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Baron T, Laroche S, Wagner M, Lim C, Renaud F, Charlotte F, Scatton O, Goumard C. On-site recurrence risk after parenchymal R1 liver resection for colorectal metastases. Surgery 2025; 181:109137. [PMID: 39879880 DOI: 10.1016/j.surg.2024.109137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 12/18/2024] [Accepted: 12/30/2024] [Indexed: 01/31/2025]
Abstract
BACKGROUND Histologic microscopic positive resection margin is a debated prognostic factor in patients resected for colorectal liver metastases. This study aimed to assess whether patients with R1 resection experience recurrence at the site of the resection (on-site recurrence) and to identify predictive factors for recurrence profiles in patients with R1 margins after resection of colorectal liver metastases. METHODS All surgical colorectal liver metastasis resection cases with R1 parenchymal margin from September 2014 to March 2020 in our center were retrospectively included. Imaging was reviewed for each metastasis. All the analyses were performed per metastasis. Recurrence location was examined for each metastasis according to the site of the R1 margin and defined as on-site when recurrence was at the same place of the resected lesion. Prognostic factors for recurrence type were assessed using logistic regression. RESULTS Of 700 patients who underwent liver resection for colorectal liver metastases, 105 (15%) had at least 1 metastasis with R1 resection margin, representing 6.8% per metastasis. The median follow-up was 34 months. Overall recurrence occurred in 130 metastases (83.3%) with intrahepatic recurrence in 106 metastases (80.9%). On-site recurrence was observed for 49 metastases (31.4%) and isolated (without an additional recurrence site) for 20 metastases (12.8%). The on-site recurrence did not impact overall survival. Three predictive factors for on-site recurrence were found in the multivariate logistic regression: synchronous metastases, nonanatomic resection, and pathologic response tumor regression grade 4-5. CONCLUSION Intrahepatic localization of recurrence is more frequent than on-site recurrence after R1 parenchymal resection. Synchronous metastases, nonanatomic resection, and tumor regression grade 4-5 may impact the risk of on-site recurrence.
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Affiliation(s)
- Thomas Baron
- Hepatobiliary Surgery and Liver Transplantation Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Sophie Laroche
- Hepatobiliary Surgery and Liver Transplantation Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Mathilde Wagner
- Radiology Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Chetana Lim
- Hepatobiliary Surgery and Liver Transplantation Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Florence Renaud
- Pathology Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Frederic Charlotte
- Pathology Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
| | - Olivier Scatton
- Hepatobiliary Surgery and Liver Transplantation Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France.
| | - Claire Goumard
- Hepatobiliary Surgery and Liver Transplantation Department, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France
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2
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Moaven O, Mainali BB, Valenzuela CD, Russell G, Cheung T, Corvera CU, Wisneski AD, Cha CH, Stauffer JA, Shen P. Prognostic implications of margin status in association with systemic treatment in a cohort study of patients with resection of colorectal liver metastases. J Surg Oncol 2024; 130:1654-1661. [PMID: 39183490 DOI: 10.1002/jso.27846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 08/08/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND This study investigates the impact of margin status after colorectal liver metastasis (CLM) resection on outcomes of patients after neoadjuvant treatment versus those who underwent upfront resection. METHODS An international collaborative database of CLM patients who underwent surgical resection was used. Proportional hazard regression models were created for single and multivariable models to assess the relationship between independent measures and median overall survival (mOS). RESULTS R1 was associated with worse OS in the neoadjuvant group (mOS: 51.8 m for R0 vs. 26.0 m for R1; HR: 2.18). In the patients who underwent upfront surgery, R1 was not associated with OS. (mOS: 46.7 m for R0 vs. 42.6 m for R1). When patients with R1 in each group were stratified by adjuvant treatment, there was no significant difference in the neoadjuvant group, while in the upfront surgery group with R1, adjuvant treatment was associated with significant improvement in OS (mOS: 42.6 m for adjuvant vs. 25.0 m for no adjuvant treatment; HR: 0.21). CONCLUSION R1 is associated with worse outcomes in the patients who receive neoadjuvant treatment with no significant improvement with the addition of adjuvant therapy, likely representing an aggressive tumor biology. R1 did not impact OS in patients with upfront surgery who received postoperative chemotherapy.
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Affiliation(s)
- Omeed Moaven
- Division of Surgical Oncology, Department of Surgery, Louisiana State University (LSU) Health, New Orleans, Louisiana, USA
- LSU-LCMC Cancer Center, New Orleans, Louisiana, USA
| | - Bigyan B Mainali
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Cristian D Valenzuela
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Gregory Russell
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Tanto Cheung
- Department of Surgery, University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Carlos U Corvera
- Department of Hepatobiliary & Pancreatic Surgery, University of California San Francisco, San Francisco, California, USA
| | - Andrew D Wisneski
- Department of Hepatobiliary & Pancreatic Surgery, University of California San Francisco, San Francisco, California, USA
| | - Charles H Cha
- Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA
| | - John A Stauffer
- Department of Surgical Oncology, Mayo Clinic in Florida, Jacksonville, Florida, USA
| | - Perry Shen
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
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3
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Kato T, Imamura M, Kyuno D, Kimura Y, Kukita K, Murakami T, Yoshida E, Mizuguchi T, Takemasa I. Impact of Infrared Indocyanine Green Fluorescence Imaging-guided Laparoscopic Hepatectomy on Securing the Resection Margin for Colorectal Liver Metastasis. Surg Laparosc Endosc Percutan Tech 2024; 34:551-558. [PMID: 39183534 DOI: 10.1097/sle.0000000000001320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 08/01/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND Laparoscopic hepatectomy for colorectal liver metastases (CRLM) is performed worldwide. However, owing to a lack of palpatory information and difficulties associated with accurate intraoperative ultrasonographic diagnosis, the tumor may be exposed at the hepatic transection margin. This study aimed to investigate the pathological significance of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG)-guided laparoscopic hepatectomy and determine its usefulness in securing the resection margin for CRLMs. METHODS Fifty-nine patients who underwent laparoscopic hepatectomy for CRLM using NIR fluorescence imaging between February 2017 and June 2021 at Sapporo Medical University Hospital were included. Generally, all patients received intravenous ICG (2.5 mg/body) as a fluorescence agent 1 to 2 days before surgery. During the surgical procedure, real-time NIR fluorescence imaging was repeatedly performed to assess the surgical margins. RESULTS Of the 94 tumors in 59 patients, laparoscopic NIR fluorescence imaging identified 56 tumors (59.6%) on the liver surface. Pathological analysis indicated clear margins in 96.6% (57/59) of patients. Examination of paraffin-embedded sections, which were successful in only 20 of 94 cases (21.3%), revealed that there were no tumor cells positive for NIR fluorescence, and the median distance of the continuous fluorescent signal from the tumor margin was 1.074 mm. CONCLUSIONS We demonstrated a high R0 rate using NIR fluorescence-guided hepatectomy. This technique has the potential to improve intraoperative tumor identification and tumor margin assurance and reduce the rate of positive resection margins in patients with CRLMs.
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Affiliation(s)
- Toru Kato
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Hokkaido, Japan
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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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Sakamoto K, Beppu T, Honda G, Kotake K, Yamamoto M, Takahashi K, Endo I, Hasegawa K, Itabashi M, Hashiguchi Y, Kotera Y, Kobayashi S, Yamaguchi T, Natsume S, Tabuchi K, Kobayashi H, Yamaguchi K, Tani K, Morita S, Miyazaki M, Sugihara K. Comprehensive data of 4502 patients newly diagnosed with colorectal liver metastasis between 2015 and 2017, and prognostic data of 2427 patients newly diagnosed with colorectal liver metastasis in 2013 and 2014: Third report of a nationwide survey in Japan. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023; 30:570-590. [PMID: 36259160 DOI: 10.1002/jhbp.1252] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 08/18/2022] [Accepted: 09/14/2022] [Indexed: 02/20/2025]
Abstract
To improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. The aim of the study was to evaluate transition in the characteristics and treatment strategy in CRLM patients and analyze prognostic factors using large-scale data. The present study summarizes the data of patients newly diagnosed between 2015 and 2017 and presents prognostic data of patients newly diagnosed in 2013 and 2014. Survival curves were generated by the Kaplan-Meier method and compared by log-rank test. Multivariate analyses were carried out using Cox proportional hazard modeling. The data of 4502 patients newly diagnosed with CRLM between 2015 and 2017 and the prognostic data of 2427 patients diagnosed in 2013 and 2014 are included. Regarding the 2013 and 2014 prognostic data, the 5-year overall survival (OS) rates of patients who underwent hepatectomy alone was 59.8%. Multivariate analyses identified age at diagnosis of CRLM ≥70 years, concomitant extrahepatic metastasis at diagnosis of CRLM, tumor depth of primary lesion ≥subserosa/pericolic or perirectal tissue, mutant KRAS status, number of CRLM ≥5, maximum diameter of CRLM >5 cm, and surgical curability R1/R2 as independent predictors of OS. Analysis of the latest nationwide database of patients diagnosed with CRLM revealed changes in patients and oncological characteristics, a transition in treatment strategy, and different independent prognosticators to those reported previously.
