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1
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Harrison JM, Visser BC. Cholangiocarcinoma. Surg Clin North Am 2024; 104:1281-1293. [PMID: 39448128 DOI: 10.1016/j.suc.2024.04.003] [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: 10/26/2024]
Abstract
Management of intrahepatic cholangiocarcinoma relies on a thorough understanding of the tumor's location and proximity to critical vasculobiliary structures. Mid-common bile duct tumors may require hemihepatectomy or pancreatoduodenectomy based on the status of the intraoperative frozen section. Distal common bile tumors are treated with pancreatoduodenectomy. When appropriate, volumetric assessment of the remnant liver should be performed to identify cases requiring preoperative liver augmentation strategies. A similar strategy should be employed for perihilar tumors, which require a right trisegmentectomy with bilioenteric reconstruction to achieve a negative margin. Adjuvant systemic therapy is recommended and increasing usage of neoadjuvant treatment is being incorporated into borderline resectable or regionally advanced cases.
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Affiliation(s)
- Jon M Harrison
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Shanford Univeristy Hospital, 300 Pasteur Drive, H3680, Stanford, CA 94305-5655, USA
| | - Brendan C Visser
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Shanford Univeristy Hospital, 300 Pasteur Drive, H3680, Stanford, CA 94305-5655, USA.
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2
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Leiphrakpam PD, Newton R, Anaya DA, Are C. Evolution and current trends in the management of colorectal cancer liver metastasis. Minerva Surg 2024; 79:455-469. [PMID: 38953758 DOI: 10.23736/s2724-5691.24.10363-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/04/2024]
Abstract
Metastatic colorectal cancer (mCRC) is a major cause of cancer-related death, with a 5-year relative overall survival of up to 20%. The liver is the most common site of distant metastasis in colorectal cancer (CRC), with about 50% of CRC patients metastasizing to their liver over the course of their disease. Complete liver resection is the primary modality of treatment for resectable colorectal cancer liver metastasis (CRLM), with an overall 5-year survival rate of up to 58%. However, only 15% to 20% of patients with CRLM are deemed suitable for resection at presentation. For unresectable diseases, the median survival of patients remains low even with the best chemotherapy. In recent decades, the management of CRLM has continued to evolve with the expansion of resection criteria, novel targeted systemic therapies, and improved locoregional therapies. However, due to the heterogeneity of the CRC patient population, the optimal evaluation of treatment options for CRLM remains complex. Therefore, effective management requires a multidisciplinary team to help define resectability and devise a personalized treatment approach, from the initial diagnosis to the final treatment.
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Affiliation(s)
- Premila D Leiphrakpam
- Graduate Medical Education, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
- Division of Surgical Oncology, Department of Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Rachael Newton
- Department of Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Daniel A Anaya
- Section of Hepatobiliary Tumors, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Chandrakanth Are
- Graduate Medical Education, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA -
- Division of Surgical Oncology, Department of Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
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3
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Ai XN, Zhang Q, Jin CG, Hu H, Zhang WX, Wu ZY, Xiu DR. Relationship between hepatic surgical margins of colorectal cancer liver metastases and prognosis: A review. Medicine (Baltimore) 2024; 103:e37038. [PMID: 38335431 PMCID: PMC10860945 DOI: 10.1097/md.0000000000037038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/17/2023] [Accepted: 01/03/2024] [Indexed: 02/12/2024] Open
Abstract
Colorectal cancer (CRC) remains a significant global health concern, as characterized by its high mortality rate ranking second among all the leading causes of death. The liver serves as the primary site of CRC metastasis, and the occurrence of liver metastasis is a significant contributor to mortality among patients diagnosed with CRC. The survival rate of patients with colorectal liver metastasis has significantly increased with the advancement of comprehensive tumor therapy. However, radical surgery remains the key factor. Since there are frequently multiple liver metastases, which are prone to recurrence after surgery, it is crucial to preserve as much liver parenchyma as possible without affecting the prognosis. The issue of surgical margins plays a crucial role in this regard. In this review, we begin by examining the occurrence of positive surgical margins in liver metastases of patients diagnosed with CRC. We aim to define positive margins in hepatic surgery, examine the relationship between margins and prognosis and establish a foundation for future research in this field.
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Affiliation(s)
- Xiang-Nan Ai
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Qiang Zhang
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Chang-Guo Jin
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Hao Hu
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Wen-Xuan Zhang
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Zhen-Yu Wu
- Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, China
| | - Dian-Rong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
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4
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Marion S, Facchino S, Cheng-Oviedo S, Collin Y. Colorectal cancer hepatic metastases resection margins outcomes: a single-centre retrospective cohort study. Ann Med Surg (Lond) 2023; 85:4694-4702. [PMID: 37811094 PMCID: PMC10553064 DOI: 10.1097/ms9.0000000000001113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 07/17/2023] [Indexed: 10/10/2023] Open
Abstract
Background Surgical resection is the most efficient treatment for isolated colorectal cancer hepatic metastases. Among the known prognostic factors of this procedure, the impact of the resection margin width is still a controversial matter in the literature. Methods A retrospective cohort study was performed including 170 patients who underwent surgical resection of colorectal cancer liver metastases (CRLMs) between 2006 and 2016 in our hepatobiliary unit. Resection margin width was determined histologically by measuring the distance from the tumour in millimetres or centimetres. Patients' clinical characteristics were also collected. Patients were then stratified in two tumour margin groups: below 5 mm (group A) and equal to or above 5 mm (group B). Overall survival (OS) and disease-free survival (DFS) were the primary outcomes. Results Kaplan-Meier curves showed significantly better outcomes for cases having resection margins above 5 mm for both DFS with 1508.7 days (range 1151.2-1866.2) in group A, compared to 2463.9 days (range 2021.3-2906.5) in group B (P=0.049), and OS with 1557.8 days (range 1276.3-1839.3) for group A and 2303.8 days (range 1921.2--2686.4) for group B (P=0.020). This survival benefit was not significant for patients presenting with stage IV CRC at diagnosis or cases where extended (7+ segments) resections were performed. Conclusion Five-millimetre margins provide a significant survival advantage and should be aimed for in the treatment of CRLMs. Further research on the cause for this finding, including tumour biology's impact on survival, is required.
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Affiliation(s)
- Samuel Marion
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
| | - Sabrina Facchino
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
- Department of Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Sonia Cheng-Oviedo
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
- Department of Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Yves Collin
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
- Department of Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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5
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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] [Download PDF] [Figures] [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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6
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Galli R, Siciliano T, Aust D, Korn S, Kirsche K, Baretton GB, Weitz J, Koch E, Riediger C. Label-free multiphoton microscopy enables histopathological assessment of colorectal liver metastases and supports automated classification of neoplastic tissue. Sci Rep 2023; 13:4274. [PMID: 36922643 PMCID: PMC10017791 DOI: 10.1038/s41598-023-31401-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/10/2023] [Indexed: 03/18/2023] Open
Abstract
As the state of resection margins is an important prognostic factor after extirpation of colorectal liver metastases, surgeons aim to obtain negative margins, sometimes elaborated by resections of the positive resection plane after intraoperative frozen sections. However, this is time consuming and results sometimes remain unclear during surgery. Label-free multimodal multiphoton microscopy (MPM) is an optical technique that retrieves morpho-chemical information avoiding all staining and that can potentially be performed in real-time. Here, we investigated colorectal liver metastases and hepatic tissue using a combination of three endogenous nonlinear signals, namely: coherent anti-Stokes Raman scattering (CARS) to visualize lipids, two-photon excited fluorescence (TPEF) to visualize cellular patterns, and second harmonic generation (SHG) to visualize collagen fibers. We acquired and analyzed over forty thousand MPM images of metastatic and normal liver tissue of 106 patients. The morphological information with biochemical specificity produced by MPM allowed discriminating normal liver from metastatic tissue and discerning the tumor borders on cryosections as well as formalin-fixed bulk tissue. Furthermore, automated tissue type classification with a correct rate close to 95% was possible using a simple approach based on discriminant analysis of texture parameters. Therefore, MPM has the potential to increase the precision of resection margins in hepatic surgery of metastases without prolonging surgical intervention.
