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Paramythiotis D, Karlafti E, Tsavdaris D, Apostolidou Kiouti F, Haidich AB, Ioannidis A, Panidis S, Michalopoulos A. The Effect of Hepatic Surgical Margins of Colorectal Liver Metastases on Prognosis: A Systematic Review and Meta-Analysis. J Clin Med 2024; 13:7776. [PMID: 39768699 PMCID: PMC11727772 DOI: 10.3390/jcm13247776] [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: 11/13/2024] [Revised: 12/14/2024] [Accepted: 12/16/2024] [Indexed: 01/16/2025] Open
Abstract
Introduction: Colorectal cancer is the third most common malignancy, with around half of patients developing liver metastases. Hepatectomy is the preferred treatment, but its success depends on several factors, including surgical margins. Various surgical margins have been suggested to achieve optimal results. This systematic review and meta-analysis aim to explore the impact of negative surgical margins ranging from 1 to 10 mm, and >10 mm on survival, with the objective of identifying optimal surgical margins. Methods: A systematic literature search was conducted on the MEDLINE, Scopus, and Cochrane databases. The six included studies that examined the effect of surgical margins at the aforementioned distances on patient survival. Studies were assessed for risk of bias using the Quality in Prognosis Studies tool. Statistical analysis was performed using SPSS software. Results: The results of the meta-analysis revealed the superiority of wider surgical margins (>10) on overall survival compared to smaller margins (1-10 mm), as the HR was calculated to be 1.38 [1.10; 1.73]. Specifically, negative margins between 1 and 10 mm are linked to a 38% increased risk of mortality compared to margins larger than 10 mm. The low heterogeneity indicates consistent findings across studies, and the statistically significant hazard ratio underscores the importance of aiming for larger surgical margins to enhance patient outcomes. In the subgroup that included only studies in which patients received neoadjuvant therapy, the HR was 1.48 [1.06; 2.07], further emphasizing the importance of ensuring negative surgical margins in today's era. Conclusions: In summary, this systematic review and meta-analysis highlights the impact of surgical margin width on the survival of patients with colorectal liver metastases, as well as the importance of margin optimization in surgical management strategies.
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Affiliation(s)
- Daniel Paramythiotis
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.I.); (S.P.); (A.M.)
| | - Eleni Karlafti
- Emergency Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
- First Propaedeutic Department of Internal Medicine, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Dimitrios Tsavdaris
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.I.); (S.P.); (A.M.)
| | - Fani Apostolidou Kiouti
- Department of Hygiene, Social-Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece (A.-B.H.)
| | - Anna-Bettina Haidich
- Department of Hygiene, Social-Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece (A.-B.H.)
| | - Aristeidis Ioannidis
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.I.); (S.P.); (A.M.)
| | - Stavros Panidis
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.I.); (S.P.); (A.M.)
| | - Antonios Michalopoulos
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.I.); (S.P.); (A.M.)
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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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Sakamoto K, Beppu T, Ogawa K, Tamura K, Honjo M, Funamizu N, Takada Y. Prognostic Impact of Surgical Margin Width in Hepatectomy for Colorectal Liver Metastasis. J Clin Transl Hepatol 2023; 11:705-717. [PMID: 36969881 PMCID: PMC10037520 DOI: 10.14218/jcth.2022.00383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 10/01/2022] [Accepted: 11/06/2022] [Indexed: 01/19/2023] Open
Abstract
As for resection for colorectal liver metastasis (CRLM), securing an adequate surgical margin is important for achieving a better prognosis. However, it is often difficult to achieve adequate margins for the resection of CRLM. So the current survival impact of sub-centi/millimeter surgical margins in hepatectomy for CRLM should be evaluated. In the current era of multidisciplinary treatment options, this review focused on the prognostic impact of a sub-centi/millimeter surgical margin width in hepatectomy for CRLM. We systematically reviewed retrospective studies that clearly described the surgical margin width for hepatectomy for CRLM. We selected studies conducted since 2000 that involved patients diagnosed as having CRLM. We focused on studies that investigated not only surgical margins, but also microscopic surgical curability such as R0 (microscopically complete resection) or R1 (microscopically incomplete resection), which clearly describe their definitions. Based on our literature review, 1, 2, or 5 mm was considered the minimum surgical margin width for hepatectomy for CRLM. Although a surgical margin width of 1 mm is acceptable for hepatectomy for CRLM, submillimeter margins, which are defined as R1 in many reports, are only acceptable for limited patients such as those who have undergone preoperative chemotherapy. Zero-mm margins are also acceptable in limited patients such as those who show a good response to preoperative chemotherapy. New chemotherapy agents have been reported to reduce the prognostic impact of a narrow surgical margin width. The incidence of margin recurrence, which is a major concern regarding R1 resection of CRLM, is about 20-30% according to the majority of earlier reports. As evaluations of the actual prognostic impact of the surgical margin remain difficult, further study is warranted.
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Affiliation(s)
- Katsunori Sakamoto
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
| | - Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
| | - Kohei Ogawa
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
| | - Kei Tamura
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
| | - Masahiko Honjo
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
| | - Naotake Funamizu
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
| | - Yasutsugu Takada
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
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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: 25] [Impact Index Per Article: 8.3] [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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5
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Germani MM, Borelli B, Boraschi P, Antoniotti C, Ugolini C, Urbani L, Morelli L, Fontanini G, Masi G, Cremolini C, Moretto R. The management of colorectal liver metastases amenable of surgical resection: How to shape treatment strategies according to clinical, radiological, pathological and molecular features. Cancer Treat Rev 2022; 106:102382. [PMID: 35334281 DOI: 10.1016/j.ctrv.2022.102382] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/16/2022] [Accepted: 03/17/2022] [Indexed: 02/05/2023]
Abstract
Metastatic colorectal cancer (mCRC) patients have poor chances of long term survival, being < 15% of them still alive after 5 years from diagnosis. Nonetheless, patients with colorectal liver metastases (CRLM) may be eligible for metastases resection thus being able to achieve long-term disease remission and survival. The likelihood for patients with CRLM of being or becoming eligible for liver metastasectomy is increasing, thanks to the evolution of surgical techniques, the availability of active systemic treatments and the widespread diffusion of experienced multidisciplinary boards to manage these patients. However, disease relapse after liver surgery is common and occurs in two-thirds of resected patients. Therefore, adequate radiological staging and risk stratification is crucial for the optimal selection of patients candidate to surgery in order to maximize the benefit-risk ratio of liver metastasectomy and to individualize the treatment strategy. Based on the multidimensional assessment, three possible approaches are available: upfront liver surgery followed by adjuvant chemotherapy, perioperative chemotherapy preceding and following liver surgery, and an upfront systemic treatment including chemotherapy plus a targeted agent, both chosen according to patients' and tumours' characteristics, then followed by liver surgery if indicated. In this review, we describe the most important factors impacting the therapeutic choices in patients with resectable and potentially resectable CRLM, and we discuss the most promising factors that may reshape the future decision-making process of these patients.
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Affiliation(s)
- Marco Maria Germani
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Beatrice Borelli
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Piero Boraschi
- Department of Diagnostic and Interventional Radiology, and Nuclear Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Carlotta Antoniotti
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Clara Ugolini
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Lucio Urbani
- Unit of General Surgery, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Luca Morelli
- General Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Gabriella Fontanini
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Gianluca Masi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Chiara Cremolini
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Roberto Moretto
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
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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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7
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Ausania F, Landi F, Martínez-Pérez A, Sandomenico R, Cuatrecasas M, Pages M, Maurel J, Garcia R, Fuster J, Garcia-Valdecasas JC. Impact of microscopic incomplete resection for colorectal liver metastases on surgical margin recurrence: R1-Contact vs R1 < 1 mm margin width. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:449-459. [PMID: 34995418 DOI: 10.1002/jhbp.1107] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 11/18/2021] [Accepted: 11/29/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Several studies highlighted an inferior outcome of R1 resection for colorectal cancer liver metastases (CRLM); it is still unclear whether directly involved margins (R1-contact) are associated with a poorer outcome compared to R1 < 1 mm. The aim of this study is to analyze the impact on surgical margin recurrence (SMR) of R1-contact vs R1 < 1 mm patients. METHODS Patients who underwent surgery for CRLM between 2009-2018 with both R1 resections on final histology were included and compared in terms of recurrence and survival. Factors associated with SMR were assessed by univariate and multivariate analysis. RESULTS Out of 477, 77 (17.2%) patients showed R1 resection (53 R1-Contact and 24 R1 < 1 mm). Overall recurrence rate was 79.2% (R1 < 1 mm = 70.8% vs R1-contact group = 83%, P = .222). Median disease-free survival (DFS) and disease-specific survival (DSS) were significantly higher in R1 < 1 mm vs R1-contact group (93 vs 55 months; P = .025 and 69 vs 46 months; P = .038, respectively). The SMR rate was higher in R1-contact compared to R1 < 1 mm group (30.2% vs 8.3%; P = .036). At univariate analysis, age, number of metastases, open surgical approach, RAS status, and R1-contact were associated with SMR. At multivariate analysis, R1-contact margin was the only factor independently associated with higher SMR (OR = 5.6; P = .046). CONCLUSIONS R1-contact margin is independently associated with SMR after liver resection for CRLM. Patients with R1-contact margin will also experience poorer DFS and DSS.
