, Canada
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13
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[Role of the radiologist in surgery of colorectal liver metastases : What should be removed and what must remain]. Radiologe 2019; 59:791-798. [PMID: 31410495 DOI: 10.1007/s00117-019-0577-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The radical resection of colorectal liver metastases is the only curative option for affected patients. If properly performed, surgery provides the chance of long-term tumor-free survival. OBJECTIVE Summary of the critical interaction points between radiology and surgery in the planning and performance of (complex) liver resections. RESULTS There are many interaction points between radiology and surgery in the treatment of patients with colorectal liver metastases. Radiology supports surgery by providing detailed information of the localization of metastases, information on liver inflow and outflow as well as basic information on liver quality and function. Perioperatively, it provides interventional treatment options for postoperative complications as well as ablation of non-resectable metastases. CONCLUSION Complex liver resections can only be performed properly and successfully after thorough planning by an interdisciplinary board of surgeons, radiologists and associated disciplines.
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Georgakis GV, Goldberg I, Sasson AR. Current Trends in the Surgical Management of Colorectal Cancer Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2019. [DOI: 10.1007/s11888-019-00440-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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15
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Sasaki K, Morioka D, Conci S, Margonis GA, Sawada Y, Ruzzenente A, Kumamoto T, Iacono C, Andreatos N, Guglielmi A, Endo I, Pawlik TM. The Tumor Burden Score: A New "Metro-ticket" Prognostic Tool For Colorectal Liver Metastases Based on Tumor Size and Number of Tumors. Ann Surg 2018; 267:132-141. [PMID: 27763897 DOI: 10.1097/sla.0000000000002064] [Citation(s) in RCA: 317] [Impact Index Per Article: 45.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To apply the principles of the Metro-ticket paradigm to develop a prognostic model for patients undergoing hepatic resection of colorectal liver metastasis (CRLM). BACKGROUND Whereas the hepatocellular "Metro-ticket" prognostic tool utilizes a continuum of tumor size and number, a similar concept of a CRLM Metro-ticket paradigm has not been investigated. METHODS Tumor Burden Score (TBS) was defined using distance from the origin on a Cartesian plane incorporating maximum tumor size (x-axis) and number of lesions (y-axis). The discriminatory power [area under the curve (AUC)] and goodness-of-fit (Akaike information criteria) of the TBS model versus standard tumor morphology categorization were assessed. The TBS model was validated using 2 external cohorts from Asia and Europe. RESULTS TBS (AUC 0.669) out-performed both maximum tumor size (AUC 0.619) and number of tumors (AUC 0.595) in predicting overall survival (OS) (P < 0.05). As TBS increased, survival incrementally worsened (5-year OS: zone 1, zone 2, and zone 3-68.9%, 49.4%, and 25.5%; P < 0.05). The stratification of survival based on traditional tumor size and number cut-off criteria was poor. Specifically, 5-year survival for patients in category 1, category 2, and category 3 was 58.3%, 45.5%, and 50.6%, respectively (P > 0.05). The corrected Akaike score information criteria value of the TBS model (2865) was lower than the traditional tumor morphologic categorization model (2905). Survival analysis revealed excellent prognostic discrimination for the TBS model among patients in both external cohorts (P< 0.05). CONCLUSIONS An externally validated "Metro-ticket" TBS model had excellent prognostic discriminatory power. TBS may be an accurate tool to account for the impact of tumor morphology on long-term survival among patients undergoing resection of CRLM.
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Affiliation(s)
- Kazunari Sasaki
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Daisuke Morioka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Simone Conci
- General and Hepatobiliary Surgery, Department of Surgery, University of Verona, Verona, Italy
| | - Georgios A Margonis
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Yu Sawada
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Andrea Ruzzenente
- General and Hepatobiliary Surgery, Department of Surgery, University of Verona, Verona, Italy
| | - Takafumi Kumamoto
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Calogero Iacono
- General and Hepatobiliary Surgery, Department of Surgery, University of Verona, Verona, Italy
| | - Nikolaos Andreatos
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Alfredo Guglielmi
- General and Hepatobiliary Surgery, Department of Surgery, University of Verona, Verona, Italy
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
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Moris D, Pawlik TM. Personalized treatment in patients with colorectal liver metastases. J Surg Res 2017; 216:26-29. [PMID: 28807210 DOI: 10.1016/j.jss.2017.04.013] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Revised: 02/19/2017] [Accepted: 04/11/2017] [Indexed: 12/31/2022]
Abstract
BACKGROUND Precision Medicine Initiative is a new research effort aiming to offer personalized treatment in many diseases, including cancer. The aim of the present article is to offer novel insights about the role of personalized treatment in patients with colorectal liver metastases (CRLM). METHODS A review of the literature regarding personalized medicine and colorectal liver metastases was performed mainly in the MEDLINE/PubMed database. RESULTS Surgical resection remains the only hope for cure of CRLM. Improved surgical strategies to optimize remnant liver volume are recently introduced and gaining ground. Following resection of CRLM scoring systems have been developed by combining certain preoperative factors such as microsatellite instability KRAS expression and sensitivity to immunotherapy with Programmed Death-1 inhibitor. CONCLUSIONS Multidisciplinary management of patients with CRLM has markedly contributed to increased survival. While the last several decades have been characterized by these important developments, future advances for patients with CRLM will depend on a better understanding of genomics and molecular biology to facilitate characterization of a specific tumor "identity" so that individualized treatment for each CRLM patient becomes the rule, and not the exception.
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Affiliation(s)
- Dimitrios Moris
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio.
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio
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17
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Al Bandar MH, Kim NK. Current status and future perspectives on treatment of liver metastasis in colorectal cancer (Review). Oncol Rep 2017; 37:2553-2564. [PMID: 28350137 DOI: 10.3892/or.2017.5531] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2016] [Accepted: 03/13/2017] [Indexed: 12/29/2022] Open
Abstract
Liver metastasis is the most common site of colorectal cancer (CRC) metastasis. Approximately half of all colorectal cancer patients will develop liver metastases. Although radical surgery is the standard treatment modality, only 10-20% of patients are deemed eligible for resection. Despite advances in survival with chemotherapy, surgical resection is still considered the only curative option for patients with liver metastases. Much effort has been expended to address patients with metastatic liver disease. The majority of evidence stated a significant survival benefit with surgical resection to reach an overall 5-year survival rate of 35-55% after hepatic resection. However, still majority of patients will experience disease recurrence even after a successful resection. In this review, we describe current status and controversies related to treatment options for CRC liver metastases and its potential for enhancing oncologic outcomes and improving quality of life.