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Affiliation(s)
- Roberta Galli
- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
| | - Tiziana Siciliano
- Center for Regenerative Therapies (CRTD), Technische Universität Dresden, Fetscherstr. 105, 01307, Dresden, Germany
| | - Daniela Aust
- Institute of Pathology, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
| | - Sandra Korn
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Katrin Kirsche
- Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Gustavo B Baretton
- Institute of Pathology, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
| | - Jürgen Weitz
- National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.,Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Edmund Koch
- Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Carina Riediger
- National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.,Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
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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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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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9
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Bellver Oliver M, Escrig-Sos J, Rotellar Sastre F, Moya-Herráiz Á, Sabater-Ortí L. Outcome quality standards for surgery of colorectal liver metastasis. Langenbecks Arch Surg 2020; 405:745-756. [PMID: 32577822 DOI: 10.1007/s00423-020-01908-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 06/03/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE Liver metastases are the most common malignant solid liver lesions, approximately 40% of which stem from colorectal tumors. Liver resection is currently the only curative treatment for colorectal cancer liver metastases (CRLM). However, there is a lack of consensus criteria to assess the results of this treatment. In order to evaluate the quality of surgical outcomes, it is necessary to identify quality indicators (QIs) and their corresponding quality standards (QS). We propose a simple method to determine QI and QS in CRLM surgery (CRLMS) and establish acceptable quality limits (AQL) for each QI. MATERIAL AND METHODS A systematic review of CRLMS results published from 2006 to 2016. Clinical guidelines, consensus conferences, and publications related to the CRLMS were reviewed to identify and select QIs. Once selected, a new review of the papers including the results of at least one of the QIs was performed. Statistical process control (SPC) method was applied to calculate the QS and AQL of each QI. The limits of variability were established from mean and confidence intervals at 95% and 99.8%. RESULTS The most relevant QIs and its AQLs were postoperative mortality (2%, < 4.5%), overall postoperative morbidity (33%, < 41%), liver failure (5%, < 8%), postoperative hemorrhage (1%, < 3%), biliary fistula (6%, < 10%), reoperation (3%, < 6%), R1 resection margins (18%, < 25%), and overall survival at 12 and 60 months (84%, > 77%; and 34%, > 25%, respectively). CONCLUSIONS Despite its limitations, the present study constitutes the most extensive scientific evidence to date on QI and AQL in CRLMS and may constitute a reference in future studies.
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Affiliation(s)
- Manuel Bellver Oliver
- Department of Surgery, HPB Unit, Hospital General Universitario Castellón, Jaume I University, Castellón de la Plana, Spain.
| | - Javier Escrig-Sos
- Department of Surgery, HPB Unit, Hospital General Universitario Castellón, Jaume I University, Castellón de la Plana, Spain
| | - Fernando Rotellar Sastre
- HPB and Liver Transplant Unit, General and Digestive Surgery, University Clinic of Navarra, University of Navarra, Pamplona, Spain
| | - Ángel Moya-Herráiz
- Department of Surgery, HPB Unit, Hospital General Universitario Castellón, Jaume I University, Castellón de la Plana, Spain
| | - Luis Sabater-Ortí
- Department of Surgery, Biomedical Research Institute INCLIVA, Hospital Clínico, University of Valencia, Valencia, Spain
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10
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Nierop PMH, Höppener DJ, van der Stok EP, Galjart B, Buisman FE, Balachandran VP, Jarnagin WR, Kingham TP, Allen PJ, Shia J, Vermeulen PB, Groot Koerkamp B, Grünhagen DJ, Verhoef C, D'Angelica MI. Histopathological growth patterns and positive margins after resection of colorectal liver metastases. HPB (Oxford) 2020; 22:911-919. [PMID: 31735649 PMCID: PMC7888172 DOI: 10.1016/j.hpb.2019.10.015] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 08/23/2019] [Accepted: 10/03/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Histopathological growth patterns (HGPs) of colorectal liver metastases (CRLM) may be an expression of biological tumour behaviour impacting the risk of positive resection margins. The current study aimed to investigate whether the non-desmoplastic growth pattern (non-dHGP) is associated with a higher risk of positive resection margins after resection of CRLM. METHODS All patients treated surgically for CRLM between January 2000 and March 2015 at the Erasmus MC Cancer Institute and between January 2000 and December 2012 at the Memorial Sloan Kettering Cancer Center were considered for inclusion. RESULTS Of all patients (n = 1302) included for analysis, 13% (n = 170) had positive resection margins. Factors independently associated with positive resection margins were the non-dHGP (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.11-2.87, p = 0.016) and a greater number of CRLM (OR: 1.15, 95% CI: 1.08-1.23 p < 0.001). Both positive resection margins (HR: 1.41, 95% CI: 1.13-1.76, p = 0.002) and non-dHGP (HR: 1.57, 95% CI: 1.26-1.95, p < 0.001) were independently associated with worse overall survival. CONCLUSION Patients with non-dHGP are at higher risk of positive resection margins. Despite this association, both positive resection margins and non-dHGP are independent prognostic indicators of worse overall survival.
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Affiliation(s)
- Pieter M H Nierop
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Diederik J Höppener
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Eric P van der Stok
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Boris Galjart
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Florian E Buisman
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | | | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Peter J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Jinru Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA
| | | | | | - Dirk J Grünhagen
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
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11
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Watanabe Y, Matsuyama Y, Izumi N, Kubo S, Kokudo N, Sakamoto M, Shiina S, Takayama T, Nakashima O, Kudo M. Effect of surgical margin width after R0 resection for intrahepatic cholangiocarcinoma: A nationwide survey of the Liver Cancer Study Group of Japan. Surgery 2020; 167:793-802. [PMID: 32044110 DOI: 10.1016/j.surg.2019.12.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 12/13/2019] [Accepted: 12/18/2019] [Indexed: 01/22/2023]
Abstract
BACKGROUND Data are inconsistent regarding the effects of a wide surgical margin for intrahepatic cholangiocarcinoma on recurrence-free survival and overall survival. This study was performed to investigate the effect of surgical margin width in patients undergoing R0 resection for intrahepatic cholangiocarcinoma, using a nationwide database in Japan. METHODS In total, 635 patients with intrahepatic cholangiocarcinoma who were treated by an R0 resection from 2000 to 2007 were identified from the database of a Japanese nationwide survey. Patients were divided into quartiles of the surgical margin width as follows: marginal (<1 mm), narrow (1-4 mm), intermediate (5-9 mm), and wide groups (≥10 mm). Multivariable Cox regression models for recurrence-free survival and overall survival were constructed with adjustment for preoperative and postoperative clinicopathologic factors. RESULTS Compared with the marginal group, the risk-adjusted hazard ratios (95% confidence intervals) in the narrow, intermediate, and wide groups for recurrence-free survival were 0.92 (0.62-1.37), 0.91 (0.61-1.37), and 0.81 (0.56-1.17), and those for overall survival were 0.79 (0.51-1.24), 0.93 (0.59-1.47), and 0.70 (0.46-1.08), respectively. In 398 patients without lymph node metastasis, the hazard ratios for overall survival were 0.62 (0.34-1.11), 0.63 (0.34-1.17), and 0.51 (0.29-0.90), and those of mass-forming type intrahepatic cholangiocarcinoma were 0.48 (0.21-1.08), 0.43 (0.19-0.96), and 0.40 (0.19-0.82), respectively. CONCLUSION Surgical margin width appears to have a limited effect on the prognosis of intrahepatic cholangiocarcinoma except in patients without lymph node metastasis, where a wide surgical margin is associated with favorable outcomes. This survival benefit of a wide surgical margin is especially apparent for the mass-forming type intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Yukihiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Saitama, Japan; Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan
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12
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Xu D, Wang HW, Yan XL, Li J, Wang K, Xing BC. Sub-millimeter surgical margin is acceptable in patients with good tumor biology after liver resection for colorectal liver metastases. Eur J Surg Oncol 2019; 45:1551-1558. [PMID: 30879931 DOI: 10.1016/j.ejso.2019.03.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 01/09/2019] [Accepted: 03/05/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The definition of R1 resection in colorectal cancer liver metastases (CRLM) remains debatable. This retrospective study was conducted to clarify the impact of R1 margin on patient survival after liver resection for CRLM, taking into consideration tumor biology, including RAS status and chemotherapy response. METHODS We retrospectively analysed the clinical and survival data of 214 CRLM patients with initially resectable liver metastases who underwent liver resection after receiving neoadjuvant chemotherapy between January 2006 and December 2016. RESULTS R1 resection significantly impacted patients' overall survival (OS) and disease-free survival (DFS) in the overall patient cohort (5-year OS: 53.2% for R0 vs 38.2% for R1, P = 0.001; 5-year DFS: 26.5% for R0 vs 10.5% for R1, P = 0.002). In the RAS wild-type subgroup and respond to chemotherapy (RC) subgroup, R1 reached a similar OS to those who underwent R0 resection (RAS wild-type, P = 0.223; RC, P = 0.088). For the RAS mutated subgroup and no response to chemotherapy (NRC) subgroup, OS was significantly worse underwent R1 resection (RAS mutant, P = 0.002; NRC, P = 0.022). When considering tumor biology combining RAS and chemotherapy response status, R1 resection was only acceptable in patients with both RAS wild-type and RC (5-year OS: 66.4% for R0 vs 65.2% for R1, p = 0.884), but was significantly worse in those with either RAS mutation or NRC. CONCLUSIONS Tumor biology plays an important role in deciding the appropriate resection margin in patients with CRLM undergoing radical surgery. R1 resection margin is only acceptable in RAS wild-type patients who respond to chemotherapy.
