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Trehub Y, Malovanna A, Zemskov S. The Current State of Perioperative Chemotherapy in Resectable Colorectal Liver Metastases: A Narrative Review. J Surg Oncol 2025. [PMID: 39866030 DOI: 10.1002/jso.28101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Accepted: 01/06/2025] [Indexed: 01/28/2025]
Abstract
Perioperative chemotherapy has emerged as a critical component in managing resectable colorectal liver metastases (CRLM), aiming to improve long-term survival, although data supporting its use remains controversial. This narrative review explores the current state of perioperative chemotherapy in patients with resectable CRLM, focusing on its role in different oncological risk categories. The review highlights ongoing controversies, such as optimal patient selection and the role of post- versus preoperative treatment in specific scenarios.
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Affiliation(s)
- Yevhenii Trehub
- The Center of Organ and Anatomical Tissues Transplantation, Feofaniya Clinical Hospital, Kyiv, Ukraine
| | - Anna Malovanna
- Department of Surgery and Transplantation, Kyiv City Center of Nephrology and Dialysis, Kyiv, Ukraine
| | - Sergii Zemskov
- Department of General Surgery N1, Bogomolets National Medical University, Kyiv, Ukraine
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2
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McIntyre SM, Soares KC, Chou JF, D'Amico F, Shin PJ, Gönen M, Shia J, Balachandran VP, Wei AC, Kingham TP, Drebin JA, Jarnagin WR, D'Angelica MI. Surgical Margin of Resected Colorectal Liver Metastases: How Accurate Is Surgeon Prediction? Ann Surg 2024; 280:311-316. [PMID: 38054376 PMCID: PMC11153333 DOI: 10.1097/sla.0000000000006138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2023]
Abstract
OBJECTIVE The aim of this study was to describe the surgeon's ability to accurately predict the margin following resection of colorectal liver metastases (CRLMs). BACKGROUND The decision to resect CRLM is based on the surgeon's ability to predict tumor-free resection margins. However, to date, no study has evaluated the accuracy of surgeon margin prediction. METHODS In this single-institution prospective study, the operating attending and fellow independently completed a preoperative and postoperative questionnaire describing their expected resection margin in 100 consecutive cases (200 assessments) of CRLM resections. In cases with multiple metastases, the closest margin was assessed as the margin of interest for the primary outcome. Surgeon assessments were compared with the gold-standard histopathologic assessment. RESULTS After excluding aborted cases, 190 preoperative and 190 postoperative assessments from 95 cases were included in the analysis. The pathologic margin was noted to be wide (≥1 cm), 1 mm to 1 cm, narrow (<1 mm), and positive in 28 (29.5%), 55 (57.9%), 5 (5.3%), and 7 (7.4%) cases, respectively. The 88 cases with negative margins were all predicted to be negative. None of the cases with positive margins were predicted to be positive. Ninety-one (48%) preoperative and 104 (55%) postoperative predictions were accurate. The sensitivity of predicting a margin <1 mm was 8.3% preoperatively and 16.7% postoperatively. The positive predictive value for preoperative and postoperative predictions of margin <1 mm was 18.2% and 26.7%, respectively. CONCLUSIONS Surgeons are inaccurate at predicting positive and close surgical margins following resection of CRLM. A predicted close margin should not necessarily preclude resection.
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Affiliation(s)
- Sarah M McIntyre
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Kevin C Soares
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Joanne F Chou
- Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Francesco D'Amico
- Department of Surgical, Oncological, and Gastroenterological Sciences (DiSCOG), University of Padova, Padua, Italy
| | - Paul J Shin
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Mithat Gönen
- Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Jinru Shia
- Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Vinod P Balachandran
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Alice C Wei
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - T Peter Kingham
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Jeffrey A Drebin
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - William R Jarnagin
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Michael I D'Angelica
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
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Östrand E, Rystedt J, Engstrand J, Frühling P, Hemmingsson O, Sandström P, Sternby Eilard M, Tingstedt B, Buchwald P. Importance of resection margin after resection of colorectal liver metastases in the era of modern chemotherapy: population-based cohort study. BJS Open 2024; 8:zrae035. [PMID: 38717909 PMCID: PMC11078257 DOI: 10.1093/bjsopen/zrae035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 01/14/2024] [Accepted: 03/04/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Resection margin has been associated with overall survival following liver resection for colorectal liver metastasis. The aim of this study was to examine how resection margins of 0.0 mm, 0.1-0.9 mm and ≥1 mm influence overall survival in patients resected for colorectal liver metastasis in a time of modern perioperative chemotherapy and surgery. METHODS Using data from the national registries Swedish Colorectal Cancer Registry and Swedish National Quality Registry for Liver, Bile Duct and Gallbladder Cancer, patients that had liver resections for colorectal liver metastasis between 2009 and 2013 were included. In patients with a narrow or unknown surgical margin the original pathological reports were re-reviewed. Factors influencing overall survival were analysed using a Cox proportional hazard model. RESULTS A total of 754 patients had a known margin status, of which 133 (17.6%) patients had a resection margin <1 mm. The overall survival in patients with a margin of 0 mm or 0.1-0.9 mm was 42 (95% c.i. 31 to 53) and 48 (95% c.i. 35 to 62) months respectively, compared with 75 (95% c.i. 65 to 85) for patients with ≥1 mm margin, P < 0.001. Margins of 0 mm or 0.1-0.9 mm were associated with poor overall survival in the multivariable analysis, HR 1.413 (95% c.i. 1.030 to 1.939), P = 0.032, and 1.399 (95% c.i. 1.025 to 1.910), P = 0.034, respectively. CONCLUSIONS Despite modern chemotherapy the resection margin is still an important factor for the survival of patients resected for colorectal liver metastasis, and a margin of ≥1 mm is needed to achieve the best possible outcome.
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Affiliation(s)
- Emil Östrand
- Department of Surgery, Skåne University Hospital, Lund, Sweden
- Department of Clinical Sciences Lund, Lund University, Lund, Sweden
| | - Jenny Rystedt
- Department of Surgery, Skåne University Hospital, Lund, Sweden
- Department of Clinical Sciences Lund, Lund University, Lund, Sweden
| | - Jennie Engstrand
- Division of Surgery, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
| | - Petter Frühling
- Department of Surgery, Akademiska University Hospital, Uppsala, Sweden
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Oskar Hemmingsson
- Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden
| | - Per Sandström
- Department of Surgery, Linköping University Hospital, Linköping, Sweden
- Department of Clinical and Experimental Medicine Sciences, Linköping University, Linköping, Sweden
| | - Malin Sternby Eilard
- Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Bobby Tingstedt
- Department of Surgery, Skåne University Hospital, Lund, Sweden
- Department of Clinical Sciences Lund, Lund University, Lund, Sweden
| | - Pamela Buchwald
- Department of Surgery, Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences Malmö, Lund University, Lund, Sweden
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Pourfaraji SM, Moghadam MN, Moradi AM, Shirmard FO, Mohammadzadeh N, Jafarian A. Long-term survival after hepatic resection for colorectal liver metastases: a single-center study in Iran. BMC Surg 2024; 24:131. [PMID: 38702645 PMCID: PMC11067153 DOI: 10.1186/s12893-024-02420-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 04/18/2024] [Indexed: 05/06/2024] Open
Abstract
BACKGROUND Surgical resection of colorectal cancer liver metastasis (CRLM) has been associated with improved survival in these patients. The purpose of this study was to investigate the usefulness of liver metastasectomy, also finding independent factors related to survival after liver metastasectomy. METHODS In a retrospective study, all patients with CRLM who underwent resection of liver metastases between 2012 and 2022 at Imam Khomeini Hospital Complex in Tehran, Iran, were enrolled. All patients were actively followed based on clinicopathologic and operative data. RESULTS A total of 248 patients with a median follow-up time of 46 months (Range, 12 to 122) were studied. Eighty-six patients (35.0%) underwent major hepatectomy, whereas 160 (65.0%) underwent minor hepatectomy. The median overall survival was 43 months (Range, 0 to 122 months), with estimated 1-, 3- and 5-year overall survival rates of 91%, 56%, and 42%, respectively. Multivariate analysis demonstrated that a metastasis size > 6 cm, major hepatectomy, rectum as the primary tumor site, and involved margin (< 1 mm) were independent factors associated with decreased overall survival (OS). CONCLUSION Surgical resection is an effective treatment for patients with CRLM that is associated with relatively favorable survival. A negative margin of 1 mm seems to be sufficient for oncological resection.
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Affiliation(s)
| | - Mehdi Nazari Moghadam
- Division of Hepatopancreatobiliary and Liver Transplantation, School of Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Mohammad Moradi
- Division of Hepatopancreatobiliary and Liver Transplantation, School of Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Narjes Mohammadzadeh
- Department of Surgery, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Ali Jafarian
- Division of Hepatopancreatobiliary and Liver Transplantation, School of Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
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Chandra P, Sacks GD. Contemporary Surgical Management of Colorectal Liver Metastases. Cancers (Basel) 2024; 16:941. [PMID: 38473303 DOI: 10.3390/cancers16050941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 02/13/2024] [Accepted: 02/19/2024] [Indexed: 03/14/2024] Open
Abstract
Colorectal cancer is the third most common cancer in the United States and the second most common cause of cancer-related death. Approximately 20-30% of patients will develop hepatic metastasis in the form of synchronous or metachronous disease. The treatment of colorectal liver metastasis (CRLM) has evolved into a multidisciplinary approach, with chemotherapy and a variety of locoregional treatments, such as ablation and portal vein embolization, playing a crucial role. However, resection remains a core tenet of management, serving as the gold standard for a curative-intent therapy. As such, the input of a dedicated hepatobiliary surgeon is paramount for appropriate patient selection and choice of surgical approach, as significant advances in the field have made management decisions extremely nuanced and complex. We herein aim to review the contemporary surgical management of colorectal liver metastasis with respect to both perioperative and operative considerations.
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Affiliation(s)
- Pratik Chandra
- Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA
| | - Greg D Sacks
- Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA
- VA New York Harbor Healthcare System, New York, NY 10010, USA
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Ai XN, Zhang Q, Jin CG, Hu H, Zhang WX, Wu ZY, Xiu DR. Relationship between hepatic surgical margins of colorectal cancer liver metastases and prognosis: A review. Medicine (Baltimore) 2024; 103:e37038. [PMID: 38335431 PMCID: PMC10860945 DOI: 10.1097/md.0000000000037038] [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: 11/15/2023] [Revised: 12/17/2023] [Accepted: 01/03/2024] [Indexed: 02/12/2024] Open
Abstract
Colorectal cancer (CRC) remains a significant global health concern, as characterized by its high mortality rate ranking second among all the leading causes of death. The liver serves as the primary site of CRC metastasis, and the occurrence of liver metastasis is a significant contributor to mortality among patients diagnosed with CRC. The survival rate of patients with colorectal liver metastasis has significantly increased with the advancement of comprehensive tumor therapy. However, radical surgery remains the key factor. Since there are frequently multiple liver metastases, which are prone to recurrence after surgery, it is crucial to preserve as much liver parenchyma as possible without affecting the prognosis. The issue of surgical margins plays a crucial role in this regard. In this review, we begin by examining the occurrence of positive surgical margins in liver metastases of patients diagnosed with CRC. We aim to define positive margins in hepatic surgery, examine the relationship between margins and prognosis and establish a foundation for future research in this field.