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Affiliation(s)
- Mahdi Hussain Al Bandar
- Department of Surgery, Yonsei University, College of Medicine, Seoul 120-752, Republic of Korea
| | - Nam Kyu Kim
- Department of Surgery, Yonsei University, College of Medicine, Seoul 120-752, Republic of Korea
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18
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Asencio JM, García-Sabrido JL, López-Baena JA, Olmedilla L, Peligros I, Lozano P, Morales-Taboada Á, Fernández-Mena C, Steiner MA, Sola E, Perez-Peña JM, Herrero M, Laso J, Lisbona C, Bañares R, Casanova J, Vaquero J. Preconditioning by portal vein embolization modulates hepatic hemodynamics and improves liver function in pigs with extended hepatectomy. Surgery 2017; 161:1489-1501. [PMID: 28117095 DOI: 10.1016/j.surg.2016.12.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Revised: 12/01/2016] [Accepted: 12/03/2016] [Indexed: 01/10/2023]
Abstract
BACKGROUND Portal vein embolization is performed weeks before extended hepatic resections to increase the future liver remnant and prevent posthepatectomy liver failure. Portal vein embolization performed closer to the operation also could be protective, but worsening of portal hyper-perfusion is a major concern. We determined the hepatic hemodynamic effects of a portal vein embolization performed 24 hours prior to hepatic operation. METHODS An extended (90%) hepatectomy was performed in swine undergoing (portal vein embolization) or not undergoing (control) a portal vein embolization 24 hours earlier (n = 10/group). Blood tests, hepatic and systemic hemodynamics, hepatic function (plasma disappearance rate of indocyanine green), liver histology, and volumetry (computed tomographic scanning) were assessed before and after the hepatectomy. Hepatocyte proliferating cell nuclear antigen expression and hepatic gene expression also were evaluated. RESULTS Swine in the control and portal vein embolization groups maintained stable systemic hemodynamics and developed similar increases of portal blood flow (302 ± 72% vs 486 ± 92%, P = .13). Portal pressure drastically increased in Controls (from 9.4 ± 1.3 mm Hg to 20.9 ± 1.4 mm Hg, P < .001), while being markedly attenuated in the portal vein embolization group (from 11.4 ± 1.5 mm Hg to 16.1 ± 1.3 mm Hg, P = .061). The procedure also improved the preservation of the hepatic artery blood flow, liver function, and periportal edema. These effects occurred in the absence of hepatocyte proliferation or hepatic growth and were associated with the induction of the vasoprotective gene Klf2. CONCLUSION Portal vein embolization preconditioning represents a potential hepato-protective strategy for extended hepatic resections. Further preclinical studies should assess its medium-term effects, including survival. Our study also supports the relevance of hepatic hemodynamics as the main pathogenetic factor of post-hepatectomy liver failure.
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Affiliation(s)
- José M Asencio
- Servicio de Cirugía General III, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Facultad de Medicina, Univ. Complutense de Madrid, Madrid, Spain.
| | - José L García-Sabrido
- Servicio de Cirugía General III, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Facultad de Medicina, Univ. Complutense de Madrid, Madrid, Spain
| | - José A López-Baena
- Servicio de Cirugía General III, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Facultad de Medicina, Univ. Complutense de Madrid, Madrid, Spain
| | - Luis Olmedilla
- Servicio de Anestesia y Reanimación, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Isabel Peligros
- Servicio de Anatomía Patológica, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Pablo Lozano
- Servicio de Cirugía General III, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Álvaro Morales-Taboada
- Servicio de Cirugía General III, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Carolina Fernández-Mena
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Miguel A Steiner
- Servicio de Cirugía General III, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Emma Sola
- Servicio de Anatomía Patológica, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - José M Perez-Peña
- Servicio de Anestesia y Reanimación, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Miriam Herrero
- Servicio de Anestesia y Reanimación, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Juan Laso
- Servicio de Anestesia y Reanimación, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Cristina Lisbona
- Servicio de Anestesia y Reanimación, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Rafael Bañares
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Facultad de Medicina, Univ. Complutense de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Javier Casanova
- Servicio de Anestesia y Reanimación, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Javier Vaquero
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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Zampino M, Magni E, Ravenda P, Cella C, Bonomo G, Della Vigna P, Galdy S, Spada F, Varano G, Mauri G, Fazio N, Orsi F. Treatments for colorectal liver metastases: A new focus on a familiar concept. Crit Rev Oncol Hematol 2016; 108:154-163. [DOI: 10.1016/j.critrevonc.2016.11.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Revised: 10/09/2016] [Accepted: 11/13/2016] [Indexed: 11/17/2022] Open
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Sasaki K, Margonis GA, Andreatos N, Wilson A, Gani F, Amini N, Pawlik TM. Pre-hepatectomy carcinoembryonic antigen (CEA) levels among patients undergoing resection of colorectal liver metastases: do CEA levels still have prognostic implications? HPB (Oxford) 2016; 18:1000-1009. [PMID: 27769662 PMCID: PMC5144549 DOI: 10.1016/j.hpb.2016.09.004] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 08/07/2016] [Accepted: 09/14/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND The impact of prehepatectomy carcinoembryonic antigen (CEA) levels in the era of modern chemotherapy and expanded surgical indications for colorectal liver metastasis (CRLM) remains not well defined. METHODS 484 patients were identified and divided into two groups by surgical time period (group 1: 2000-2007 vs. group 2: 2008-2015). The prognostic significance of pre-hepatectomy CEA was determined by assessing the HRs associated with various cut-off levels ranging from 5 to 200 ng/mL. RESULTS Median CRLM number was comparable in both groups (group 1: 2 vs. group 2: 2, P = 0.504). Bilobar disease was more frequent in group 2 (30.1% vs. 42.5%, P = 0.006). The administration of modern chemotherapy and/or biologic agents increased over time (49.5% vs. 67.9%, P < 0.001). Preoperative CEA independently predicted OS in group 1, even with a cut-off as low as >5 ng/mL. However, in group 2 it predicted recurrence and survival only after exceeding 70 and 50 ng/mL, respectively. Of note, in group 2, CEA was strongly associated with survival when CEA levels exceeded 70 ng/mL (HR 4.84). CONCLUSIONS While pre-hepatectomy CEA level may still have prognostic utility in CRLM resection, the optimal cut-off value has increased in the era of modern chemotherapy.