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Affiliation(s)
- Fabio Ausania
- Department of General and Digestive Surgery, Hospital Clínic, Universidad de Barcelona, IDIBAPS, Barcelona, Spain
| | - Filippo Landi
- Department of General and Digestive Surgery, Hospital Clínic, Universidad de Barcelona, IDIBAPS, Barcelona, Spain
| | | | - Raffaele Sandomenico
- Department of General and Digestive Surgery, Hospital Clínic, Universidad de Barcelona, IDIBAPS, Barcelona, Spain
| | - Miriam Cuatrecasas
- Department of Pathology, Hospital Clínic, Universidad de Barcelona, IDIBAPS, Barcelona, Spain
| | - Mario Pages
- Department of Radiology, Hospital Clínic, Universidad de Barcelona, IDIBAPS, Barcelona, Spain
| | - Joan Maurel
- Department of Medical Oncology, Hospital Clínic, Universidad de Barcelona, IDIBAPS, Barcelona, Spain
| | - Rocio Garcia
- Department of General and Digestive Surgery, Hospital Clínic, Universidad de Barcelona, IDIBAPS, Barcelona, Spain
| | - Josep Fuster
- Department of General and Digestive Surgery, Hospital Clínic, Universidad de Barcelona, IDIBAPS, Barcelona, Spain
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8
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Masetti M, Fallani G, Ratti F, Ferrero A, Giuliante F, Cillo U, Guglielmi A, Ettorre GM, Torzilli G, Vincenti L, Ercolani G, Cipressi C, Lombardi R, Aldrighetti L, Jovine E. Minimally invasive treatment of colorectal liver metastases: does robotic surgery provide any technical advantages over laparoscopy? A multicenter analysis from the IGoMILS (Italian Group of Minimally Invasive Liver Surgery) registry. Updates Surg 2022; 74:535-545. [DOI: 10.1007/s13304-022-01245-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 01/15/2022] [Indexed: 12/27/2022]
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9
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Benedetti Cacciaguerra A, Görgec B, Cipriani F, Aghayan D, Borelli G, Aljaiuossi A, Dagher I, Gayet B, Fuks D, Rotellar F, D'Hondt M, Vanlander A, Troisi RI, Vivarelli M, Edwin B, Aldrighetti L, Abu Hilal M. Risk Factors of Positive Resection Margin in Laparoscopic and Open Liver Surgery for Colorectal Liver Metastases: A New Perspective in the Perioperative Assessment: A European Multicenter Study. Ann Surg 2022; 275:e213-e221. [PMID: 32657916 DOI: 10.1097/sla.0000000000004077] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To assess the risk factors associated with R1 resection in patients undergoing OLS and LLS for CRLMs. BACKGROUND The clinical impact of R1 resection in liver surgery for CRLMs has been continuously appraised, but R1 risk factors have not been clearly defined yet. METHODS A cohort study of patients who underwent OLS and LLS for CRLMs in 9 European high-volume referral centers was performed. A multivariate analysis and the receiver operating characteristic curves were used to investigate the risk factors for R1 resection. A model predicting the likelihood of R1 resection was developed. RESULTS Overall, 3387 consecutive liver resections for CRLMs were included. OLS was performed in 1792 cases whereas LLS in 1595; the R1 resection rate was 14% and 14.2%, respectively. The risk factors for R1 resection were: the type of resection (nonanatomic and anatomic/nonanatomic), the number of nodules and the size of tumor. In the LLS group only, blood loss was a risk factor, whereas the Pringle maneuver had a protective effect. The predictive size of tumor for R1 resection was >45 mm in OLS and >30 mm in LLS, > 2 lesions was significative in both groups and blood loss >350 cc in LLS. The model was able to predict R1 resection in OLS (area under curve 0.712; 95% confidence interval 0.665-0.739) and in LLS (area under curve 0.724; 95% confidence interval 0.671-0.745). CONCLUSIONS The study describes the risk factors for R1 resection after liver surgery for CRLMs, which may be used to plan better the perioperative strategies to reduce the incidence of R1 resection during OLS and LLS.
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Affiliation(s)
- Andrea Benedetti Cacciaguerra
- Department of Hepatobiliary and Pancreatic Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
- Department of Surgery, Hepato-Pancreato-Biliary, Minimally Invasive and Robotic Unit, Istituto Fondazione Poliambulanza, Brescia, Italy
| | - Burak Görgec
- Department of Hepatobiliary and Pancreatic Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
- Department of Surgery, Hepato-Pancreato-Biliary, Minimally Invasive and Robotic Unit, Istituto Fondazione Poliambulanza, Brescia, Italy
| | - Federica Cipriani
- Department of Surgery, Hepatobiliary Surgery Unit, San Raffaele Scientific Institute, Milan, Italy
| | - Davit Aghayan
- The Intervention Center, Department of HPB Surgery, Oslo University Hospital and Institute of Clinical Medicine, Oslo University, Oslo, Norway
- Department of General and Abdominal Surgery, ArtMed MRC, Yerevan, Armenia
| | - Giulia Borelli
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Riuniti Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Anas Aljaiuossi
- Department of Hepatobiliary and Pancreatic Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
| | - Ibrahim Dagher
- Department of Digestive Minimally Invasive Surgery, Antoine Béclère Hospital, Paris, France
| | - Brice Gayet
- Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Université Paris Descartes, Paris 75014, France
| | - David Fuks
- Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Université Paris Descartes, Paris 75014, France
| | - Fernando Rotellar
- Department of General and Digestive Surgery, Clinica Universidad de Navarra, Pamplona, Spain
| | - Mathieu D'Hondt
- Department of Digestive and Hepatobiliary/Pancreatic Surgery, Groeninge Hospital, Kortrijk, Belgium
| | - Aude Vanlander
- Department of General, Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital Medical School, Ghent, Belgium
| | - Roberto I Troisi
- Department of Human Structure and Repair, Ghent University, Faculty of Medicine, Ghent, Belgium
- Department of Clinical Medicine and Surgery, Federico II University Naples, Italy
| | - Marco Vivarelli
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Riuniti Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Bjorn Edwin
- The Intervention Center, Department of HPB Surgery, Oslo University Hospital and Institute of Clinical Medicine, Oslo University, Oslo, Norway
| | - Luca Aldrighetti
- Department of Surgery, Hepatobiliary Surgery Unit, San Raffaele Scientific Institute, Milan, Italy
| | - Mohammad Abu Hilal
- Department of Hepatobiliary and Pancreatic Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
- Department of Surgery, Hepato-Pancreato-Biliary, Minimally Invasive and Robotic Unit, Istituto Fondazione Poliambulanza, Brescia, Italy
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10
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Relevance of chemotherapy and margin status in colorectal liver metastasis. Langenbecks Arch Surg 2021; 406:2725-2737. [PMID: 34023941 DOI: 10.1007/s00423-021-02205-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 05/16/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE This retrospective, single-center study aimed to investigate the importance of chemotherapy and to come up with the optimal liver resection margin length for patients with resectable colorectal liver metastasis (CRLM). METHODS Patients who had undergone any form of liver resection for CRLM were reviewed and analyzed. The analyses were broken down into three parts: (1) overall effect of chemotherapy, (2) effect of chemotherapy with positive/negative resection margin, and (3) result of discriminative analysis with optimal margin length analysis. RESULTS In total, 381 patients were studied. Among them, 279 received chemotherapy whereas 102 did not. Survival was significantly better in patients with chemotherapy (5-year, 43.6% vs. 25.8%) (p < 0.001). Patients who received chemotherapy (n = 93) with negative margins had better survival than patients (n = 8) with positive margins (5-year, 28.1% vs. 0%) (p = 0.019). On multivariate analysis, margin involvement was the poor prognostic factor for survival. Patients who had chemotherapy (n = 238) with negative margin showed a trend of better survival than patients (n = 41) with positive margins (5-year, 45.7% vs. 29.3%) (p = 0.085). Patients (n = 93) with negative margin and no chemotherapy and patients (n = 41) with positive margin and chemotherapy had comparable survival at 5 years (p = 0.422). On multivariate analysis, tumor number was the prognostic factor for survival. By the discriminant method, 1.09 cm (sensitivity 0.242, specificity 0.718) was determined as the cut-off for optimal margin length. Patients who had margin ≥ 1.09 cm (n = 81) enjoyed significantly better survival (5-year, 54.3% vs. 33.5%) (p = 0.041). On multivariate analysis, margin length ≥ 1.09 cm was the prognostic factor for favorable survival. CONCLUSION The results demonstrated the important effect of perioperative chemotherapy and negative margin liver resection in management of patients suffered from CRLM.