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Affiliation(s)
- Katsunori Sakamoto
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Toru Beppu
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
| | - Goro Honda
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Kenjiro Kotake
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Sano City Hospital, Sano, Tochigi, Japan
| | - Masakazu Yamamoto
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Utsunomiya Memorial Hospital, Utsunomiya, Tochigi, Japan
| | - Keiichi Takahashi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Tokyo Metropolitan Health and Hospitals Corporation Ohkubo Hospital, Shinjuku-ku, Tokyo, Japan
| | - Itaru Endo
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
| | - Kiyoshi Hasegawa
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Hepato-Biliary-Pancreatic Surgery Division, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Michio Itabashi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Yojiro Hashiguchi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Yoshihito Kotera
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Shin Kobayashi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa-shi, Chiba, Japan
| | - Tatsuro Yamaguchi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan
| | - Soichiro Natsume
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan
| | - Ken Tabuchi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Pediatrics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan
| | - Hirotoshi Kobayashi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Teikyo University Hospital, Kawasaki, Kanagawa, Japan
| | - Kensei Yamaguchi
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Gastrointestinal Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
| | - Kimitaka Tani
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Satoshi Morita
- Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Bunkyo-ku, Tokyo, Japan
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan
| | - Masaru Miyazaki
- International University of Health and Welfare, Narita Hospital, Minato-ku, Tokyo, Japan
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7
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Bertsimas D, Margonis GA, Sujichantararat S, Boerner T, Ma Y, Wang J, Kamphues C, Sasaki K, Tang S, Gagniere J, Dupré A, Løes IM, Wagner D, Stasinos G, Macher-Beer A, Burkhart R, Morioka D, Imai K, Ardiles V, O'Connor JM, Pawlik TM, Poultsides G, Seeliger H, Beyer K, Kaczirek K, Kornprat P, Aucejo FN, de Santibañes E, Baba H, Endo I, Lønning PE, Kreis ME, Weiss MJ, Wolfgang CL, D'Angelica M. Using Artificial Intelligence to Find the Optimal Margin Width in Hepatectomy for Colorectal Cancer Liver Metastases. JAMA Surg 2022; 157:e221819. [PMID: 35648428 DOI: 10.1001/jamasurg.2022.1819] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Importance In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon's direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width. Objective To determine the optimal margin width in CRLM by using artificial intelligence-based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics. Design, Setting, and Participants The internal cohort of the study included patients who underwent curative-intent surgery for KRAS-variant CRLM between January 1, 2000, and December 31, 2017, at Johns Hopkins Hospital, Baltimore, Maryland, Memorial Sloan Kettering Cancer Center, New York, New York, and Charité-University of Berlin, Berlin, Germany. Patients from institutions in France, Norway, the US, Austria, Argentina, and Japan were retrospectively identified from institutional databases and formed the external cohort of the study. Data were analyzed from April 15, 2019, to November 11, 2021. Exposures Hepatectomy. Main Outcomes and Measures Patients with KRAS-variant CRLM who underwent surgery between 2000 and 2017 at 3 tertiary centers formed the internal cohort (training and testing). In the training cohort, an artificial intelligence-based technique called optimal policy trees (OPTs) was used by building on random forest (RF) predictive models to infer the margin width associated with the maximal decrease in death probability for a given patient (ie, optimal margin width). The RF component was validated by calculating its area under the curve (AUC) in the testing cohort, whereas the OPT component was validated by a game theory-based approach called Shapley additive explanations (SHAP). Patients from international institutions formed an external validation cohort, and a new RF model was trained to externally validate the OPT-based optimal margin values. Results This cohort study included a total of 1843 patients (internal cohort, 965; external cohort, 878). The internal cohort included 386 patients (median [IQR] age, 58.3 [49.0-68.7] years; 200 men [51.8%]) with KRAS-variant tumors. The AUC of the RF counterfactual model was 0.76 in both the internal training and testing cohorts, which is the highest ever reported. The recommended optimal margin widths for patient subgroups A, B, C, and D were 6, 7, 12, and 7 mm, respectively. The SHAP analysis largely confirmed this by suggesting 6 to 7 mm for subgroup A, 7 mm for subgroup B, 7 to 8 mm for subgroup C, and 7 mm for subgroup D. The external cohort included 375 patients (median [IQR] age, 61.0 [53.0-70.0] years; 218 men [58.1%]) with KRAS-variant tumors. The new RF model had an AUC of 0.78, which allowed for a reliable external validation of the OPT-based optimal margin. The external validation was successful as it confirmed the association of the optimal margin width of 7 mm with a considerable prolongation of survival in the external cohort. Conclusions and Relevance This cohort study used artificial intelligence-based methodologies to provide a possible resolution to the long-standing debate on optimal margin width in CRLM.
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Affiliation(s)
- Dimitris Bertsimas
- Operations Research Center, Massachusetts Institute of Technology, Cambridge
| | - Georgios Antonios Margonis
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.,Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, Berlin, Germany
| | - Suleeporn Sujichantararat
- Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge
| | - Thomas Boerner
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Yu Ma
- Operations Research Center, Massachusetts Institute of Technology, Cambridge
| | - Jane Wang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Carsten Kamphues
- Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, Berlin, Germany
| | - Kazunari Sasaki
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Seehanah Tang
- Operations Research Center, Massachusetts Institute of Technology, Cambridge
| | - Johan Gagniere
- Service de Chirurgie Digestive, CHU Clermont-Ferrand, Inserm, Université Clermont Auvergne, Clermont-Ferrand, France
| | - Aurelien Dupré
- Service de Chirurgie Digestive, CHU Clermont-Ferrand, Inserm, Université Clermont Auvergne, Clermont-Ferrand, France
| | - Inger Marie Løes
- Department of Clinical Science, University of Bergen, Bergen, Norway.,Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | - Doris Wagner
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | | | | | - Richard Burkhart
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Daisuke Morioka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Victoria Ardiles
- Hepatopancreatobiliary Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Columbus, Ohio
| | - George Poultsides
- Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Hendrik Seeliger
- Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, Berlin, Germany
| | - Katharina Beyer
- Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, Berlin, Germany
| | - Klaus Kaczirek
- Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Peter Kornprat
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | - Federico N Aucejo
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Eduardo de Santibañes
- Hepatopancreatobiliary Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Per Eystein Lønning
- Department of Clinical Science, University of Bergen, Bergen, Norway.,Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | - Martin E Kreis
- Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, Berlin, Germany
| | - Matthew J Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, Zucker School of Medicine at Hofstra, Northwell Health Cancer Institute, Lake Success, New York
| | - Christopher L Wolfgang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, New York University School of Medicine, New York
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
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Germani MM, Borelli B, Boraschi P, Antoniotti C, Ugolini C, Urbani L, Morelli L, Fontanini G, Masi G, Cremolini C, Moretto R. The management of colorectal liver metastases amenable of surgical resection: How to shape treatment strategies according to clinical, radiological, pathological and molecular features. Cancer Treat Rev 2022; 106:102382. [PMID: 35334281 DOI: 10.1016/j.ctrv.2022.102382] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/16/2022] [Accepted: 03/17/2022] [Indexed: 02/05/2023]
Abstract
Metastatic colorectal cancer (mCRC) patients have poor chances of long term survival, being < 15% of them still alive after 5 years from diagnosis. Nonetheless, patients with colorectal liver metastases (CRLM) may be eligible for metastases resection thus being able to achieve long-term disease remission and survival. The likelihood for patients with CRLM of being or becoming eligible for liver metastasectomy is increasing, thanks to the evolution of surgical techniques, the availability of active systemic treatments and the widespread diffusion of experienced multidisciplinary boards to manage these patients. However, disease relapse after liver surgery is common and occurs in two-thirds of resected patients. Therefore, adequate radiological staging and risk stratification is crucial for the optimal selection of patients candidate to surgery in order to maximize the benefit-risk ratio of liver metastasectomy and to individualize the treatment strategy. Based on the multidimensional assessment, three possible approaches are available: upfront liver surgery followed by adjuvant chemotherapy, perioperative chemotherapy preceding and following liver surgery, and an upfront systemic treatment including chemotherapy plus a targeted agent, both chosen according to patients' and tumours' characteristics, then followed by liver surgery if indicated. In this review, we describe the most important factors impacting the therapeutic choices in patients with resectable and potentially resectable CRLM, and we discuss the most promising factors that may reshape the future decision-making process of these patients.
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Affiliation(s)
- Marco Maria Germani
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Beatrice Borelli
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Piero Boraschi
- Department of Diagnostic and Interventional Radiology, and Nuclear Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Carlotta Antoniotti
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Clara Ugolini
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Lucio Urbani
- Unit of General Surgery, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Luca Morelli
- General Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Gabriella Fontanini
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Gianluca Masi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Chiara Cremolini
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Roberto Moretto
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
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BOZBIYIK O, ÇOKER A. Factors affecting survival in liver metastasis of colorectal cancer. EGE TIP DERGISI 2021. [DOI: 10.19161/etd.1036904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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10
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Recurrence patterns and their effects on clinical outcomes after R1 resection of colorectal liver metastases: a propensity score-matched analysis. Langenbecks Arch Surg 2021; 406:2739-2747. [PMID: 34031728 DOI: 10.1007/s00423-021-02096-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 01/18/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE The prognostic significance of the surgical margin status remains controversial for patients who undergo hepatectomy for colorectal liver metastases. This study evaluated the influence of R1 resection on recurrence patterns and prognosis in these patients. METHODS Between January 2001 and December 2016, 232 consecutive Japanese patients underwent initial hepatic resection for colorectal liver metastases. Their medical records were reviewed to evaluate recurrence and survival outcomes. RESULTS Relative to patients with R0 resection, patients with R1 resection had significantly poorer recurrence-free survival (RFS) and overall survival (OS). However, after propensity score matching, there were no significant differences in RFS and OS associated with the margin status. Nevertheless, R1 resection was associated with a significantly higher incidence of intrahepatic recurrence and early recurrence, while R0 resection was associated with a significantly higher re-resection rate for hepatic recurrence. Only eight of 55 patients with R1 resection developed recurrence at the R1 resection margin, whereas 36 patients developed recurrence at other sites/organs. CONCLUSION Among patients with similar characteristics, R1 resection does not affect long-term outcomes. This suggests that R1 resection itself is not a cause of a poor prognosis, but rather a potent indicator of aggressive tumor biology.