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Affiliation(s)
- Xiang-Nan Ai
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Qiang Zhang
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Chang-Guo Jin
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Hao Hu
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Wen-Xuan Zhang
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Zhen-Yu Wu
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Dian-Rong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
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Brandão GR, Trindade BO, Flores LHF, Motter SB, Alves CB, Remonti TAP, Lucchese AM, Junior ADP, Kalil AN. Does RAS Status Increase the Prevalence of Positive Resection Margin in Colorectal Liver Metastasis? A Systematic Review and Meta-Analysis. Am Surg 2023; 89:5638-5647. [PMID: 36896840 DOI: 10.1177/00031348231156763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/11/2023]
Abstract
BACKGROUND Colorectal liver metastasis has a high incidence, and RAS oncogene mutation status carries significant prognostic information. We aimed to assess whether RAS-mutated patients present more or less frequently with positive margins in their hepatic metastasectomy. METHODS We performed a systematic review and meta-analysis of studies from PubMed, Embase, and Lilacs databases. We analyzed liver metastatic colorectal cancer studies, which included information on RAS status and had surgical margin analysis of the liver metastasis. Odds ratios were computed using a random-effect model due to anticipated heterogeneity. We further performed a subanalysis limited to studies that included only patients with KRAS instead of all-RAS mutations. RESULTS From the 2,705 studies screened, 19 articles were included in the meta-analysis. There were 7,391 patients. The prevalence of positive resection margin was not significantly different between patients carrier vs non-carrier for the all-RAS mutations (OR .99; 95% CI 0.83-1.18; P = .87), and for only KRAS mutation (OR .93; 95% CI 0.73-1.19; P = .57). CONCLUSIONS Despite the strong correlation between colorectal liver metastasis prognosis and RAS mutation status, our meta-analysis's results suggest no correlation between the RAS status and the prevalence of positive resection margins. The findings contribute to a better understanding of the RAS mutation's role in the surgical resections of colorectal liver metastasis.
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Affiliation(s)
| | | | | | | | - Cassio Bona Alves
- Surgical Oncology, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil
| | | | | | | | - Antonio Nocchi Kalil
- Surgical Oncology, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil
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Marion S, Facchino S, Cheng-Oviedo S, Collin Y. Colorectal cancer hepatic metastases resection margins outcomes: a single-centre retrospective cohort study. Ann Med Surg (Lond) 2023; 85:4694-4702. [PMID: 37811094 PMCID: PMC10553064 DOI: 10.1097/ms9.0000000000001113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 07/17/2023] [Indexed: 10/10/2023] Open
Abstract
Background Surgical resection is the most efficient treatment for isolated colorectal cancer hepatic metastases. Among the known prognostic factors of this procedure, the impact of the resection margin width is still a controversial matter in the literature. Methods A retrospective cohort study was performed including 170 patients who underwent surgical resection of colorectal cancer liver metastases (CRLMs) between 2006 and 2016 in our hepatobiliary unit. Resection margin width was determined histologically by measuring the distance from the tumour in millimetres or centimetres. Patients' clinical characteristics were also collected. Patients were then stratified in two tumour margin groups: below 5 mm (group A) and equal to or above 5 mm (group B). Overall survival (OS) and disease-free survival (DFS) were the primary outcomes. Results Kaplan-Meier curves showed significantly better outcomes for cases having resection margins above 5 mm for both DFS with 1508.7 days (range 1151.2-1866.2) in group A, compared to 2463.9 days (range 2021.3-2906.5) in group B (P=0.049), and OS with 1557.8 days (range 1276.3-1839.3) for group A and 2303.8 days (range 1921.2--2686.4) for group B (P=0.020). This survival benefit was not significant for patients presenting with stage IV CRC at diagnosis or cases where extended (7+ segments) resections were performed. Conclusion Five-millimetre margins provide a significant survival advantage and should be aimed for in the treatment of CRLMs. Further research on the cause for this finding, including tumour biology's impact on survival, is required.
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Affiliation(s)
- Samuel Marion
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
| | - Sabrina Facchino
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
- Department of Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Sonia Cheng-Oviedo
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
- Department of Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Yves Collin
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
- Department of Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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Tseng CW, Teng HW, Lin CC, Lei HJ, Hung JJ, Liang WY, Hsia CY, Chou SC, Lin HH, Huang SC, Cheng HH, Lan YT, Wang HS, Yang SH, Chen WS, Lin JK, Jiang JK, Chang SC, Chau GY. Surgical strategy for colorectal cancer with synchronous liver and extrahepatic metastases: A scoring system and decision tree model. J Chin Med Assoc 2023; 86:732-739. [PMID: 37294150 DOI: 10.1097/jcma.0000000000000947] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/10/2023] Open
Abstract
BACKGROUND The role of hepatectomy in a specific group of patients with synchronous colorectal cancer with liver metastases (SCRLM) and synchronous extrahepatic disease (SEHD) is still unclear. The aim of this study was to evaluate the efficacy of liver surgery and define the selection criteria for surgical candidates in patients with SCRLM + SEHD. METHODS Between July 2007 and October 2018, 475 patients with colorectal cancer with liver metastases (CRLM) who underwent liver resection were retrospectively reviewed. Sixty-five patients with SCRLM + SEHD were identified and included in the study. Clinical pathological data of these patients were analyzed to evaluate the influence on survival. Important prognostic factors were identified by univariate and multivariate analyses. The risk score system and decision tree analysis were generated according to the important prognostic factors for better patient selection. RESULTS The 5-year survival rate of patients with SCRLM + SEHD was 21.9%. The most important prognostic factors were SCRLM number of more than five, site of SEHD other than the lung only, inability to achieve SCRLM + SEHD R0 resection, and BRAF mutation of cancer cells. The proposed risk score system and decision tree model easily discriminated between patients with different survival rates and identified the profile of suitable surgical patients. CONCLUSION Liver surgery should not be a contraindication for patients with SCRLM + SEHD. Patients with complete SCRLM + SEHD R0 resection, SCRLM number less than or equal to five, SEHD confined to the lung only, and wild-type BRAF could have favorable survival outcomes. The proposed scoring system and decision tree model may be beneficial to patient selection in clinical use.
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Affiliation(s)
- Chan-Wei Tseng
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Hao-Wei Teng
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chun-Chi Lin
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Hao-Jan Lei
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Jung-Jyh Hung
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Wen-Yih Liang
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Cheng-Yuan Hsia
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Shu-Cheng Chou
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Hung-Hsin Lin
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Sheng-Chieh Huang
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Hou-Hsuan Cheng
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yuan-Tzu Lan
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Huann-Sheng Wang
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shung-Haur Yang
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Wei-Shone Chen
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Jen-Kou Lin
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Jeng-Kai Jiang
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shih-Ching Chang
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Gar-Yang Chau
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
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10
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Carconi C, Cerreti M, Roberto M, Arrivi G, D'Ambrosio G, De Felice F, Di Civita MA, Iafrate F, Lucatelli P, Magliocca FM, Picchetto A, Picone V, Catalano C, Cortesi E, Tombolini V, Mazzuca F, Tomao S. The Management of Oligometastatic Disease in Colorectal Cancer: Present Strategies and Future Perspectives. Crit Rev Oncol Hematol 2023; 186:103990. [PMID: 37061075 DOI: 10.1016/j.critrevonc.2023.103990] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 03/29/2023] [Accepted: 04/11/2023] [Indexed: 04/17/2023] Open
Abstract
Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns. We present an overview of the available local treatment strategies, including surgical procedures, stereotactic body radiation therapy (SBRT), thermal ablation, as well as trans-arterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). Moreover, since imaging methods provide crucial information for the early diagnosis and management of oligometastatic CRC, we discuss the role of modern radiologic techniques in selecting patients that are amenable to potentially curative locoregional treatments.
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Affiliation(s)
- Catia Carconi
- Sant'Andrea University Hospital, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy
| | - Micaela Cerreti
- Sant'Andrea University Hospital, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy
| | - Michela Roberto
- UOC Oncologia A, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, 00161 Rome, Italy.
| | - Giulia Arrivi
- Oncology Unit, Sant' Andrea University Hospital, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Giancarlo D'Ambrosio
- Department of General Surgery, Surgical Specialties and Organ Transplantation, Policlinico Umberto I, "Sapienza" University of Rome, 00161 Rome, Italy
| | - Francesca De Felice
- Department of Radiotherapy, Policlinico Umberto I "Sapienza" University of Rome, Rome, Italy
| | - Mattia Alberto Di Civita
- UOC Oncologia A, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, 00161 Rome, Italy
| | - Franco Iafrate
- Department of Radiological Sciences, Oncology and Pathology, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Pierleone Lucatelli
- Vascular and Interventional radiology Unit, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Fabio Massimo Magliocca
- Vascular and Interventional radiology Unit, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Andrea Picchetto
- Emergency Department, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Vincenzo Picone
- UOC Oncologia B, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Carlo Catalano
- Vascular and Interventional radiology Unit, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Enrico Cortesi
- UOC Oncologia B, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Vincenzo Tombolini
- Department of Radiotherapy, Policlinico Umberto I "Sapienza" University of Rome, Rome, Italy
| | - Federica Mazzuca
- Oncology Unit, Sant' Andrea University Hospital, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Silverio Tomao
- Oncology Unit, Sant' Andrea University Hospital, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
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11
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Dumarco RB, Fonseca GM, Coelho FF, Jeismann VB, Makdissi FF, Kruger JAP, Nahas SC, Herman P. Multiple colorectal liver metastases resection can offer long-term survival: The concept of a chronic neoplastic disease. Surgery 2023; 173:983-990. [PMID: 36220666 DOI: 10.1016/j.surg.2022.08.032] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 08/25/2022] [Accepted: 08/27/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Resection for colorectal liver metastases has evolved significantly and, currently, there are no limits to the number of resected nodules. This study aimed to evaluate the outcomes and prognostic factors after liver resection for patients with ≥4 colorectal liver metastases, emphasizing long-term survival. METHODS The study population consisted of 137 patients with ≥4 colorectal liver metastases out of a total of 597 patients with colorectal liver metastases who underwent curative intent liver resection from January 2010 to July 2019 in a single hepatobiliary center. RESULTS The probability of overall and disease-free survival at 1, 3, and 5 years was 90.8%, 64.5%, 40.6%, and 37.7%, 19.3%, 18.1%, respectively. In a multivariate analysis for overall survival, the size of the largest metastatic nodule was the only unfavorable factor (P = .001). For disease-free survival, complete pathological response was a favorable factor (P = .04), and the following were negative factors: number of nodules ≥7 (P = .034), radiofrequency ablation during surgery (P = .04), positive primary tumor lymph nodes (P = .034), R1 resection (P = .011), and preoperative carcinoembryonic antigen >20 ng/mL (P = .015). After the first and second years of follow-up, 59 patients (45.3%) and 45 patients (34.6%), respectively, were not receiving chemotherapy. After 5 years of follow-up, 21 (16.1%) multimetastatic patients were chemotherapy-free. CONCLUSION A significant number of patients with multiple colorectal liver metastases will present long-term survival and should not be denied surgery. The long-term survival rates, even in the presence of recurrence, characterize a chronic neoplastic disease.
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Affiliation(s)
- Rodrigo Blanco Dumarco
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Gilton Marques Fonseca
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil. https://twitter.com/medgilton
| | - Fabricio Ferreira Coelho
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Vagner Birk Jeismann
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil. https://twitter.com/vjeismann
| | - Fabio Ferrari Makdissi
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Jaime Arthur Pirolla Kruger
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Sergio Carlos Nahas
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil. https://twitter.com/SergioNahasDr
| | - Paulo Herman
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil.
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12
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Papaconstantinou D, Pararas N, Pikouli A, Nastos C, Charalampopoulos A, Dellaportas D, Bagias G, Pikoulis E. Precision Surgery of Colorectal Liver Metastases in the Current Era: A Systematic Review. Cancers (Basel) 2023; 15:cancers15072083. [PMID: 37046744 PMCID: PMC10093504 DOI: 10.3390/cancers15072083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 03/23/2023] [Accepted: 03/24/2023] [Indexed: 04/03/2023] Open
Abstract
Liver resection for colorectal liver metastases (CRLM) is widely considered the treatment with the highest curative potential. However, not all patients derive the same oncological benefit, underlining the need for better patient stratification and treatment allocation. In this context, we performed a systematic review of the literature to determine the role of RAS status in selecting the optimal surgical strategy. Evidence comparing anatomical with non-anatomical resections depending on RAS mutational status was scarce and conflicting, with two studies reporting superiority in mutated RAS (mutRAS) patients and two studies reporting equivalent outcomes. The rate of incomplete microscopic resection (R1) was found to be increased among mutRAS patients, possibly due to higher micrometastatic spread lateral to the primary lesion. The impact of R1 resection margins was evaluated separately for mutRAS and wild-type patients in three studies, of which, two indicated an additive detriment to long-term survival in the former group. In the current era of precision surgery, RAS status can be utilized to predict the efficacy of liver resection in the treatment of CRLM, avoiding a potentially morbid operation in patients with adverse tumor profiles.