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11
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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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12
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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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13
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Ren W, Sell NM, Ferrone CR, Tanabe KK, Lillemoe KD, Qadan M. Size of the Largest Colorectal Liver Metastasis Is an Independent Prognostic Factor in the Neoadjuvant Setting. J Surg Res 2020; 259:253-260. [PMID: 33160635 DOI: 10.1016/j.jss.2020.09.039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 07/31/2020] [Accepted: 09/22/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Up to 50% of patients diagnosed with colorectal cancer develop metastases during the course of their disease. Surgical resection remains the only curative treatment option for colorectal liver metastases (CRLM), frequently in conjunction with neoadjuvant chemotherapy. This study sought to determine if the pathologic size of the largest CRLM impacted disease-free survival (DFS) and disease-specific survival (DSS) in the setting of neoadjuvant chemotherapy. METHODS All patients diagnosed with CRLM who underwent neoadjuvant chemotherapy for liver resection at the Massachusetts General Hospital between 2004 and 2016 were reviewed. The median size of the largest liver lesion was used as the cutoff for grouped evaluation. RESULTS A total of 214 patients were included. Median follow-up was 100.0 mo (interquartile range 68.9-133.8 mo). The median size of the largest lesion was 21 mm. Patients with lesions ≥21 mm exhibited significantly worse median DFS (12.5 mo versus 16.6 mo; P = 0.033) and median DSS (71.3 mo versus 103.5 mo; P = 0.038). CRLM lesions ≥21 mm were associated with poorer DFS on univariate analysis (hazard ratio (HR) = 1.42, 95% confidence interval (CI) 1.03-1.95 P = 0.033) and multivariable analysis (HR = 1.58, 95% CI 1.07-2.35, P = 0.023). CRLM lesions ≥21 mm were also independently associated with poorer DSS after liver resection on univariate analysis (HR = 1.51, 95% CI 1.02-2.24; P = 0.037) and multivariable analysis (HR = 1.98, 95% CI: 1.27-3.07; P = 0.002). CONCLUSIONS The size of the largest CRLM is an important prognostic factor for both DFS and DSS after neoadjuvant therapy and serves as a useful indicator of tumor biology.
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Affiliation(s)
- Weizheng Ren
- Department of Hepatopancreatobiliary Surgery, PLA General Hospital, First Medical Center, Beijing, PR China; Harvard Medical School, Boston, Massachusetts
| | - Naomi M Sell
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Cristina R Ferrone
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Kenneth K Tanabe
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Keith D Lillemoe
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Motaz Qadan
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
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14
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Zhang Q, Peng J, Ye M, Weng W, Tan C, Ni S, Huang D, Sheng W, Wang L. KRAS Mutation Predicted More Mirometastases and Closer Resection Margins in Patients with Colorectal Cancer Liver Metastases. Ann Surg Oncol 2019; 27:1164-1173. [PMID: 31720935 DOI: 10.1245/s10434-019-08065-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND The presence of micrometastases is a source of recurrence after surgical resection of colorectal liver metastases (CRLM). The KRAS mutation is common in colorectal cancer, however the correlation between KRAS status and micrometastases has not been thoroughly clarified. METHODS We enrolled a cohort of 251 consecutive CRLM patients who received complete liver surgery with known KRAS mutation status, and collected clinicopathological information, including micrometastases, margin status, preoperative chemotherapy, and liver recurrence-free survival (LRFS) and overall survival (OS) rates. RESULTS KRAS-mutant (mutKRAS) patients had a higher incidence (60.3 vs. 40.8%; p = 0.002) and higher number of micrometastases [2.0 (range 0-38.0) vs. 0 (range 0-15.0); p < 0.001] than KRAS wild-type (wtKRAS) patients. The micrometastases in the mutKRAS group were more distant than those in the wtKRAS group [0.7 (range 0.1-9.0) vs. 0.6 (range 0.2-5.0) mm; p = 0.018). The mutKRAS group had more involved margin resections (21.5 vs. 9.2%; p = 0.07) and narrower margin widths [2.0 (range 0-40.0) vs. 4.3 (0-50.0) mm; p = 0.002] than the wtKRAS group. In addition, preoperative chemotherapy was associated with a lower rate of micrometastases in mutKRAS CRLM tumors (p < 0.05). mutKRAS status, positive margins, and micrometastases were all related to worse LRFS and OS (p < 0.05); however, micrometastases were not significantly correlated with OS in the multivariate analysis (p = 0.106). CONCLUSIONS mutKRAS patients had more micrometastases, increased R1 resections, and narrower margins. The presence of micrometastases may have led to the narrow margin width observed in these cases.
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Affiliation(s)
- Qiongyan Zhang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Junjie Peng
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Min Ye
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Weiwei Weng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Cong Tan
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shujuan Ni
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Dan Huang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Weiqi Sheng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Lei Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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15
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Solaini L, Gardini A, Passardi A, Mirarchi MT, D'Acapito F, La Barba G, Cucchi M, Gardini AC, Frassineti GL, Cucchetti A, Ercolani G. Preoperative Chemotherapy and Resection Margin Status in Colorectal Liver Metastasis Patients: A Propensity Score–Matched Analysis. Am Surg 2019. [DOI: 10.1177/000313481908500525] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
In this article, we compared the early and long-term outcomes of patients with metastatic colorectal cancer treated with chemotherapy followed by resection with those of patients undergoing surgery first, focusing our analysis on resection margin status. Patients who underwent liver resection with curative intent for colorectal liver metastases from July 2001 to January 2018 were included in the analysis. Propensity score matching was used to reduce treatment allocation bias. The cohort comprised 164 patients; 117 (71.3%) underwent liver resection first, whereas the remaining 47 (28.7%) had preoperative chemotherapy. After a 1:1 ratio of propensity score matching, 47 patients per group were evaluated. A positive resection margin was found in 13 patients in the surgery-first group (25.5%) versus 4 (8.5%) in the preoperative chemotherapy group ( P = 0.029). Postmatched logistic regression analysis showed that only preoperative chemotherapy was significantly associated with the rate of positive resection margin (odds ratio 0.24, 95% confidence interval 0.07–0.81; P = 0.022). Median follow-up was 41 months (interquartile range 8–69). Cox proportional hazard regression analysis revealed that only positive resection margin was a significant negative prognostic factor (hazard ratio 2.2, 95% CI 1.18–4.11; P = 0.014). Within the preoperative chemotherapy group, median overall survival was 40 months in R0 patients and 10 months in R1 patients ( P = 0.016). Although preoperative chemotherapy in colorectal liver metastasis patients may affect the rate of positive resection margin, its impact on survival seems to be limited. In the present study, the most important prognostic factor was the resection margin status.
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Affiliation(s)
- Leonardo Solaini
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; and
| | - Andrea Gardini
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Alessandro Passardi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Maria Teresa Mirarchi
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Fabrizio D'Acapito
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Giuliano La Barba
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Michele Cucchi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; and
| | - Andrea Casadei Gardini
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Giovanni L. Frassineti
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Alessandro Cucchetti
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; and
| | - Giorgio Ercolani
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; and
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16
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Schrempf M, Anthuber M. [Influence of tumor-free resection margins on overall and disease-free survival after resection of colorectal liver metastases]. Chirurg 2019; 90:62. [PMID: 30758633 DOI: 10.1007/s00104-019-0899-z] [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- Transplantationschirurgie, Klinikum Augsburg, Stenglinstr. 2, 86156, Augsburg, Deutschland
| | - M Anthuber
- Klinik für Allgemein‑, Viszeral- Transplantationschirurgie, Klinikum Augsburg, Stenglinstr. 2, 86156, Augsburg, Deutschland.
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17
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Lu X, Guo W, Xu W, Zhang X, Shi Z, Zheng L, Zhao W. Prognostic value of the Glasgow prognostic score in colorectal cancer: a meta-analysis of 9,839 patients. Cancer Manag Res 2018; 11:229-249. [PMID: 30636896 PMCID: PMC6307678 DOI: 10.2147/cmar.s185350] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Purpose The aim of this study was to perform a systematic review and meta-analysis to evaluate the value of the Glasgow prognostic score (GPS) or modified Glasgow prognostic score (mGPS) in patients with colorectal cancer (CRC). Methods A comprehensive medical literature search was performed using the online databases PubMed, Embase, Web of Science, and the Cochrane Library. After extracting basic characteristics and prognostic data from the included studies, overall survival (OS) and cancer-specific survival (CSS) were pooled as primary outcomes. Subgroup analyses were performed according to therapeutic strategies, models, cutoff values, regions, tumor, node, metastasis stages, sample size, and ages. Results Forty-three independent cohorts from 41 studies with 9,839 CRC patients were included in the present study. Correlation between GPS or mGPS and OS was analyzed in 32 cohorts of 7,714 patients, and 23 independent cohorts of 5,375 patients focused on the correlation between GPS or mGPS and CSS. The overall outcomes showed that patients with elevated GPS or mGPS were associated with poor OS (HR: 2.20, 95% CI: 1.88–2.57, P<0.001). Elevated GPS or mGPS also resulted in worse CSS (HR: 1.86, 95% CI: 1.59–2.17, P<0.001). The results of the subgroup analyses confirmed the overall outcomes. Conclusion GPS or mGPS is an accurate prognostic predictor in patients with CRC. Patients with elevated pretreatment GPS or mGPS have a poor prognosis. Subgroup analyses confirmed the overall outcomes. Pretreatment GPS is a useful biomarker in the management of CRC.