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Affiliation(s)
- Da Xu
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China
| | - Hong-Wei Wang
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China
| | - Xiao-Luan Yan
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China
| | - Juan Li
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China
| | - Kun Wang
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China
| | - Bao-Cai Xing
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China.
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Oshi M, Margonis GA, Sawada Y, Andreatos N, He J, Kumamoto T, Morioka D, Wolfgang CL, Tanaka K, Weiss MJ, Endo I. Higher Tumor Burden Neutralizes Negative Margin Status in Hepatectomy for Colorectal Cancer Liver Metastasis. Ann Surg Oncol 2018; 26:593-603. [PMID: 30483976 DOI: 10.1245/s10434-018-6830-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The aim of this study was to examine if the prognostic significance of margin status in hepatectomy for colorectal cancer liver metastasis (CRLM) varies for different levels of tumor burden because hepatectomy indications for CRLM have been recently expanded to include patients with a higher tumor burden in whom achieving an R0 resection is difficult. METHODS Clinicopathological variables in an exploration cohort of 290 patients receiving hepatectomy in Japan for CRLM were investigated. R0 resection was defined as a margin width > 0 mm. Tumor burden was assessed using the recently introduced Tumor Burden Score (TBS), which was calculated as TBS2 = (maximum tumor diameter in cm)2 + (number of lesions)2. The principal findings were validated using a cohort from the United States. RESULTS R1 resection rates significantly increased as TBS increased: 4/86 (4.7%) in patients with TBS < 3, 29/171 (17.0%) in patients with TBS ≥ 3 and < 9, and 9/33 (27.3%) in patients with TBS ≥ 9 (p < 0.001). R0 resection was significantly superior to R1 resection in patients with TBS ≥ 5; however, this was not the case for TBS ≥ 6, as confirmed by both univariate and multivariate analyses. Furthermore, prehepatectomy chemotherapy was associated with significantly improved survival for patients with TBS ≥ 8. Analysis of the validation cohort yielded similar results. CONCLUSIONS R0 resection appeared to have a positive impact on prognosis among patients with low tumor burden; however, this was not the case for patients with high tumor burden. As such, systemic treatment, in addition to surgery, may be central to achieving satisfactory outcomes in the latter patient population.
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Affiliation(s)
- Masanori Oshi
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | | | - Yu Sawada
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Nikolaos Andreatos
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Takafumi Kumamoto
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Daisuke Morioka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | | | - Kuniya Tanaka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Matthew John Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
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Prognostic influence of hepatic margin after resection of colorectal liver metastasis: role of modern preoperative chemotherapy. Int J Colorectal Dis 2018; 33:71-78. [PMID: 29098384 DOI: 10.1007/s00384-017-2916-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/09/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE Modern chemotherapy (CTX) increases survival in stage IV colorectal cancer. In colorectal liver metastases (CLM), neoadjuvant (neo) CTX may increase resectability and improve survival. Due to widespread use of CTX in CLM, recent studies assessed the role of the hepatic margin after CTX, with conflicting results. We evaluated the outcome after resection of CLM in relation to CTX and hepatic resection status. METHODS Since 2000, 334 patients with first hepatic resection for isolated CLM were analyzed. Thirty-two percent had neoadjuvant chemotherapy (targeted therapy in 42%). Sixty-eight percent never had CTX before hepatectomy or longer than 6 months before resection. The results were gained by analysis of our prospective database. RESULTS Positive hepatic margins occurred in 8% (independent of neoCTx). Patients after neoCTX had higher numbers of CLM (p < 0.01) and a longer duration of surgery (p < 0.03). After hepatectomy, 5-year survival was 45% and correlated strongly with the margin status (47% in R-0 and 21% in R-1; p < 0.001). Survival also correlated with margin status in the subgroups with neoCTX (p < 0.01) or without neoCTx (p < 0.01). In multivariate analysis of the entire group, hepatic margin status (RR 3.2; p < 0.001) and age > 65 years (RR 1.6; p < 0.01) were associated with poorer survival. In the subgroup of patients after neoCTX (n = 106), only the resection margin was an independent predictor of survival (p < 0.001). CONCLUSION In patients with isolated colorectal liver metastases undergoing resection, the hepatic margin status was the strongest independent prognostic factor. This effect was also present after neoadjuvant chemotherapy for CLM.
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15
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Prognostic Significance of Surgical Margin Size After Neoadjuvant FOLFOX and/or FOLFIRI for Colorectal Liver Metastases. J Gastrointest Surg 2017; 21:1831-1840. [PMID: 28884391 DOI: 10.1007/s11605-017-3557-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Accepted: 08/18/2017] [Indexed: 02/08/2023]
Abstract
PURPOSE Optimal margin size when resecting colorectal liver metastases (CRLM) remains unclear, particularly in the setting of perioperative chemotherapy. We evaluated the prognostic significance of margin size in patients who received neoadjuvant FOLFOX and/or FOLFIRI prior to resection of CRLM. METHODS Clinicopathologic factors were collected for patients who underwent curative liver resections for CRLM between 4/2004-1/2016 and received neoadjuvant oxaliplatin and/or irinotecan and 5-FU (FOLFOX, FOLFIRI). Margins were categorized as < 1, ≥ 1-< 5, ≥ 5-< 10, or ≥ 10 mm and evaluated for association with overall survival (OS) and disease-free survival (DFS) by Cox multiple regression analysis. Margin status was classified as positive (< 1 mm) or negative (≥ 1 mm) and similarly evaluated. RESULTS Of 227 patients, the median age was 58 years and most had synchronous (80%) lesions. The majority had colon cancers (75%). Margin sizes were 13% < 1 mm, 27% ≥ 1-< 5 mm, 23% ≥ 5-< 10 mm, 36% ≥ 10 mm. Most (63%) received chemotherapy post-liver resection. Five-year OS and DFS were 54% (95% CI 46-62%) and 22% (95% CI 16-28%), respectively. Positive margins significantly increased the risk of death without post-liver resection chemotherapy (HR = 3.32, p = 0.0077), but not with post-liver resection chemotherapy (HR = 1.00, p = 0.99). Negative margin sizes of ≥ 1-< 5, ≥ 5-< 10, and ≥ 10 mm were not significant predictors of OS (p > 0.05). CONCLUSION Patients undergoing liver resection for CRLM should receive post-resection chemotherapy if negative margins (≥ 1 mm) cannot be achieved. For patients receiving FOLFOX and/or FOLFIRI chemotherapy, wider margins did not improve OS.
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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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Di Carlo S, Yeung D, Mills J, Zaitoun A, Cameron I, Gomez D. Resection margin influences the outcome of patients with bilobar colorectal liver metastases. World J Hepatol 2016; 8:1502-1510. [PMID: 28008341 PMCID: PMC5143431 DOI: 10.4254/wjh.v8.i34.1502] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 09/16/2016] [Accepted: 10/24/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the outcome of patients with bilobar colorectal liver metastases (CRLM) and identify clinico-pathological variables that influenced survival.
METHODS Patients with bilobar CRLM were identified from a prospectively maintained hepatobiliary database during the study period (January 2010-June 2014). Collated data included demographics, primary tumour treatment, surgical data, histopathology analysis and clinical outcome. Down-staging therapy included Oxaliplatin- or Irinotecan- based regimens, and Cetuximab was also used in patients that were K-RAS wild-type. Response to neo-adjuvant therapy was assessed at the multi-disciplinary team meeting and considered for surgery if all macroscopic CRLM were resectable with a clear margin while preserving sufficient liver parenchyma.
RESULTS Of the 136 patients included, thirty-two (23.5%) patients were considered inoperable and referred for palliative chemotherapy, and thirty-four (25%) patients underwent liver resection. Seventy (51.4%) patients underwent down-staging therapy, of which 37 (52.8%) patients responded sufficiently to undergo liver resection. Patients that failed to respond to down-staging therapy (n = 33, 47.1%) were referred for palliative therapy. There was a significant difference in overall survival between the three groups (surgery vs down-staging therapy vs inoperable disease, P < 0.001). All patients that underwent hepatic resection, including patients that had down-staging therapy, had a significantly better overall survival compared to patients that were inoperable (P < 0.001). On univariate analysis, only resection margin significantly influenced disease-free survival (P = 0.017). On multi-variate analysis, R0 resection (P = 0.030) and female (P = 0.036) gender significantly influenced overall survival.