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Affiliation(s)
| | | | | | | | | | | | - Timothy M. Pawlik
- Correspondence Timothy M. Pawlik, Division of Surgical Oncology, Department of Surgery, Johns Hopkins Hospital, 600 N. Wolfe Street, Blalock 688, Baltimore, MD 21287, USA. Tel: +1 (410) 502 2387. Fax: +1 (410) 502 2388.Division of Surgical OncologyDepartment of SurgeryJohns Hopkins Hospital600 N. Wolfe StreetBlalock 688BaltimoreMD21287USA
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Li J, Ewald F, Gulati A, Nashan B. Associating liver partition and portal vein ligation for staged hepatectomy: From technical evolution to oncological benefit. World J Gastrointest Surg 2016; 8:124-133. [PMID: 26981186 PMCID: PMC4770166 DOI: 10.4240/wjgs.v8.i2.124] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Revised: 10/08/2015] [Accepted: 12/11/2015] [Indexed: 02/06/2023] Open
Abstract
Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel approach in liver surgery that allows for extensive resection of liver parenchyma by inducing a rapid hypertrophy of the future remnant liver. However, recent reports indicate that not all patients eligible for ALPPS will benefit from this procedure. Therefore, careful patient selection will be necessary to fully exploit possible benefits of ALPPS. Here, we provide a comprehensive overview of the technical evolution of ALPPS with a special emphasis on safety and oncologic efficacy. Furthermore, we review the contemporary literature regarding indication and benefits, but also limitations of ALPPS.
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Abstract
For the 20% of patients with resectable colorectal liver metastases (CRLM), hepatic resection is safe, effective and potentially curative. Factors related to the primary and metastatic tumors individually and in clinical risk-scoring schemes are the best prognostic factors, although it is difficult to define patient groups with resectable, liver-limited CRLM that should be excluded from surgery. Systemic chemotherapy for metastatic colorectal cancer has improved but does not improve overall survival as adjuvant therapy after resection. Conversion to complete resection with systemic and/or hepatic arterial infusion chemotherapy is an appropriate goal for patients with unresectable CRLM.
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Abstract
OPINION STATEMENT When possible, surgical resection remains the "gold standard" for the treatment of hepatic colorectal metastases. Liver resection should be considered when complete removal of all macroscopic disease can be achieved safely. For those patients with unresectable metastases, or when a patient may not be a candidate for liver resection, many choices are available to the clinician in an attempt to achieve locoregional control, including tumor ablation, intra-arterial therapies, and radiation therapy. Whereas with surgical resection, durable local control can be considered potentially curable, other liver-directed approaches currently are mostly palliative. Ongoing trials are being undertaken to evaluate the role of such cytoreductive therapies. During the initial evaluation of any patient who might be a candidate for liver-directed therapy, particularly when the intent may be curative, complete assessment with high-quality imaging should be done before any therapy to determine the full extent of disease. Most importantly, the establishment of a multidisciplinary team upon initial diagnosis can optimize the choice and sequencing of the various systemic and locoregional choices available to the colorectal cancer patient.
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Affiliation(s)
- Michael A Choti
- Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9031, USA,
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Conversion Chemotherapy for Unresectable Colorectal Liver Metastases: Are We Making a Difference? CURRENT COLORECTAL CANCER REPORTS 2015. [DOI: 10.1007/s11888-015-0271-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Navarro-Freire F, Navarro-Sánchez P, García-Agua N, Pérez-Cabrera B, Palomeque-Jiménez A, Jiménez-Rios JA, García-López PA, García-Ruiz AJ. Effectiveness of surgery in liver metastasis from colorectal cancer: experience and results of a continuous improvement process. Clin Transl Oncol 2015; 17:547-56. [PMID: 25775916 DOI: 10.1007/s12094-015-1277-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 01/22/2015] [Indexed: 12/12/2022]
Abstract
PURPOSE The aim of this study was to estimate the effectiveness of surgery in liver metastasis from colorectal cancer. METHODS We conducted a prospective and observational study of patients with colorectal liver metastasis operated on at the San Cecilio University Hospital of Granada from March 2003 until June 2013. The primary variables of the result were survival and morbidity before 30 days of the post-operative period. We also measured preoperative and surgical variables. RESULTS A total of 147 patients with liver metastasis of colorectal origin underwent surgical removal during the period of study, 38 of whom had repeat surgery. 34 had a second resection, 3 had a third one and one only patient had a fourth one, for a total of 185 registered operations. The global 5-year survival rate was 38 and 17 % after 10 years. There were 115 patients who had neither radiofrequency nor exploratory laparotomy, 38 % of them survived over 60 months. The average disease-free time was 23.6 months ± 47.3, with significant differences observed between types of procedures. Patients that were operated on just once (n = 25) had a five-year actuarial survival rate of 35 %, a morbidity rate of 24 % and a mortality rate of 0.6 % (1 patient only). The average hospital stay was 13.8 days and the disease-free time was 15.8 months. CONCLUSION The results obtained in our surgical unit in terms of morbidity, mortality and five-year actuarial survival rates are comparable to those of other units at large institutions, which are currently considered the standards of quality.
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Affiliation(s)
- F Navarro-Freire
- Department of Surgery, Faculty of Medicine, University of Granada, Av de Madrid, 11, 18012, Granada, Spain,
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Hernandez-Alejandro R, Bertens KA, Pineda-Solis K, Croome KP. Can we improve the morbidity and mortality associated with the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure in the management of colorectal liver metastases? Surgery 2014; 157:194-201. [PMID: 25282528 DOI: 10.1016/j.surg.2014.08.041] [Citation(s) in RCA: 93] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Accepted: 08/15/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Meticulous selection of patients who can undergo the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure safely will be paramount to minimize the associated morbidity and mortality. METHODS We collected data prospectively on 14 consecutive patients who underwent the ALPPS procedure for planned resection of colorectal liver metastases at London Health Sciences Centre, Canada, between April 2012 and November 2013. RESULTS The median relative increase of the standardized future liver remnant after the ALPPS procedure was 93 ± 28%. The standardized future liver remnant rate of volume increase was 35 ± 13 mL/day. Biopsies of the FLR were taken during stage 1 and 2. These biopsies showed a mean preregeneration Ki-67 index of 0% and a postregeneration index of 14 ± 3%. All 14 ALPPS patients completed the 2-stage hepatectomy. No complications occurred after ALPPS stage 1. After ALPPS stage 2, 5 patients had complications (36%), with 2 patients (14%) having a severe complication (Clavien-Dindo ≥ IIIB). Median follow-up was 9 months. Overall survival at the time of follow-up was 100%. Recurrence developed in 2 patients. One patient had recurrence in the liver and lungs 5 months after stage 2 and was offered more chemotherapy. The other patient developed recurrence in the liver remnant 9 months after stage 2 and underwent additional chemotherapy with a possible future resection of the recurrence. CONCLUSION Low morbidity and negligible mortality can be achieved with the ALPPS procedure, and the high rates published in previous reports can be improved with refinements in technique and patient selection. The ALPPS approach may be a valid option to enable resection in selected patients with colorectal liver metastases considered unresectable previously by standard techniques.