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Affiliation(s)
- Xin Lu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
| | - Wanying Guo
- Department of Breast Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | - Wei Xu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
| | - Xuelei Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
| | - Zhijie Shi
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
| | - Leizhen Zheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
| | - Wenzhao Zhao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China,
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18
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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: 18] [Impact Index Per Article: 2.6] [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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19
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Scorsetti M, Comito T, Clerici E, Franzese C, Tozzi A, Iftode C, Di Brina L, Navarria P, Mancosu P, Reggiori G, Fogliata A, Tomatis S, Torzilli G, Cozzi L. Phase II trial on SBRT for unresectable liver metastases: long-term outcome and prognostic factors of survival after 5 years of follow-up. Radiat Oncol 2018; 13:234. [PMID: 30477560 PMCID: PMC6258482 DOI: 10.1186/s13014-018-1185-9] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 11/16/2018] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The aim of this study was to evaluate long-term efficacy and survival prognostic factors of stereotactic body radiation therapy (SBRT) for un-resectable liver metastases in patients enrolled in a prospective phase II trial. METHODS AND MATERIALS 5-year local control (LC), overall survival (OS), progression free survival (PFS) and toxicity rates were analyzed in patients with un-resectable liver metastases enrolled in a Phase II Trial on liver SBRT, with a prescription dose of 75Gy in 3 consecutive fractions. RESULTS A total of 61 patients with 76 lesions were enrolled, with a median follow-up time of 6.1 years. One, three and 5 year LC rates were 94 ± 3.1%, 78.0 ± 5.9% and 78.0 ± 5.9%, without reaching the median LC time. Median OS was 27.6 months and the survival rates were 85.2 ± 4.5%, 31.1 ± 5.9% and 18.0 ± 4.9% at 1, 3 and 5-year after SBRT, respectively. Univariate analysis showed that favorable primary site (colorectal, breast and gynecological) of metastases (p = 0.001) improved survival. Toxicity was moderate. One patient experienced G3 late chest wall pain, which resolved within 1 year from SBRT. No cases of Radiation Induced Liver Disease (RILD) were detected. CONCLUSIONS Long-term results of this Phase II study suggest the efficacy and safety of SBRT for un-resectable liver metastases after 5-year of follow up. Selection of cases with positive prognostic factors may improve long-term survival of these oligo-metastastic patients and may confirm the role of SBRT as an effective alternative local therapy for liver metastases.
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Affiliation(s)
- Marta Scorsetti
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089, Rozzano, Milan, Italy
| | - Tiziana Comito
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Elena Clerici
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Ciro Franzese
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Angelo Tozzi
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Cristina Iftode
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Lucia Di Brina
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Pierina Navarria
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Pietro Mancosu
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Giacomo Reggiori
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Antonella Fogliata
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Stefano Tomatis
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089, Rozzano, Milan, Italy.,Department of Hepato-biliary Surgery, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Luca Cozzi
- Radiotherapy and Radiosurgery Department, Humanitas Cancer Center, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy. .,Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089, Rozzano, Milan, Italy. .,Radiotherapy and Radiosurgery Department, Humanitas Research Hospital and Cancer Center, Via Manzoni 56, 20089, Milan, Rozzano, Italy.
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20
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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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21
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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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22
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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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23
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[Influence of tumor-free resection margins on overall and disease-free survival after resection of colorectal liver metastases]. Chirurg 2018; 89:733. [PMID: 30014255 DOI: 10.1007/s00104-018-0687-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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24
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Impact of Surgical Margin Width on Recurrence and Overall Survival Following R0 Hepatic Resection of Colorectal Metastases. Ann Surg 2018; 267:1047-1055. [DOI: 10.1097/sla.0000000000002552] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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25
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Interaction of margin status and tumour burden determines survival after resection of colorectal liver metastases: A retrospective cohort study. Int J Surg 2018; 53:371-377. [DOI: 10.1016/j.ijsu.2017.12.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Revised: 12/02/2017] [Accepted: 12/06/2017] [Indexed: 01/02/2023]
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26
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Hand F, Sanabria Mateos R, Durand M, Fennelly D, McDermott R, Maguire D, Geoghegan J, Winter D, Hoti E. Multivisceral Resection for Locally Invasive Colorectal Liver Metastases: Outcomes of a Matched Cohort Analysis. Dig Surg 2018; 35:514-519. [PMID: 29346790 DOI: 10.1159/000485198] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 11/09/2017] [Indexed: 12/12/2022]
Abstract
UNLABELLED Local invasion of adjacent viscera by colorectal liver metastases (CRLM) is no longer considered an absolute contraindication to curative hepatic resection. A growing number of observational analyses have illustrated the feasibility of such resections; however, the evidence base is at best heterogeneous with a lack of evidence comparing similar patient groups. We aimed to evaluate the outcomes of hepatectomy for CRLM when combined with other viscera and compare to a matched cohort of isolated hepatic resections. METHODS From 2005 to 2015, 523 patients underwent hepatic resection for CRLM at our institution, 19 of whom underwent hepatectomy with extrahepatic resection. A 3: 1 matched cohort analysis was performed between those who underwent isolated hepatectomy (control group) and those who underwent hepatectomy with extrahepatic resection (combined group). Clinicopathological data were reviewed along with 30-day postoperative morbidity and mortality. Furthermore, overall survival for the multivisceral cohort was compared to all other isolated hepatectomies over the same time period. RESULTS Nineteen patients underwent liver resection accompanied by either/or diaphragmatic resection (n = 13), major vein resection and reconstruction (n = 5), and visceral resection (n = 3). Maximum tumor size was significantly larger in the combined group (60.58 vs. 15.34 mm p < 0.0001). Postoperative morbidity was similar in both groups (p = 0.41). Following multivisceral resection, 1-, 3- and 5-year survival rates were 75, 56.6, and 25.7% respectively. Overall survival showed no significant difference between combined and control groups (p = 0.78). Similarly, when compared to the total cohort of isolated liver resections (n = 504), no significant difference in overall mortality was noted. CONCLUSION In patients presenting with concomitant CRLM and extrahepatic extension where R0 margins can be achieved, this present study supports the rationale to proceed to -surgery with comparable morbidity and mortality rates to -isolated hepatectomy.
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Affiliation(s)
- Fiona Hand
- Department of Hepatobiliary and Liver Transplant Surgery, St. Vincent's University Hospital, Dublin, Ireland
| | - Rebeca Sanabria Mateos
- Department of Hepatobiliary and Liver Transplant Surgery, St. Vincent's University Hospital, Dublin, Ireland
| | - Michael Durand
- Department of Hepatobiliary and Liver Transplant Surgery, St. Vincent's University Hospital, Dublin, Ireland
| | - David Fennelly
- Department of Medical Oncology, St. Vincent's University Hospital, Dublin, Ireland
| | - Ray McDermott
- Department of Medical Oncology, St. Vincent's University Hospital, Dublin, Ireland
| | - Donal Maguire
- Department of Hepatobiliary and Liver Transplant Surgery, St. Vincent's University Hospital, Dublin, Ireland
| | - Justin Geoghegan
- Department of Hepatobiliary and Liver Transplant Surgery, St. Vincent's University Hospital, Dublin, Ireland
| | - Des Winter
- Department of Surgery, St. Vincent's University Hospital, Dublin, Ireland
| | - Emir Hoti
- Department of Hepatobiliary and Liver Transplant Surgery, St. Vincent's University Hospital, Dublin, Ireland
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27
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Fonseca GM, Herman P, Faraj SF, Kruger JAP, Coelho FF, Jeismann VB, Cecconello I, Alves VAF, Pawlik TM, de Mello ES. Pathological factors and prognosis of resected liver metastases of colorectal carcinoma: implications and proposal for a pathological reporting protocol. Histopathology 2017; 72:377-390. [PMID: 28858385 DOI: 10.1111/his.13378] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Colorectal cancer is a leading cause of death worldwide. The liver is the most common site of distant metastases, and surgery is the only potentially curative treatment, although the recurrence rate following surgery is high. In order to define prognosis after surgery, many histopathological features have been identified in the primary tumour. In turn, pathologists routinely report specific findings to guide oncologists on the decision to recommend adjuvant therapy. In general, the pathological report of resected colorectal liver metastases is limited to confirmation of the malignancy and details regarding the margin status. Most pathological reports of a liver resection for colorectal liver metastasis lack information on other important features that have been reported to be independent prognostic factors. We herein review the evidence to support a more detailed pathological report of the resected liver specimen, with attention to: the number and size of liver metastases; margin size; the presence of lymphatic, vascular, perineural and biliary invasion; mucinous pattern; tumour growth pattern; the presence of a tumour pseudocapsule; and the pathological response to neoadjuvant chemotherapy. In addition, we propose a new protocol for the evaluation of colorectal liver metastasis resection specimens.