CONCLUSION Patients undergoing liver resection with bilobar CRLM have a significantly better survival outcome. R0 resection is associated with improved disease-free and overall survival in this patient group.
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18
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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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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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Akyuz M, Aucejo F, Quintini C, Miller C, Fung J, Berber E. Factors affecting surgical margin recurrence after hepatectomy for colorectal liver metastases. Gland Surg 2016; 5:263-9. [PMID: 27294032 DOI: 10.21037/gs.2015.12.03] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Hepatic recurrence after resection of colorectal liver metastasis (CLM) occurs in 50% of patients during follow-up, with 2.8% to 13.9% presenting with surgical margin recurrence (SMR). The aim of this study is to analyze factors that related to SMR in patients with CLM undergoing hepatectomy. METHODS Demographics, clinical and survival data of patients who underwent hepatectomy were identified from a prospectively maintained, institutional review board (IRB)-approved database between 2000 and 2012. Statistical analysis was performed using univariate Kaplan Meier and Cox proportional hazard model. RESULTS There were 85 female and 121 male patients who underwent liver resection for CLM. An R0 resection was performed in 157 (76%) patients and R1 resection in 49. SMR was detected in 32 patients (15.5%) followed up for a median of 29 months (range, 3-121 months). A half of these patients had undergone R1 (n=16) and another half R0 resection (n=16). Tumor size, preoperative carcinoembryonic antigen (CEA) level and margin status were associated with SMR on univariate analysis. On multivariate analysis, a positive surgical margin was the only independent predictor of SMR. The receipt of adjuvant chemotherapy did not affect margin recurrence. SMR was an independent risk factor associated with worse disease-free (DFS) and overall survival (OS). CONCLUSIONS This study shows that SMR, which can be detected in up to 15.5% of patients after liver resection for CLM, adversely affects DFS and OS. The fact that a positive surgical margin was the only predictive factor for SMR in these patients underscores the importance of achieving negative margins during hepatectomy.
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Affiliation(s)
- Muhammet Akyuz
- Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - Federico Aucejo
- Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | | | - Charles Miller
- Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - John Fung
- Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - Eren Berber
- Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, USA
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Paniccia A, Schulick RD. Surgical Margin in Hepatic Resections for Colorectal Metastasis: Should We Care? CURRENT COLORECTAL CANCER REPORTS 2016. [DOI: 10.1007/s11888-016-0323-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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22
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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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Negative surgical margin improved long-term survival of colorectal cancer liver metastases after hepatic resection: a systematic review and meta-analysis. Int J Colorectal Dis 2015. [PMID: 26198997 DOI: 10.1007/s00384-015-2323-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The need to achieve a tumor-free margin of ≥1 mm (R0) for colorectal liver metastases (CRLM) after hepatic resection has been questioned recently. This study conducted a meta-analysis to determine whether status of the surgical margin still influenced the long-term outcome of survival and recurrence rate. METHODS Eligible trials that compared survival and recurrence rates of R0 versus the tumor-free margin <1 mm (R1) were identified from Embase, PubMed, the Web of Science, and the Cochrane Library since their inception to 1 March 2015. The study outcomes included long-term outcome of survival and recurrence rate. Hazard ratio (HR) with a 95 % confidence interval was used to measure the pooled effect according to a random-effects model or fixed-effects model, depending on the heterogeneity among the included studies. The heterogeneity among these trials was statistically evaluated using the χ(2) and I(2) tests. Sensitivity analyses and publication bias were also carried out. RESULTS A total of 18 studies containing 6790 patients were included. The comparison between R1 and R0 revealed that a pooled HR for 5-year overall survival was 1.603 (95 % CI; 1.464-1.755; p = 0.000; I(2) = 31.2 %, p = 0.141). For patients received modern chemotherapy; a pooled HR of R1 resection for 5-year overall survival was 1.924 (95 % CI; 1.567-2.361, p = 0.000; I(2) = 20.5 %, p = 0.273). The pooled HR for 5-year OS of ≥1 cm in the included studies calculated using the random-effects model was 0.819 (95 % CI; 0.715-0.938, p = 0.004; I(2) = 0 %, p = 0.492). CONCLUSIONS R1 resections decreased long-term survival, and modern chemotherapy did not alter an adverse outcome. Surgeons should attempt to obtain a 1-cm margin.
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Langella S, Russolillo N, D'Eletto M, Forchino F, Lo Tesoriere R, Ferrero A. Oncological safety of ultrasound-guided laparoscopic liver resection for colorectal metastases: a case-control study. Updates Surg 2015. [PMID: 26220046 DOI: 10.1007/s13304-015-0325-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Laparoscopic liver surgery has gained widespread acceptance and nowadays it is suggested even for malignant disease. Although the benefits on short-term outcomes have been proven, data on oncological safety are still lacking. The aim of this study is to assess oncologic results after ultrasound-guided laparoscopic liver resection (LLR) or open liver resection (OLR) for colorectal metastases. 37 consecutive patients undergoing LLR between 01/2004 and 03/2014 were matched at a ratio of 1:1 with 37 OLR. Matching criteria were male sex, number and diameter of liver metastases, segment location, synchronous presentation, site and stage of primary tumor, positive lymph nodes of the primary, and concomitant extrahepatic disease. Demographic characteristics were similar among groups. Parenchymal transection time was longer in the LLR group (68 ± 38.2 SD vs 40 ± 33.7 SD, p = 0.01). Mortality was nil in LLR and OLR. Overall morbidity was significantly lower in LLR (13.5 vs 37.8%, p = 0.02), although severe complications were similar among the two groups. Patients undergoing LLR were discharged earlier (5 ± 2.3 SD vs 8 ± 6.6 SD days, p < 0.001). The median margin width was 5 (0-40) mm in LLR vs 8 (0-25) mm in OLR, p = 0.897. R1 resection was recorded in four LLR and three OLR (p = 1). Overall recurrences were similar among groups. Eight patients with hepatic or extrahepatic recurrence among LLR underwent surgery vs four of OLR (p = 0.03). After a median follow-up of 35.7 months in LLR and 47.9 months in OLR, 3-year overall survival was 91.8% LLR and 74.8% OLR (p = 0.14). 3-year disease-free survival was 69.1% LLR and 65.9% OLR (p = 0.53). Multivariate analysis showed that postoperative complications [HR 3.42 (95% CI 1.32-8.89)] and multiple metastases [HR 3.84 (95% CI 1.34-10.83)] were independent predictors of worse survival (p = 0.01). Ultrasound-LLR for colorectal hepatic metastases is safe, ensuring oncologic outcomes comparable to OLR.
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Affiliation(s)
- Serena Langella
- Department of General and Oncological Surgery, "Umberto I" Mauriziano Hospital, Largo Turati, 62, 10128, Turin, Italy
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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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Margonis GA, Spolverato G, Kim Y, Ejaz A, Pawlik TM. Intraoperative surgical margin re-resection for colorectal liver metastasis: is it worth the effort? J Gastrointest Surg 2015; 19:699-707. [PMID: 25451734 DOI: 10.1007/s11605-014-2710-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 11/18/2014] [Indexed: 02/07/2023]
Abstract
OBJECTIVE This study was conducted to evaluate recurrence and survival among patients who underwent intraoperative margin re-resection for colorectal cancer liver metastases (CRLM). BACKGROUND Among patients who receive intraoperative margin re-resection, the relation between final margin status, pattern of recurrence, and survival is largely unknown. METHODS Three hundred thirty-two patients who underwent hepatic resection for CRLM between 2000 and 2013 were identified. Demographics, operative data, pathologic margin status, site of recurrence, and long-term survival data were collected and analyzed. Patients were stratified in three groups based on their margin status: R0, R1, and R1 → R0. RESULTS R0 resections were achieved in 247 (74.4%) patients, 61 (18.4%) patients had an R1 resection, whereas 24 (7.2%) had an R1 → R0. Median survival for patients undergoing R0 resections was 50.2 (95% confidence interval (CI) 49.2-66.2) months versus 63.0 (95% CI 50.3-70.5) months for patients undergoing R1 resections versus 49.2 (95% CI 29.9-NA) months for patients undergoing intraoperative margin re-resection (P > 0.05). Differences in recurrence rate and pattern were not significant between the three groups (P > 0.05). CONCLUSION In the era of modern systemic chemotherapy, it seems that the impact of margin status on outcomes may be minimal compared to that of patient and tumor factors. In this scenario, margin re-resection to achieve R0 status does not improve long-term outcomes.