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Affiliation(s)
| | - Kimberly A Bertens
- Department of Surgery, Division of General Surgery, Western University, London, Ontario, Canada
| | - Karen Pineda-Solis
- Department of Surgery, Division of General Surgery, Western University, London, Ontario, Canada
| | - Kristopher P Croome
- Department of Surgery, Division of General Surgery, Western University, London, Ontario, Canada; Division of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, MN
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Khan K, Wale A, Brown G, Chau I. Colorectal cancer with liver metastases: Neoadjuvant chemotherapy, surgical resection first or palliation alone? World J Gastroenterol 2014; 20:12391-12406. [PMID: 25253940 PMCID: PMC4168073 DOI: 10.3748/wjg.v20.i35.12391] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2013] [Revised: 01/30/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is one of the commonest cancers with 1.2 million new cases diagnosed each year in the world. It remains the fourth most common cause of cancer-related mortality in the world and accounts for > 600000 cancer-related deaths each year. There have been significant advances in treatment of metastatic CRC in last decade or so, due to availability of new active targeted agents and more aggressive approach towards the management of CRC, particularly with liver-only-metastases; however, these drugs work best when combined with conventional chemotherapy agents. Despite these advances, there is a lack of biomarkers to inform us about the accurate management of the patients with metastatic CRC. It is therefore imperative to carefully select the patients with comprehensive multi-disciplinary team input in order to optimise the management of these patients. In this review we will discuss various treatment options available in management of colorectal liver metastases with potential guidance on how and when to choose these options along with consideration on future directions in management of this disease.
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van Dam RM, Lodewick TM, van den Broek MAJ, de Jong MC, Greve JW, Jansen RLH, Bemelmans MHA, Neumann UP, Olde Damink SWM, Dejong CHC. Outcomes of extended versus limited indications for patients undergoing a liver resection for colorectal cancer liver metastases. HPB (Oxford) 2014; 16:550-9. [PMID: 24246003 PMCID: PMC4048077 DOI: 10.1111/hpb.12181] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Accepted: 07/16/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Currently, resection criteria for colorectal cancer liver metastases (CRCLM) are only limited by remnant liver function. Morbidity and survival after a partial hepatectomy with limited or extended indication criteria were compared. METHODS/DESIGN Between 1991 and 2010, patients undergoing a liver resection for CRCLM with limited (n = 169) or extended indication criteria (n = 129) were retrospectively identified in a prospectively collected single-centre database. Limited indication criteria were defined as less than three unilateral, not centrally located liver metastases in the absence of extra hepatic metastases. The extended criteria were only limited by predicted remnant liver volume and patients fitness. Data on co-morbidity, resection margin, short- and long-term morbidity, disease-free (DFS) and overall survival were compared. RESULTS Patients with limited indications had less major complications (19.5% vs. 33.1%, P < 0.01), longer overall survival of 68.8 months [confidence interval (CI) 46.5-91.1] vs. 41.4 months (CI 33.4-49.0, P ≤ 0.001) and longer median DFS of 22.0 months [confidence interval (CI) 15.8-28.2] vs 10.2 months (CI 8.4-11.9, P < 0.001) compared with the extended indication group. Cure rates, defined as 10-year DFS, were 35.5% and 15.8%, respectively. Fewer patients in the extended indication group underwent an R0 resection (92.9% vs. 77.5%, P < 0.001). Only 17% of all R1 resected patients had recurrences at the transection plane. CONCLUSION A partial hepatectomy for CRCLM with extended indications seems justified but is associated with higher complication rates, earlier recurrence and lower overall survival compared with limited indications. However, the median 5-year survival was substantial and a cure was achieved in 15.8% of patients.
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Affiliation(s)
- Ronald M van Dam
- Department of Surgery, Maastricht University Medical CentreMaastricht, The Netherlands,Euregional Surgical HPB collaboration Aachen-MaastrichtGermany–The Netherlands
| | - Toine M Lodewick
- Department of Surgery, Maastricht University Medical CentreMaastricht, The Netherlands,Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht, The Netherlands,Department of General, Visceral and Transplant Surgery, University Hospital RWTH AachenAachen, Germany,Euregional Surgical HPB collaboration Aachen-MaastrichtGermany–The Netherlands
| | - Maartje AJ van den Broek
- Department of Surgery, Maastricht University Medical CentreMaastricht, The Netherlands,Euregional Surgical HPB collaboration Aachen-MaastrichtGermany–The Netherlands
| | - Mechteld C de Jong
- Department of Surgery, Maastricht University Medical CentreMaastricht, The Netherlands,Euregional Surgical HPB collaboration Aachen-MaastrichtGermany–The Netherlands
| | - Jan Willem Greve
- Department of Surgery, Atrium Medical CenterHeerlen, The Netherlands
| | - Rob LH Jansen
- Department of Medical Oncology, Maastricht University Medical CentreMaastricht, The Netherlands
| | - Marc HA Bemelmans
- Department of Surgery, Maastricht University Medical CentreMaastricht, The Netherlands,Euregional Surgical HPB collaboration Aachen-MaastrichtGermany–The Netherlands
| | - Ulf P Neumann
- Department of General, Visceral and Transplant Surgery, University Hospital RWTH AachenAachen, Germany,Euregional Surgical HPB collaboration Aachen-MaastrichtGermany–The Netherlands
| | - Steven WM Olde Damink
- Department of Surgery, Maastricht University Medical CentreMaastricht, The Netherlands,Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht, The Netherlands,Department of HPB Surgery and Liver Transplantation, Royal Free Hospital- University College LondonLondon, UK,Euregional Surgical HPB collaboration Aachen-MaastrichtGermany–The Netherlands
| | - Cornelis HC Dejong
- Department of Surgery, Maastricht University Medical CentreMaastricht, The Netherlands,Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht, The Netherlands,Euregional Surgical HPB collaboration Aachen-MaastrichtGermany–The Netherlands
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The Evolving Use of Prognostic Factors After Resection of Colorectal Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2014. [DOI: 10.1007/s11888-014-0220-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Cooper AB, Aloia TA, Vauthey JN, Curley SA. Controversies in Advanced Disease - Surgical Approaches for Metastatic Resection. COLORECTAL CANCER 2014. [DOI: 10.1002/9781118337929.ch13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Christophi C, Nguyen L, Muralidharan V, Nikfarjam M, Banting J. Lymphatics and colorectal liver metastases: the case for sentinel node mapping. HPB (Oxford) 2014; 16:124-30. [PMID: 23869986 PMCID: PMC3921007 DOI: 10.1111/hpb.12118] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Accepted: 03/21/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatic resection remains the treatment of choice for patients with colorectal liver metastases (CLM). Indications for hepatic resection have been extended to include extrahepatic lymph node groups, resulting in increased survival benefits. The identification of specific lymph pathways and involved nodes is necessary to support the development of guidelines for a more focused approach to the management of this disease. The feasibility of sentinel node mapping should be investigated to define specific lymphatic groups involved in CLM. METHODS Scientific papers published from 1950 to 2012 were sought and extracted from the MEDLINE, PubMed and University of Melbourne databases. RESULTS Several studies have reported microscopic lymph node involvement in 10-15% of patients undergoing hepatic resection for CLM in which no macroscopic involvement was evident. In retrospect, over 80% of lymphadenectomies are proven unnecessary. Traditional imaging modalities have limited predictive value in detecting lymph node involvement. Sentinel node mapping has proved an extremely accurate tool in detecting lymph node involvement and can identify patients in whom lymphadenectomy may be beneficial. CONCLUSIONS Current imaging techniques are inadequate to detect microscopic lymph node involvement in patients with resectable CLM. The use of sentinel node mapping is proposed to identify nodal groups involved and provide management strategies.