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11
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Sakai N, Furukawa K, Takayashiki T, Kuboki S, Takano S, Ohtsuka M. Differential effects of KRAS mutational status on long-term survival according to the timing of colorectal liver metastases. BMC Cancer 2021; 21:412. [PMID: 33858364 PMCID: PMC8048293 DOI: 10.1186/s12885-021-08144-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 03/30/2021] [Indexed: 12/12/2022] Open
Abstract
Background The relationship between KRAS mutational status and timing of colorectal liver metastasis (CRLM) remains unclear. This study evaluated the relationship between KRAS mutational status and long-term survival in patients with synchronous CRLM. Methods Of the 255 patients who underwent initial hepatic resection for CRLM between January 2001 and December 2018, the KRAS mutational status was examined in 101 patients. Medical records of these patients were reviewed to evaluate recurrence and survival outcomes. Results KRAS mutant status was identified in 38 patients (37.6%). The overall survival (OS) was significantly better in patients with wild-type KRAS than in those with mutant KRAS status. In patients with synchronous metastases, the OS of patients with wild-type KRAS was significantly better than those with mutant KRAS. Multivariate analyses indicated shorter OS to be independently associated with positive primary lymph node, and large tumor size and R1 resection in patients with metachronous metastasis, whereas to be independently associated with mutant KRAS status in patients with synchronous metastasis. Furthermore, in the subgroup of patients with synchronous metastases, the repeat resection rate for hepatic recurrence was significantly high in those with wild type KRAS than in those with mutant KRAS. Conclusion KRAS mutation is an independent prognostic factor in patients with synchronous CRLM, but not in patients with metachronous CRLM.
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Affiliation(s)
- Nozomu Sakai
- Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Katsunori Furukawa
- Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Tsukasa Takayashiki
- Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Satoshi Kuboki
- Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Shigetsugu Takano
- Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
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12
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Preoperative CA19-9: a competitive predictor of recurrence in patients with colorectal cancer liver metastases after hepatectomy. Int J Colorectal Dis 2021; 36:767-778. [PMID: 33420522 DOI: 10.1007/s00384-020-03828-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/25/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE The role of preoperative carbohydrate antigen 19-9 (CA19-9) in colorectal cancer liver metastases (CRLM) patients is still unclear. The present study aimed to explore the prognostic significance of preoperative CA19-9 in those patients. METHODS A total of 691 CRLM patients were included in this study. X-tile analyses were performed to determine the optimal cut-off values of CA19-9 and carcinoembryonic antigen (CEA). Prognostic predictors were identified by multivariate analyses. RESULTS The optimal cut-off values of CA19-9 and CEA for 5-year recurrence-free survival (RFS) were 35.24 U/ml and 20.4 ng/ml, respectively. Patients with high-level CA19-9 had significantly worse RFS and overall survival (OS) than those with low-level CA19-9 (P = 0.001 and P = 0.002, respectively). In addition, patients with high-level CA19-9 had poor RFS and OS (P = 0.028 and P = 0.011, respectively) at low-level CEA. Multivariate analyses confirmed that preoperative CA19-9 was an independent predictor for RFS (hazard ratio [HR] 1.295; 95% confidence interval [CI] 1.043-1.607; P = 0.019) but not for OS (HR 1.213; 95% CI 0.902-1.631; P = 0.201). CONCLUSION CA19-9 is a promising predictor of recurrence for CRLM patients undergoing hepatectomy, and an effective supplement for patients with low-level CEA.
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Hatta AAZ, Pathanki AM, Hodson J, Sutcliffe RP, Marudanayagam R, Roberts KJ, Chatzizacharias N, Isaac J, Muiesan P, Taniere P, Mirza DF, Dasari BVM. The effects of resection margin and KRAS status on outcomes after resection of colorectal liver metastases. HPB (Oxford) 2021; 23:90-98. [PMID: 32417170 DOI: 10.1016/j.hpb.2020.04.016] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 04/23/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of this study was to investigate the influence of resection margin status in patients with KRAS mutations (mt-KRAS) when compared to those with wild-type KRAS (wt-KRAS) on long-term outcomes in patients with resected CRLM. METHODS All patients who underwent resection of CRLM with curative intent between January 2011 and December 2016 and had a KRAS type recorded were included in the study. Overall survival (OS), as well as death-censored overall (RFS) and liver-specific (LS-RFS) recurrence-free survival between KRAS types and the margin status within KRAS subgroups were compared using Cox regression models. RESULTS Data were available for N = 500 patients (30.4% mt-KRAS). mt-KRAS status was independently associated with significantly shorter OS. Within the wt-KRAS subgroup, smaller margins were found to be associated with significantly shorter death-censored LS-RFS (p < 0.001), with HRs of 1.93 (p = 0.005) for 1-4 mm margins and 2.83 (p < 0.001) for <1 mm margins, relative to those with clear margins. No such association was observed in the mt-KRAS subgroup (p = 0.721). CONCLUSION The resection margin status is of greater importance in patients with wt-KRAS. Such information could be useful in the operative planning, especially for those with multiple metastatic deposits, and also in the post-operative counselling and surveillance based on the margin and KRAS status.
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Affiliation(s)
- Ayiesha Ahmad Zalmani Hatta
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Adithya M Pathanki
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - James Hodson
- Institute of Translational Medicine, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Robert P Sutcliffe
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Ravi Marudanayagam
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Keith J Roberts
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Nikolaos Chatzizacharias
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - John Isaac
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Paolo Muiesan
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Phillipe Taniere
- Department of Histopathology, Queen Elizabeth Hospital, Birmingham, B15 2WB, UK
| | - Darius F Mirza
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Bobby V M Dasari
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom.
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Sato M, Hirose K, Ichise K, Yoshino H, Harada T, Hatayama Y, Kawaguchi H, Tanaka M, Fujioka I, Takai Y, Aoki M. Not Only Hypoxia- but Radiation-Induced Epithelial-Mesenchymal Transition Is Modulated by Hypoxia-Inducible Factor 1 in A549 Lung Cancer Cells. Folia Biol (Praha) 2021; 67:62-69. [PMID: 34624938 DOI: 10.14712/fb2021067020062] [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: 12/17/2024]
Abstract
Hypoxia leads to post-treatment metastasis and recurrences of cancer via the epithelial-mesenchymal transition (EMT). Radiotherapy itself may also contribute to the acquisition of EMT phenotypes. Despite extensive studies on the EMT driven by either hypoxia or radiation stimuli, the molecular mechanisms characterizing these EMT events remain unclear. Thus, we aimed to evaluate the differences in the molecular pathways between hypoxia-induced EMT (Hypo-EMT) and radiation-induced EMT (R-EMT). Further, we investigated the therapeutic effects of HIF-1α inhibitor (LW6) on Hypo-EMT and R-EMT cells. A549 cells, lung adenocarcinoma cell line, acquired enhanced wound-healing activity under both hypoxia and irradiation. Localization of E-cadherin was altered from the cell membrane to the cytoplasm in both hypoxia and irradiated conditions. Of note, the expression levels of vimentin, one of the major EMT markers, was enhanced in irradiated cells, while it decreased under hypoxia condition. Importantly, LW6 significantly blocked EMT-related malignant phenotypes in both Hypo-EMT cells and R-EMT cells with concomitant re-location of E-cadherin onto the cell membrane. Moreover, LW6 deflected stress responsive signalling, JNK, activated sustainably under hypoxic condition, and the blockage of JNK impaired EMT phenotypes. Together, this work demonstrated the molecular events underlying Hypo-EMT and R-EMT, and highlighted HIF-1α as a therapeutic target not only in Hypo- EMT, but also in R-EMT.