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13
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Galli R, Siciliano T, Aust D, Korn S, Kirsche K, Baretton GB, Weitz J, Koch E, Riediger C. Label-free multiphoton microscopy enables histopathological assessment of colorectal liver metastases and supports automated classification of neoplastic tissue. Sci Rep 2023; 13:4274. [PMID: 36922643 PMCID: PMC10017791 DOI: 10.1038/s41598-023-31401-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/10/2023] [Indexed: 03/18/2023] Open
Abstract
As the state of resection margins is an important prognostic factor after extirpation of colorectal liver metastases, surgeons aim to obtain negative margins, sometimes elaborated by resections of the positive resection plane after intraoperative frozen sections. However, this is time consuming and results sometimes remain unclear during surgery. Label-free multimodal multiphoton microscopy (MPM) is an optical technique that retrieves morpho-chemical information avoiding all staining and that can potentially be performed in real-time. Here, we investigated colorectal liver metastases and hepatic tissue using a combination of three endogenous nonlinear signals, namely: coherent anti-Stokes Raman scattering (CARS) to visualize lipids, two-photon excited fluorescence (TPEF) to visualize cellular patterns, and second harmonic generation (SHG) to visualize collagen fibers. We acquired and analyzed over forty thousand MPM images of metastatic and normal liver tissue of 106 patients. The morphological information with biochemical specificity produced by MPM allowed discriminating normal liver from metastatic tissue and discerning the tumor borders on cryosections as well as formalin-fixed bulk tissue. Furthermore, automated tissue type classification with a correct rate close to 95% was possible using a simple approach based on discriminant analysis of texture parameters. Therefore, MPM has the potential to increase the precision of resection margins in hepatic surgery of metastases without prolonging surgical intervention.
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Affiliation(s)
- Roberta Galli
- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
| | - Tiziana Siciliano
- Center for Regenerative Therapies (CRTD), Technische Universität Dresden, Fetscherstr. 105, 01307, Dresden, Germany
| | - Daniela Aust
- Institute of Pathology, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
| | - Sandra Korn
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Katrin Kirsche
- Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Gustavo B Baretton
- Institute of Pathology, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
| | - Jürgen Weitz
- National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.,Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Edmund Koch
- Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Carina Riediger
- National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.,Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
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14
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Ai XN, Tao M, Wang HY, Li JL, Sun T, Xiu DR. Analysis of survival factors after hepatic resection for colorectal cancer liver metastases: Does the R1 margin matter? Front Surg 2023; 9:1020240. [PMID: 36684119 PMCID: PMC9852629 DOI: 10.3389/fsurg.2022.1020240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 11/28/2022] [Indexed: 01/07/2023] Open
Abstract
Introduction The effect of liver margin on colorectal cancer liver metastases (CRLM) after hepatectomy has been controversial. In this study, we conducted a postoperative follow-up study of 205 patients with CRLM to clarify whether a positive margin is significant and to define the risk factors affecting CRLM survival. Methods The data of 205 patients with CRLM who underwent surgical treatment at the Third Hospital of Peking University in the Department of General Surgery from January 2009 to December 2020 were retrospectively analyzed. The general data, surgical data and postoperative follow-up of the patients were statistically analyzed. Results There were 130 cases (63.4%) of R0 resection and 75 cases (36.6%) of R1 resection. There were 136 males and 69 females, age 61 ± 11 years, and body mass index (BMI 24.5 ± 3.3 kg/m2). The overall survival rates at 1, 3, and 5 years for the entire cohort were 93.4%, 68.4%, and 45.5% in the R0 resection group vs. 93.2%, 53.7%, and 42% in the R1 resection group, respectively, which were not statistically significant (P = 0.520). The 1-, 3-, and 5-year disease-free survival rates of 63.2%, 33.3%, and 29.7% were significantly better in the R0 resection group than in the R1 resection group of 47.9%, 22.7%, and 17.7% (P = 0.016), respectively. After multivariable analysis, carbohydrate antigen 19-9 (CA19-9) > 39 U/ml (HR = 2.29, 95% CI: 1.39-3.79, P = 0.001), primary tumor perineural invasion (HR = 1.78, 95% CI: 1.01-3.13, P = 0.047), and BMI > 24 kg/m2 (HR = 1.75, 95% CI: 1.05-2.93, P = 0.033) were independently associated with poorer overall patient survival. The number of liver metastases >2 (HR = 1.65, 95% CI: 1.10-2.47, P = 0.016), the maximum diameter of metastases ≥50 mm (HR = 1.67, 95% CI: 1.06-2.64, P = 0.026), and vascular invasion of the primary tumor (HR = 1.65, 95% CI: 1.03-2.64, P = 0.038) were also independently associated with poorer disease-free survival. Conclusion In patients undergoing hepatectomy for CRLM, the negative effect of the R1 margin should be downplayed, and although the disease-free survival of the R1 margin is shorter than that of the R0 margin, it has no impact on overall survival. To improve overall survival, extra attention should be given to the factors of preoperative BMI, preoperative CA19-9, and the presence of perineural invasion of the primary tumor.
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Affiliation(s)
- Xiang-nan Ai
- Department of General Surgery, Peking University Third Hospital, Beijing, China,Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Ming Tao
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Hang-yan Wang
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Jing-lin Li
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Tao Sun
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Dian-rong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing, China,Correspondence: Dian-rong Xiu
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15
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ADAM R, ACCARDO C, ALLARD MA. Cytoreductive surgery for colorectal liver metastases: is it worthwhile? Minerva Surg 2022; 77:433-440. [DOI: 10.23736/s2724-5691.22.09669-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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16
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Margonis GA, Vauthey J. Precision surgery for colorectal liver metastases: Current knowledge and future perspectives. Ann Gastroenterol Surg 2022; 6:606-615. [PMID: 36091304 PMCID: PMC9444843 DOI: 10.1002/ags3.12591] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 06/05/2022] [Indexed: 11/08/2022] Open
Abstract
Precision surgery for colorectal liver metastases (CRLM) includes optimal selection of both the patient and surgery. Initial attempts of using clinical risk scores to identify patients for whom technically feasible surgery is oncologically futile failed. Since then, patient selection for single-stage hepatectomy followed three distinct approaches, all of which incorporated biomarkers. The BRAF V600E mutation, the G12V KRAS variant, and the triple mutation of RAS, TP53, and SMAD4 appear to be the most promising, but none can be used in isolation to deny surgery in otherwise resectable cases. Combining biomarkers with clinicopathologic factors that predict poor prognosis may be used to select patients for surgery, but external validation and matched analyses with medically treated counterparts are needed. Patient selection for special surgical procedures (two-stage hepatectomy [TSH], Associating Liver Partition and Portal vein Ligation for staged hepatectomy [ALPPS], and liver transplant [LT]) has been recently refined. Specifically, BRAF mutations and right-sided laterality have been proposed as separate contraindications to LT. A similar association of right-sided laterality, particularly when combined with RAS mutations, with very poor outcomes has been observed for ALPPS and has been suggested as a biologic contraindication. Data are scarce for TSH but RAS mutations may portend very poor survival following TSH completion. The selection of the best single-stage hepatectomy (optimal margin and type of resection) based on biomarkers remains debated, although there is some evidence that RAS may play a significant role. Lastly, although there are currently no criteria to select among the three special techniques based on their efficacy or appropriateness in different settings, RAS mutational status may be used to select patients for TSH, while right-sided tumor in conjunction with a RAS mutation may be a contraindication to LT and ALPPS.
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Affiliation(s)
- Georgios Antonios Margonis
- Department of SurgeryMemorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA
- Department of General and Visceral SurgeryCharité Campus Benjamin FranklinBerlinGermany
| | - Jean‐Nicolas Vauthey
- Department of Surgical OncologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
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17
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Chen FL, Wang YY, Liu W, Xing BC. Prognostic factors in colorectal liver metastases patients with various tumor numbers treated by liver resection: a single-center, retrospective study. World J Surg Oncol 2022; 20:237. [PMID: 35854361 PMCID: PMC9297581 DOI: 10.1186/s12957-022-02700-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 07/11/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Multiple liver metastases is considered a risk factor for overall survival of colorectal liver metastases patients (CRLM) after curative resection. However, whether the prognostic factors were constant in patients with various liver metastases (LM) numbers has not been adequately investigated. This retrospective study aimed to evaluate the changing of prognostic factors on overall survival (OS) in CRLM patients with various LM after curative resection. METHODS Patients who underwent liver resection for CRLM between January 2000 and November 2020 were retrospectively studied. They were divided into three subgroups according to LM numbers by X-tile analysis. Multivariable analysis identified prognostic factors in each subgroup. Nomograms were built using different prognostic factors in three subgroups, respectively. Performance of the nomograms was assessed according to the concordance index (C-index) and calibration plots. The abilities of different scoring systems predicting OS were compared by calculating the area under the time-dependent receiver operating characteristic (ROC) curve (AUC). RESULTS A total of 1095 patients were included. Multivariable analysis showed tumor number increasing was an independent risk factor. Patients were subsequently divided into 3 subgroups according to the number of LM by X-tile analysis, namely solitary (n = 375), 2-4 (n = 424), and ≥ 5 (n = 296). The 3-year and 5-year OS rates were 64.1% and 54.0% in solitary LM group, 58.1% and 41.7% in 2-4 LM group, and 50.9% and 32.0% in ≥ 5 LM group, respectively (p < 0.001). In multivariable analysis, RAS mutation was the only constant independent risk factor in all subgroups. The nomograms were built to predict survival based on independent factors in three subgroups. The C-index for OS prediction was 0.707 (95% CI 0.686-0.728) in the solitary LM group, 0.695 (95% CI 0.675-0.715) in the 2-4 LM group, and 0.687 (95% CI 0.664-0.710) in the ≥ 5 LM group. The time-dependent AUC values of nomograms developed using different risk factors after stratifying patients by tumor number were higher than the traditional scoring systems without patient stratification. CONCLUSIONS The prognostic factors varied among CRLM patients with different LM numbers. RAS mutation was the only constant risk factor. Building prediction models based on different prognostic factors improve patient stratification.
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Affiliation(s)
- Feng-Lin Chen
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China
| | - Yan-Yan Wang
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China
| | - Wei Liu
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China.
| | - Bao-Cai Xing
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China.
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18
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Bertsimas D, Margonis GA, Sujichantararat S, Boerner T, Ma Y, Wang J, Kamphues C, Sasaki K, Tang S, Gagniere J, Dupré A, Løes IM, Wagner D, Stasinos G, Macher-Beer A, Burkhart R, Morioka D, Imai K, Ardiles V, O'Connor JM, Pawlik TM, Poultsides G, Seeliger H, Beyer K, Kaczirek K, Kornprat P, Aucejo FN, de Santibañes E, Baba H, Endo I, Lønning PE, Kreis ME, Weiss MJ, Wolfgang CL, D'Angelica M. Using Artificial Intelligence to Find the Optimal Margin Width in Hepatectomy for Colorectal Cancer Liver Metastases. JAMA Surg 2022; 157:e221819. [PMID: 35648428 DOI: 10.1001/jamasurg.2022.1819] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Importance In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon's direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width. Objective To determine the optimal margin width in CRLM by using artificial intelligence-based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics. Design, Setting, and Participants The internal cohort of the study included patients who underwent curative-intent surgery for KRAS-variant CRLM between January 1, 2000, and December 31, 2017, at Johns Hopkins Hospital, Baltimore, Maryland, Memorial Sloan Kettering Cancer Center, New York, New York, and Charité-University of Berlin, Berlin, Germany. Patients from institutions in France, Norway, the US, Austria, Argentina, and Japan were retrospectively identified from institutional databases and formed the external cohort of the study. Data were analyzed from April 15, 2019, to November 11, 2021. Exposures Hepatectomy. Main Outcomes and Measures Patients with KRAS-variant CRLM who underwent surgery between 2000 and 2017 at 3 tertiary centers formed the internal cohort (training and testing). In the training cohort, an artificial intelligence-based technique called optimal policy trees (OPTs) was used by building on random forest (RF) predictive models to infer the margin width associated with the maximal decrease in death probability for a given patient (ie, optimal margin width). The RF component was validated by calculating its area under the curve (AUC) in the testing cohort, whereas the OPT component was validated by a game theory-based approach called Shapley additive explanations (SHAP). Patients from international institutions formed an external validation cohort, and a new RF model was trained to externally validate the OPT-based optimal margin values. Results This cohort study included a total of 1843 patients (internal cohort, 965; external cohort, 878). The internal cohort included 386 patients (median [IQR] age, 58.3 [49.0-68.7] years; 200 men [51.8%]) with KRAS-variant tumors. The AUC of the RF counterfactual model was 0.76 in both the internal training and testing cohorts, which is the highest ever reported. The recommended optimal margin widths for patient subgroups A, B, C, and D were 6, 7, 12, and 7 mm, respectively. The SHAP analysis largely confirmed this by suggesting 6 to 7 mm for subgroup A, 7 mm for subgroup B, 7 to 8 mm for subgroup C, and 7 mm for subgroup D. The external cohort included 375 patients (median [IQR] age, 61.0 [53.0-70.0] years; 218 men [58.1%]) with KRAS-variant tumors. The new RF model had an AUC of 0.78, which allowed for a reliable external validation of the OPT-based optimal margin. The external validation was successful as it confirmed the association of the optimal margin width of 7 mm with a considerable prolongation of survival in the external cohort. Conclusions and Relevance This cohort study used artificial intelligence-based methodologies to provide a possible resolution to the long-standing debate on optimal margin width in CRLM.