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Affiliation(s)
- Gilton M Fonseca
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Paulo Herman
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Sheila F Faraj
- Department of Pathology, São Paulo State Cancer Institute, University of São Paulo Medical School, São Paulo, Brazil
| | - Jaime A P Kruger
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Fabricio F Coelho
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Vagner B Jeismann
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Ivan Cecconello
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Venancio A F Alves
- Department of Pathology, São Paulo State Cancer Institute, University of São Paulo Medical School, São Paulo, Brazil
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Evandro S de Mello
- Department of Pathology, São Paulo State Cancer Institute, University of São Paulo Medical School, São Paulo, Brazil
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28
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Sasaki K, Margonis GA, Maitani K, Andreatos N, Wang J, Pikoulis E, He J, Wolfgang CL, Weiss M, Pawlik TM. The Prognostic Impact of Determining Resection Margin Status for Multiple Colorectal Metastases According to the Margin of the Largest Lesion. Ann Surg Oncol 2017; 24:2438-2446. [PMID: 28695393 DOI: 10.1245/s10434-017-5904-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND Although the prognostic role of surgical margin status after resection of colorectal liver metastasis (CRLM) has been previously examined, controversy still surrounds the importance of surgical margin status in patients with multiple tumors. METHODS Patients who underwent curative-intent surgery for CRLM from 2000 to 2015 and who presented with multiple tumors were identified. Patients with R1 resection status determined by the closest resection margin of the non-largest tumor were classified as R1-Type 1; patients with R1 status determined by the resection margin of the largest tumor were defined as R1-Type 2. Data regarding surgical margin status, size of tumors, and overall survival (OS) were collected and assessed. RESULTS A total of 251 patients met inclusion criteria; 156 patients (62.2%) had a negative margin (R0), 50 had an R1-type 1 (19.9%), and 45 had an R1-type 2 (17.9%) margin. Median and 5-year OS in the entire cohort was 56.4 months and 48.0%, respectively. When all R1 (Type 1 + Type 2) patients were compared with R0 patients, an R1 was not associated with worse prognosis (P = 0.05). In contrast, when R1-type 2 patients were compared with R0 patients, an R1 was strongly associated with worse OS (P = 0.009). On multivariate analysis, although the prognostic impact of all R1 was not associated with OS (hazard ratio [HR] 1.56; P = 0.08), R1-Type 2 margin status independently predicted a poor outcome (HR 1.93; P = 0.03). CONCLUSIONS The impact of margin status varied according to the size of the tumor assessed. While R1 margin status defined according to the non-largest tumor was not associated with OS, R1 margin status relative to the largest index lesion was associated with prognosis.
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Affiliation(s)
- Kazunari Sasaki
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Georgios A Margonis
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Kosuke Maitani
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Nikolaos Andreatos
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jaeyun Wang
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Emmanouil Pikoulis
- First Department of Surgery, Laiko Hospital, University of Athens, Athens, Greece
| | - Jin He
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Christopher L Wolfgang
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Matthew Weiss
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Margonis GA, Sasaki K, Kim Y, Samaha M, Buettner S, Amini N, Antoniou E, Pawlik TM. Tumor Biology Rather Than Surgical Technique Dictates Prognosis in Colorectal Cancer Liver Metastases. J Gastrointest Surg 2016; 20:1821-1829. [PMID: 27384430 DOI: 10.1007/s11605-016-3198-8] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 06/22/2016] [Indexed: 01/31/2023]
Abstract
INTRODUCTION The interplay of tumor biology and surgical margin status after resection for colorectal liver metastasis (CRLM) remains controversial. Consequently, we sought to determine the impact of surgical margin status on overall survival (OS) stratified by KRAS mutational status. MATERIALS AND METHODS Four hundred eighty-five patients with known KRAS mutational status were identified. Clinicopathologic and long-term survival data were collected and assessed. RESULTS On pathology, most patients (n = 380; 78.3 %) had an R0 margin, while 105 (21.7 %) had an R1. Roughly two thirds of tumors were KRAS wild type (wtKRAS) (n = 307, 63.3 %), while 36.7 % (n = 178) had KRAS mutations (mutKRAS). Median and 5-year OS of the entire cohort was 65.8 months and 53.8 %, respectively. An R1 resection was associated with worse 5-year OS compared with R0 (42.4 % vs. 57.1 %; hazard ratio (HR) 1.82, 95 % CI 1.28-2.57; P = 0.001). After controlling for KRAS status, the survival benefit associated with an R0 resection persisted only among patients with wtKRAS tumors (HR 2.16, 95 % CI 1.42-3.30; P < 0.001). In contrast, surgical margin had no impact on OS among patients with mutKRAS tumors (5-year OS R0, 40.7 % vs. R1, 46.7 %; HR 1.34, 95 % CI 0.73-2.48; P = 0.348). CONCLUSION The impact of margin status differed by KRAS mutation status. An R0 margin only provided a survival benefit to patients with wtKRAS tumors. Tumor biology and not surgical technique determined prognosis.
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Affiliation(s)
| | - Kazunari Sasaki
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Yuhree Kim
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mario Samaha
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Stefan Buettner
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Neda Amini
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Efstathios Antoniou
- Second Department of Propaedeutic Surgery, Laiko Hospital, University of Athens, Athens, Greece
| | - Timothy M Pawlik
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Long D, Yu PC, Huang W, Luo YL, Zhang S. Systematic review of partial hepatic resection to treat hepatic metastases in patients with gastric cancer. Medicine (Baltimore) 2016; 95:e5235. [PMID: 27858875 PMCID: PMC5591123 DOI: 10.1097/md.0000000000005235] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To examine overall survival and mortality following hepatic resection in patients with hepatic metastases from gastric cancer. METHODS EMBASE, PubMed, Web of Science, and Cochrane databases were systematically searched for publications involving more than 10 patients who underwent hepatic resection to treat hepatic metastases from gastric cancer and who did not have peritoneal disease or involvement of other distant organs. RESULTS A total of 39 studies were included, involving a median of 21 hepatic resections (range, 10-64). Resection was associated with median 30-day morbidity of 24% (range, 0%-47%) and 30-day mortality of 0% (range, 0%-30%). Median overall survival was 68% at 1 year, 31% at 3 years, and 27% at 5 years. Asian studies reported higher rates than Western studies for overall survival at 1 year (73% vs 59%), 3 years (34% vs 25%), and 5 years (27% vs 17%). Compared with palliative treatment, resection was associated with significantly lower mortality at 1 year (risk ratio [RR] 0.47, P < 0.001) and 2 years (RR 0.70, P < 0.001). CONCLUSION Patients with hepatic metastases from gastric cancer may benefit from hepatic resection in case of good physical condition, absence of peritoneal dialysis, and optimum liver function with single metastases. More trials are needed to confirm this finding.
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Affiliation(s)
- Di Long
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
- Department of General Surgery, The Second People's Hospital of Qinzhou, Qinzhou, China
| | - Peng-Cheng Yu
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
| | - Wei Huang
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
| | - Yu-Long Luo
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
| | - Sen Zhang
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning
- Correspondence: Sen Zhang, Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Rd #22, Nanning 530021, China (e-mail: )
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Coimbra FJF, Ribeiro HSDC, Marques MC, Herman P, Chojniak R, Kalil AN, Wiermann EG, Cavallero SRDA, Coelho FF, Fernandes PHDS, Silvestrini AA, Almeida MFA, de Araújo ALE, Pitombo M, Teixeira HM, Waechter FL, Ferreira FG, Diniz AL, D'Ippolito G, D'Ippolito G, Begnami MDFDS, Prolla G, Balzan SMP, de Oliveira TB, Szultan LA, Lendoire J, Torres OJM. FIRST BRAZILIAN CONSENSUS ON MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 1: PRE-TREATMENT EVALUATION. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2016; 28:222-30. [PMID: 26734788 PMCID: PMC4755170 DOI: 10.1590/s0102-6720201500040002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Accepted: 08/11/2015] [Indexed: 02/07/2023]
Abstract
Background : Liver metastases of colorectal cancer are frequent and potentially fatal event
in the evolution of patients with these tumors. Aim : In this module, was contextualized the clinical situations and parameterized
epidemiological data and results of the various treatment modalities established.
Method: Was realized deep discussion on detecting and staging metastatic colorectal
cancer, as well as employment of imaging methods in the evaluation of response to
instituted systemic therapy. Results : The next step was based on the definition of which patients would have their
metastases considered resectable and how to expand the amount of patients elegible
for modalities with curative intent. Conclusion : Were presented clinical, pathological and molecular prognostic factors,
validated to be taken into account in clinical practice.
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Affiliation(s)
| | | | | | - Paulo Herman
- American Hepato-Pancreato-Biliary Association, São Paulo, Brazil
| | - Rubens Chojniak
- American Hepato-Pancreato-Biliary Association, São Paulo, Brazil
| | | | | | | | | | | | | | | | | | - Marcos Pitombo
- American Hepato-Pancreato-Biliary Association, São Paulo, Brazil
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Fairhurst K, Leopardi L, Satyadas T, Maddern G. The safety and effectiveness of liver resection for breast cancer liver metastases: A systematic review. Breast 2016; 30:175-184. [PMID: 27764727 DOI: 10.1016/j.breast.2016.09.011] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 08/11/2016] [Accepted: 09/15/2016] [Indexed: 02/08/2023] Open
Abstract
Breast cancer liver metastases have traditionally been considered incurable and any treatment given therefore palliative. Liver resections for breast cancer metastases are being performed, despite there being no robust evidence for which patients benefit. This review aims to determine the safety and effectiveness of liver resection for breast cancer metastases. A systematic literature review was performed and resulted in 33 papers being assembled for analysis. All papers were case series and data extracted was heterogeneous so a meta-analysis was not possible. Safety outcomes were mortality and morbidity (in hospital and 30-day). Effectiveness outcomes were local recurrence, re-hepatectomy, survival (months), 1-, 2-, 3-, 5- year overall survival rate (%), disease free survival (months) and 1-, 2-, 3-, 5- year disease free survival rate (%). Overall median figures were calculated using unweighted median data given in each paper. Results demonstrated that mortality was low across all studies with a median of 0% and a maximum of 5.9%. The median morbidity rate was 15%. Overall survival was a median of 35.1 months and a median 1-, 2-, 3- and 5-year survival of 84.55%, 71.4%, 52.85% and 33% respectively. Median disease free survival was 21.5 months with a 3- and 5-year median disease free survival of 36% and 18%. Whilst the results demonstrate seemingly satisfactory levels of overall survival and disease free survival, the data are of poor quality with multiple confounding variables and small study populations. Recommendations are for extensive pilot and feasibility work with the ultimate aim of conducting a large pragmatic randomised control trial to accurately determine which patients benefit from liver resection for breast cancer liver metastases.