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Affiliation(s)
- M Sato
- Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Japan
- Southern Tohoku BNCT Research Center, Yatsuyamada, Koriyama, Japan
- Department of Radiation Oncology, Southern Tohoku General Hospital, Yatsuyamada, Koriyama, Japan
| | - K Hirose
- Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Japan
- Southern Tohoku BNCT Research Center, Yatsuyamada, Koriyama, Japan
- Department of Radiation Oncology, Southern Tohoku General Hospital, Yatsuyamada, Koriyama, Japan
| | - K Ichise
- Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Japan
| | - H Yoshino
- Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hon-cho, Hirosaki, Japan
| | - T Harada
- Southern Tohoku BNCT Research Center, Yatsuyamada, Koriyama, Japan
| | - Y Hatayama
- Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Japan
| | - H Kawaguchi
- Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Japan
| | - M Tanaka
- Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Japan
| | - I Fujioka
- Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Japan
| | - Y Takai
- Southern Tohoku BNCT Research Center, Yatsuyamada, Koriyama, Japan
- Department of Radiation Oncology, Southern Tohoku General Hospital, Yatsuyamada, Koriyama, Japan
| | - M Aoki
- Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Japan
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De Raffele E, Mirarchi M, Cuicchi D, Lecce F, Casadei R, Ricci C, Selva S, Minni F. Simultaneous colorectal and parenchymal-sparing liver resection for advanced colorectal carcinoma with synchronous liver metastases: Between conventional and mini-invasive approaches. World J Gastroenterol 2020; 26:6529-6555. [PMID: 33268945 PMCID: PMC7673966 DOI: 10.3748/wjg.v26.i42.6529] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 10/05/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
The optimal timing of surgery in case of synchronous presentation of colorectal cancer and liver metastases is still under debate. Staged approach, with initial colorectal resection followed by liver resection (LR), or even the reverse, liver-first approach in specific situations, is traditionally preferred. Simultaneous resections, however, represent an appealing strategy, because may have perioperative risks comparable to staged resections in appropriately selected patients, while avoiding a second surgical procedure. In patients with larger or multiple synchronous presentation of colorectal cancer and liver metastases, simultaneous major hepatectomies may determine worse perioperative outcomes, so that parenchymal-sparing LR should represent the most appropriate option whenever feasible. Mini-invasive colorectal surgery has experienced rapid spread in the last decades, while laparoscopic LR has progressed much slower, and is usually reserved for limited tumours in favourable locations. Moreover, mini-invasive parenchymal-sparing LR is more complex, especially for larger or multiple tumours in difficult locations. It remains to be established if simultaneous resections are presently feasible with mini-invasive approaches or if we need further technological advances and surgical expertise, at least for more complex procedures. This review aims to critically analyze the current status and future perspectives of simultaneous resections, and the present role of the available mini-invasive techniques.
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Affiliation(s)
- Emilio De Raffele
- Division of Pancreatic Surgery, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Mariateresa Mirarchi
- Dipartimento Strutturale Chirurgico, Ospedale SS Antonio e Margherita, 15057 Tortona (AL), Italy
| | - Dajana Cuicchi
- Surgery of the Alimentary Tract, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Ferdinando Lecce
- Surgery of the Alimentary Tract, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Riccardo Casadei
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Claudio Ricci
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Saverio Selva
- Division of Pancreatic Surgery, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Francesco Minni
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
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Wang CZ, Yan GX, Xin H, Liu ZY. Oncological outcomes and predictors of radiofrequency ablation of colorectal cancer liver metastases. World J Gastrointest Oncol 2020; 12:1044-1055. [PMID: 33005297 PMCID: PMC7509997 DOI: 10.4251/wjgo.v12.i9.1044] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 06/21/2020] [Accepted: 08/16/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Surgical resection is considered the standard treatment option for long-term survival in colorectal cancer liver metastasis (CRLM) patients, but only a small number of patients are suitable for resection following diagnosis. Radiofrequency ablation (RFA) is an accepted alternative therapy for CRLM patients who are not suitable for resection. However, the relatively high rate of local tumor progression (LTP) is an obstacle to the more widespread use of RFA.
AIM To determine the oncological outcomes and predictors of RFA in CRLM patients.
METHODS A retrospective analyze was performed on the clinical data of 85 consecutive CRLM patients with a combined total of 138 liver metastases, who had received percutaneous RFA treatment at our institution from January 2013 to December 2018. Contrast-enhanced computed tomography was performed the first month after RFA to assess the technique effectiveness of the RFA and to serve as a baseline for subsequent evaluations. The Kaplan-Meier method was used to calculate overall survival (OS) and LTP-free survival (LTPFS). The log-rank test and Cox regression model were used for univariate and multivariate analyses to determine the predictors of the oncological outcomes.
RESULTS There were no RFA procedure-related deaths, and the technique effectiveness of the treatment was 89.1% (123/138). The median follow-up time was 30 mo. The LTP rate was 32.6% (45/138), and the median OS was 36 mo. The 1-, 3-, and 5-year OS rates were 90.6%, 45.6%, and 22.9%, respectively. Univariate analysis revealed that tumor size and ablative margin were the factors influencing LTPFS, while extrahepatic disease (EHD), tumor number, and tumor size were the factors influencing OS. Multivariate analysis showed that tumor size larger than 3 cm and ablative margin of 5 mm or smaller were the independent predictors of shorter LTPFS, while tumor number greater than 1, size larger than 3 cm, and presence of EHD were the independent predictors of shorter OS.
CONCLUSION RFA is a safe and effective treatment method for CRLM. Tumor size and ablative margin are the important factors affecting LTPFS. Tumor number, tumor size, and EHD are also critical factors for OS.
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Affiliation(s)
- Chuan-Zhuo Wang
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Guang-Xin Yan
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - He Xin
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Zhao-Yu Liu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
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Zimmitti G, Panettieri E, Ardito F, Rosso E, Mele C, Nuzzo G, Giuliante F. Type of response to conversion chemotherapy strongly impacts survival after hepatectomy for initially unresectable colorectal liver metastases. ANZ J Surg 2020; 90:558-563. [PMID: 31927783 DOI: 10.1111/ans.15632] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Revised: 11/27/2019] [Accepted: 11/28/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatectomy for initially unresectable colorectal liver metastases (IU-CLM) is considered at high risk due to the extensive preoperative chemotherapy (CHT) and complex surgical procedures required, and its results are questioned due to frequent and early post-operative recurrence. We aim to compare patients with initially resectable CLM (IR-CLM) and IU-CLM and identify prognostic factors among IU-CLM patients. METHODS A total of 81 patients with IU-CLM, undergoing hepatectomy following conversion CHT, were compared to 526 IR-CLM patients. Predictors of overall (OS) and disease-free survival (DFS) were identified for IU-CLM patients. RESULTS Patients resected for IU-CLM, compared to IR-CLM, had more and larger CLM and more frequently underwent prolonged CHT and major/extended hepatectomy (P < 0.001 for all comparisons). Such characteristics paralleled higher rates of overall and major (Clavien-Dindo ≥3) complications, longer median post-operative length of stay and lower 5-year survival rates (P < 0.001 for all comparisons) among IU-CLM patients compared to IR-CLM, with similar mortality (1.2% and nil for IU-CLM and IR-CLM, respectively). Among IU-CLM patients, 62 with partial response to CHT (versus tumour stability according to the Response Evaluation Criteria in Solid Tumors criteria) had better DFS (hazard ratio 2.76, P = 0.001) and OS (hazard ratio 2.83, P = 0.002), and their 5-year survival rates (DFS 19.8%, OS 46.7%) approached those of IR-CLM patients (DFS 31%, OS 59%, P > 0.05 for both comparisons). CONCLUSION Resection of IU-CLM has acceptable perioperative results. Tumour responsiveness to conversion CHT improves IU-CLM patient selection for hepatectomy.
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Affiliation(s)
- Giuseppe Zimmitti
- Department of General Surgery, Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy
| | - Elena Panettieri
- Hepatobiliary Surgery Unit, Foundation 'Policlinico Universitario A. Gemelli', Catholic University, Rome, Italy
| | - Francesco Ardito
- Hepatobiliary Surgery Unit, Foundation 'Policlinico Universitario A. Gemelli', Catholic University, Rome, Italy
| | - Edoardo Rosso
- Department of General Surgery, Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy
| | - Caterina Mele
- Hepatobiliary Surgery Unit, Foundation 'Policlinico Universitario A. Gemelli', Catholic University, Rome, Italy
| | - Gennaro Nuzzo
- Hepatobiliary Surgery Unit, Foundation 'Policlinico Universitario A. Gemelli', Catholic University, Rome, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, Foundation 'Policlinico Universitario A. Gemelli', Catholic University, Rome, Italy
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Procopio F, Viganò L, Cimino M, Donadon M, Del Fabbro D, Torzilli G. Does KRAS mutation status impact the risk of local recurrence after R1 vascular resection for colorectal liver metastasis? An observational cohort study. Eur J Surg Oncol 2019; 46:818-824. [PMID: 31839435 DOI: 10.1016/j.ejso.2019.12.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 11/26/2019] [Accepted: 12/02/2019] [Indexed: 12/18/2022] Open
Abstract
INTRODUCTION R0 margin is the standard in the surgical treatment of colorectal liver metastases (CLM). Recently R1 surgery, at least that enabling CLM vessel-detachment (R1vasc), seems comparable to R0. As a possible background of that biologic factors could play some role. Among them, KRAS has been investigated in the present study. METHODS Patients who underwent curative surgery for CLM between 2008 and 2016 were identified. R0, R1vasc and parenchymal R1 (R1par; tumor exposure once dissected from the parenchyma) resections with known KRAS status were analyzed. RESULTS Of 1000 resection areas in 340 patients, 654 (65%) R0, 98 (10%) R1vasc and 248 (25%) R1par. In mutated KRAS (mKRAS), local recurrence (LR) was similar between R0 and R1vasc (per-patient 4,8% vs. 2%, p = 0.628; per-area 2,1% vs. 1,9%, p = 0.940), while higher in R1par (per-patient 25,4% and per-area 19,5%; p < 0.001 for both). In wild-type KRAS (wtKRAS), R0 had less LR compared to R1vasc (per-patient 7,6% vs 14,6%, p = 0.335; per-area 3,1% vs 13,3%, p = 0.012) and R1par (per-patient 18,3%, p = 0.060; per-area 9,9%, p = 0.013). KRAS did not impact LR in R0 (per-patient 7,6% vs. 4,8%, p = 0.491; per-area 3,1% vs. 2,1%, p = 0.555), while wtKRAS R1par had less LR compared to mKRAS R1par (per-patient 18,3% vs 25,4%, p = 0.404; per-area 9,9% vs 19,5%, p = 0.048). Inversely, LR was increased in wtKRAS R1vasc compared to mKRAS R1vasc (per-patient 14,6% vs 2%, p = 0.043; per-area 13,3% vs 1,9%, p = 0.046). CONCLUSION KRAS status does not impact LR risk in R0 resection. Inversely, R1vasc vs R1par LR risk is reduced in mKRAS, and increased in wtKRAS. If confirmed these results are of note.