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Affiliation(s)
- Dimitris Bertsimas
- Operations Research Center, Massachusetts Institute of Technology, Cambridge
| | - Georgios Antonios Margonis
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.,Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, Berlin, Germany
| | - Suleeporn Sujichantararat
- Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge
| | - Thomas Boerner
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Yu Ma
- Operations Research Center, Massachusetts Institute of Technology, Cambridge
| | - Jane Wang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Carsten Kamphues
- Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, Berlin, Germany
| | - Kazunari Sasaki
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Seehanah Tang
- Operations Research Center, Massachusetts Institute of Technology, Cambridge
| | - Johan Gagniere
- Service de Chirurgie Digestive, CHU Clermont-Ferrand, Inserm, Université Clermont Auvergne, Clermont-Ferrand, France
| | - Aurelien Dupré
- Service de Chirurgie Digestive, CHU Clermont-Ferrand, Inserm, Université Clermont Auvergne, Clermont-Ferrand, France
| | - Inger Marie Løes
- Department of Clinical Science, University of Bergen, Bergen, Norway.,Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | - Doris Wagner
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | | | | | - Richard Burkhart
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Daisuke Morioka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Victoria Ardiles
- Hepatopancreatobiliary Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Columbus, Ohio
| | - George Poultsides
- Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Hendrik Seeliger
- Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, Berlin, Germany
| | - Katharina Beyer
- Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, Berlin, Germany
| | - Klaus Kaczirek
- Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Peter Kornprat
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | - Federico N Aucejo
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Eduardo de Santibañes
- Hepatopancreatobiliary Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Per Eystein Lønning
- Department of Clinical Science, University of Bergen, Bergen, Norway.,Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | - Martin E Kreis
- Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, Berlin, Germany
| | - Matthew J Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, Zucker School of Medicine at Hofstra, Northwell Health Cancer Institute, Lake Success, New York
| | - Christopher L Wolfgang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, New York University School of Medicine, New York
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
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Tonini V, Vigutto G, Donati R. Liver surgery for colorectal metastasis: New paths and new goals with the help of artificial intelligence. Artif Intell Gastroenterol 2022; 3:28-35. [DOI: 10.35712/aig.v3.i2.28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 03/28/2022] [Accepted: 04/19/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer is one of the most common neoplasia with an high risk to metastatic spread. Improving medical and surgical treatment is moving along with improving the precision of diagnosis and patient's assessment, the latter two aided more and more with the use of artificial intelligence (AI). The management of colorectal liver metastasis is multidisciplinary, and surgery is the main option. After the diagnosis, a surgical assessment of the patient is fundamental. Reaching a R0 resection with a proper remnant liver volume can be done using new techniques involving also artificial intelligence. Considering the recent application of artificial intelligence as a valid substitute for liver biopsy in chronic liver diseases, several authors tried to apply similar techniques to pre-operative imaging of liver metastasis. Radiomics showed good results in identifying structural changes in a unhealthy liver and in evaluating the prognosis after a liver resection. Recently deep learning has been successfully applied in estimating the remnant liver volume before surgery. Moreover AI techniques can help surgeons to perform an early diagnosis of neoplastic relapse or a better differentiation between a colorectal metastasis and a benign lesion. AI could be applied also in the histopathological diagnostic tool. Although AI implementation is still partially automatized, it appears faster and more precise than the usual diagnostic tools and, in the short future, could become the new gold standard in liver surgery.
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Affiliation(s)
- Valeria Tonini
- Department of Medical and Surgical Sciences, Sant' Orsola Hospital University of Bologna, Bologna 40138, Italy
| | - Gabriele Vigutto
- Department of Medical and Surgical Sciences, St Orsola Hospital, University of Bologna, Bologna 40138, Italy
| | - Riccardo Donati
- Department of Electrical, Electronic and Information Engineering ”Guglielmo Marconi” (DEI), University of Bologna, Bologna 40138, Italy
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20
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Nicolás M, Czerwonko M, Ardiles V, Sánchez Claria R, Mazza O, de Santibañes E, Pekolj J, de Santibañes M. Laparoscopic vs open liver resection for metastatic colorectal cancer: analysis of surgical margin status and survival. Langenbecks Arch Surg 2022; 407:1113-1119. [PMID: 34988643 DOI: 10.1007/s00423-021-02396-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 11/28/2021] [Indexed: 12/07/2022]
Abstract
BACKGROUND Liver resection represents the curative treatment of choice for patients with colorectal liver metastases (CRLM). Laparoscopic hepatectomy in CRLM is considered a safe approach. However, the information on their oncological results in the different series is deficient. This study aimed to compare the surgical margin, overall survival (OS), and disease-free survival (DFS) in patients with oncological resections of CRLM according to the type of surgical approach performed. METHODS Between April 2007 and June 2017, 263 patients with CRLM underwent hepatic resection. Inclusion criteria were initial resectability, tumor size ≤ 50 mm, 3 or less metastases, no bilobar involvement, and absence of extrahepatic disease. A propensity score was performed to adjust the indication bias. RESULTS Eighty-two patients were included (56 open and 26 laparoscopic). Twenty-eight (50%) patients had synchronous presentation in the open approach and 6 (23%) in the laparoscopic approach (p = 0.021), with more frequent simultaneous open resections (p = 0.037). The resection margin was positive (R1) in 5 patients with an open approach and 2 with a laparoscopic approach (8.9% and 7.6% respectively; p = 0.852). Nine patients (16%) with conventional approach and 2 (7.7%) with laparoscopic approach had local complications (p = 0.3). There was one death in the open group and none in the laparoscopic. There were no significant differences in OS and DFS rate between both groups (1-3 years, OS: 92-77% and 96-75% respectively; 1-3 years, DFS: 63-20% and 73-36% respectively). CONCLUSIONS There were no significant differences in terms of surgical margin, OS rate, and DFS rate between the laparoscopic and open approach in patients with CRLM.
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Affiliation(s)
- Miguel Nicolás
- Department of General Surgery, Division of HPB Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina
| | - Matías Czerwonko
- Department of General Surgery, Division of HPB Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina
| | - Victoria Ardiles
- Department of General Surgery, Division of HPB Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina
| | - Rodrigo Sánchez Claria
- Department of General Surgery, Division of HPB Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina
| | - Oscar Mazza
- Department of General Surgery, Division of HPB Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina
| | - Eduardo de Santibañes
- Department of General Surgery, Division of HPB Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina
| | - Juan Pekolj
- Department of General Surgery, Division of HPB Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina
| | - Martín de Santibañes
- Department of General Surgery, Division of HPB Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Juan D. Perón 4190, C1181ACH, Buenos Aires, Argentina.
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21
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BOZBIYIK O, ÇOKER A. Factors affecting survival in liver metastasis of colorectal cancer. EGE TIP DERGISI 2021. [DOI: 10.19161/etd.1036904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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22
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Acciuffi S, Meyer F, Bauschke A, Croner R, Settmacher U, Altendorf-Hofmann A. Solitary colorectal liver metastasis: overview of treatment strategies and role of prognostic factors. J Cancer Res Clin Oncol 2021; 148:657-665. [PMID: 34914005 PMCID: PMC8881245 DOI: 10.1007/s00432-021-03880-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 12/07/2021] [Indexed: 12/09/2022]
Abstract
The following is an overview of the treatment strategies and the prognostic factors to consider in the therapeutic choice of patients characterized by solitary colorectal liver metastasis. Liver resection is the only potential curative option; nevertheless, only 25% of the patients are considered to be eligible for surgery. To expand the potentially resectable pool of patients, surgeons developed multidisciplinary techniques like portal vein embolization, two-stage hepatectomy or associating liver partition and portal vein ligation for staged hepatectomy. Moreover, mini-invasive surgery is gaining support, since it offers lower post-operative complication rates and shorter hospital stay with no differences in long-term outcomes. In case of unresectable disease, various techniques of local ablation have been developed. Radiofrequency ablation is the most commonly used form of thermal ablation: it is widely used for unresectable patients and is trying to find its role in patients with small resectable metastasis. The identification of prognostic factors is crucial in the choice of the treatment strategy. Previous works that focused on patients with solitary colorectal liver metastasis obtained trustable negative predictive factors such as presence of lymph-node metastasis in the primary tumour, synchronous metastasis, R status, right-sided primary colon tumor, and additional presence of extrahepatic tumour lesion. Even the time factor could turn into a predictor of tumour biology as well as further clinical course, and could be helpful to discern patients with worse prognosis.
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Affiliation(s)
- S Acciuffi
- Department of General, Abdominal and Vascular Surgery, University Hospital, Leipziger Str. 44, 39120, Magdeburg, Germany
| | - F Meyer
- Department of General, Abdominal and Vascular Surgery, University Hospital, Leipziger Str. 44, 39120, Magdeburg, Germany
| | - A Bauschke
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - R Croner
- Department of General, Abdominal and Vascular Surgery, University Hospital, Leipziger Str. 44, 39120, Magdeburg, Germany
| | - U Settmacher
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - A Altendorf-Hofmann
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany.
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23
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Ba L, Wang Q, Wang H, Zhu L, Zhang T, Ren J, Lin Z. Survival analysis and prognostic factors of palliative radiotherapy in patients with metastatic colorectal cancer: a propensity score analysis. J Gastrointest Oncol 2021; 12:2211-2222. [PMID: 34790386 DOI: 10.21037/jgo-21-540] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 09/28/2021] [Indexed: 12/16/2022] Open
Abstract
Background Radiation therapy (RT) is known to have beneficial effects on the palliative treatment of patients with advanced cancer. However, valid data on this treatment method are limited, especially for patients with metastatic colorectal cancer (mCRC). This study aimed to identify prognostic factors and investigate the outcomes of mCRC patients who received palliative RT. Methods A total of 488 mCRC patients who underwent systemic therapy with or without palliative RT between 2014 and 2019 were included in the study. Of the 488 patients, 155 received systemic treatment combined with palliative RT (RT group), while 333 were only administered systemic treatment (non-RT group). Propensity score matching (PSM) was conducted to eliminate possible bias, and overall survival (OS) was calculated using the Kaplan-Meier (KM) method. A log-rank test was used to compare the survival outcomes of each group, and a multivariate analysis was conducted using a Cox proportional hazards model. Results The RT group had a higher OS than that of the non-RT group (P=0.001). After PSM, the median OS of the RT group was 50.8 months, and for the non-RT group it was 32.2 months (P=0.003). Subgroup analysis revealed that RT had a better effect on the OS of patients who had synchronous metastasis, or who didn't receive targeted therapy or local treatment (including surgery, ablation, and intervention). Multivariate analysis of the whole cohort showed that palliative RT was associated with improved OS. Moreover, multivariate analysis of the RT group showed that systemic therapy before RT, and the site of RT was in the liver and lung, were independent prognostic factors affecting survival time. Conclusions We demonstrated that systemic treatment followed by palliative RT led to a better OS for mCRC patients. This combination method can therefore be seen as a suitable treatment approach for patients with mCRC.