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Affiliation(s)
- Katherine Fairhurst
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
| | - Lisa Leopardi
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
| | - Thomas Satyadas
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
| | - Guy Maddern
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
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Modern Technical Approaches in Hepatic Surgery for Colorectal Metastases. CURRENT COLORECTAL CANCER REPORTS 2016. [DOI: 10.1007/s11888-016-0327-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Tang H, Lu W, Li B, Meng X, Dong J. Influence of surgical margins on overall survival after resection of intrahepatic cholangiocarcinoma: A meta-analysis. Medicine (Baltimore) 2016; 95:e4621. [PMID: 27583880 PMCID: PMC5008564 DOI: 10.1097/md.0000000000004621] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Surgical resection is shown to present the best chance of cure in the treatment of intrahepatic cholangiocarcinoma (ICC). However, the appropriate length of the negative margin remains unclear. The aim of the present meta-analysis was to investigate whether a clear margin of 10 mm or more (≥10 mm) conferred any survival benefit over a margin of less than 10 mm (<10 mm) in patients with resected ICC. METHODS The meta-analysis was conducted in adherence with the PRISMA guidelines. PubMed, Web of Science, EMBASE, and the Cochrane Library were systematically searched to identify eligible studies published in English from the initiation of the databases to February 2016. Overall survival rates were pooled by using the hazard ratio and the corresponding 95% confidence interval (CI). Random-effect models were utilized because of between-study heterogeneity. RESULTS Six studies (eight cohorts) reporting on 712 patients were analyzed: 269 (37.80%) were in the 10 mm or more negative margin group, and 443 (62.20%) were in the less than 10 mm negative margin group. The pooled hazard ratio for the less than 10 mm group was found to be 1.59 (95% CI: 1.09-2.32) when this group was compared with the 10 mm or more group (reference), with moderate between-study heterogeneity (I = 45.30%, P = 0.07). Commensurate results were identified by sensitivity analysis. CONCLUSION The result of this meta-analysis suggests a long-term survival (overall survival) advantage for negative margins of 10 mm or more in comparison with negative margins less than 10 mm for patients undergoing surgical resection of ICC.
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Affiliation(s)
- Haowen Tang
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital
| | - Wenping Lu
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital
| | | | - Xuan Meng
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital
| | - Jiahong Dong
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital
- Center for Hepatopancreatobiliary Diseases, Beijing Tsinghua Changgung Hospital, Tsinghua University Medical Center, Changping, Beijing, China
- Correspondence: Jiahong Dong, Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, 28 Fuxing Road, Haidian, Beijing, 100853, China (e-mail: )
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Takamoto T, Sugawara Y, Hashimoto T, Shimada K, Inoue K, Maruyama Y, Makuuchi M. Two-dimensional assessment of submillimeter cancer-free margin area in colorectal liver metastases. Medicine (Baltimore) 2016; 95:e4080. [PMID: 27399096 PMCID: PMC5058825 DOI: 10.1097/md.0000000000004080] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The aim of the study is to evaluate the prognostic impact of the extent of submillimeter or zero surgical margin (SubMM) area among the patients who underwent liver resection for colorectal liver metastases (CRLM).The influence of suboptimal margin width of <1 mm on long-term outcome is unclear.A total of 423 liver resections for CRLM were performed at Japanese Red Cross Medical Center between 2007 and 2015. Among them, we identified 235 patients who underwent curative initial liver resection and classified them into 2 groups: R0 (margin: ≥1 mm) and R1 (SubMM). The R1 group was further divided into 2 groups by the extent of SubMM area: small SubMM area (≤4 cm) and broad SubMM area (>4 cm).The median tumor number was 4 (range 1-97), 23% had solitary and 37% had 8 or more number of metastases. With a median follow-up period of 30 months, the overall 1-, 3-, 5-year survival for R0 (n = 72) versus R1 (n = 163) groups were 98.4% vs 87.5%, 75.5% versus 57.1%, and 50.1% versus 36.6%, respectively (P = 0.004). After propensity score analysis allowing for matching the tumor number (<8 vs 8 or more), tumor size, and serum carcinoembryonic antigen level, the DFS and OS were significantly higher in the small SubMM area group (P = 0.024, P = 0.049), respectively.Although wide margins >1 mm should be attempted whenever possible, reducing the extent of SubMM area (≤4 cm) can contribute to better long-term outcome when wide margin is not practicable.
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Affiliation(s)
- Takeshi Takamoto
- Divisions of Hepato–Biliary–Pancreatic and Liver Transplantation Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
- Correspondence: Takeshi Takamoto, Divisions of Hepato–Biliary–Pancreatic Surgery and Liver Transplantation, Japanese Red Cross Medical Center, Hiroo, Shibuya-ku, Tokyo, Japan (e-mail: )
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Silberhumer GR, Paty PB, Denton B, Guillem J, Gonen M, Araujo RLC, Nash GM, Temple LK, Allen PJ, DeMatteo RP, Weiser MR, Wong WD, Jarnagin WR, D'Angelica MI, Fong Y. Long-term oncologic outcomes for simultaneous resection of synchronous metastatic liver and primary colorectal cancer. Surgery 2016; 160:67-73. [PMID: 27079362 DOI: 10.1016/j.surg.2016.02.029] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 02/05/2016] [Accepted: 02/24/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND Twenty-five percent of patients with colorectal cancer present with simultaneous liver metastasis. Complete resection is the only potential curative treatment. Due to improvements in operative and perioperative management, simultaneous liver and colon resections are an accepted procedure at specialized centers for selected patients. Nevertheless, little is known about the long-term, oncologic results of simultaneous operative procedures compared with those of staged operations. METHODS Patients with colorectal cancer and simultaneous liver metastases presenting for complete resection at a tertiary cancer center were identified. Patients who received the primary colon resection at an outside institution were excluded from analysis. RESULTS Between 1984 and 2008, 429 patients underwent operative treatment for colorectal cancer with simultaneous liver metastasis. Of these, 320 (75%) had simultaneous resection and 109 had staged resection. There was no difference in the distribution of primary tumor locations between the 2 groups. Mean size of the hepatic metastases was significantly greater in the staged group (median 4 cm vs 2.5 cm; P < .01). Neither disease-free nor overall survival differed significantly between the 2 treatment strategies. The extent of the liver procedure (more than 3 segments) was identified as a risk factor for decreased disease-free and overall survival (both P < .01). CONCLUSION Simultaneous liver and colorectal resections for metastatic colorectal cancer are associated with similar long-term cancer outcome compared with staged procedures.
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Affiliation(s)
- Gerd R Silberhumer
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Surgery, Medical University Vienna, Vienna, Austria
| | - Philip B Paty
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Brian Denton
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Jose Guillem
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Raphael L C Araujo
- Department of Surgery, Hepatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Garret M Nash
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Larissa K Temple
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Peter J Allen
- Department of Surgery, Hepatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Ronald P DeMatteo
- Department of Surgery, Hepatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Martin R Weiser
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - W Douglas Wong
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - William R Jarnagin
- Department of Surgery, Hepatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Michael I D'Angelica
- Department of Surgery, Hepatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Yuman Fong
- Department of Surgery, City of Hope, Duarte, CA.
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Wada Y, Takami Y, Tateishi M, Ryu T, Mikagi K, Saitsu H. Efficacy of surgical treatment using microwave coagulo-necrotic therapy for unresectable multiple colorectal liver metastases. Onco Targets Ther 2016; 9:937-43. [PMID: 26955286 PMCID: PMC4772915 DOI: 10.2147/ott.s97824] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Five or more colorectal liver metastases (CRLM) are considered marginally resectable and cannot be treated solely by hepatic resection (Hr). This study investigated the long-term effectiveness of surgical treatment using microwave coagulo-necrotic therapy (MCN) and/or Hr for marginally resectable or unresectable multiple CRLM. METHODS This study retrospectively analyzed 82 consecutive CRLM patients with ≥5 CRLM who underwent MCN, Hr, or both, at our institution from 1994 to 2012. Presuming all CRLM were resected curatively, virtual remnant liver volume was calculated using preoperative computed tomography or magnetic resonance imaging. Virtual remnant liver volume <30% was defined as unresectable. Patients were divided into marginally resectable (Group Y; n=29) and unresectable (Group N; n=53). Overall and recurrence-free survival were assessed. RESULTS Mean maximum tumor diameter and tumor number were 3.1 and 6.0 cm in Group Y and 3.3 and 11.3 cm in Group N. Surgical methods included MCN (n=16), MCN+Hr (n=9), and Hr (n=4) in Group Y, and MCN (n=28) and MCN+Hr (n=25) in Group N. One- and 2-year recurrence-free survival rates were 38.0% and 22.8% in Group Y, and 18.9% and 3.8% in Group N (P=0.01). However, 1-, 3-, and 5-year overall survival rates of Group N (86.8%, 44.6%, and 33.7%, respectively) were similar to those of Group Y (82.8%, 51.4%, and 33.3%, respectively; P= not significant each). CONCLUSION MCN may improve survival for patients with unresectable multiple CRLM, similar to that in patients with marginally resectable multiple CRLM.