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Affiliation(s)
- Georgios A Margonis
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins Hospital, 600 N. Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA
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27
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Spolverato G, Yakoob MY, Kim Y, Alexandrescu S, Marques HP, Lamelas J, Aldrighetti L, Gamblin TC, Maithel SK, Pulitano C, Bauer TW, Shen F, Poultsides GA, Marsh JW, Pawlik TM. The Impact of Surgical Margin Status on Long-Term Outcome After Resection for Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2015; 22:4020-8. [PMID: 25762481 DOI: 10.1245/s10434-015-4472-9] [Citation(s) in RCA: 118] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Indexed: 12/15/2022]
Abstract
BACKGROUND The influence of margin status on long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) remains controversial. We sought to study the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ICC. METHODS From a multi-institutional database, 583 patients who underwent hepatic resection for ICC were identified. Demographics data, operative details, pathologic margin status, and long-term outcomes were collected and analyzed. RESULTS Margin status was positive (R1) in 95 (17.8 %) patients; among patients who underwent an R0 resection (80.9 %), margin width was negative by 1-4 mm in 166 (31.0 %) patients, 5-9 mm in 100 (18.7 %) patients, and ≥1 cm in 174 (32.5 %) patients. Overall, 379 (65.0 %) patients had a recurrence: 61.5 % intrahepatic, 13.5 % extrahepatic, and 25.0 % both intra- and extrahepatic. Median and 5-year RFS and OS was 10.0 months and 9.2 %, and 26.4 months and 23.0 %, respectively. Patients who had an R1 resection had a higher risk of recurrence (hazard ratio [HR] 1.61, 95 % CI 1.15-2.27; p = 0.01) and shorter OS (HR 1.54, 95 % CI 1.12-2.11). Among patients with an R0 resection, margin width was also associated with RFS (1-4 mm: HR 1.32, 95 % CI 0.98-1.78 vs. 5-9 mm: HR 1.21, 95 % CI 0.89-1.66) and OS (1-4 mm: HR 1.95, 95 % CI 0.45-2.63 vs. 5-9 mm: HR 1.21, 95 % CI 0.88-1.68) (referent ≥1 cm; both p ≤ 0.002). Margin status and width remain independently associated with RFS and OS on multivariable analyses. CONCLUSIONS For patients undergoing resection of ICC, R1 margin status was associated with an inferior long-term outcome. Moreover, there was an incremental worsening RFS and OS as margin width decreased.
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Affiliation(s)
- Gaya Spolverato
- The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Yuhree Kim
- The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | | | | | | | | | | | | | - Todd W Bauer
- University of Virginia, Charlottesville, VA, USA
| | - Feng Shen
- Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | | | - J Wallis Marsh
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Timothy M Pawlik
- The Johns Hopkins University School of Medicine, Baltimore, MD, USA. .,Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
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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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Bredt LC, Rachid AF. Predictors of recurrence after a first hepatectomy for colorectal cancer liver metastases: a retrospective analysis. World J Surg Oncol 2014; 12:391. [PMID: 25528650 PMCID: PMC4364583 DOI: 10.1186/1477-7819-12-391] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Accepted: 12/03/2014] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Surgical resection is considered the standard therapy in the treatment of liver metastases from colorectal cancer (CRCLM); however, most patients experience tumor recurrence after curative hepatic resection. The objective was to determine potential prognostic factors for tumor recurrence after an initial hepatectomy for CRCLM. METHODS A study population of 101 patients who had undergone a first curative hepatectomy for CRCLM was retrospectively analyzed. Selected biological tumor markers, and clinical and pathological features were then tested by Cox regression. RESULTS Synchronous liver metastases occurred in 38 patients (37.6%) and 63 patients (62.3%) presented with metachronous liver metastases. In a median follow-up time of 68 months, recurrence was observed in 64 patients (63.3%). The 5-year cumulative risk of recurrence was 56.7%. The median survival after recurrence was 24.5 months (range 1 to 41 months) and 5-year cumulative overall survival was 31.8%. Of all variables tested by Cox regression, intra- and extrahepatic resectable disease, CEA levels≥50 ng/mL and bilobar liver disease remained significant as predictors of recurrence in the multivariate analysis. CONCLUSIONS Independent risk factors for recurrence after an initial hepatectomy for CRCLM, such as intra- and extrahepatic resectable disease, CEA levels≥50 ng/mL and bilobar liver disease, can eventually help in making decisions in this very complex scenario.
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Affiliation(s)
- Luis Cesar Bredt
- Department of Abdominal Surgery, Hepatobiliary Section, Cancer Hospital-UOPECCAN, Cascavel, PR 85812-270 Brazil
| | - Alex Francovig Rachid
- Department of Abdominal Surgery, Hepatobiliary Section, Cancer Hospital-UOPECCAN, Cascavel, PR 85812-270 Brazil
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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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Kataoka K, Kanazawa A, Iwamoto S, Kato T, Nakajima A, Arimoto A. Does "conversion chemotherapy" really improve survival in metastatic colorectal cancer patients with liver-limited disease? World J Surg 2014; 38:936-46. [PMID: 24166026 DOI: 10.1007/s00268-013-2305-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND The clinical benefits of conversion chemotherapy followed by liver resection for initially unresectable colorectal liver metastases are still controversial. The criteria for unresectability vary from one team to another. To clarify this issue, we retrospectively assessed the survival and characteristics of metastatic colorectal cancer (mCRC) patients with liver-limited disease (LLD) who underwent conversion therapy. METHOD Our criteria for resectability depended on the size of the remnant liver volume (>30 %) and expected function after removal of all metastases. Between December 2007 and September 2011, a total of 115 patients were diagnosed as having mCRC with LLD and received chemotherapy. Among them, 47 had tumors that were initially diagnosed as resectable. They underwent hepatic resection after chemotherapy (resected group). Of the 67 tumors were initially diagnosed as unresectable, 12 became resectable after chemotherapy (conversion group), leaving 55 tumors that remained unresectable after chemotherapy (unresected group). RESULTS The median follow-up was 25.2 months. Hepatic resection was more invasive in the conversion group than in the resected group. Median disease-free survival was significantly higher in the resected group than in the conversion group (p = 0.013). Overall survival (OS) was also higher in the resected group, but the difference was not significant (p = 0.36). However, OS was significantly higher in the conversion group than in the unresected group (p = 0.034). Multivariate analysis of the resected and conversion groups showed that OS was significantly negatively influenced by abnormal carcinoembryonic antigen levels at surgery (p = 0.037) and a hospital stay >30 days (p = 0.009). CONCLUSIONS Our results showed that conversion chemotherapy could contribute to longer OS in mCRC patients with LLD.
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Affiliation(s)
- K Kataoka
- Department of Surgery, Osaka Red Cross Hospital, 5-30 Fudegasaki, Tennoji, Osaka, 543-8555, Japan,
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Gomez D, Zaitoun AM, De Rosa A, Hossaini S, Beckingham IJ, Brooks A, Cameron IC. Critical review of the prognostic significance of pathological variables in patients undergoing resection for colorectal liver metastases. HPB (Oxford) 2014; 16:836-44. [PMID: 24617566 PMCID: PMC4159457 DOI: 10.1111/hpb.12216] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Accepted: 12/13/2013] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The aim of this study was to identify prognostic factors, particularly pathological variables, that influence disease-free and overall survival following resection for colorectal liver metastases (CRLM). METHODS Patients undergoing CRLM resection from January 2005 to December 2011 were included. Data analysed included information on demographics, laboratory results, operative findings, histopathological features and survival. RESULTS A total of 259 patients were included. Of these, 138 (53.3%) patients developed recurrent disease, of which 95 died. The median length of follow-up in the remaining patients was 28 months (range: 12-96 months). There were significant associations between recurrence and higher tumour number (P = 0.002), presence of perineural invasion (P = 0.009) and positive margin (R1) resection (P = 0.002). Multivariate analysis showed all three prognostic factors to be independent predictors of disease-free survival. Significantly poorer overall survival after hepatic resection for CRLM was observed in patients undergoing hemi-hepatectomy or more radical resection (P = 0.021), patients with a higher number of tumours (P = 0.024) and patients with perineural invasion (P < 0.001). Multivariate analysis showed perineural invasion to be the only independent predictor of overall survival. CONCLUSIONS The presence of perineural invasion, multiple tumours and an R1 margin were associated with recurrent disease. Perineural invasion was also an independent prognostic factor with respect to overall survival.