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Affiliation(s)
- Li Ba
- Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qingrui Wang
- Department of Oncology, The Sixth Hospital of Wuhan (Affiliated Hospital of Jianghan University), Jianghan University, Wuhan, China
| | - Haihong Wang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lisheng Zhu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jinghua Ren
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhenyu Lin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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24
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The evolution of surgery for colorectal liver metastases: A persistent challenge to improve survival. Surgery 2021; 170:1732-1740. [PMID: 34304889 DOI: 10.1016/j.surg.2021.06.033] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/01/2021] [Accepted: 06/21/2021] [Indexed: 02/07/2023]
Abstract
Only a few decades ago, the opinion that colorectal liver metastases were a palliative diagnosis changed. In fact, previously, the prevailing view was strongly resistant against resecting colorectal liver metastases. Constant technical improvement of liver surgery and, much later, effective chemotherapy allowed for a successful wider application of surgery. The clinical use of portal vein embolization was the starting signal of regenerative liver surgery, where insufficient liver volume can be expanded to an extent where safe resection is possible. Today, a number of these techniques including portal vein ligation, associating liver partition and portal vein ligation for staged hepatectomy, and bi-embolization (portal and hepatic vein) can be successfully used to address an insufficient future liver remnant in staged resections. It turned out that the road to success is embedding surgery in a well-orchestrated oncological concept of controlling systemic disease. This concept was the prerequisite that meant liver transplantation could enter the treatment strategy for colorectal liver metastases, ending up with a 5-year overall survival of 80% in highly selected cases. In particular, techniques combining principles of 2-stage hepatectomy and liver transplantation, such as "resection and partial liver segment 2-3 transplantation with delayed total hepatectomy" (RAPID) are on the rise. These techniques enable the use of partial liver grafts with primarily insufficient liver volume. All this progress also prompted a number of innovative local therapies to address recurrences ultimately transferring colorectal liver metastases from instantly deadly into a chronic disease in some cases.
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25
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Protic M, Krsmanovic O, Solajic N, Kukic B, Nikolic I, Bogdanovic B, Radovanovic Z, Kresoja M, Mannion C, Man YG, Stojadinovic A. Prospective Non-Randomized Study of Intraoperative Assessment of Surgical Resection Margin of Colo-Rectal Liver Metastases. J Cancer 2021; 12:3701-3714. [PMID: 33995645 PMCID: PMC8120181 DOI: 10.7150/jca.58580] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Accepted: 04/19/2021] [Indexed: 01/10/2023] Open
Abstract
Introduction: More than 50% of patients with colorectal cancer (CRC) develop liver metastases during the natural course of disease. Surgical resection is currently the most potentially curative method in the treatment of colorectal liver metastases (CRLM). The goal of surgery is to achieve a negative resection margin (RM) of at least 1 mm, which provides the best prognosis for patients. The RM can be assessed by the pathologist of the resected liver specimen (RLS) and by the surgeon intraoperatively. The aim of this research paper is to determine the degree of agreement on intraoperative assessment of the RM by the surgeon and histopathological RM assessment by the pathologist. Material and methods: This prospective non-randomized double-blind study was approved by the Ethics Committee of the Oncology Institute of Vojvodina and registered on ClinicalTrials.gov #NCT04634526. The study was conducted at the Oncology Institute of Vojvodina, Sremska Kamenica, Serbia. An experienced hepatobiliary surgeon assessed RM for every specimen intra-operatively, immediately after CRLM resection. Resected CRLM lesions were analyzed by two experienced pathologists. These data were compared with pathological RM assessment as a “gold standard”. RM of 1 mm or more was rated as negative RM (RM-). Disease-free survival (DFS) and recurrence rate was calculated by RM status defined by surgeon and by pathologist. Results: From 01 January 2015 to 31 August 2019, 98 patients were enrolled in the study. There were 219 RLS with 245 CRLM. The surgeon registered positive RM (RM+) of <1mm in 41 (18.7%) RLS. Taking the result of the histopathological assessment (HPA) as the “gold standard”, it was determined that RM was true positive in 32 (14.6%) cases. False positive RM was found in 9 (4.1%) cases. False negative RM was found in 20 (9.1%) cases. True negative RM was found in 158 (72.2%) cases. Sensitivity of surgical assessment (SA) of RM+ was 61.5% (32/52). Specificity of SA of RM+ was 94.6% (158/167). The positive predictive value (PPV) was 78.0% (32/41), while the negative predictive value (NPV) was 88.8% (158/178). The overall accuracy of the RM+ SA was 86.8% (190/219). There was no statistically significant difference in the assessment of RM+ per RLS by surgeon and pathologists (p=0.061), but it was significant when analyses per patients was performed (p=0.017). Recurrence rate for RM+ patients was 48.1% (13/27, p=0.05) for SA and 35.0% (14/40, p=0.17) for HPA. Three year DFS for RM- and RM+ was 66.5% and 27.9% (p=0.04), respectively, by SA, and 64.8% and 42.1% (p=0.106), respectively, by HPA. Conclusion: Intraoperative assessment of RM- by surgeon of RLS is clinically meaningful. There is not a statistically significant difference in the assessment of RM+ by surgeon and pathologists per RLS, but it was statically significant on a per patient basis. RM determined by surgeon has better prognostic impact on recurrence rate and 1- and 3-year DFS than standard histopathological assessment.
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Affiliation(s)
- Mladjan Protic
- Clinic for Surgical Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia.,Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Olivera Krsmanovic
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.,Armed Forces of Bosnia and Herzegovina, Logistics Command, Doboj, Bosnia and Herzegovina
| | - Nenad Solajic
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.,Department of Pathoanatomical and Laboratory Diagnostics, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Biljana Kukic
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.,Clinic for Internal Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Ivan Nikolic
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.,Clinic for Internal Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Bogdan Bogdanovic
- Clinic for Internal Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Zoran Radovanovic
- Clinic for Surgical Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia.,Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Milana Kresoja
- Clinic for Surgical Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia.,Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Ciaran Mannion
- Department of Pathology, Hackensack University Medical Center, Hackensack, New Jersey, USA.,Department of Pathology, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA
| | - Yan-Gao Man
- Department of Pathology, Hackensack University Medical Center, Hackensack, New Jersey, USA
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Bosma NA, Cheung WY, Thiessen M, Speers C, Renouf DJ, Tilley D, Tang PA, Ball CG, Dixon E, Lee-Ying RM. Real-World Outcomes of Oxaliplatin-Based Chemotherapy on R0 Resected Colonic Liver Metastasis. Clin Colorectal Cancer 2021; 20:e201-e209. [PMID: 34016533 DOI: 10.1016/j.clcc.2021.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 04/09/2021] [Accepted: 04/12/2021] [Indexed: 12/24/2022]
Abstract
INTRODUCTION In resected colonic liver metastasis (CLM), randomized studies of oxaliplatin-based chemotherapy have demonstrated improvements in disease-free survival (DFS), but not overall survival (OS). Additionally, oxaliplatin regimens have not been compared to non-oxaliplatin chemotherapy. Despite limited evidence, perioperative chemotherapy is often used in the management of CLM. The primary aim of this study was to assess the impact of oxaliplatin chemotherapy regimens on OS in patients who have undergone resection of CLM in a real-world setting. PATIENTS AND METHODS Patients who underwent resection of CLM in the provinces of Alberta and British Columbia, Canada, were identified from 1996 to 2016. Perioperative (pre- and/or post-) systemic therapy was categorized as oxaliplatin or non-oxaliplatin-based chemotherapy or no chemotherapy. The primary and secondary outcomes were OS and DFS, respectively. RESULTS We identified 511 patients who underwent R0 resection of CLM. A significant difference in median OS was identified among the oxaliplatin, non-oxaliplatin, and no-chemotherapy groups of 100, 60, and 59 months, respectively (P = .009). In multivariate analysis, patients who received oxaliplatin regimens had a lower risk of death (hazard ratio, 0.68; 95% confidence interval, 0.51-0.92; P = .012), whereas the non-oxaliplatin chemotherapy group did not (hazard ratio, 0.88; 95% confidence interval, 0.65-1.20; P = .422) compared with no chemotherapy. CONCLUSIONS In this multicenter, retrospective, population-based study, perioperative oxaliplatin-based chemotherapy was associated with improved OS in conjunction with R0 resection of CLM. Further studies should evaluate the optimal duration and sequencing of perioperative chemotherapy in relation to curative-intent surgical resection of CLM.
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Affiliation(s)
- Nicholas A Bosma
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
| | - Winson Y Cheung
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada
| | - Maclean Thiessen
- Research Institute in Hematology and Oncology, Cancer Care Manitoba, Winnipeg, MB, Canada
| | - Caroline Speers
- Gastrointestinal Cancer Outcomes Unit, BC Cancer, Vancouver, BC, Canada
| | - Daniel J Renouf
- Department of Oncology, University of British Columbia, BC Cancer, Vancouver, BC
| | - Derek Tilley
- Cancer Care Alberta, Alberta Health Services, Calgary, AB, Canada
| | - Patricia A Tang
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada
| | - Chad G Ball
- Department of Surgery, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada
| | - Elijah Dixon
- Department of Surgery, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada
| | - Richard M Lee-Ying
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada
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Chang HL, Jones AL. Current Status of Biologics in Perioperative Treatment for Resectable or Borderline Resectable Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2021. [DOI: 10.1007/s11888-021-00464-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Taillieu E, De Meyere C, D'Hondt M. The role of the laparoscopic approach in two-stage hepatectomy for colorectal liver metastases: a single-center experience. Surg Endosc 2021; 36:559-568. [PMID: 33537846 DOI: 10.1007/s00464-021-08317-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 01/09/2021] [Indexed: 10/22/2022]
Abstract
BACKGROUND In selected patients, laparoscopic liver surgery for the treatment of colorectal liver metastases (CRLM) leads to better short-term outcomes and comparable oncologic outcomes in comparison with an open approach. However, its role in two-stage hepatectomy (TSH) remains poorly explored. METHODS A single-center retrospective study was performed to evaluate the role of laparoscopic liver resection (LLR) in the first and second stage of TSH. Demographic data, comorbid factors, perioperative outcomes, and short-term outcomes were evaluated. RESULTS Between September 2011 and May 2020, 23 patients were planned to undergo a TSH. The first stage hepatectomy (FSH) was performed laparoscopically in 22 patients (96%) without need for conversion. The median blood loss was 50 cc (IQR 30-100 cc) and postoperative length of hospital stay was 4 days (IQR 2.5-5 days). R0 resections were obtained in 18 FSHs (78%), while all others were R1 vascular (22%). Fourteen patients (61%) underwent a second stage hepatectomy (SSH). All SSHs were anatomically major hepatectomies. SSH was performed laparoscopically in 7 patients (50%), with need for conversion in 1 case (14%). The median blood loss was slightly lower in the open liver resection (OLR) group compared to the LLR group (200 cc (IQR 110-375 cc) vs. 240 cc (IQR 150-400 cc), respectively. The median postoperative length of hospital stay was 3 days shorter in the LLR group compared to the OLR group (4 days (IQR 3.5-4 days) vs. 7 days (IQR 4.5-8.5 days), respectively). CONCLUSIONS The already proven advantages of LLR in the treatment of CRLM favor the role of a laparoscopic approach in TSH for CRLM. In first stage minor or technically major hepatectomy, LLR is progressively becoming the gold standard. Laparoscopic second stage anatomically major hepatectomy is feasible in experienced hands, but should be limited to selected cases and should be performed in expert centers.
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Affiliation(s)
- Emily Taillieu
- Department of Digestive and Hepatobiliary/Pancreatic Surgery, Groeninge Hospital, President Kennedylaan 4, 8500, Kortrijk, Belgium
| | - Celine De Meyere
- Department of Digestive and Hepatobiliary/Pancreatic Surgery, Groeninge Hospital, President Kennedylaan 4, 8500, Kortrijk, Belgium
| | - Mathieu D'Hondt
- Department of Digestive and Hepatobiliary/Pancreatic Surgery, Groeninge Hospital, President Kennedylaan 4, 8500, Kortrijk, Belgium.