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Affiliation(s)
- Fabio Procopio
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Research Hospital, Humanitas University, Rozzano, MI, Italy
| | - Luca Viganò
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Research Hospital, Humanitas University, Rozzano, MI, Italy
| | - Matteo Cimino
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Research Hospital, Humanitas University, Rozzano, MI, Italy
| | - Matteo Donadon
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Research Hospital, Humanitas University, Rozzano, MI, Italy
| | - Daniele Del Fabbro
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Research Hospital, Humanitas University, Rozzano, MI, Italy
| | - Guido Torzilli
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Research Hospital, Humanitas University, Rozzano, MI, Italy.
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Abstract
Colorectal cancer (CRC) is one of the most common cancers in the world. About two third of patients with CRC will develop distant recurrence at some point in time. Liver is the most common site where distant metastasis takes place. While the overall survival (OS) of patients with metastatic CRC was poor about 3 decades ago, there has been tremendous improvement in this area in the recent years. With the advent of effective systemic chemotherapy and biologic agents and better understanding of the biological behaviour of the tumour, aggressive treatment strategies such as metastatectomy of the liver metastases (or lung metastases) are now acceptable. More importantly, it has transformed the way how stage IV CRCs are being managed. From predominantly palliative as the primary aim, a comprehensive multidisciplinary approach is now the mainstay of treatment with very successful outcomes. Combination of systemic therapies with liver resection has been shown to be effective in providing promising survival benefits. In addition, other adjunctive modalities in targeting the liver metastases such as ablation, combining resection and ablation, transarterial chemoembolization, stereotactic body radiotherapy (SBRT), hepatic artery perfusion, etc. have also been demonstrated variable outcome in treating colorectal liver metastasis (CRLM). Very recently, transplant oncologists have also explored using liver transplantation as a treatment modality for unresectable CRLM, which has demonstrated very good long-term survival in well selected cases. The new paradigm in the treatment of metastatic CRC has dawned.
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Affiliation(s)
- Alfred Wei Chieh Kow
- Division of Hepatopancreaticobiliary Surgery and Liver Transplantation, Department of Surgery, National University Health System, Singapore, Singapore.,Department of Surgery, National University of Singapore, Singapore, Singapore
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20
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Kim YI, Park IJ, Kim JE, Kim SY, Park JH, Lee JH, Ha TY, Hong YS, Kim SY, Kim TW, Lim SB, Yu CS, Kim JC. Hepatic resection after neoadjuvant chemotherapy for patients with liver metastases from colorectal cancer: need for cautious planning. Ann Surg Treat Res 2019; 97:245-253. [PMID: 31742209 PMCID: PMC6848007 DOI: 10.4174/astr.2019.97.5.245] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/03/2019] [Accepted: 10/05/2019] [Indexed: 11/30/2022] Open
Abstract
Purpose Current neoadjuvant chemotherapy (NAC) may enable therapies such as surgical resection and local ablation of metastases in patients with colorectal liver metastasis (CLM). We evaluated outcomes in CLM patients who underwent resection and/or local treatment after NAC and identified prognostic factors for oncologic outcomes. Methods Patients who received NAC followed by resection and/or local treatment of hepatic metastasis from 2013 to 2015 were included. Treatment and tumor-related variables were tabulated. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox regression analysis was used to identify factors associated with RFS and OS. Results Sixty-eight patients received NAC followed by resection and/or local treatment of hepatic metastases. Targeted therapy was administered in 50% of the patients. RFS was 35.8% at 1 year and 19.4% at 2 years postoperatively. OS was 95.6% at 1 year and 88.2% at 2 years postoperatively. In the multivariable analysis, R1 resection margin (hazard ratio [HR], 3.95; P = 0.008) of the liver metastases and ypN1/ypN2 (HR, 2.356 and 1.983, respectively; P = 0.041) were associated with poor RFS. Both factors were also significantly related to OS. Conclusion Resection margin of the metastatic tumor and ypN status are the only relevant factors for RFS and OS in CLM patients treated with NAC. Despite early and high rates of recurrence, CLM patients treated with NAC who undergo resection and/or local treatment have acceptable OS. Multidisciplinary review of candidates for surgery and cautious planning are crucial for achieving optimal outcomes.
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Affiliation(s)
- Young Il Kim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In Ja Park
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Eun Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - So Yeon Kim
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin-Hong Park
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae Yong Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Sang Hong
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sun Young Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae Won Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seok-Byung Lim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chang Sik Yu
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Cheon Kim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Diaz-Nieto R, Vyas S, Sharma D, Malik H, Fenwick S, Poston G. Robotic Surgery for Malignant Liver Disease: a Systematic Review of Oncological and Surgical Outcomes. Indian J Surg Oncol 2019; 11:565-572. [PMID: 33281400 DOI: 10.1007/s13193-019-00945-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Accepted: 05/21/2019] [Indexed: 12/23/2022] Open
Abstract
Robot-assisted laparoscopic surgery is yet another modification of minimally invasive liver surgery. It is described as feasible and safe from the surgical point of view; however, oncological outcomes need to be adequately analysed to justify the use of this technique when resecting malignant liver tumours. We reviewed existing English medical literature on robot-assisted laparoscopic liver surgery. We analysed surgical outcomes and oncological outcomes. We analysed operative parameters including operative time, type of hepatectomy, blood loss, conversion rate, morbidity and mortality rates and length of stay. We also analysed oncological outcomes including completeness of resection (R status), recurrence, survival and follow-up data. A total of 582 patients undergoing robot-assisted laparoscopic liver surgery were analysed from 17 eligible publications. Only 5 publications reported survival data. The overall morbidity was 19% with 0.2% reported mortality. R0 resection was achieved in 96% of patients. Robotic liver surgery is feasible and safe with acceptable morbidity and oncological outcomes including resection margins. However, well-designed trials are required to provide evidence in terms of survival and disease-free intervals when performed for malignancy.
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Affiliation(s)
- Rafael Diaz-Nieto
- Hepatobiliary Surgery Unit, Aintree University Hospital, Longmoor Ln, L9 7AL, Liverpool, UK
| | - Soumil Vyas
- Division of HPB surgery, Surgical Gastroenterology and Surgical Oncology Sir H N Reliance Foundation Hospital, Mumbai, India
| | - Dinesh Sharma
- HPB/Liver Transplant Surgery Unit, Royal Free Hospital, London, UK
| | - Hassan Malik
- Hepatobiliary Surgery Unit, Aintree University Hospital, Longmoor Ln, L9 7AL, Liverpool, UK
| | - Stephen Fenwick
- Hepatobiliary Surgery Unit, Aintree University Hospital, Longmoor Ln, L9 7AL, Liverpool, UK
| | - Graeme Poston
- Hepatobiliary Surgery Unit, Aintree University Hospital, Longmoor Ln, L9 7AL, Liverpool, UK
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22
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Kawaguchi Y, Lillemoe HA, Panettieri E, Chun YS, Tzeng CWD, Aloia TA, Kopetz S, Vauthey JN. Conditional Recurrence-Free Survival after Resection of Colorectal Liver Metastases: Persistent Deleterious Association with RAS and TP53 Co-Mutation. J Am Coll Surg 2019; 229:286-294.e1. [PMID: 31054911 DOI: 10.1016/j.jamcollsurg.2019.04.027] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 03/19/2019] [Accepted: 04/22/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND Conditional recurrence-free survival (RFS) probability, that is, the probability of remaining recurrence-free after a given interval without recurrence, has not been reported after resection of colorectal liver metastases (CLMs). We aimed to estimate conditional RFS and identify factors affecting conditional RFS. STUDY DESIGN Patients undergoing initial resection of CLMs during 2000-2016 with mutation data were identified. The RFS and risk factors for recurrence were evaluated at the time of resection for all patients and at 1 year and 2 years after resection for patients who remained recurrence-free. RESULTS Of 2,118 patients, 485 met the inclusion criteria, of which 225 were recurrence-free at 1 year and 109 were recurrence-free at 2 years. The 5-year RFS rates were 17.3%, 36.8%, and 70.7% for all patients and the 1-year and 2-year recurrence-free groups, respectively, when assessed from the time of initial CLM resection. RAS/TP53 co-mutation was the only factor independently associated with increased risk of recurrence for all groups (all patients, hazard ratio 1.47; 95% CI 1.19 to 1.82; p < 0.001; 1-year recurrence-free, hazard ratio 1.69; 95% CI 1.17 to 2.43; p = 0.005; 2-year recurrence-free, hazard ratio 2.41; 95% CI 1.12 to 5.17; p = 0.024). T category, extrahepatic disease, multiple CLMs, largest CLM diameter, and surgical margin status were risk factors for recurrence in all patients and/or the 1-year recurrence-free group, but not the 2-year recurrence-free group. Median RFS was lower for patients with RAS/TP53 co-mutation than for those with RAS/TP53 wild-type in the 1-year (1.5 vs 2.8 years; p = 0.006) and 2-year recurrence-free groups (3.0 vs 5.9 years; p = 0.024). CONCLUSIONS Conditional RFS is useful for updating prognosis after a given time interval without recurrence after CLM resection. Importantly, RAS/TP53 co-mutation has a persistent deleterious association with recurrence.