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Affiliation(s)
- Yoshiyuki Wada
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Yuko Takami
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Masaki Tateishi
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Tomoki Ryu
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Kazuhiro Mikagi
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Hideki Saitsu
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
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Li MX, Bi XY, Li ZY, Huang Z, Han Y, Zhao JJ, Zhao H, Cai JQ. Impaction of surgical margin status on the survival outcome after surgical resection of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. J Surg Res 2016; 203:163-73. [PMID: 27338547 DOI: 10.1016/j.jss.2016.02.012] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Revised: 02/03/2016] [Accepted: 02/11/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Conflicting results about the prognostic value of surgical margin status in patients with intrahepatic cholangiocarcinoma (ICC) have been reported. We aimed to assess the association between surgical margin status and prognosis in ICC through a meta-analysis. MATERIALS AND METHODS We conducted a literature search of the articles evaluating the prognostic value of surgical margin status in patients with ICC. The pooled estimation of the hazard ratio (HR) with the 95% confidence interval (CI) was performed to determine the influence of surgical margin status on the survival outcome. RESULTS A total of 21 studies involving 3201 patients were finally included into the meta-analysis. The percentage of patients with positive surgical margin ranged from 7.2% to 75.9% in the enrolled studies. The pooled estimates showed that patients with positive surgical margin had inferior overall survival (HR: 1.864; 95% CI: 1.542-2.252; P < 0.001) and progression-free survival (HR: 2.033; 95% CI: 1.030-4.011; P = 0.041) than patients with negative ones. The subgroup analyses and sensitivity analyses were consistent with the overall results. CONCLUSIONS Patients with negative surgical margin had significantly favorable overall survival and progression-free survival after surgical resection for ICC. The notion of achieving the R0 resection should be emphasized.
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Affiliation(s)
- Mu-Xing Li
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Xin-Yu Bi
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Zhi-Yu Li
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Zhen Huang
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Yue Han
- Department of Radiofrequency Ablation, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Jian-Jun Zhao
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Hong Zhao
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China.
| | - Jian-Qiang Cai
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China.
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Mattar RE, Al-alem F, Simoneau E, Hassanain M. Preoperative selection of patients with colorectal cancer liver metastasis for hepatic resection. World J Gastroenterol 2016; 22:567-581. [PMID: 26811608 PMCID: PMC4716060 DOI: 10.3748/wjg.v22.i2.567] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 09/24/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023] Open
Abstract
Surgical resection of colorectal liver metastases (CRLM) has a well-documented improvement in survival. To benefit from this intervention, proper selection of patients who would be adequate surgical candidates becomes vital. A combination of imaging techniques may be utilized in the detection of the lesions. The criteria for resection are continuously evolving; currently, the requirements that need be met to undergo resection of CRLM are: the anticipation of attaining a negative margin (R0 resection), whilst maintaining an adequate functioning future liver remnant. The timing of hepatectomy in regards to resection of the primary remains controversial; before, after, or simultaneously. This depends mainly on the tumor burden and symptoms from the primary tumor. The role of chemotherapy differs according to the resectability of the liver lesion(s); no evidence of improved survival was shown in patients with resectable disease who received preoperative chemotherapy. Presence of extrahepatic disease in itself is no longer considered a reason to preclude patients from resection of their CRLM, providing limited extra-hepatic disease, although this currently is an area of active investigations. In conclusion, we review the indications, the adequate selection of patients and perioperative factors to be considered for resection of colorectal liver metastasis.
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Dhir M, Sasson AR. Surgical Management of Liver Metastases From Colorectal Cancer. J Oncol Pract 2016; 12:33-9. [DOI: 10.1200/jop.2015.009407] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Surgical resection remains one of the major curative treatment options available to patients with colorectal liver metastases. Surgery and chemotherapy form the backbone of the treatment in patients with colorectal liver metastases. With more effective chemotherapy regimens being available, the optimal timing and sequencing of treatments are important. A multidisciplinary approach with the involvement of medical oncologists and surgical oncologists from the beginning is crucial. Identification of the clinical and molecular prognostic factors may help personalize the treatment approaches for these patients. This article provides an overview of the surgical management of colorectal liver metastases.
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Affiliation(s)
- Mashaal Dhir
- University of Pittsburgh Medical Center, Pittsburgh, PA; and Stony Brook University School of Medicine, Stony Brook, NY
| | - Aaron R. Sasson
- University of Pittsburgh Medical Center, Pittsburgh, PA; and Stony Brook University School of Medicine, Stony Brook, NY
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Bhutiani N, Philips P, Martin RCG, Scoggins CR. Impact of surgical margin clearance for resection of secondary hepatic malignancies. J Surg Oncol 2015; 113:289-95. [PMID: 26662026 DOI: 10.1002/jso.24107] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 11/14/2015] [Indexed: 12/11/2022]
Abstract
Over the past several decades, there has been increasing discussion regarding the optimal management of secondary liver malignancies. Traditionally, resection has only been recommended if it could be accomplished with negative microscopic margins of at least 10 mm. However, many investigators have pushed this limit to offer resection to patients with narrower margins. We review the data regarding the impact of margin clearance on outcomes for patients undergoing hepatic metastasectomy.
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Affiliation(s)
- Neal Bhutiani
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky
| | - Prejesh Philips
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky
| | - Robert C G Martin
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky
| | - Charles R Scoggins
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky
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Controversies in defining prognostic relevant selection criteria that determine long-term effectiveness of liver resection for noncolorectal nonneuroendocrine liver metastasis. Int J Surg 2015; 24:85-90. [DOI: 10.1016/j.ijsu.2015.11.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Accepted: 11/04/2015] [Indexed: 12/20/2022]
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Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate? Ann Surg 2015; 262:476-85; discussion 483-5. [PMID: 26258316 DOI: 10.1097/sla.0000000000001427] [Citation(s) in RCA: 141] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVES The impact of margin width on overall survival (OS) in the context of other prognostic factors after resection for colorectal liver metastases is unclear. We evaluated the relationship between resection margin and OS utilizing high-resolution histologic distance measurements. METHODS A single-institution prospectively maintained database was queried for all patients who underwent an initial complete resection of colorectal liver metastases between 1992 and 2012. R1 resection was defined as tumor cells at the resection margin (0 mm). R0 resection was further divided into 3 groups: 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or greater. RESULTS A total of 4915 liver resections were performed at Memorial Sloan Kettering Cancer Center between 1992 and 2012, from which 2368 patients were included in the current study. Half of the patients presented with synchronous disease, 43% had solitary metastasis, and the median tumor size was 3.4 cm. With a median follow-up for survivors of 55 months, the median OS of the R1, 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or more groups was 32, 40, 53, and 56 months, respectively (P < 0.001). Compared with R1 resection, all margin widths, including submillimeter margins correlated with prolonged OS (P < 0.05). The association between the margin width and OS remained significant when adjusted for all other clinicopathologic prognostic factors. CONCLUSIONS Resection margin width is independently associated with OS. Wide margins should be attempted whenever possible. However, resection should not be precluded if narrow margins are anticipated, as submillimeter margin clearance is associated with improved survival. The prolonged OS observed with submillimeter margins is likely a microscopic surrogate for the biologic behavior of a tumor rather than the result of surgical technique.
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Abstract
Modern therapeutic regimens have improved the prognosis of patients with metastatic tumours. This requires a subclassification of metastases with more categories than M0 versus M1/pM1. For some tumour entities UICC proposals exist for a subclassification of metastases: colorectal cancer, lung cancer, malignant bone tumours, malignant melanoma and Merkel cell carcinomas of skin, as well as uterine and prostate cancer. Metastases are graded according to the same principles as the corresponding primary tumours. Differences in the grade between primary tumour and metastases have been described without evident differences in prognosis. Recent reports showed a similar prognosis for colorectal carcinoma liver metastasis resected R0 or R1. In a certain percentage of R1 resections an inconsistent use of the R classification as to R1 may be responsible.