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29
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Martínez-Cecilia D, Wicherts DA, Cipriani F, Berardi G, Barkhatov L, Lainas P, D'Hondt M, Rotellar F, Dagher I, Aldrighetti L, Troisi RI, Edwin B, Abu Hilal M. Impact of resection margins for colorectal liver metastases in laparoscopic and open liver resection: a propensity score analysis. Surg Endosc 2021; 35:809-818. [PMID: 32107633 DOI: 10.1007/s00464-020-07452-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Accepted: 02/11/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND There is no clear consensus over the optimal width of resection margin for colorectal liver metastases (CRLM), with evolving definitions alongside the advances on the management of the disease. In addition, data on the impact of resection margin after laparoscopic liver resection are still scarce. METHODS Prospectively maintained databases of patients undergoing open or laparoscopic CRLM resection in 7 European tertiary hepatobiliary referral centres were reviewed. After propensity score matching (PSM), the influence of 1 mm and wider margins on OS and DFS were evaluated in open and laparoscopic cohorts. RESULTS After PSM, 648 patients were comparable in each group. The incidence of positive margins (< 1 mm) was similar in open and laparoscopic groups (17% vs 13%, p = 0,142). Margins < 1 mm were associated with shorter RFS in open (12 vs 26 months, p = 0.042) and in laparoscopic group (13 vs 23, p = 0,002). Margins < 1 mm were associated with shorter OS in open (36 vs 57 months, p = 0.027), but not in laparoscopic group (49 vs 60, p = 0,177). Subgroups with margins ≥ 1 mm (1-4 mm, 5-9 mm, ≥ 10 mm) presented similar RFS in open (p = 0,251) or laparoscopic cohorts (p = 0.117), as well as similar OS in open (p = 0.295) or laparoscopic cohorts (p = 0.908). In the presence of liver recurrence, repeat liver resection was performed in 70 (30%) patients in the open group and 88 (48%) in the laparoscopic group (p < 0.001). CONCLUSIONS Our study suggests that a positive resection margin (less than 1 mm) width does not impact OS after laparoscopic resection of CRLMs as it does in open liver resection. However, a positive margin continues to affect RFS in open and laparoscopic resection. Wider margins than 1 mm do not seem to improve oncological results in open or laparoscopic surgery.
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Affiliation(s)
- David Martínez-Cecilia
- Department of Hepatobiliary and Pancreatic Surgery, University Hospital Southampton NHS Foundation Trust, E Level Tremona Road, Southampton, SO16 6YD, UK.
- Department of Hepatobiliary Surgery, Hospital Universitario de Toledo, Toledo, Spain.
| | - Dennis A Wicherts
- Department of Hepatobiliary and Pancreatic Surgery, University Hospital Southampton NHS Foundation Trust, E Level Tremona Road, Southampton, SO16 6YD, UK
| | - Federica Cipriani
- Department of Surgery, Hepatobiliary Surgery Unit, San Raffaele Scientific Institute, Milan, Italy
| | - Giammauro Berardi
- Department of General, Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital Medical School, Ghent, Belgium
| | - Leonid Barkhatov
- Department of Hepatic, Pancreatic and Biliary Surgery, Leader Professor at The Intervention Centre, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Oslo, Norway
| | - Panagiotis Lainas
- Department of Digestive Minimally Invasive Surgery, Antoine Béclère Hospital, Paris, France
| | - Mathieu D'Hondt
- Department of Digestive and Hepatobiliary/Pancreatic Surgery, Groeninge Hospital, Kortrijk, Belgium
| | - Fernando Rotellar
- Department of General and Digestive Surgery, Clinica Universidad de Navarra, Pamplona, Spain
| | - Ibrahim Dagher
- Department of Digestive Minimally Invasive Surgery, Antoine Béclère Hospital, Paris, France
| | - Luca Aldrighetti
- Department of Surgery, Hepatobiliary Surgery Unit, San Raffaele Scientific Institute, Milan, Italy
| | - Roberto I Troisi
- Department of General, Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital Medical School, Ghent, Belgium
| | - Bjorn Edwin
- Department of Hepatic, Pancreatic and Biliary Surgery, Leader Professor at The Intervention Centre, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Oslo, Norway
| | - Mohammad Abu Hilal
- Department of Hepatobiliary and Pancreatic Surgery, University Hospital Southampton NHS Foundation Trust, E Level Tremona Road, Southampton, SO16 6YD, UK
- Department of Hepato-Biliary and Pancreatic Surgery, Instituto Fondazione Poliambulanza, Brescia, Italy
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Glinka J, Ardiles V, Pekolj J, de Santibañes E, de Santibañes M. The role of associating liver partition and portal vein ligation for staged hepatectomy in the management of patients with colorectal liver metastasis. Hepatobiliary Surg Nutr 2020; 9:694-704. [PMID: 33299825 DOI: 10.21037/hbsn.2019.08.03] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) approach emerged as a promising surgical strategy for rapid and large hypertrophy of the future liver remnant (FLR) when a major liver resection is necessary. Colorectal liver metastasis (CRLM) is their main indication. However, the promising results published so far, are very difficult to interpret since they usually focus on the technique and not on the underlying disease. Moreover, they are usually made up of complex populations, which received different chemotherapy schemes, with the ALPPS technical variations implemented over time and without consistent long-term follow-up results as well. Whereby, its role in CRLM should be analyzed as carefully as possible to indicate and select the best candidates who will benefit the most from this approach. We conducted a computerized search using PubMed and Google Scholar for reports published so far, using mesh headings and keywords related to the ALPPS and CRLM.
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Affiliation(s)
- Juan Glinka
- Department of General Surgery, Hepato-Bilio-Pancreatic & Liver Transplantation Unit Hospital Italiano de Buenos Aires, BuenosAires, Argentina
| | - Victoria Ardiles
- Department of General Surgery, Hepato-Bilio-Pancreatic & Liver Transplantation Unit Hospital Italiano de Buenos Aires, BuenosAires, Argentina
| | - Juan Pekolj
- Department of General Surgery, Hepato-Bilio-Pancreatic & Liver Transplantation Unit Hospital Italiano de Buenos Aires, BuenosAires, Argentina
| | - Eduardo de Santibañes
- Department of General Surgery, Hepato-Bilio-Pancreatic & Liver Transplantation Unit Hospital Italiano de Buenos Aires, BuenosAires, Argentina
| | - Martin de Santibañes
- Department of General Surgery, Hepato-Bilio-Pancreatic & Liver Transplantation Unit Hospital Italiano de Buenos Aires, BuenosAires, Argentina
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31
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De Raffele E, Mirarchi M, Cuicchi D, Lecce F, Casadei R, Ricci C, Selva S, Minni F. Simultaneous colorectal and parenchymal-sparing liver resection for advanced colorectal carcinoma with synchronous liver metastases: Between conventional and mini-invasive approaches. World J Gastroenterol 2020; 26:6529-6555. [PMID: 33268945 PMCID: PMC7673966 DOI: 10.3748/wjg.v26.i42.6529] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 10/05/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
The optimal timing of surgery in case of synchronous presentation of colorectal cancer and liver metastases is still under debate. Staged approach, with initial colorectal resection followed by liver resection (LR), or even the reverse, liver-first approach in specific situations, is traditionally preferred. Simultaneous resections, however, represent an appealing strategy, because may have perioperative risks comparable to staged resections in appropriately selected patients, while avoiding a second surgical procedure. In patients with larger or multiple synchronous presentation of colorectal cancer and liver metastases, simultaneous major hepatectomies may determine worse perioperative outcomes, so that parenchymal-sparing LR should represent the most appropriate option whenever feasible. Mini-invasive colorectal surgery has experienced rapid spread in the last decades, while laparoscopic LR has progressed much slower, and is usually reserved for limited tumours in favourable locations. Moreover, mini-invasive parenchymal-sparing LR is more complex, especially for larger or multiple tumours in difficult locations. It remains to be established if simultaneous resections are presently feasible with mini-invasive approaches or if we need further technological advances and surgical expertise, at least for more complex procedures. This review aims to critically analyze the current status and future perspectives of simultaneous resections, and the present role of the available mini-invasive techniques.
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Affiliation(s)
- Emilio De Raffele
- Division of Pancreatic Surgery, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Mariateresa Mirarchi
- Dipartimento Strutturale Chirurgico, Ospedale SS Antonio e Margherita, 15057 Tortona (AL), Italy
| | - Dajana Cuicchi
- Surgery of the Alimentary Tract, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Ferdinando Lecce
- Surgery of the Alimentary Tract, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Riccardo Casadei
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Claudio Ricci
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Saverio Selva
- Division of Pancreatic Surgery, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Francesco Minni
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
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Schadde E, Grunhagen DJ, Verhoef C, Krzywon L, Metrakos P. Limitations in resectability of colorectal liver metastases 2020 - A systematic approach for clinicians and patients. Semin Cancer Biol 2020; 71:10-20. [PMID: 32980499 DOI: 10.1016/j.semcancer.2020.09.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 09/12/2020] [Indexed: 12/12/2022]
Abstract
Colorectal liver metastases (CRLM) affect over 50 % of all patients with colorectal cancer, which is the second leading cause of cancer in the western world. Resection of CRLM may provide cure and improves survival over chemotherapy alone. However, resectability of CLRM has to be decided in multidisciplinary tumor boards and is based on oncological factors, technical factors and patient factors. The advances of chemotherapy lead to the abolition of contraindications to resection in favor of technical resectability, but somatic mutations and molecular subtyping may improve selection of patients for resection in the future. Technical factors center around anatomy of the lesions, volume of the remnant liver and quality of the liver parenchymal. Multiple strategies have been developed to overcome volume limitations and they are reviewed here. The least investigated topic is how to select the right patients among an elderly and frail patient population for the large variety of technical options specifically for bi-lobar CRLM to keep 90-day mortality as low as possible. The review is an overview over the current state-of-the art and a systematic guide to the topic of resectability of CRLM for both clinicians and patients.
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Affiliation(s)
- Erik Schadde
- Division of Surgical Oncology and Division of Transplant Surgery, Department of Surgery, Rush University Medical Center, Chicago, IL, USA; Institute of Physiology, University of Zurich, Zurich, Switzerland; Department of Surgery, Cantonal Hospital Winterthur, Zurich, Switzerland.
| | - Dirk J Grunhagen
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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Civil O, Okkabaz N, Sahin TT, Tiryaki C, Yazicioglu MB, Kement M. Long-Term Results and Prognostic Significance of Non-ANATOMIC Liver Resection for Colorectal Liver Metastasis: Single Center Experience. Indian J Surg 2020; 82:197-204. [DOI: 10.1007/s12262-019-02041-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 11/28/2019] [Indexed: 02/05/2023] Open
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Adam R, Kitano Y, Abdelrafee A, Allard MA, Baba H. Debulking surgery for colorectal liver metastases: Foolish or chance? Surg Oncol 2020; 33:266-269. [PMID: 32561091 DOI: 10.1016/j.suronc.2020.02.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 02/13/2020] [Indexed: 12/21/2022]
Abstract
Even with the recent advances of surgical techniques and systemic therapies, we are often facing patients with multinodular bilateral disease for whom neither R0 nor R1 resection appears possible to perform. For such extensive cases, the tumor debulking approaches might provide a survival benefit, provided that an objective tumor response is obtained with chemotherapy. Here, we review all the arguments which may defend this strategy and propose some recommendations.