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Affiliation(s)
- Yoshikuni Kawaguchi
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Heather A Lillemoe
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Elena Panettieri
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
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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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24
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Ardito F, Panettieri E, Vellone M, Ferrucci M, Coppola A, Silvestrini N, Arena V, Adducci E, Capelli G, Vecchio FM, Giovannini I, Nuzzo G, Giuliante F. The impact of R1 resection for colorectal liver metastases on local recurrence and overall survival in the era of modern chemotherapy: An analysis of 1,428 resection areas. Surgery 2018; 165:712-720. [PMID: 30482518 DOI: 10.1016/j.surg.2018.09.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 09/09/2018] [Accepted: 09/19/2018] [Indexed: 01/03/2023]
Abstract
BACKGROUND It is still unclear whether a positive surgical margin after resection of colorectal liver metastases remains a poor prognostic factor in the era of modern perioperative chemotherapy. The aim of this study was to evaluate whether preoperative chemotherapy has an impact on reducing local recurrence after R1 resection, and the impact of local recurrence on overall survival. METHODS Between 2000 and 2014, a total of 421 patients underwent resection for colorectal liver metastases at our unit after preoperative chemotherapy. The overall number of analyzed resection areas was 1,428. RESULTS The local recurrence rate was 12.8%, significantly higher after R1 resection than after R0 (24.5% vs 8.7%; P < .001). These results were also confirmed in patients with response to preoperative chemotherapy (23.1% after R1 vs 11.2% after R0; P < .001). At multivariate analysis, R1 resection was the only independent risk factor for local recurrence (P < .001). At the analysis of the 1,428 resection areas, local recurrence significantly decreased according to the increase of the surgical margin width (from 19.1% in 0 mm margin to 2.4% in ≥10 mm). At multivariable logistic regression analysis for overall survival, the presence of local recurrence showed a significant negative impact on 5-year overall survival (P < .001). CONCLUSION Surgical margin recurrence after modern preoperative chemotherapy for colorectal liver metastases was still significantly higher after R1 resection than it was after R0 resection. Local recurrence showed a negative prognostic impact on overall survival. R0 resection should be recommended whenever technically achievable, as well as in patients treated by modern preoperative chemotherapy.
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Affiliation(s)
- Francesco Ardito
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy.
| | - Elena Panettieri
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Maria Vellone
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Massimo Ferrucci
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Alessandro Coppola
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Nicola Silvestrini
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Vincenzo Arena
- Department of Pathology, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Enrica Adducci
- Department of Anesthesiology and Intensive Care, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | | | - Fabio M Vecchio
- Department of Pathology, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Ivo Giovannini
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Gennaro Nuzzo
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
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De Raffele E, Mirarchi M, Cuicchi D, Lecce F, Ricci C, Casadei R, Cola B, Minni F. Simultaneous curative resection of double colorectal carcinoma with synchronous bilobar liver metastases. World J Gastrointest Oncol 2018; 10:293-316. [PMID: 30364774 PMCID: PMC6198303 DOI: 10.4251/wjgo.v10.i10.293] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 07/28/2018] [Accepted: 08/21/2018] [Indexed: 02/05/2023] Open
Abstract
Synchronous colorectal carcinoma (SCRC) indicates more than one primary colorectal carcinoma (CRC) discovered at the time of initial presentation, accounts for 3.1%-3.9% of CRC, and may occur either in the same or in different colorectal segments. The accurate preoperative diagnosis of SCRC is difficult and diagnostic failures may lead to inappropriate treatment and poorer prognosis. SCRC requires colorectal resections tailored to individual patients, based on the number, location, and stage of the tumours, from conventional or extended hemicolectomies to total colectomy or proctocolectomy, when established predisposing conditions exist. The overall perioperative risks of surgery for SCRC seem to be higher than for solitary CRC. Simultaneous colorectal and liver resection represents an appealing surgical strategy in selected patients with CRC and synchronous liver metastases (CRLM), even though the cumulative risks of the two procedures need to be adequately evaluated. Simultaneous resections have the noticeable advantage of avoiding a second laparotomy, give the opportunity of an earlier initiation of adjuvant therapy, and may significantly reduce the hospital costs. Because an increasing number of recent studies have shown good results, with morbidity, perioperative hospitalization, and mortality rates comparable to staged resections, simultaneous procedures can be selectively proposed even in case of complex colorectal resections, including those for SCRC and rectal cancer. However, in patients with multiple bilobar CRLM, major hepatectomies performed simultaneously with colorectal resection have been associated with significant perioperative risks. Conservative or parenchymal-sparing hepatectomies reduce the extent of hepatectomy while preserving oncological radicality, and may represent the best option for selected patients with multiple CRLM involving both liver lobes. Parenchymal-sparing liver resection, instead of major or two-stage hepatectomy for bilobar disease, seemingly reduces the overall operative risk of candidates to simultaneous colorectal and liver resection, and may represent the most appropriate surgical strategy whenever possible, also for patients with advanced SCRC and multiple bilobar liver metastases.
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Affiliation(s)
- Emilio De Raffele
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Mariateresa Mirarchi
- U.O. di Chirurgia Generale, Dipartimento Strutturale Chirurgico, Ospedale “Antonio e Margherita, ” Tortona (AL) 15057, Italy
| | - Dajana Cuicchi
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Ferdinando Lecce
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Claudio Ricci
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Riccardo Casadei
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Bruno Cola
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, Policlinico S.Orsola-Malpighi, University of Bologna, Bologna 40138, Italy
| | - Francesco Minni
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
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26
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Viganò L, Costa G, Cimino MM, Procopio F, Donadon M, Del Fabbro D, Belghiti J, Kokudo N, Makuuchi M, Vauthey JN, Torzilli G. R1 Resection for Colorectal Liver Metastases: a Survey Questioning Surgeons about Its Incidence, Clinical Impact, and Management. J Gastrointest Surg 2018; 22:1752-1763. [PMID: 29948554 DOI: 10.1007/s11605-018-3820-z] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 05/15/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND A ≥ 1-mm margin is standard for resection of colorectal liver metastases (CLM). However, R1 resection is not rare (10-30%), and chemotherapy could mitigate its impact. The possibility of detaching CLM from vessels (R1 vascular margin) has been described. A reappraisal of R1 resection is needed. METHODS A 19-question survey regarding R1 resection for CLM was sent to hepatobiliary surgeons worldwide. Seven clinical cases were included. RESULTS In total, 276 surgeons from 52 countries completed the survey. Ninety percent reported a negative impact of R1 resection (74% local recurrence, 31% hepatic recurrence, and 36% survival), but 50% considered it sometimes required for resectability. Ninety-one percent of responders suggested that the impact of R1 resection is modulated by the response to chemotherapy and/or CLM characteristics. Half considered the risk of R1 resection to be an indication for preoperative chemotherapy in patients who otherwise underwent upfront resection, and 40% modified the chemotherapy regimen when the tumor response did not guarantee R0 resection. Nevertheless, 80% scheduled R1 resection for multiple bilobar CLM that responded to chemotherapy. Forty-five percent considered the vascular margin equivalent to R0 resection. However, for lesions in contact with the right hepatic vein, right hepatectomy remained the standard. Detachment from the vein was rarely considered (10%), but 27% considered detachment in the presence of multiple bilobar CLM. CONCLUSIONS A negative margin is still standard for CLM, but R1 resection is no longer just a technical error. R1 resection should be part of the modern multidisciplinary, aggressive approach to CLM.
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Affiliation(s)
- Luca Viganò
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
| | - Guido Costa
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Matteo Maria Cimino
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Fabio Procopio
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Matteo Donadon
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
| | - Daniele Del Fabbro
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Jacques Belghiti
- Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital Beaujon, Assistance Publique des Hôpitaux de Paris, Clichy, France
| | - Norihiro Kokudo
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masatoshi Makuuchi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, Hepato-Pancreato-Biliary Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. .,Department of Biomedical Sciences, Humanitas University, Rozzano, Italy.
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The Prognostic Value of Varying Definitions of Positive Resection Margin in Patients with Colorectal Cancer Liver Metastases. J Gastrointest Surg 2018; 22:1350-1357. [PMID: 29633114 DOI: 10.1007/s11605-018-3748-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 03/15/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Varying definitions of resection margin clearance are currently employed among patients with colorectal cancer liver metastases (CRLM). Specifically, a microscopically positive margin (R1) has alternatively been equated with an involved margin (margin width = 0 mm) or a margin width < 1 mm. Consequently, patients with a margin width of 0-1 mm (sub-mm) are inconsistently classified in either the R0 or R1 categories, thus obscuring the prognostic implications of sub-mm margins. METHODS Six hundred thirty-three patients who underwent resection of CRLM were identified. Both R1 definitions were alternatively employed and multivariable analysis was used to determine the predictive power of each definition, as well as the prognostic implications of a sub-mm margin. RESULTS Five hundred thirty-nine (85.2%) patients had a margin width ≥ 1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0 mm). A margin width ≥ 1 mm was associated with improved survival vs. a sub-mm margin (65 vs. 36 months; P = 0.03) or an involved margin (65 vs. 33 months; P < 0.001). No significant difference in survival was detected between patients with involved vs. sub-mm margins (P = 0.31). A sub-mm margin and an involved margin were both independent predictors of worse OS (HR 1.66, 1.04-2.67; P = 0.04, and HR 2.14, 1.46-3.16; P < 0.001, respectively) in multivariable analysis. Importantly, after combining the two definitions, patients with either an involved margin or a sub-mm margin were associated with worse OS in multivariable analysis (HR 1.94, 1.41-2.65; P < 0.001). CONCLUSIONS Patients with involved or sub-mm margins demonstrated a similar inferior OS vs. patients with a margin width > 1 mm. Consequently, a uniform definition of R1 as a margin width < 1 mm should perhaps be employed by future studies.