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Affiliation(s)
- Christopher Christophi
- Christopher Christophi, Department of Surgery, University of Melbourne, Austin Hospital, Lance Townsend Building Level 8, Studley Road, Heidelberg, Vic 3084, Australia. Tel: + 61 3 9496 5492. Fax: + 61 3 9458 1650. E-mail:
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Spolverato G, Ejaz A, Azad N, Pawlik TM. Surgery for colorectal liver metastases: The evolution of determining prognosis. World J Gastrointest Oncol 2013; 5:207-221. [PMID: 24363829 PMCID: PMC3868716 DOI: 10.4251/wjgo.v5.i12.207] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Revised: 11/05/2013] [Accepted: 11/16/2013] [Indexed: 02/05/2023] Open
Abstract
Despite improvements in the multi-modality treatment of colorectal liver metastasis (CRLM), survival after resection remains varied. Determining prognosis after surgical resection has historically been predicated on preoperative clinicopathological factors such as primary tumor stage, carcinoembryonic antigen levels, number of liver metastases, presence of extrahepatic disease, as well as other factors. While scoring systems have been developed by combining certain preoperative factors, these have been inconsistent in accurately determining prognosis. There has been increasing interest in the use of biologic and molecular markers to predict prognosis following CRLM. The role of markers such as KRAS, BRAF, p53, human telomerase reverse transcriptase, thymidylate synthase, Ki-67, and hypoxia inducible factor-1α and their correlation with accurately predicting survival after surgical resection have been supported by several studies. Furthermore, other elements such as pathological response to chemotherapy and the presence of circulating tumor cells have shown promise in accurately determining prognosis after resection for colorectal liver metastasis. We herein review past, present, and possible future markers of prognosis among colorectal cancer patients with liver metastasis undergoing resection with curative intent.
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Gur I, Diggs BS, Wagner JA, Vaccaro GM, Lopez CD, Sheppard BC, Orloff SL, Billingsley KG. Safety and outcomes following resection of colorectal liver metastases in the era of current perioperative chemotherapy. J Gastrointest Surg 2013; 17:2133-42. [PMID: 24091909 DOI: 10.1007/s11605-013-2295-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Accepted: 07/16/2013] [Indexed: 01/31/2023]
Abstract
BACKGROUND Preoperative chemotherapy is increasingly utilized in the treatment of colorectal liver metastases (CRLM). Although this strategy may improve resectability, long-term advantages of preoperative chemotherapy for resectable CRLM are less clear. The objective of this study is to report safety and outcomes when perioperative chemotherapy is routinely added to surgery for CRLM. METHODS A retrospective review of patients undergoing liver resections for CRLM during 2003-2011 in single academic oncology center. Demographic data, tumor characteristics, chemotherapy, surgical details, complications and survival were analyzed. RESULTS The study included 157 patients that underwent 168 liver operations. One hundred eighteen patients (70 %) underwent preoperative chemotherapy (75 % oxaliplatin-based). Preoperative portal vein embolization was utilized in 16 (10.1 %) patients. Overall survival (OS) was 89, 57, and 27 % at 1, 3, and 5 years, respectively (median survival-42.8 months). Eleven (7 %) patients had repeat resections for liver recurrence. Thirty-day mortality was 1.26 %, morbidity-24 % (6 %-liver related). Complications were not significantly different in patients that had preoperative chemotherapy. On a multivariate analysis advanced age and >3 lesions predicted poor OS, while advanced age, lesions >5 cm, synchronous lesions, margin-positivity and resection less than hepatectomy were associated with decreased DFS. CONCLUSIONS Our results suggest that even with chemotherapy and resection only a subset of patients remain disease-free after 5 years. However, even in a high-risk patient with multiple lesions, preoperative chemotherapy can be administered safely without apparent increase in postoperative complications. Perioperative chemotherapy should be considered particularly in patients with multifocal or large lesions, synchronous disease and short disease-free interval.