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Affiliation(s)
- René Adam
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France.
| | - Yuki Kitano
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Ahmed Abdelrafee
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France; Gastrointestinal Surgery Center, Department of Surgery, Mansoura University, Egypt
| | - Marc-Antoine Allard
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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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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37
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Even Storli P, Johnsen G, Juel IS, Grønbech JE, Bringeland EA. Impact of increased resection rates and a liver parenchyma sparing strategy on long-term survival after surgery for colorectal liver metastases. A population-based study. Scand J Gastroenterol 2019; 54:890-898. [PMID: 31318299 DOI: 10.1080/00365521.2019.1641215] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background and aims: Expanded criteria for resection of colorectal liver metastases (CRLM) have led to a more aggressive surgical attitude. The aim is to evaluate any impact of expanded criteria on perioperative mortality and long-term survival. Materials and methods: A population based study from 2001 to 2015 for patients undergoing surgery for CRLM. The cohort was divided into three 5-year periods. Results: A total of 341 patients underwent resection of CRLM. Relative to the number of colorectal primaries, patients resected for CRLM increased from 82/2520 (3.3%) in 2001-2005 to 151/3071 (4.9%) in 2011-2015 (p = .007). The proportion of patients who underwent formal resections declined from 62% to 21%. There was a substantial increase in resections of synchronous liver metastases, portal vein embolizations, two-stage resections, and the share of octogenarians who underwent resection. The proportion of patients undergoing reresections of new liver recurrences increased from 6% to 24%. The 90-d postoperative mortality for 2001-2005, 2006-2010, and 2011-2015 were 7.9%, 0.8%, and 2.0%, respectively. The median overall survival was 47 months during the two first periods, for the last period not reached. The 5-year overall survival remained at 40% from 2001 to 2010, and estimated at 55.2% from 2011 to 2015. The 5-year disease-free survival was well above 30%. The 5-year overall survival following liver reresection was 52.6%. Conclusion: Postoperative mortality remained at approximately 2%, and the 5-year overall survival at 40% in the first 10 years, but increased to 55% in the last 5 years under study, despite a marked increase in resection rates.
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Affiliation(s)
- Per Even Storli
- Department of Gastrointestinal Surgery, Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway.,Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology , Trondheim , Norway
| | - Gjermund Johnsen
- Department of Gastrointestinal Surgery, Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway
| | - Ingebjørg S Juel
- Department of Gastrointestinal Surgery, Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway
| | - Jon Erik Grønbech
- Department of Gastrointestinal Surgery, Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway.,Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology , Trondheim , Norway
| | - Erling A Bringeland
- Department of Gastrointestinal Surgery, Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway.,Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology , Trondheim , Norway
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Rehman AH, Jones RP, Poston G. Prognostic and predictive markers in liver limited stage IV colorectal cancer. Eur J Surg Oncol 2019; 45:2251-2256. [PMID: 31279594 DOI: 10.1016/j.ejso.2019.06.038] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 06/19/2019] [Accepted: 06/27/2019] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer is the third most commonly diagnosed cancer among both men and women. Personalised treatment options remain complex, although there is broad agreement over which patients with colorectal liver metastases (CRLM) should and should not be offered resection. Decisions on an optimal management strategy involves careful assessment of both technical and oncological factors. In this review we aim to summarise current prognostic biomarkers for metastatic colorectal cancers, specifically patients considered for resection. A number of clinico-pathological factors have been identified as prognostically important with good internal validity, but limited external validity. Furthermore, these prognostic scoring systems do not take factor in modern chemotherapeutic agents and the disease modification these agents produce. Histopathological response to chemotherapy is of significant prognostic importance. Molecular markers can help predict the efficacy of a biological agent. An important prognostic factor of liver metastasis is the recognition that location of the primary colorectal cancer impacts on metastatic phenotype and represents difference in genotype, i.e. proximal tumours are more aggressive than distal tumours with an increased likelihood of disease progression. Several mutational molecular markers identified include microsatellite instability, BRAF, and KRAS/NRAS and combination mutations, which confer poorer outcomes. Accurate prognostication in patients with liver limited colorectal metastases remains crucial, as this allows tailoring treatment options to each disease and improving outcomes. Access to tissue before treatment remains a limitation although advances in ability to assess tumour biology by non-invasive methods are promising.
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Affiliation(s)
- Adeeb H Rehman
- Liverpool Hepatobiliary Unit, University Hospital Aintree NHS Foundation Trust, England, UK.
| | - Robert P Jones
- Liverpool Hepatobiliary Unit, University Hospital Aintree NHS Foundation Trust, England, UK
| | - Graeme Poston
- Liverpool Hepatobiliary Unit, University Hospital Aintree NHS Foundation Trust, England, UK
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Conditional Survival Analysis of Metastatic Colorectal Cancer Patients Living ≥24 Months: A Single Institutional Study. Am J Clin Oncol 2019; 42:512-518. [PMID: 30973370 DOI: 10.1097/coc.0000000000000535] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES The survival of patients with metastatic colorectal cancer (CRC) has been increasing over recent decades due to improvements in chemotherapy and surgery. There is a need to refine prognostic information to more accurately predict survival as patients survive for any given length of time to assist multidisciplinary cancer management teams in treatment decisions. MATERIALS AND METHODS We performed a single center retrospective analysis of patients treated with metastatic CRC (unresectable and resectable) who survived >24 months between 2005 and 2015 (N=155). Patient tumor and treatment related variables were collected. Overall survival (OS) estimates conditional on surviving >24 months were compared with actuarial survival estimates of a cohort of patients (33,104 resected, 39,382 unresected) from the National Cancer Database (NCDB). RESULTS With a median follow-up of 44.2 months, the median OS of resected patients (n=86) was not reached. The median OS of unresected patients was 75.9 months. The conditional survival probabilities of living 1, 2, or 3 years longer after 24 months of survival are 92%, 72%, and 52%, respectively, in unresectable patients and 98%, 92%, and 89% in patients who were resected. The corresponding NCDB 1, 2, and 3 year actuarial survival was 38%, 20%, and 11% for unresected patients and 68%, 46%, and 32% for resected. CONCLUSIONS These results indicate that CRC patients who survive 24 months with metastatic colorectal cancer have an excellent prognosis and surgery may be appropriate in a subset of patients initially deemed unresectable.
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Xu D, Wang HW, Yan XL, Li J, Wang K, Xing BC. Sub-millimeter surgical margin is acceptable in patients with good tumor biology after liver resection for colorectal liver metastases. Eur J Surg Oncol 2019; 45:1551-1558. [PMID: 30879931 DOI: 10.1016/j.ejso.2019.03.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 01/09/2019] [Accepted: 03/05/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The definition of R1 resection in colorectal cancer liver metastases (CRLM) remains debatable. This retrospective study was conducted to clarify the impact of R1 margin on patient survival after liver resection for CRLM, taking into consideration tumor biology, including RAS status and chemotherapy response. METHODS We retrospectively analysed the clinical and survival data of 214 CRLM patients with initially resectable liver metastases who underwent liver resection after receiving neoadjuvant chemotherapy between January 2006 and December 2016. RESULTS R1 resection significantly impacted patients' overall survival (OS) and disease-free survival (DFS) in the overall patient cohort (5-year OS: 53.2% for R0 vs 38.2% for R1, P = 0.001; 5-year DFS: 26.5% for R0 vs 10.5% for R1, P = 0.002). In the RAS wild-type subgroup and respond to chemotherapy (RC) subgroup, R1 reached a similar OS to those who underwent R0 resection (RAS wild-type, P = 0.223; RC, P = 0.088). For the RAS mutated subgroup and no response to chemotherapy (NRC) subgroup, OS was significantly worse underwent R1 resection (RAS mutant, P = 0.002; NRC, P = 0.022). When considering tumor biology combining RAS and chemotherapy response status, R1 resection was only acceptable in patients with both RAS wild-type and RC (5-year OS: 66.4% for R0 vs 65.2% for R1, p = 0.884), but was significantly worse in those with either RAS mutation or NRC. CONCLUSIONS Tumor biology plays an important role in deciding the appropriate resection margin in patients with CRLM undergoing radical surgery. R1 resection margin is only acceptable in RAS wild-type patients who respond to chemotherapy.
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Affiliation(s)
- Da Xu
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China
| | - Hong-Wei Wang
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China
| | - Xiao-Luan Yan
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China
| | - Juan Li
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China
| | - Kun Wang
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China
| | - Bao-Cai Xing
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China.
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41
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Schrempf M, Anthuber M. [Prognostic importance of resection margins in multiple colorectal liver metastases]. Chirurg 2019; 90:76. [PMID: 30758598 DOI: 10.1007/s00104-019-0864-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- M Schrempf
- Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Klinikum Augsburg, Stenglinstr. 2, 86156, Augsburg, Deutschland
| | - M Anthuber
- Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Klinikum Augsburg, Stenglinstr. 2, 86156, Augsburg, Deutschland.
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42
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Adam R, Kitano Y. Multidisciplinary approach of liver metastases from colorectal cancer. Ann Gastroenterol Surg 2019; 3:50-56. [PMID: 30697610 PMCID: PMC6345652 DOI: 10.1002/ags3.12227] [Citation(s) in RCA: 122] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 12/10/2018] [Accepted: 12/16/2018] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer liver metastases (CRLM) represent most of the causes of death in patients with colorectal cancer. Surgical resection is the only treatment that can provide the possibility of prolonged survival, or even cure, for patients with CRLM. Over the last few decades, survival of these patients has improved dramatically thanks to more effective chemotherapy, extension of surgical indications, and development of new surgical procedures. In particular, patients with initially unresectable CRLM can achieve downsizing of the tumor by using various chemotherapies and the tumor can become resectable. It has been shown that such patients have a 33% 5‐year survival and a 23% 10‐year survival rate after surgery, which is a little bit lower than that of patents with resectable CRLM but significantly higher than patients without surgery. However, a decision‐making strategy for patients with CRLM is difficult because there is a wide variety of treatments and no definitive consensus. As an example, much variation among institutions exists on the resectability rate in patients with unresectable CRLM. Also, it is recommended that all patients with CRLM be managed by a multidisciplinary approach (MDA) to select the best strategy. In the future, new treatment procedures (e.g. immune checkpoint blockade, liver transplantation) may contribute to improve prognosis; hence, the necessity for MDA for the treatment of CRLM will further increase.
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Affiliation(s)
- René Adam
- AP-HP Paul Brousse Hospital, Hepato-Biliary Center Paris Sud University Inserm U 935 Villejuif France
| | - Yuki Kitano
- AP-HP Paul Brousse Hospital, Hepato-Biliary Center Paris Sud University Inserm U 935 Villejuif France.,Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
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Pencovich N, Houli R, Lubezky N, Goykhman Y, Nakache R, Klausner JM, Nachmany I. R1 resection of colorectal liver metastasis - What is the cost of marginal resection? J Surg Oncol 2018; 119:347-354. [PMID: 30548552 DOI: 10.1002/jso.25321] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 11/13/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND OBJECTIVES The impact of resection margins on the outcome of patients with colorectal liver metastasis (CRLM) remains controversial. We evaluated the short and long-term results of R1 resection. METHODS Between 2006 and 2016, 202 patients underwent liver resection for CRLM. R1 resection was defined as a distance of less than 1 mm between tumor cells and the transection plain. Patient and tumor characteristics, perioperative, and long-term outcomes were assessed. RESULTS In 161 (79.7%) and 41 (20.3%) patients, an R0 and R1 resections were achieved, respectively. Patients that underwent an R1 resection had higher rates of disease progression while on chemotherapy (12.1% vs 5.5%, P = 0.001), need for second-line chemotherapy (17% vs 6.2%, P < 0.001), increased use of preoperative volume manipulation (14.6% vs 5.5%, P = 0.001), and inferior vena-cava involvement (21.9% vs 8.7%, P < 0.001). These patients had higher rates of major postoperative complications (19.5% vs 6.8%, P < 0.001) and reoperations (7.3% vs 2.4%, P < 0.001). Multivariate analysis demonstrated that R1 resections were not associated with decreased recurrence-free survival or overall survival. CONCLUSIONS Although R1 resection is associated with worse disease behavior and postoperative complications, the long-term outcome of patients following an R1 resection is non-inferior to those who underwent an R0 resection.