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Determination of the surgical margin in laparoscopic liver resections using infrared indocyanine green fluorescence. Langenbecks Arch Surg 2018; 403:671-680. [DOI: 10.1007/s00423-018-1685-y] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 05/29/2018] [Indexed: 01/06/2023]
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Impact of Surgical Margin Width on Recurrence and Overall Survival Following R0 Hepatic Resection of Colorectal Metastases. Ann Surg 2018; 267:1047-1055. [DOI: 10.1097/sla.0000000000002552] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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30
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Memeo R, de Blasi V, Adam R, Goéré D, Piardi T, Lermite E, Turrini O, Navarro F, de'Angelis N, Cunha AS, Pessaux P. Margin Status is Still an Important Prognostic Factor in Hepatectomies for Colorectal Liver Metastases: A Propensity Score Matching Analysis. World J Surg 2018; 42:892-901. [PMID: 28929341 DOI: 10.1007/s00268-017-4229-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The width of resection margin is still a matter of debate in case of colorectal liver metastasis resection. The aim of this study was to determine the risk factors for R1 resection. Once risk factors had been identified, patients were matched according to Fong's prognostic criteria, in order to evaluate whether R1 resection still remained a negative prognostic factor impacting overall and disease-free survival. METHODS A total of 1784 hepatectomies were analyzed from a multicentric retrospective cohort of hepatectomies. Patients were compared before and after a 1:1 propensity score analysis in order to compare R0 versus R1 resections according to Fong criteria. RESULTS Primary tumor nodes found positive after colorectal resection (RR = 1.20, p = 0.02), operative time (> 240 min) (RR = 1.26, p = 0.05), synchronous liver metastasis (RR = 1.27, p = 0.02), pedicle clamping (> 40 min) (RR = 1.52, p = 0.001), lesion size larger than 50 mm (RR = 1.54, p = 0.001), rehepatectomy (RR = 1.68, p = 0.001), more than 3 lesions (RR = 1.69, p = 0.0001), and bilateral lesions (RR = 1.74, p = 0.0001) were identified as risk factors in multivariate analysis. After a 1:1 PSM according to Fong criteria, R1 resection still remained a negative prognostic factor impacting overall and disease-free survival, with 1-, 3-, 5-year OS at 94, 81, and 70% in R0 and 92, 75, and 58% in R1, respectively, (p = 0.008), and disease-free survival (DFS) with 1-, 3-, 5-year survival at 64, 41, and 28% in R0 versus 51, 28, and 18% in R1 (p = 0.0002), respectively. CONCLUSION Even after using PSM as an oncological prognostic criterion, R1 resection still impacts overall and disease-free survival negatively.
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Affiliation(s)
- Riccardo Memeo
- Institut Hospitalo-Universitaire (IHU), Institute for Minimally Invasive Hybrid Image-Guided Surgery, Université de Strasbourg, Strasbourg, France
- Institut de Recherche Contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France
- General, Digestive, and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France
| | - Vito de Blasi
- Institut Hospitalo-Universitaire (IHU), Institute for Minimally Invasive Hybrid Image-Guided Surgery, Université de Strasbourg, Strasbourg, France
- Institut de Recherche Contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France
- General, Digestive, and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France
| | - Rene Adam
- Department of Surgery, Hôpital Paul Brousse, Villejuif, France
| | - Diane Goéré
- Department of Surgery, Institut Gustave Roussy, Villejuif, France
| | - Tullio Piardi
- Department of Surgery, Hôpital Robert Debré, Reims, France
| | | | - Olivier Turrini
- Department of Surgery, Institut Paoli-Calmettes, Marseilles, France
| | - Francis Navarro
- Department of Digestive Surgery, Université de Montpellier, Hôpital Saint-Eloi, Montpellier, France
| | | | | | - Patrick Pessaux
- Institut Hospitalo-Universitaire (IHU), Institute for Minimally Invasive Hybrid Image-Guided Surgery, Université de Strasbourg, Strasbourg, France.
- Institut de Recherche Contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France.
- General, Digestive, and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France.
- HepatoBiliary and Pancreatic Surgery Department, 1, place de l'Hôpital, 67091, Strasbourg, France.
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Swaid F, Tsung A. Current Management of Liver Metastasis From Colorectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2018. [DOI: 10.1007/s11888-018-0397-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Nishioka Y, Shindoh J, Yoshioka R, Gonoi W, Abe H, Okura N, Yoshida S, Sakamoto Y, Hasegawa K, Fukayama M, Kokudo N. Clinical Impact of Preoperative Chemotherapy on Microscopic Cancer Spread Surrounding Colorectal Liver Metastases. Ann Surg Oncol 2017; 24:2326-2333. [PMID: 28349338 DOI: 10.1245/s10434-017-5845-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND A potentially favorable effect of chemotherapy on the incidence of micrometastases has been reported in patients with colorectal liver metastases (CLMs); however, the actual influence of chemotherapy on the distribution of micrometastases and surgical curability remains unclear. METHOD The clinical impact of preoperative chemotherapy on the incidence and distribution of micrometastases was assessed in 191 patients with 357 CLM nodules. Potential radiologic measures for predicting the extent of microscopic cancer spread and surgical curability were then sought among the size-based and non-size-based radiologic response criteria. RESULTS Multivariate analysis estimated a reduced incidence of micrometastases in patients receiving preoperative chemotherapy (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.26-0.76, p = 0.003). Furthermore, the addition of biologic agents to the preoperative chemotherapy regimen was correlated with a reduced incidence of microscopic cancer spread beyond a width of 1 mm from the margin of the main tumor (OR 0.28, 95% CI 0.11-0.74, p = 0.010 for bevacizumab; and OR 0.29, 95% CI 0.09-0.99, p = 0.048 for anti-epidermal growth factor receptor antibody). Receiver operating characteristic analyses revealed that the computed tomography (CT) morphologic response showed a moderate predictive power for the distribution of micrometastases, with an area under the curve of 0.687, while size-based response criteria were not reliable for estimating the extent of microscopic cancer spread. CONCLUSION Notwithstanding the potential selection of patients after preoperative chemotherapy, the incidence and distribution of micrometastases may be reduced by preoperative chemotherapy. CT morphologic response may be a reliable predictor of both the degree of microscopic cancer spread and the curability of surgery.
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Affiliation(s)
- Yujiro Nishioka
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Junichi Shindoh
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan.
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | - Ryuji Yoshioka
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Wataru Gonoi
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroyuki Abe
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Naoki Okura
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shuntaro Yoshida
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshihiro Sakamoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masashi Fukayama
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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Dulundu E, Attaallah W, Tilki M, Yegen C, Coskun S, Coskun M, Erdim A, Tanrikulu E, Yardimci S, Gunal O. Simultaneous resection for colorectal cancer with synchronous liver metastases is a safe procedure: Outcomes at a single center in Turkey. Biosci Trends 2017; 11:235-242. [PMID: 28216517 DOI: 10.5582/bst.2017.01019] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The optimal surgical strategy for treating colorectal cancer with synchronous liver metastases is subject to debate. The current study sought to evaluate the outcomes of simultaneous colorectal cancer and liver metastases resection in a single center. Prospectively collected data on all patients with synchronous colorectal liver metastases who underwent simultaneous resection with curative intent were analyzed retrospectively. Patient outcomes were compared depending on the primary tumor location and type of liver resection (major or minor). Between January 2005 and August 2016, 108 patients underwent simultaneous resection of primary colorectal cancer and liver metastases. The tumor was localized to the right side of the colon in 24 patients (22%), to the left side in 40 (37%), and to the rectum in 44 (41%). Perioperative mortality occurred in 3 patients (3%). Postoperative complications were noted in 32 patients (30%), and most of these complications (75%) were grade 1 to 3 according to the Clavien-Dindo classification. Neither perioperative mortality nor the rate of postoperative complications after simultaneous resection differed among patients with cancer of the right side of the colon, those with cancer of the left side of the colon, and those with rectal cancer (4%, 2.5%, and 2%, respectively, p = 0.89) and (17%, 33%, and 34%, respectively; p = 0.29)]. The 5-year overall survival of the entire sample was 54% and the 3-year overall survival was 67 %. In conclusion, simultaneous resection for primary colorectal cancer and liver metastases is a safe procedure and can be performed without excess morbidity in carefully selected patients regardless of the location of the primary tumor and type of hepatectomy.