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Affiliation(s)
- Dhanwant Gomez
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Abed M Zaitoun
- Department of Cellular Pathology, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Antonella De Rosa
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Sina Hossaini
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Ian J Beckingham
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Adam Brooks
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Iain C Cameron
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
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Postriganova N, Kazaryan AM, Røsok BI, Fretland ÅA, Barkhatov L, Edwin B. Margin status after laparoscopic resection of colorectal liver metastases: does a narrow resection margin have an influence on survival and local recurrence? HPB (Oxford) 2014; 16:822-9. [PMID: 24308605 PMCID: PMC4159455 DOI: 10.1111/hpb.12204] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Accepted: 10/30/2013] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Recent studies of margin-related recurrence have raised questions on the necessity of ensuring wide resection margins in the resection of colorectal liver metastases. The aim of the current study was to determine whether resection margins of 10 mm provide a survival benefit over narrower resection margins. METHODS A total of 425 laparoscopic liver resections were carried out in 351 procedures performed in 317 patients between August 1998 and April 2012. Primary laparoscopic liver resections for colorectal metastases were included in the study. Two-stage resections, procedures accompanied by concomitant liver ablations and one case of perioperative mortality were excluded. A total of 155 eligible patients were classified into four groups according to resection margin width: Group 1, margins of < 1 mm [n = 33, including 17 patients with positive margins (Group 1a)]; Group 2, margins of 1 mm to < 3 mm (n = 31); Group 3, margins of ≥ 3 mm to <10 mm (n = 55), and Group 4, margins of ≥ 10 mm (n = 36). Perioperative and survival data were compared across the groups. Median follow-up was 31 months (range: 2-136 months). RESULTS Perioperative outcomes were similar in all groups. Unfavourable intraoperative incidents occurred in 9.7% of procedures (including 3.2% of conversions). Postoperative complications developed in 11.0% of patients. Recurrence in the resection bed developed in three (1.9%) patients, including two (6.1%) patients in Group 1. Rates of actuarial 5-year overall, disease-free and recurrence-free survival were 49%, 41% and 33%, respectively. Median survival was 65 months. Margin status had no significant impact on patient survival. The Basingstoke Predictive Index (BPI) generally underestimated survival. This underestimation was especially marked in Group 1 when postoperative BPI was applied. CONCLUSIONS Patients with margins of <1 mm achieved survival comparable with that in patients with margins of ≥ 10 mm. When modern surgical equipment that generates an additional coagulation zone is applied, the association between resection margin and survival may not be apparent. Further studies in this field are required. Postoperative BPI, which includes margin status among the core factors predicting postoperative survival, seems to be less precise than preoperative BPI.
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Affiliation(s)
- Nadya Postriganova
- Intervention Centre, Oslo University Hospital – RikshospitaletOslo, Norway,Department of Hospital Surgery, Moscow State University of Medicine and DentistryMoscow, Russia,Correspondence, Nadya Postriganova, Intervention Centre, Oslo University Hospital – Rikshospitalet, Oslo 0027, Norway. Tel: + 47 23070100. Fax: + 47 23070110. E-mail:
| | - Airazat M Kazaryan
- Intervention Centre, Oslo University Hospital – RikshospitaletOslo, Norway,Department of Surgery, Telemark HospitalSkien, Norway
| | - Bård I Røsok
- Department of Hepatopancreatobiliary Surgery, Oslo University Hospital – RikshospitaletOslo, Norway
| | - Åsmund A Fretland
- Intervention Centre, Oslo University Hospital – RikshospitaletOslo, Norway,Department of Hepatopancreatobiliary Surgery, Oslo University Hospital – RikshospitaletOslo, Norway
| | - Leonid Barkhatov
- Intervention Centre, Oslo University Hospital – RikshospitaletOslo, Norway
| | - Bjørn Edwin
- Intervention Centre, Oslo University Hospital – RikshospitaletOslo, Norway,Department of Hepatopancreatobiliary Surgery, Oslo University Hospital – RikshospitaletOslo, Norway,Institute of Clinical Medicine, Medical Faculty, University of OsloOslo, Norway
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Ker CG. Surgical safety margin of gastroenterological cancer surgery: A truth or a dream? FORMOSAN JOURNAL OF SURGERY 2014; 47:83-89. [DOI: 10.1016/j.fjs.2013.07.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022] Open
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One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach. Ann Surg 2014; 259:543-8. [PMID: 23732261 DOI: 10.1097/sla.0b013e3182902b6e] [Citation(s) in RCA: 123] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To investigate the influence of clear surgical resection margin width on disease recurrence rate after intentionally curative resection of colorectal liver metastases. BACKGROUND There is consensus that a histological positive resection margin is a predictor of disease recurrence after resection of colorectal liver metastases. The dispute, however, over the width of cancer-free resection margin required is ongoing. METHODS Analysis of observational prospectively collected data for 2715 patients who underwent primary resection of colorectal liver metastases from 2 major hepatobiliary units in the United Kingdom. Histological cancer-free resection margin was classified as positive (if cancer cells present at less than 1 mm from the resection margin) or negative (if the distance between the cancer and the margin is 1 mm or more). The negative margin was further classified according to the distance from the tumor in millimeters. Predictors of disease-free survival were analyzed in univariate and multivariate analyses. A case-match analysis by a propensity score method was undertaken to reduce bias. RESULTS A 1-mm cancer-free resection margin was sufficient to achieve 33% 5-year overall disease-free survival. Extra margin width did not add disease-free survival advantage (P > 0.05). After the propensity case-match analysis, there is no statistical difference in disease-free survival between patients with negative narrow and wider margin clearance [hazard ratio (HR) 1.0; 95% (confidence interval) CI: 0.9-1.2; P = 0.579 at 5-mm cutoff and HR 1.1; 95% CI: 0.96-1.3; P = 0.149 at 10-mm cutoff]. Patients with extrahepatic disease and positive lymph node primary tumor did not have disease-free survival advantage despite surgical margin clearance (9 months for <1-mm vs 12 months for ≥1-mm margin clearance; P = 0.062). CONCLUSION One-mm cancer-free resection margin achieved in patients with colorectal liver metastases should now be considered the standard of care.
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Khan SA, Matthews JB. Intraoperative margin re-resection for colorectal cancer liver metastases. Hepatobiliary Surg Nutr 2014; 2:108-12. [PMID: 24570924 DOI: 10.3978/j.issn.2304-3881.2012.10.16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2012] [Accepted: 10/30/2012] [Indexed: 01/16/2023]
Abstract
One of the basic tenets of surgical oncology is the achievement of margin-negative resection. The importance of surgical margins in hepatic resection for colorectal cancer liver metastases (CRCLM) is reflected in the abundance of literature written about this topic. However, the definition of the ideal surgical margin has evolved in parallel with advances in systemic chemotherapy, biologic therapy and surgical technology. A better understanding of the biology of liver metastasis is of critical importance in the context of surgical strategy for CRCLM. The value of intraoperative margin re-resection to achieve R0 status for CRCLM is addressed, taking into consideration current understandings of cancer biology.
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Affiliation(s)
- Sajid A Khan
- Department of Surgery, the University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Jeffrey B Matthews
- Department of Surgery, the University of Chicago Medical Center, Chicago, IL 60637, USA
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Murakami S, Ajiki T, Okazaki T, Ueno K, Kido M, Matsumoto I, Fukumoto T, Ku Y. Factors affecting survival after resection of intrahepatic cholangiocarcinoma. Surg Today 2014; 44:1847-54. [PMID: 24452507 DOI: 10.1007/s00595-013-0825-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Accepted: 09/05/2013] [Indexed: 12/16/2022]
Abstract
PURPOSE This study aimed at assessing the prognostic factors of resection of intrahepatic cholangiocarcinoma (IHCC), which remain unclear. METHODS Among 70 patients with IHCC, who were admitted to our hospital between 1998 and 2011, 45 (64 %) underwent resection and 25 had unresectable tumors. Univariate and multivariate analyses were conducted retrospectively to assess the factors influencing survival of the patients who underwent resection. RESULTS The median survival times of the patients who underwent resection versus those who did not were 16 months versus 9 months, respectively (P < 0.001). Multivariate analysis identified residual tumor status (relative risk 4.12, P = 0.04) and pathological differentiation (relative risk 5.55, P = 0.04) as independent factors predicting survival. Patients who underwent R1 resection had a significantly higher rate of local recurrence than those who underwent R0 resection (P = 0.008). With R0 resection, there were no significant differences in patterns and rates of recurrence between patients with narrow (≤ 5 mm) versus wide (>5 mm) surgical margins. CONCLUSIONS R0/1 resection and a well-differentiated tumor were found to be independent prognostic factors for long-term survival after IHCC resection. If R0 resection was achieved, the width of the negative surgical margin did not affect the patterns and rates of recurrence.