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Affiliation(s)
- Niv Pencovich
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Rotem Houli
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Nir Lubezky
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Yaacov Goykhman
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Richard Nakache
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Joseph M Klausner
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Ido Nachmany
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Oshi M, Margonis GA, Sawada Y, Andreatos N, He J, Kumamoto T, Morioka D, Wolfgang CL, Tanaka K, Weiss MJ, Endo I. Higher Tumor Burden Neutralizes Negative Margin Status in Hepatectomy for Colorectal Cancer Liver Metastasis. Ann Surg Oncol 2018; 26:593-603. [PMID: 30483976 DOI: 10.1245/s10434-018-6830-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The aim of this study was to examine if the prognostic significance of margin status in hepatectomy for colorectal cancer liver metastasis (CRLM) varies for different levels of tumor burden because hepatectomy indications for CRLM have been recently expanded to include patients with a higher tumor burden in whom achieving an R0 resection is difficult. METHODS Clinicopathological variables in an exploration cohort of 290 patients receiving hepatectomy in Japan for CRLM were investigated. R0 resection was defined as a margin width > 0 mm. Tumor burden was assessed using the recently introduced Tumor Burden Score (TBS), which was calculated as TBS2 = (maximum tumor diameter in cm)2 + (number of lesions)2. The principal findings were validated using a cohort from the United States. RESULTS R1 resection rates significantly increased as TBS increased: 4/86 (4.7%) in patients with TBS < 3, 29/171 (17.0%) in patients with TBS ≥ 3 and < 9, and 9/33 (27.3%) in patients with TBS ≥ 9 (p < 0.001). R0 resection was significantly superior to R1 resection in patients with TBS ≥ 5; however, this was not the case for TBS ≥ 6, as confirmed by both univariate and multivariate analyses. Furthermore, prehepatectomy chemotherapy was associated with significantly improved survival for patients with TBS ≥ 8. Analysis of the validation cohort yielded similar results. CONCLUSIONS R0 resection appeared to have a positive impact on prognosis among patients with low tumor burden; however, this was not the case for patients with high tumor burden. As such, systemic treatment, in addition to surgery, may be central to achieving satisfactory outcomes in the latter patient population.
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Affiliation(s)
- Masanori Oshi
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | | | - Yu Sawada
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Nikolaos Andreatos
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Takafumi Kumamoto
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Daisuke Morioka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | | | - Kuniya Tanaka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Matthew John Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
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Xu F, Tang B, Jin TQ, Dai CL. Current status of surgical treatment of colorectal liver metastases. World J Clin Cases 2018; 6:716-734. [PMID: 30510936 PMCID: PMC6264988 DOI: 10.12998/wjcc.v6.i14.716] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Revised: 09/14/2018] [Accepted: 10/22/2018] [Indexed: 02/05/2023] Open
Abstract
Liver metastasis (LM) is one of the major causes of death in patients with colorectal cancer (CRC). Approximately 60% of CRC patients develop LM during the course of their illness. About 85% of these patients have unresectable disease at the time of presentation. Surgical resection is currently the only curative treatment for patients with colorectal LM (CRLM). In recent years, with the help of modern multimodality therapy including systemic chemotherapy, radiation therapy, and surgery, the outcomes of CRLM treatment have significantly improved. This article summarizes the current status of surgical treatment of CRLM including evaluation of resectability, treatment for resectable LM, conversion therapy and liver transplantation for unresectable cases, liver resection for recurrent CRLM and elderly patients, and surgery for concomitant hepatic and extra-hepatic metastatic disease (EHMD). We believe that with the help of modern multimodality therapy, an aggressive oncosurgical approach should be implemented as it has the possibility of achieving a cure, even when EHMD is present in patients with CRLM.
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Affiliation(s)
- Feng Xu
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
| | - Bin Tang
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
| | - Tian-Qiang Jin
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
| | - Chao-Liu Dai
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
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Ardito F, Panettieri E, Vellone M, Ferrucci M, Coppola A, Silvestrini N, Arena V, Adducci E, Capelli G, Vecchio FM, Giovannini I, Nuzzo G, Giuliante F. The impact of R1 resection for colorectal liver metastases on local recurrence and overall survival in the era of modern chemotherapy: An analysis of 1,428 resection areas. Surgery 2018; 165:712-720. [PMID: 30482518 DOI: 10.1016/j.surg.2018.09.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 09/09/2018] [Accepted: 09/19/2018] [Indexed: 01/03/2023]
Abstract
BACKGROUND It is still unclear whether a positive surgical margin after resection of colorectal liver metastases remains a poor prognostic factor in the era of modern perioperative chemotherapy. The aim of this study was to evaluate whether preoperative chemotherapy has an impact on reducing local recurrence after R1 resection, and the impact of local recurrence on overall survival. METHODS Between 2000 and 2014, a total of 421 patients underwent resection for colorectal liver metastases at our unit after preoperative chemotherapy. The overall number of analyzed resection areas was 1,428. RESULTS The local recurrence rate was 12.8%, significantly higher after R1 resection than after R0 (24.5% vs 8.7%; P < .001). These results were also confirmed in patients with response to preoperative chemotherapy (23.1% after R1 vs 11.2% after R0; P < .001). At multivariate analysis, R1 resection was the only independent risk factor for local recurrence (P < .001). At the analysis of the 1,428 resection areas, local recurrence significantly decreased according to the increase of the surgical margin width (from 19.1% in 0 mm margin to 2.4% in ≥10 mm). At multivariable logistic regression analysis for overall survival, the presence of local recurrence showed a significant negative impact on 5-year overall survival (P < .001). CONCLUSION Surgical margin recurrence after modern preoperative chemotherapy for colorectal liver metastases was still significantly higher after R1 resection than it was after R0 resection. Local recurrence showed a negative prognostic impact on overall survival. R0 resection should be recommended whenever technically achievable, as well as in patients treated by modern preoperative chemotherapy.
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Affiliation(s)
- Francesco Ardito
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy.
| | - Elena Panettieri
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Maria Vellone
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Massimo Ferrucci
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Alessandro Coppola
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Nicola Silvestrini
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Vincenzo Arena
- Department of Pathology, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Enrica Adducci
- Department of Anesthesiology and Intensive Care, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | | | - Fabio M Vecchio
- Department of Pathology, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Ivo Giovannini
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Gennaro Nuzzo
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
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De Raffele E, Mirarchi M, Cuicchi D, Lecce F, Ricci C, Casadei R, Cola B, Minni F. Simultaneous curative resection of double colorectal carcinoma with synchronous bilobar liver metastases. World J Gastrointest Oncol 2018; 10:293-316. [PMID: 30364774 PMCID: PMC6198303 DOI: 10.4251/wjgo.v10.i10.293] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 07/28/2018] [Accepted: 08/21/2018] [Indexed: 02/05/2023] Open
Abstract
Synchronous colorectal carcinoma (SCRC) indicates more than one primary colorectal carcinoma (CRC) discovered at the time of initial presentation, accounts for 3.1%-3.9% of CRC, and may occur either in the same or in different colorectal segments. The accurate preoperative diagnosis of SCRC is difficult and diagnostic failures may lead to inappropriate treatment and poorer prognosis. SCRC requires colorectal resections tailored to individual patients, based on the number, location, and stage of the tumours, from conventional or extended hemicolectomies to total colectomy or proctocolectomy, when established predisposing conditions exist. The overall perioperative risks of surgery for SCRC seem to be higher than for solitary CRC. Simultaneous colorectal and liver resection represents an appealing surgical strategy in selected patients with CRC and synchronous liver metastases (CRLM), even though the cumulative risks of the two procedures need to be adequately evaluated. Simultaneous resections have the noticeable advantage of avoiding a second laparotomy, give the opportunity of an earlier initiation of adjuvant therapy, and may significantly reduce the hospital costs. Because an increasing number of recent studies have shown good results, with morbidity, perioperative hospitalization, and mortality rates comparable to staged resections, simultaneous procedures can be selectively proposed even in case of complex colorectal resections, including those for SCRC and rectal cancer. However, in patients with multiple bilobar CRLM, major hepatectomies performed simultaneously with colorectal resection have been associated with significant perioperative risks. Conservative or parenchymal-sparing hepatectomies reduce the extent of hepatectomy while preserving oncological radicality, and may represent the best option for selected patients with multiple CRLM involving both liver lobes. Parenchymal-sparing liver resection, instead of major or two-stage hepatectomy for bilobar disease, seemingly reduces the overall operative risk of candidates to simultaneous colorectal and liver resection, and may represent the most appropriate surgical strategy whenever possible, also for patients with advanced SCRC and multiple bilobar liver metastases.
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Affiliation(s)
- Emilio De Raffele
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Mariateresa Mirarchi
- U.O. di Chirurgia Generale, Dipartimento Strutturale Chirurgico, Ospedale “Antonio e Margherita, ” Tortona (AL) 15057, Italy
| | - Dajana Cuicchi
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Ferdinando Lecce
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Claudio Ricci
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Riccardo Casadei
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Bruno Cola
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, Policlinico S.Orsola-Malpighi, University of Bologna, Bologna 40138, Italy
| | - Francesco Minni
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
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Stewart CL, Warner S, Ito K, Raoof M, Wu GX, Kessler J, Kim JY, Fong Y. Cytoreduction for colorectal metastases: liver, lung, peritoneum, lymph nodes, bone, brain. When does it palliate, prolong survival, and potentially cure? Curr Probl Surg 2018; 55:330-379. [PMID: 30526930 DOI: 10.1067/j.cpsurg.2018.08.004] [Citation(s) in RCA: 147] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 08/28/2018] [Indexed: 12/19/2022]
Affiliation(s)
- Camille L Stewart
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Susanne Warner
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Kaori Ito
- Department of Surgery, Michigan State University, Lansing, MI
| | - Mustafa Raoof
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Geena X Wu
- Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, CA
| | - Jonathan Kessler
- Department of Diagnostic Radiology, City of Hope National Medical Center, Duarte, CA
| | - Jae Y Kim
- Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, CA
| | - Yuman Fong
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA.
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The Prognostic Value of Varying Definitions of Positive Resection Margin in Patients with Colorectal Cancer Liver Metastases. J Gastrointest Surg 2018; 22:1350-1357. [PMID: 29633114 DOI: 10.1007/s11605-018-3748-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 03/15/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Varying definitions of resection margin clearance are currently employed among patients with colorectal cancer liver metastases (CRLM). Specifically, a microscopically positive margin (R1) has alternatively been equated with an involved margin (margin width = 0 mm) or a margin width < 1 mm. Consequently, patients with a margin width of 0-1 mm (sub-mm) are inconsistently classified in either the R0 or R1 categories, thus obscuring the prognostic implications of sub-mm margins. METHODS Six hundred thirty-three patients who underwent resection of CRLM were identified. Both R1 definitions were alternatively employed and multivariable analysis was used to determine the predictive power of each definition, as well as the prognostic implications of a sub-mm margin. RESULTS Five hundred thirty-nine (85.2%) patients had a margin width ≥ 1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0 mm). A margin width ≥ 1 mm was associated with improved survival vs. a sub-mm margin (65 vs. 36 months; P = 0.03) or an involved margin (65 vs. 33 months; P < 0.001). No significant difference in survival was detected between patients with involved vs. sub-mm margins (P = 0.31). A sub-mm margin and an involved margin were both independent predictors of worse OS (HR 1.66, 1.04-2.67; P = 0.04, and HR 2.14, 1.46-3.16; P < 0.001, respectively) in multivariable analysis. Importantly, after combining the two definitions, patients with either an involved margin or a sub-mm margin were associated with worse OS in multivariable analysis (HR 1.94, 1.41-2.65; P < 0.001). CONCLUSIONS Patients with involved or sub-mm margins demonstrated a similar inferior OS vs. patients with a margin width > 1 mm. Consequently, a uniform definition of R1 as a margin width < 1 mm should perhaps be employed by future studies.
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Falcão D, Alexandrino H, Caetano Oliveira R, Martins J, Ferreira L, Martins R, Serôdio M, Martins M, Tralhão JG, Cipriano MA, Castro E Sousa F. Histopathologic patterns as markers of prognosis in patients undergoing hepatectomy for colorectal cancer liver metastases - Pushing growth as an independent risk factor for decreased survival. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2018; 44:1212-1219. [PMID: 29691114 DOI: 10.1016/j.ejso.2018.03.023] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Revised: 03/11/2018] [Accepted: 03/27/2018] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). PATIENTS AND METHODS Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). RESULTS The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis. CONCLUSION The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients.
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Affiliation(s)
- Daniela Falcão
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal
| | - Henrique Alexandrino
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
| | - Rui Caetano Oliveira
- Serviço de Anatomia Patológica - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - João Martins
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal
| | | | - Ricardo Martins
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Marco Serôdio
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Mónica Martins
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - José Guilherme Tralhão
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Maria Augusta Cipriano
- Serviço de Anatomia Patológica - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Francisco Castro E Sousa
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
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