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Affiliation(s)
- Ilia Gur
- Division of Surgical Oncology, Oregon Health and Science University, Portland, OR, USA,
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Gómez Dorronsoro ML, Vera R, Ortega L, Plaza C, Miquel R, García M, Díaz E, Ortiz MR, Pérez J, Hörndler C, Villar C, Antúnez J, Pereira S, López-Rios F, González-Cámpora R. Recommendations of a group of experts for the pathological assessment of tumour regression of liver metastases of colorectal cancer and damage of non-tumour liver tissue after neoadjuvant therapy. Clin Transl Oncol 2013; 16:234-42. [PMID: 24019036 DOI: 10.1007/s12094-013-1104-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2013] [Accepted: 08/13/2013] [Indexed: 01/22/2023]
Abstract
Colorectal cancer (CRC) incidence has increased during the past decades in Spain, being the first malignant tumour in incidence. Observed mortality for CRC is mainly due to liver and lung metastases. The only curative treatment is surgery; new surgical techniques and neoadjuvant treatments have increased the number of surgery candidate patients. Patients should be managed with a multidisciplinary approach that includes imaging techniques, chemotherapy, surgery and pathological assessment. As an answer to this approach, a group of pathology experts interested on CRC liver metastases aimed to review the diagnosis and prognosis of liver mestastases and developed practical recommendations for its assessment. The expert group revised the current literature and prepared questions to be discussed based on available evidence and on their clinical practise. As a result, recommendations for the assessment of tumour regression of liver metastases are proposed, which could be implemented in oncology centres allowing assessment standardisation for these patients. Prospective multi-center studies to evaluate these recommendations validity will further contribute to improve the standard care of CRC liver metastases patients.
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Affiliation(s)
- M L Gómez Dorronsoro
- Servicio de Anatomía Patológica, Hospital de Navarra, C/de Irunlarrea 3, 31008, Pamplona, Spain,
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Zhong Y, Zhu D, Liang L, Ye Q, Wei Y, Ren L, Pan X, Fan J, Xu J, Qin X. The results of surgery for colorectal hepatic metastases following expansion of the indications in 2005. Colorectal Dis 2013; 15:e429-34. [PMID: 23663516 DOI: 10.1111/codi.12275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2012] [Revised: 12/13/2012] [Accepted: 01/13/2013] [Indexed: 02/08/2023]
Abstract
AIM Safety and survival were investigated in patients treated according to expanded surgical indications for colorectal hepatic metastases. METHOD A retrospective analysis of all consecutive patients who underwent resection of colorectal hepatic metastases at Zhongshan Hospital from 2000 to 2010 was conducted. The patients were divided into two groups based on a change in the surgical indications introduced in 2005. Patients in Group I underwent hepatic surgery between 2000 and 2004 and those in Group II between 2005 and 2010. The clinicopathological data and survival rates of both groups were analysed. RESULTS There were 530 patients who underwent hepatic surgery between 2000 and 2010. After the expansion of surgical indications, the rate of surgical resection rose from 25.1 to 35.1% (P < 0.05). There was no significant difference in perioperative mortality (2.2% vs 0.9%) or morbidity (20.9% vs 29.8%). Recurrence occurred in 27.5% and 36.7% in Groups I and II, respectively, and 5-year overall survival was 43% and 49%, respectively (not significant). CONCLUSION Expanding the indications for surgical resection of hepatic metastases increased the resection rate but had no significant effect on survival.
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Affiliation(s)
- Y Zhong
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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Ribero D, Viganò L, Amisano M, Capussotti L. Prognostic factors after resection of colorectal liver metastases: from morphology to biology. Future Oncol 2013; 9:45-57. [PMID: 23252563 DOI: 10.2217/fon.12.159] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Despite improved overall survival rates after potentially curative liver resection (~50-58% at 5 years), almost half of patients experience disease recurrence highlighting the need for a precise definition of outcomes to stratify patients for clinical trials and to guide treatment decisions. In the past, several factors, such as an advanced primary T stage, the primary N+ status, a large tumor size, multiple tumors, a disease-free interval of <12 months, an elevated carcinoembryonic antigen level, the presence of an extrahepatic disease, and the margin width (<1 cm) and status (positive), have been recognized to predict poor outcomes, but most of them lack the sensitivity for accurate individual prognostication. Thus, in recent years, new factors, such as response to chemotherapy, either clinical or pathological, that more closely reflect tumor biology have been established and adopted in the clinical practice. Similarly, biomarkers of poor prognosis, especially mutations in KRAS and BRAF and the expression of thymidylate synthase, have been studied, yielding promising results. However, robust evidence of their prognostic utility awaits prospective validation.
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Affiliation(s)
- Dario Ribero
- Department of General Surgery & Surgical Oncology, Ospedale Mauriziano Umberto I, Torino, Italy
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Newton PK, Mason J, Bethel K, Bazhenova L, Nieva J, Norton L, Kuhn P. Spreaders and sponges define metastasis in lung cancer: a Markov chain Monte Carlo mathematical model. Cancer Res 2013; 73:2760-9. [PMID: 23447576 PMCID: PMC3644026 DOI: 10.1158/0008-5472.can-12-4488] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The classic view of metastatic cancer progression is that it is a unidirectional process initiated at the primary tumor site, progressing to variably distant metastatic sites in a fairly predictable, although not perfectly understood, fashion. A Markov chain Monte Carlo mathematical approach can determine a pathway diagram that classifies metastatic tumors as "spreaders" or "sponges" and orders the timescales of progression from site to site. In light of recent experimental evidence highlighting the potential significance of self-seeding of primary tumors, we use a Markov chain Monte Carlo (MCMC) approach, based on large autopsy data sets, to quantify the stochastic, systemic, and often multidirectional aspects of cancer progression. We quantify three types of multidirectional mechanisms of progression: (i) self-seeding of the primary tumor, (ii) reseeding of the primary tumor from a metastatic site (primary reseeding), and (iii) reseeding of metastatic tumors (metastasis reseeding). The model shows that the combined characteristics of the primary and the first metastatic site to which it spreads largely determine the future pathways and timescales of systemic disease.
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Affiliation(s)
- Paul K Newton
- Department of Aerospace & Mechanical Engineering, Viterbi School of Engineering, University of Southern California, Los Angles 90089, USA.
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Wanebo HJ, LeGolvan M, Paty PB, Saha S, Zuber M, D’Angelica MI, Kemeny NE. Meeting the biologic challenge of colorectal metastases. Clin Exp Metastasis 2012; 29:821-39. [DOI: 10.1007/s10585-012-9517-x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Accepted: 07/09/2012] [Indexed: 12/20/2022]
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Munireddy S, Katz S, Somasundar P, Espat NJ. Thermal tumor ablation therapy for colorectal cancer hepatic metastasis. J Gastrointest Oncol 2012; 3:69-77. [PMID: 22811871 DOI: 10.3978/j.issn.2078-6891.2012.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2012] [Accepted: 01/13/2012] [Indexed: 12/22/2022] Open
Abstract
Surgical resection for colorectal hepatic metastases (CRHM) is the preferred treatment for suitable candidates, and the only potentially curative modality. However, due to various limitations, the majority of patients with CRHM are not candidates for liver resection. In recent years, there has been an increasing interest in the role of thermal tumor ablation (TTA) as a component of combined resection-ablation strategies, staged hepatic resections, or as standalone adjunct treatment for patients with CRHM. Thus, ablative approaches have expanded the group of patients with CRHM that may benefit from liver-directed treatment strategies.