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Cipriani F, Rawashdeh M, Ahmed M, Armstrong T, Pearce NW, Abu Hilal M. Oncological outcomes of laparoscopic surgery of liver metastases: a single-centre experience. Updates Surg 2015; 67:185-91. [PMID: 26109140 DOI: 10.1007/s13304-015-0308-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2015] [Accepted: 05/28/2015] [Indexed: 02/06/2023]
Abstract
In the era of multimodal management of liver metastases, surgical resection remains the only curative option, with open approach still being referred to as the standard of care. Currently, the feasibility and benefits of the laparoscopic approach for liver resection have been largely demonstrated. However, its oncologic adequacy remains to be confirmed. The aim of this study is to report the oncological results of laparoscopic liver resection for metastatic disease in a single-centre experience. A single-centre database of 413 laparoscopic liver resections was reviewed and procedures for liver metastases were selected. The assessment of oncologic outcomes included analysis of minimal tumour-free margin, R1 resection rate and 3-year survival. The feasibility and safety of the procedures were also evaluated through analysis of perioperative outcomes. The study comprised 209 patients (294 procedures). Colorectal liver metastases were the commonest indication (67.9%). Fourteen patients had conversion (6.7%) and oncological concern was the commonest reason for conversion (42.8%). Median tumour-free margin was 10 mm and complete radical resections were achieved in 211 of 218 curative-intent procedures (96.7%). For patients affected by colorectal liver metastases, 1- and 3-year OS resulted 85.9 and 66.7%. For patients affected by neuroendocrine liver metastases, 1- and 3-year OS resulted 93 and 77.8%. Among the patients with metastases from other primaries, 1- and 3-year OS were 83.3 and 70.5%. The laparoscopic approach is a safe and valid option in the treatment of patients with metastatic liver disease undergoing curative resection. It does offer significant perioperative benefits without compromise of oncologic outcomes.
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Affiliation(s)
- Federica Cipriani
- University Hospital Southampton NHS Foundation Trust, E level, Tremona Road, Southampton, SO166YD, UK
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Faron M, Chirica M, Tranchard H, Balladur P, de Gramont A, Afchain P, Andre T, Paye F. Impact of preoperative and postoperative FOLFOX chemotherapies in patients with resectable colorectal liver metastasis. J Gastrointest Cancer 2015; 45:298-306. [PMID: 24610400 DOI: 10.1007/s12029-014-9594-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE Whether the survival benefit of perioperative FOLFOX in patients with liver metastases of colorectal cancer (LMCRC) is provided by preoperative chemotherapy (CT), postoperative CT, or both remains unclear. This study aimed to evaluate, in patients with resectable LMCRC, the survival impact of preoperative and postoperative separately. METHODS Between 2000 and 2010, the 179 patients (126 men, age 61 ± 11 years) with initially resectable LMCRC, who underwent liver resection (LR) and were offered pre- and/or postoperative FOLFOX were included. Twenty-four (13%) patients did not receive CT, 27(15%) patients received only preoperative CT, 71 (40%) patients received only postoperative CT, and 57 (32%) patients received both pre- and postoperative CT. RESULTS Operative morbidity and mortality rates were 19 and 0.6%, respectively. At 1, 3, and 5 years, OS and DFS rates were 97, 66, 46 and 60, 32, and 24%, respectively. Postoperative FOLFOX was an independent predictor of increased OS (HR = 0.55 [95% CI, 0.35-0.87] p = 0.01) and DFS (HR = 0.54 [0.36-0.82] p = 0.0017), whereas the synchronous onset of the metastasis and the presence of radiographically occult liver metastases were independent predictors of poorer OS. Alternatively, preoperative FOLFOX had no significant influence on OS (HR = 0.96 [0.57-1.60] p = 0.83) or DFS (HR = 1.05 [0.66-1.66] p = 0.87). CONCLUSIONS The survival benefit of FOLFOX in patients with resectable LMCRC may be provided by postoperative rather than preoperative administration.
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Affiliation(s)
- Matthieu Faron
- Department of Digestive Surgery, AP-HP Hôpital Saint Antoine, 184, rue du Faubourg Saint Antoine, Paris, 75012, France
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Truant S, Séquier C, Leteurtre E, Boleslawski E, Elamrani M, Huet G, Duhamel A, Hebbar M, Pruvot FR. Tumour biology of colorectal liver metastasis is a more important factor in survival than surgical margin clearance in the era of modern chemotherapy regimens. HPB (Oxford) 2015; 17:176-84. [PMID: 25041611 PMCID: PMC4299392 DOI: 10.1111/hpb.12316] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Accepted: 06/04/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of the authors was to reassess the impact of a positive surgical margin (R1) after a liver resection for colorectal liver metastases (CLMs) on survival in the era of modern chemotherapy, through their own experience and a literature review. METHODS Inclusion criteria were: R1 or R0 resection with no local treatment modalities, extra-hepatic metastases or other cancer. RESULTS Among 337 patients operated between 2000 and 2010, 273 patients were eligible (214 R0/59 R1). The mean follow-up was 43 ± 29 months. Compared with a R0 resection, a R1 resection offered a lower 5-year overall (39.1% versus 54.2%, P = 0.010), disease-free (15.2% versus 31.1%, P = 0.021) and progression-free (i.e. time to the first non-curable recurrence; 33.1% versus 47.3%, P = 0.033) survival rates. Metastases in the R1 group were more numerous, larger and more frequently synchronous. Independent factors of poor survival were: number, size and short-time interval of CLM occurrence, N status, rectal primary, absence of adjuvant chemotherapy, but not a R1 resection. With the more-systematic administration of chemotherapy since 2005, the intergroup difference in progression-free survival disappeared (P = 0.264). CONCLUSION A R1 resection had no prognostic value per se but reflected a more severe disease. The recent change in the prognostic value of a R1 resection may be linked to the beneficial effect of chemotherapy.
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Affiliation(s)
- Stéphanie Truant
- Department of Digestive Surgery and Transplantation, Lille University Medical Center, University of Lille Nord de FranceLille, France
| | - Cédric Séquier
- Department of Digestive Surgery and Transplantation, Lille University Medical Center, University of Lille Nord de FranceLille, France
| | - Emmanuelle Leteurtre
- Department of Pathology, Lille University Medical Center, University of Lille Nord de FranceLille, France
| | - Emmanuel Boleslawski
- Department of Digestive Surgery and Transplantation, Lille University Medical Center, University of Lille Nord de FranceLille, France
| | - Mehdi Elamrani
- Department of Digestive Surgery and Transplantation, Lille University Medical Center, University of Lille Nord de FranceLille, France
| | - Guillemette Huet
- Department of Medical Oncology, Lille University Medical Center, University of Lille Nord de FranceLille, France
| | - Alain Duhamel
- INSERM U837, Lille 2 University, Jean-Pierre Aubert Centre, University of Lille Nord de FranceLille, France
| | - Mohamed Hebbar
- Department of Statistics, Lille University Medical Center, University of Lille Nord de FranceLille, France
| | - François-René Pruvot
- Department of Digestive Surgery and Transplantation, Lille University Medical Center, University of Lille Nord de FranceLille, France
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Influence of Margins on Overall Survival After Hepatic Resection for Colorectal Metastasis. Ann Surg 2015; 261:e15. [DOI: 10.1097/sla.0000000000000459] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Abstract
Hepatobiliary surgery outcomes have significantly improved since the early 1970s. Surgical and anesthetic advances related to patient selection, alternative surgical management options, and reduction of operative blood loss have been important. Postoperative analgesic regimens are being modified to include intrathecal opiates and to embrace enhanced recovery regimens.
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Montalti R, Tomassini F, Laurent S, Smeets P, De Man M, Geboes K, Libbrecht LJ, Troisi RI. Impact of surgical margins on overall and recurrence-free survival in parenchymal-sparing laparoscopic liver resections of colorectal metastases. Surg Endosc 2014; 29:2736-47. [PMID: 25427420 DOI: 10.1007/s00464-014-3999-3] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2014] [Accepted: 11/07/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND The relationship between the width of surgical margins and local and distant recurrence of colorectal liver metastases (CRLM) remain controversial. We analyzed the impact of surgical margins in laparoscopic liver resections (LLR) for CRLM, using the parenchymal-sparing approach on overall (OS) and recurrence-free survival (RFS). METHODS From January 2005 to October 2012, 114 first LLR for CRLM were performed and retrospectively analyzed. The ultrasonic aspirator was used for parenchyma division. R1 margins were defined when the tissue width was <1 mm. RESULTS After a mean follow-up of 30.9 ± 1.71 months, OS was 97.1-73.9-58.9% and the RFS 64.2-35.2-31% at 1-3-5 years, respectively. The major resection rate was 7%. The median margin width was 3 (0-40) mm, and R1 resection was recorded in 14 (12.3%) cases. Twenty-two patients (33.3%) with hepatic recurrence underwent a repeat hepatectomy. R1 margins were significantly related to lower RFS survival (p = 0.038) but did not affect OS. Multivariate analysis showed that lesions located in postero-superior segments (HR = 2.4, 95% CI 1.24-4.61, p = 0.009) as well as blood loss (HR = 3.2, 95% CI 1.23-7.99, p = 0.012) were independent risk factors for tumor recurrence. The carcinoembryonic antigen level >10 mcg/L affected OS (HR = 4.2 95% CI 2.02-16.9, p = 0.001), and the resection of more than two tumors was significantly associated with R1 margins (HR = 9.32, 95% CI 1.14-32.5, p = 0.037). DISCUSSION Laparoscopic parenchymal-sparing surgery of CRLM does not compromise the oncological outcome, allowing a higher percentage of repeat hepatectomy. R1 margins are a risk factor for tumor recurrence but not for overall survival. The presence of multiple lesions is the only independent risk factor of R1 margins and also the major disadvantage of this technique.
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Affiliation(s)
- Roberto Montalti
- Department of General & Hepato-Biliary Surgery, Liver Transplantation Service, Ghent University Hospital and Medical School, De Pintelaan 185, 2K12 IC, 9000, Ghent, Belgium
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