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Affiliation(s)
- Sae Murakami
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan,
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Herman P, Pinheiro RS, Mello ES, Lai Q, Lupinacci RM, Perini MV, Pugliese V, Andraus W, Coelho FF, Cecconello I, D'Albuquerque LC. Surgical margin size in hepatic resections for colorectal metastasis: impact on recurrence and survival. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2013; 26:309-314. [PMID: 24510040 DOI: 10.1590/s0102-67202013000400011] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Accepted: 07/11/2013] [Indexed: 11/21/2022]
Abstract
BACKGROUND Approximately 50% of the patients with a colorectal tumor develop liver metastasis, for which hepatectomy is the standard care. Several prognostic factors have been discussed, among which is the surgical margin. This is a recurring issue, since no consensus exists as to the minimum required distance between the metastatic nodule and the liver transection line. AIM To evaluate the surgical margins in liver resections for colorectal metastases and their correlation with local recurrence and survival. METHODS A retrospective study based on the review of the medical records of 91 patients who underwent resection of liver metastases of colorectal cancer. A histopathological review was performed of all the cases; the smallest surgical margin was verified, and the late outcome of recurrence and survival was evaluated. RESULTS No statistical difference was found in recurrence rates and overall survival between the patients with negative or positive margins (R0 versus R1); likewise, there was no statistical difference between subcentimeter margins and those greater than 1 cm. The disease-free survival of the patients with microscopically positive margins was significantly worse than that of the patients with negative margins. The uni- and multivariate analyses did not establish the surgical margin (R1, narrow or less than 1 cm) as a risk factor for recurrence. CONCLUSION The resections of liver metastases with negative margins, independently of the margin width, had no impact on tumor recurrence (intra- or extrahepatic) or patient survival.
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Mbah NA, Scoggins C, McMasters K, Martin R. Impact of hepatectomy margin on survival following resection of colorectal metastasis: the role of adjuvant therapy and its effects. Eur J Surg Oncol 2013; 39:1394-9. [PMID: 24084087 DOI: 10.1016/j.ejso.2013.09.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Revised: 08/23/2013] [Accepted: 09/06/2013] [Indexed: 01/12/2023] Open
Abstract
INTRODUCTION The optimal width of microscopic margin and the use of adjuvant therapy after a positive margin for hepatic resection for colorectal liver metastasis (CRCLM) has not been conclusively determined. The aim of the current study is to evaluate the influence of width of surgical margin and adjunctive therapy upon disease free and overall survival. METHODS All patients undergoing hepatectomy for CRCLM from 1997 to 2012 were identified from a prospectively maintained, IRB approved database. Patients were divided into four subgroups based on the parenchymal margin: positive, <0.1 cm, 0.1 cm-1 cm, and >1 cm. RESULTS A total of 373 patients were included for analysis with a median follow up of 26 months (range 9-103 months) and a median overall survival of 53 months. The resection margin was positive (26 patients median OS 24 months), <0.1 cm (48 patients median OS 36 mon), 0.1 cm-1 cm (82 patients median OS 44 months), and >1 cm (217 patients median OS 64 months). The most common adjunctive therapy was chemotherapy, hepatic arterial therapy, or local. Patients with positive margins also had the shortest disease free survival (DFS), 16 months. The DFS was similar amongst the other margin groups (<0.1 cm: 21 months, 0.1-1 cm: 22 months, >1 cm 25 months). Hepatectomy margin independently influenced survival (p = 0.017) and disease free survival (p = 0.034). Patients with negative margins has similar overall recurrence rates (p = 0.36) and survival rates (p = 0.89). CONCLUSIONS A positive surgical margin indicates a worse overall biology of disease for patients undergoing hepatectomy for CRCLM, and appropriate multi-disciplinary therapy should be considered in this high risk patient population. Marginal width if a complete resection has been achieved does not adversely effect overall surgical in patients with CRCLM.
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Affiliation(s)
- N A Mbah
- Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer University of Louisville School of Medicine, USA
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Stättner S, Yip V, Jones RP, Lacasia C, Fenwick SW, Poston GJ, Malik H. Liver resection with concomitant inferior vena cava resection: experiences without veno-venous bypass. Surg Today 2013; 44:1063-71. [DOI: 10.1007/s00595-013-0652-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Accepted: 05/13/2013] [Indexed: 12/13/2022]
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S Hammond J, Muirhead W, Zaitoun AM, Cameron IC, Lobo DN. Comparison of liver parenchymal ablation and tissue necrosis in a cadaveric bovine model using the Harmonic Scalpel, the LigaSure, the Cavitron Ultrasonic Surgical Aspirator and the Aquamantys devices. HPB (Oxford) 2012; 14:828-32. [PMID: 23134184 PMCID: PMC3521911 DOI: 10.1111/j.1477-2574.2012.00547.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2012] [Accepted: 06/23/2012] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The amount of tissue that is ablated or necrosed at the line of parenchymal transection is of clinical significance in the interpretation of resection margin status following hepatic resection. The aim of this study was to define the extent of parenchymal ablation and necrosis in liver tissue using the Harmonic Scalpel, the LigaSure, the Cavitron Ultrasonic Surgical Aspirator (CUSA) and the Aquamantys dissector ex vivo. METHODS Mounted blocks of non-perfused bovine liver were transected using the Harmonic Scalpel, LigaSure, CUSA and Aquamantys devices. Outcome measures included parenchymal ablation (ablation band widths and weights) and tissue necrosis band widths along the line of transection. Each experiment was replicated five times. RESULTS All devices were associated with parenchymal ablation (Harmonic Scalpel, 4.73 ± 1.62 mm; LigaSure, 4.55 ± 2.02 mm; CUSA, 7.16 ± 2.87 mm; Aquamantys, 4.75 ± 1.43 mm) and tissue necrosis (Harmonic Scalpel, 1.07 ± 0.46 mm; LigaSure, 1.36 ± 0.36 mm; CUSA, 0.81 ± 0.21 mm; Aquamantys, 0.81 ± 0.36 mm). CONCLUSIONS The Harmonic Scalpel, LigaSure, CUSA and Aquamantys devices were associated with bands of tissue loss along the hepatic parenchymal transection line in this benchtop cadaveric model. This should be taken into account in the interpretation of resection margin status following liver resection.
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Affiliation(s)
| | | | - Abed M Zaitoun
- Department of Cellular Pathology, Nottingham Digestive Diseases Centre, National Institute of Health Research Biomedical Research Unit, Nottingham University Hospitals, Queen's Medical CentreNottingham, UK
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Cauchy F, Faivre S, Belghiti J. Surgical results after downstaging of initially marginal or non-resectable liver metastases. Dig Dis 2012. [PMID: 23207947 DOI: 10.1159/000342048] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Surgery remains the best curative treatment for resectable patients with colorectal liver metastases. In patients initially considered unresectable, both refinements in surgical technique using portal vein occlusion or two-step resections and increased efficiency of chemotherapy regimen with the adjunction of antiangiogenics now allow secondary resection. Recent evidence suggests almost identical long-term survival in case of secondary downstaged lesions advocating an aggressive approach. However, these data lie on disparate and nonconsensual criteria for unresectability, which often do not gather technical and oncologic components together. Furthermore, both impaired general status and damaged underlying parenchyma as a consequence of prolonged chemotherapy to achieve resectability as well as the technical challenge required to perform adequate carcinologic resection could increase the operative risk in such patients. In our experience, a subgroup of slow chemo-responding initially unresectable patients who required preoperative liver volume modulation after ≥ 12 cycles of chemotherapy to achieve sufficient response experienced dramatically high operative risk which jeopardized postoperative chemotherapy and subsequently put these patients at increased risk of recurrence. Whether all patients preoperatively amenable to surgery using intensive chemotherapy and complex surgical strategy actually benefit from such an aggressive approach is a matter of ongoing debate, which needs a reappraisal.
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Affiliation(s)
- F Cauchy
- Department of Hepatobiliopancreatic Surgery, AP-HP, Beaujon Hospital and University Paris 7 Denis Diderot, Clichy, France
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Sulpice L, Rayar M, Boucher E, Pele F, Pracht M, Meunier B, Boudjema K. Intrahepatic cholangiocarcinoma: impact of genetic hemochromatosis on outcome and overall survival after surgical resection. J Surg Res 2012. [PMID: 23183056 DOI: 10.1016/j.jss.2012.10.051] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND The influence of genetic hemochromatosis (GH) on outcomes following surgical resections for intrahepatic cholangiocarcinoma (ICC) has not been evaluated. METHODS All patients with ICC who underwent a surgical resection between January 1997 and August 2011 were analyzed retrospectively. Risk factors were assessed by univariate and multivariate analyses. RESULTS Eighty-seven patients were analyzed; 16 of these patients (18.4%) had GH. Among the 71 non-GH patients, 52 (73.2%) and 19 (26.8%) had normal or cirrhotic parenchyma, respectively. There was no significant difference in survival between the GH and non-GH patients. A univariate analysis showed that major hepatectomy (P = 0.012), intraoperative blood transfusion (P = 0.007), tumor size >5 cm (P = 0.006), several nodules (P < 0.001), and microvascular invasion (P = 0.04) were significantly associated with poor survival. A multivariate analysis showed that intraoperative blood infusion (HR 0.37; CI 95% [0.19; 0.71]) and more than one nodule (HR 2.5; CI 95% [1.06; 5.8]) were associated with a lower survival rate. CONCLUSION Although the incidence of GH was high in our series, the presence of GH did not affect the outcomes after a liver hepatectomy for ICC. GH does not appear to increase recurrences or worsen the overall and disease-free survival.