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Affiliation(s)
- Sanjay Munireddy
- Surgical Oncology, Roger Williams Medical Center, Boston University School of Medicine, Providence, Rhode Island, USA
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Curley SA. Surgical treatment of colorectal cancer liver metastases. Am Soc Clin Oncol Educ Book 2012:209-212. [PMID: 24451736 DOI: 10.14694/edbook_am.2012.32.52] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Treatment strategies for patients with stage IV colorectal cancer have changed markedly in the last decade. Patients with colorectal cancer metastases to the liver have always been a fascinating group to consider biologically and for local-regional treatment strategies. In the late 1980s through the 1990s, resection was performed for a select subset of patients who had resectable disease. However, a high proportion of patients had bilobar unresectable disease and were treated with either 5-fluorouracil-based systemic chemotherapy or implanted hepatic arterial infusion pumps. The advent of the new millennium was associated with the availability of several new cytotoxic and biologic agents active in colorectal cancer. These agents have completely changed the approach to the treatment of patients with colorectal cancer liver metastases and thus have increased the complexity of the decision-making process for treatment of these patients.
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Affiliation(s)
- Steven A Curley
- From the Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX
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Grundmann RT. Current state of surgical treatment of liver metastases from colorectal cancer. World J Gastrointest Surg 2011; 3:183-96. [PMID: 22224173 PMCID: PMC3251742 DOI: 10.4240/wjgs.v3.i12.183] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2010] [Revised: 10/23/2011] [Accepted: 11/01/2011] [Indexed: 02/06/2023] Open
Abstract
Hepatic resection is the procedure of choice for curative treatment of colorectal liver metastases (CLM). Objectives of surgical strategy are low intraoperative blood loss, short liver ischemic times and minor postoperative morbidity and mortality. Blood loss is an independent predictor of mortality and compromises, in common with postoperative complications, long-term outcome after hepatectomy for CLM. The type of liver resection has no impact on the outcome of patients with CLM; wedge resections are not inferior to anatomical resections in terms of tumor clearance, pattern of recurrence or survival. Despite the lack of proof of survival benefit, routine lymphadenectomy has been advocated, allowing the detection of microscopic lymph node metastases and with prognostic value. In experienced hands, minimally invasive liver surgery is safe with acceptable morbidity and mortality and oncological results comparable to open hepatic surgery, but with reduced blood loss and earlier recovery. The European Colorectal Metastases Treatment Group recommended treating up front with chemotherapy for patients with both resectable and unresectable CLM. However, neoadjuvant chemotherapy can induce damage to the remnant liver, dependent on the number of chemotherapy cycles. Therefore, in our opinion, preoperative chemotherapy should be reserved for patients whose CLM are marginally resectable or unresectable. A meta analysis of randomized trials dealing with perioperative chemotherapy for the treatment of resectable CLM demonstrated a benefit of systemic chemotherapy but did not answer the question of whether a neoadjuvant or adjuvant approach should be preferred. Analysis of the literature demonstrates that the results of specialized centers cannot be attained in the reality of comprehensive patient care. Reasons behind the commonly poorer results seen in cancer networks as compared with literature-based data are, on the one hand, geographical disparities in access to specialized surgical and medical care. On the other hand, a selection bias in the reports of the literature may be assumed. Studies of surgical resection for CLM derive almost exclusively from case series generally drawn from large academic centers where patient selection or surgical expertise is superior to what is found in many communities. Therefore, we may conclude that the comprehensive propagation of the standards outlined in this paper constitutes a major task in the near future to reduce the variations in survival of patients with CLM.
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Affiliation(s)
- Reinhart T Grundmann
- Reinhart T Grundmann, Kreiskliniken Altötting-Burghausen, In den Grüben 144, D-84489 Burghausen, Germany
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Pulitanò C, Bodingbauer M, Aldrighetti L, Choti MA, Castillo F, Schulick RD, Gruenberger T, Pawlik TM. Colorectal liver metastasis in the setting of lymph node metastasis: defining the benefit of surgical resection. Ann Surg Oncol 2011; 19:435-42. [PMID: 21743977 DOI: 10.1245/s10434-011-1902-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2011] [Indexed: 01/12/2023]
Abstract
BACKGROUND For patients with colorectal liver metastasis (CLM), the presence of concomitant perihepatic/para-aortic lymph node metastasis (LNM) is considered a contraindication to liver resection. We sought to determine the benefits of liver resection among patients with CLM + LNM by examining long-term outcomes among a large cohort of patients. METHODS Between October 1996 and December 2007, 61 patients with CLM and pathologically proven LNM were identified from an international multi-institutional database of 1629 patients. The effect of LNM, as well as other prognostic factors, on recurrence-free and overall survival was analyzed. RESULTS Median overall survival was 32 months, and 1-, 3-, and 5-year overall survival were 86, 35, and 18%, respectively. Five patients were alive and disease-free at last follow-up. Survival was associated with location of LNM. Specifically, 5-year overall survival was 30% among patients with LNM along the hepatoduodenal ligament/retropancreatic area (area 1), 14% among patients with LNM along the common hepatic artery/celiac axis (area 2), and there was only one long-term survivor who experienced recurrent disease among patients who had CLM + para-aortic LNM (area 3) (P = 0.004). On multivariate analyses, overall margin status (hazard ratio [HR] = 2.0), treated number of metastases >6 (HR = 2.3) and para-aortic lymph node involvement (HR = 2.6) each remained significantly associated with increased risk of death (all P < 0.05). CONCLUSIONS Although overall survival in the setting of LNM is only 18%, certain subsets of patients with LNM can benefit from surgical resection. Specifically, patients with CLM + LNM isolated to area 1 had a 5-year survival of approximately 30%, while long-term survival among patients with para-aortic LNM was rare.
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Affiliation(s)
- Carlo Pulitanò
- Department of Surgery, Hepatobiliary Surgery Unit, Scientific Institute San Raffaele, Vita-Salute San Raffaele University, Milan, Italy
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Advances in hepatobiliary surgery. TRENDS IN ANAESTHESIA AND CRITICAL CARE 2011. [DOI: 10.1016/j.tacc.2010.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Ronnekleiv-Kelly SM, Kennedy GD. Management of stage IV rectal cancer: Palliative options. World J Gastroenterol 2011; 17:835-47. [PMID: 21412493 PMCID: PMC3051134 DOI: 10.3748/wjg.v17.i7.835] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2010] [Revised: 01/04/2011] [Accepted: 01/11/2011] [Indexed: 02/06/2023] Open
Abstract
Approximately 30% of patients with rectal cancer present with metastatic disease. Many of these patients have symptoms of bleeding or obstruction. Several treatment options are available to deal with the various complications that may afflict these patients. Endorectal stenting, laser ablation, and operative resection are a few of the options available to the patient with a malignant large bowel obstruction. A thorough understanding of treatment options will ensure the patient is offered the most effective therapy with the least amount of associated morbidity. In this review, we describe various options for palliation of symptoms in patients with metastatic rectal cancer. Additionally, we briefly discuss treatment for asymptomatic patients with metastatic disease.
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de Jong MC, van Vledder MG, Ribero D, Hubert C, Gigot JF, Choti MA, Schulick RD, Capussotti L, Dejong CH, Pawlik TM. Therapeutic efficacy of combined intraoperative ablation and resection for colorectal liver metastases: an international, multi-institutional analysis. J Gastrointest Surg 2011; 15:336-44. [PMID: 21108017 DOI: 10.1007/s11605-010-1391-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2010] [Accepted: 11/12/2010] [Indexed: 01/31/2023]
Abstract
BACKGROUND Only 10-25% of patients presenting with colorectal liver metastases (CRLM) are amenable to hepatic resection. By combining resection and ablation, the number of patients eligible for surgery can be expanded. We sought to determine the efficacy of combined resection and ablation for CRLM. METHODS Between 1984 and 2009, 1,425 patients who underwent surgery for CRLM were queried from an international multi-institutional database. Of these, 125 patients underwent resection combined with ablation as the primary mode of treatment. RESULTS Patients presented with a median of six lesions. The median number of lesions resected was 4; the median number of lesions ablated was 1. At last follow-up, 84 patients (67%) recurred with a median disease-free interval of 15 months. While total number of lesions treated (hazard ratio (HR) = 1.47, p = 0.23) and number of lesions resected (HR = 1.18, p = 0.43) did not impact risk of intrahepatic recurrence, the number of lesions ablated did (HR = 1.36, p = 0.05). Overall 5-year survival was 30%. Survival was not influenced by the number of lesions resected or ablated (both p > 0.05). CONCLUSION Combined resection and ablation is associated with long-term-survival in a subset of patients; however, recurrence is common. The number of lesions ablated increases risk of intrahepatic recurrence but does not impact overall survival.
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Affiliation(s)
- Mechteld C de Jong
- Department of Surgery, Johns Hopkins University School of Medicine, Harvey 611, 600N Wolfe Street, Baltimore, MD 21287, USA
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Van Tilborg AAJM, Meijerink MR, Sietses C, Van Waesberghe JHTM, Mackintosh MO, Meijer S, Van Kuijk C, Van Den Tol P. Long-term results of radiofrequency ablation for unresectable colorectal liver metastases: a potentially curative intervention. Br J Radiol 2010; 84:556-65. [PMID: 21159807 DOI: 10.1259/bjr/78268814] [Citation(s) in RCA: 93] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE The long-term results and prognostic factors of radiofrequency ablation (RFA) for unresectable colorectal liver metastases (CRLM) in a single centre with >10 years of experience were retrospectively analysed. METHODS A total of 100 patients with unresectable colorectal liver metastases (CRLM) (size 0.2-8.3 cm; mean 2.4 cm) underwent a total of 126 RFA sessions (237 lesions). The mean follow-up time was 29 months (range 6-93 months). Lesion characteristics (size, number and location), procedure characteristics (percutaneous or intra-operative approach) and major and minor complications were carefully noted. Local control, mean survival time and recurrence-free and overall survival were statistically analysed. RESULTS No direct procedure-related deaths were observed. Major complications were present in eight patients. Local RFA site recurrence was 12.7% (n = 30/237); for tumour diameters of <3 cm, 3-5 cm and >5 cm, recurrence was 5.6% (n = 8/143), 19.5% (n = 15/77) and 41.2% (n = 7/17), respectively. Centrally located lesions recurred more often than peripheral ones, at 21.4% (n = 21/98) vs 6.5% (n = 9/139), respectively, p = 0.009. Including additional treatments for recurring lesions when feasible, lesion-based local control reached 93%. The mean survival time from RFA was 56 (95% confidence interval (CI) 45-67) months. Overall 1-, 3-, 5- and 8-year survival from RFA was 93%, 77%, 36% and 24%, respectively. CONCLUSIONS RFA for unresectable CRLM is a safe, effective and potentially curative treatment option; the long-term results are comparable with those of previous investigations employing surgical resection. Factors determining success are lesion size, the number of lesions and location.
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Affiliation(s)
- A A J M Van Tilborg
- Department of Radiology, VU University Medical Centre, De Boelelaan 1117, Amsterdam, the Netherlands.
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Abstract
Although liver metastases from colorectal cancer previously conferred a very dismal prognosis, advances in systemic therapy combined with surgical techniques now gives these patients a reasonable chance for cure. Traditional cytoxic chemotherapy combined with biologic agents result in impressive response rates, allowing a portion of patients who were considered unresectable to undergo hepatectomy with curative intent. This review discusses the role of systemic therapy in patients with liver-limited metastatic disease for patients with resectable, potentially resectable and unresectable disease.
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Chemotherapy-induced Liver Injury in Metastatic Colorectal Cancer: Semiquantitative Histologic Analysis of 334 Resected Liver Specimens Shows That Vascular Injury but not Steatohepatitis Is Associated With Preoperative Chemotherapy. Am J Surg Pathol 2010; 34:784-91. [DOI: 10.1097/pas.0b013e3181dc242c] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Nathan H, de Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Gigot JF, Schulick RD, Choti MA, Aldrighetti L, Capussotti L, Pawlik TM. Conditional Survival after Surgical Resection of Colorectal Liver Metastasis: An International Multi-Institutional Analysis of 949 Patients. J Am Coll Surg 2010; 210:755-64, 764-6. [DOI: 10.1016/j.jamcollsurg.2009.12.041] [Citation(s) in RCA: 104] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2009] [Revised: 12/14/2009] [Accepted: 12/23/2009] [Indexed: 02/07/2023]
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