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Affiliation(s)
- Laurent Sulpice
- Service de Chirurgie Hépatobiliaire et Digestive, Hôpital Pontchaillou, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France.
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López-Gómez M, Cejas P, Merino M, Fernández-Luengas D, Casado E, Feliu J. Management of colorectal cancer patients after resection of liver metastases: can we offer a tailored treatment? Clin Transl Oncol 2012; 14:641-58. [PMID: 22911546 DOI: 10.1007/s12094-012-0853-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2012] [Accepted: 06/11/2012] [Indexed: 01/10/2023]
Abstract
Surgical resection remains the only option of cure for patients with colorectal liver metastases, and no patient should be precluded from surgery. There is much controversy not only regarding the most appropriate therapeutic approach in the neoadjuvant setting but also after surgery is performed. Many patients will experience early relapses but others will be long survivors. We need to establish reliable prognostic and predictive factors to offer a tailored treatment. Several prognostic factors after metastasectomy have been identified: high C-reactive protein levels, a high neutrophil-lymphocyte ratio, elevated neutrophil count and low serum albumin are related to a worst outcome. Elevated CEA and Ki 67 levels, intrahepatic and perihepatic lymph node invasion are also some of the markers related to a worst outcome. In contrast, the administration of preoperative chemotherapy has been associated with a better prognosis after hepatectomy. The administration of adjuvant chemotherapy should be done taking in consideration these factors. Regarding predictive factors, determination of ERCC1, TS, TP and DPD and UGT1 polymorphisms assessment could be considered prior to chemotherapy administration. This would avoid treatment related toxicities and increase this population quality of life.
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Affiliation(s)
- Miriam López-Gómez
- Clinical Oncology Department, Infanta Sofía University Hospital, Paseo de Europa 34, San Sebastián de los Reyes, 28702, Madrid, Spain.
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Laparoscopic hepatectomy: an alternative to open surgery for colorectal liver metastases? Eur Surg 2012. [DOI: 10.1007/s10353-012-0087-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
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Cucchetti A, Ercolani G, Cescon M, Bigonzi E, Peri E, Ravaioli M, Pinna AD. Impact of subcentimeter margin on outcome after hepatic resection for colorectal metastases: A meta-regression approach. Surgery 2012; 151:691-9. [DOI: 10.1016/j.surg.2011.12.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2011] [Accepted: 12/09/2011] [Indexed: 10/14/2022]
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Jones RP, Jackson R, Dunne DFJ, Malik HZ, Fenwick SW, Poston GJ, Ghaneh P. Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases2. Br J Surg 2012; 99:477-86. [DOI: 10.1002/bjs.8667] [Citation(s) in RCA: 129] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/30/2011] [Indexed: 12/22/2022]
Abstract
Abstract
Background
The evidence surrounding optimal follow-up after liver resection for colorectal metastases remains unclear. A significant proportion of recurrences occur in the early postoperative period, and some groups advocate more intensive review at this time.
Methods
A systematic review of literature published between January 2003 and May 2010 was performed. Studies that described potentially curative primary resection of colorectal liver metastases that involved a defined follow-up protocol and long-term survival data were included. For meta-analysis, studies were grouped into intensive (more frequent review in the first 5 years after resection) and uniform (same throughout) follow-up.
Results
Thirty-five studies were identified that met the inclusion criteria, involving 7330 patients. Only five specifically addressed follow-up. Patients undergoing intensive early follow-up had a median survival of 39·8 (95 per cent confidence interval 34·3 to 45·3) months with a 5-year overall survival rate of 41·9 (34·4 to 49·4) per cent. Patients undergoing routine follow-up had a median survival of 40·2 (33·4 to 47·0) months, with a 5-year overall survival rate of 38·4 (32·6 to 44·3) months.
Conclusion
Evidence regarding follow-up after liver resection is poor. Meta-analysis failed to identify a survival advantage for intensive early follow-up.
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Affiliation(s)
- R P Jones
- Division of Surgery and Oncology, School of Cancer Studies, University of Liverpool, Liverpool, UK
- Department of Hepatobiliary Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - R Jackson
- Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK
| | - D F J Dunne
- Department of Hepatobiliary Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - H Z Malik
- Department of Hepatobiliary Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - S W Fenwick
- Department of Hepatobiliary Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - G J Poston
- Department of Hepatobiliary Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - P Ghaneh
- Division of Surgery and Oncology, School of Cancer Studies, University of Liverpool, Liverpool, UK
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Lang H, Gassmann P. Chirurgische Standards und Resektionsausmaß. VISZERALMEDIZIN 2012. [DOI: 10.1159/000336696] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Abstract
Management of Neuroendocrine liver metastases (NELM) is challenging. The presence of NELM worsens survival outcome and almost 10% of all liver metastases are neuroendocrine in origin. There is no firm consensus on the optimal treatment strategy for NELM. A systematic search of the PubMed database was performed from 1995-2010, to collate the current evidence and formulate a sound management algorithm. There are 22 case series with a total of 793 patients who had undergone surgery for NELM. The overall survival ranges from 46-86% at 5 years, 35-79% at 10 years, and the median survival ranges from 52-123 months. After successful cytoreductive surgery, the mean duration of symptom reduction is between 16-26 months, and the 5-year recurrence/progression rate ranges from 59-76%. Five studies evaluated the efficacy of a combination cytoreductive strategy reporting survival rate of ranging from 83% at 3 years to 50% at 10 years. To date, there is no level 1 evidence comparing surgery versus other liver-directed treatment options for NELM. An aggressive surgical approach, including combination with additional liver-directed procedures is recommended as it leads to long-term survival, significant long-term palliation, and a good quality of life. A multidisciplinary approach should be established as the platform for decision making.
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Chan KM, Chiang JM, Lee CF, Yu MC, Lee WC, Chen JS, Wang JY. Outcomes of resection for colorectal cancer hepatic metastases stratified by evolving eras of treatment. World J Surg Oncol 2011; 9:174. [PMID: 22208884 PMCID: PMC3278383 DOI: 10.1186/1477-7819-9-174] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2011] [Accepted: 12/30/2011] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND AND PURPOSE The outcomes and management of colorectal cancer (CRC) hepatic metastasis have undergone many evolutionary changes. In this study, we aimed to analyze the outcomes of patients with CRC hepatic metastasis in terms of the era of treatment. METHODS We conducted a retrospective review of 279 patients who underwent liver resection (LR) for CRC hepatic metastases. The prognoses of patients treated pre-2003 (era 1) and post-2003 (era 2) were examined. RESULTS Of the patients included in the study, 210 (75.3%) had CRC recurrence after LR. There was a significant difference in the ratio of CRC recurrence between the 2 eras (82.0% in era 1 vs. 69.5% in era 2; p = 0.008). Analysis of recurrence-free and overall survival rates also showed that the patient outcome was significantly better in the post-2003 era than in the pre-2003 era. Further analysis showed that a significantly higher percentage of patients in era 2 had received modern chemotherapeutic regimens including irinotecan and oxaliplatin, while patients in era 1 were mainly administered fluorouracil and leucovorin for adjuvant chemotherapy. Among patients with CRC recurrence, a significant ratio of those in era 2 underwent surgical resection for recurrent lesions, and these patients had a better survival curve than did patients without resection (34.1% vs. 2.2% for 5-year survival; p < 0.0001). CONCLUSION The incidence of CRC recurrence after LR for hepatic metastasis remains very high. However, the management and outcomes of patients with CRC hepatic metastasis have greatly improved with time, suggesting that the current use of aggressive multimodality treatments including surgical resection combined with modern chemotherapeutic regimens effectively prolongs the life expectancy of these patients.
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Affiliation(s)
- Kun-Ming Chan
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Jy-Ming Chiang
- Department of Colorectal Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ming-Chin Yu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Jinn-Shiun Chen
- Department of Colorectal Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Jeng-Yi Wang
- Department of Colorectal Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
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