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Affiliation(s)
- Ender Dulundu
- Department of General Surgery, Marmara University Pendik Teaching and Research Hospital
| | - Wafi Attaallah
- Department of General Surgery, Marmara University Pendik Teaching and Research Hospital
| | - Metin Tilki
- Department of General Surgery, Marmara University Pendik Teaching and Research Hospital
| | - Cumhur Yegen
- Department of General Surgery, Marmara University Pendik Teaching and Research Hospital
| | - Safak Coskun
- Department of General Surgery, Marmara University Pendik Teaching and Research Hospital
| | - Mumin Coskun
- Department of General Surgery, Marmara University Pendik Teaching and Research Hospital
| | - Aylin Erdim
- Department of General Surgery, Marmara University Pendik Teaching and Research Hospital
| | - Eda Tanrikulu
- Department of General Surgery, Marmara University Pendik Teaching and Research Hospital
| | - Samet Yardimci
- Department of General Surgery, Marmara University Pendik Teaching and Research Hospital
| | - Omer Gunal
- Department of General Surgery, Marmara University Pendik Teaching and Research Hospital
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Laurent C, Adam JP, Denost Q, Smith D, Saric J, Chiche L. Significance of R1 Resection for Advanced Colorectal Liver Metastases in the Era of Modern Effective Chemotherapy. World J Surg 2016; 40:1191-9. [PMID: 26757718 DOI: 10.1007/s00268-016-3404-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The prognosis impact of positive margins after resection of colorectal liver metastases (CLM) in patients treated with modern effective chemotherapy has not been elucidated. The objective was to compare oncologic outcomes after R0 and R1 resections in the era of modern effective chemotherapy. METHODS Between 1999 and 2010, all consecutive patients undergoing liver resection for CLM were analyzed retrospectively. Patients with extrahepatic metastases, macroscopic residual tumor, treated with combined radiofrequency, or not treated with chemotherapy were excluded. Survival and recurrence after R0 (tumor-free margin >0 mm) and R1 resections were analyzed. RESULTS Among 466 patients undergoing hepatectomy for CLM, 191 were eligible. Of them, 164 (86 %) received preoperative chemotherapy and 105 (55 %) received postoperative chemotherapy. R1 resection (10 %) was comparable in patients treated or not by preoperative chemotherapy. R1 status was associated with more intrahepatic recurrences. Overall survival (OS) (44 vs. 61 %; p = 0.047) and disease-free survival (DFS) (8 vs. 26 %; p = 0.082) were lower in patients after R1 compared to R0 resection (32 months of median follow-up). Preoperative chemotherapy and major hepatectomy were prognostic factors of survival, whereas postoperative chemotherapy was a protective factor from recurrences. In patients treated with preoperative chemotherapy, OS and DFS were similar between R1 and R0 resections (40 vs. 55 %, p = 0.104 and 9 vs. 22 %, p = 0.174, respectively). CONCLUSION In the era of modern effective chemotherapy, R1 resection leads to more intrahepatic recurrences but did not affect OS in selected patient responders to neoadjuvant chemotherapy. Postoperative chemotherapy protects from recurrences whatever the margin resection status.
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Affiliation(s)
- Christophe Laurent
- University of Bordeaux Segalen, 33076, Bordeaux, France. .,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France.
| | - Jean-Philippe Adam
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Quentin Denost
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Denis Smith
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Digestive Oncology, CHU Bordeaux, Saint André Hospital, 33075, Bordeaux, France
| | - Jean Saric
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Laurence Chiche
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Haut-Lévèque Hospital, 33600, Pessac, France
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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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Margonis GA, Sasaki K, Andreatos N, Kim Y, Merath K, Wagner D, Wilson A, Buettner S, Amini N, Antoniou E, Pawlik TM. KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases. Ann Surg Oncol 2016; 24:264-271. [PMID: 27696170 DOI: 10.1245/s10434-016-5609-1] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2016] [Indexed: 12/30/2022]
Abstract
BACKGROUND The optimal tumor-free margin width remains controversial and may be inappropriate to investigate without considering differences in the underlying tumor biology. METHODS R1 resection was defined as margin clearance less than 1 mm. R0 resection was further divided into 3 groups: 1-4, 5-9, and ≥10 mm. The impact of margin width on overall survival (OS) relative to KRAS status [wild type (wtKRAS) vs. mutated (mutKRAS)] was assessed. RESULTS A total of 411 patients met inclusion criteria. Median patient age was 58 years (interquartile range, 49.7-66.7); most patients were male (n = 250; 60.8 %). With a median follow-up of 28.3 months, median and 5-year OS were 69.8 months and 55.1 %. Among patients with wtKRAS tumors, although margin clearance of 1-4 mm or more was associated with improved OS compared to R1 (all P < 0.05), no difference in OS was observed when comparing margin clearance of 1-4 mm to the 5-9 mm and the ≥10 mm groups (all P > 0.05). In contrast, among patients with mutKRAS tumors, all three groups of margin clearance (1-4, 5-9, and ≥10 mm) fared no better in terms of 5-year survival compared to R1 resection (all P > 0.05). CONCLUSIONS While a 1-4 mm margin clearance in patients with wtKRAS tumors was associated with improved survival, wider resection width did not confer an additional survival benefit. In contrast, margin status-including a 1 cm margin-did not improve survival among patients with mutKRAS tumors.
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Affiliation(s)
- Georgios A Margonis
- Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.,Second Department of Propaedeutic Surgery, Laiko Hospital, University of Athens, Athens, Greece
| | - Kazunari Sasaki
- Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA
| | | | - Yuhree Kim
- Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA
| | - Katiuscha Merath
- Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA
| | - Doris Wagner
- Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA
| | - Ana Wilson
- Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA
| | - Stefan Buettner
- Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA
| | - Neda Amini
- Department of Surgery, The Johns Hopkins Hospital, 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 Hospital, Baltimore, MD, USA.
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Lee SH, Kim SH, Lim JH, Kim SH, Lee JG, Kim DJ, Choi GH, Choi JS, Kim KS. Aggressive surgical resection for concomitant liver and lung metastasis in colorectal cancer. KOREAN JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 2016; 20:110-5. [PMID: 27621747 PMCID: PMC5018949 DOI: 10.14701/kjhbps.2016.20.3.110] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 04/14/2016] [Accepted: 05/10/2016] [Indexed: 01/17/2023]
Abstract
Backgrounds/Aims Aggressive surgical resection for hepatic metastasis is validated, however, concomitant liver and lung metastasis in colorectal cancer patients is equivocal. Methods Clinicopathologic data from January 2008 through December 2012 were retrospectively reviewed in 234 patients with colorectal cancer with concomitant liver and lung metastasis. Clinicopathologic factors and survival data were analyzed. Results Of the 234 patients, 129 (55.1%) had synchronous concomitant liver and lung metastasis from colorectal cancer and 36 (15.4%) had metachronous metastasis. Surgical resection was performed in 33 patients (25.6%) with synchronous and 6 (16.7%) with metachronous metastasis. Surgical resection showed better overall survival in both groups (synchronous, p=0.001; metachronous, p=0.028). In the synchronous metastatic group, complete resection of both liver and lung metastatic lesions had better survival outcomes than incomplete resection of two metastatic lesions (p=0.037). The primary site of colorectal cancer and complete resection were significant prognostic factors (p=0.06 and p=0.003, respectively). Conclusions Surgical resection for hepatic and pulmonary metastasis in colorectal cancer can improve complete remission and survival rate in resectable cases. Colorectal cancer with concomitant liver and lung metastasis is not a poor prognostic factor or a contraindication for surgical treatments, hence, an aggressive surgical approach may be recommended in well-selected resectable cases.
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Affiliation(s)
- Sung Hwan Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Hyun Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Hong Lim
- Department of Surgery, Yongin Severance Hospital, Yongin, Korea
| | - Sung Hoon Kim
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jin Gu Lee
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Dae Joon Kim
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Gi Hong Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Sub Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Kyung Sik Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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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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Viganò L, Procopio F, Cimino MM, Donadon M, Gatti A, Costa G, Del Fabbro D, Torzilli G. Is Tumor Detachment from Vascular Structures Equivalent to R0 Resection in Surgery for Colorectal Liver Metastases? An Observational Cohort. Ann Surg Oncol 2016; 23:1352-1360. [DOI: 10.1245/s10434-015-5009-y] [Citation(s) in RCA: 168] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Shady W, Petre EN, Gonen M, Erinjeri JP, Brown KT, Covey AM, Alago W, Durack JC, Maybody M, Brody LA, Siegelbaum RH, D’Angelica MI, Jarnagin WR, Solomon SB, Kemeny NE, Sofocleous CT. Percutaneous Radiofrequency Ablation of Colorectal Cancer Liver Metastases: Factors Affecting Outcomes--A 10-year Experience at a Single Center. Radiology 2016; 278:601-11. [PMID: 26267832 PMCID: PMC4734163 DOI: 10.1148/radiol.2015142489] [Citation(s) in RCA: 279] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE To identify predictors of oncologic outcomes after percutaneous radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLMs) and to describe and evaluate a modified clinical risk score (CRS) adapted for ablation as a patient stratification and prognostic tool. MATERIALS AND METHODS This study consisted of a HIPAA-compliant institutional review board-approved retrospective review of data in 162 patients with 233 CLMs treated with percutaneous RFA between December 2002 and December 2012. Contrast material-enhanced CT was used to assess technique effectiveness 4-8 weeks after RFA. Patients were followed up with contrast-enhanced CT every 2-4 months. Overall survival (OS) and local tumor progression-free survival (LTPFS) were calculated from the time of RFA by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariate and multivariate analysis to identify predictors of outcomes. RESULTS Technique effectiveness was 94% (218 of 233). Median LTPFS was 26 months. At univariate analysis, predictors of shorter LTPFS were tumor size greater than 3 cm (P < .001), ablation margin size of 5 mm or less (P < .001), high modified CRS (P = .009), male sex (P = .03), and no history of prior hepatectomy (P = .04) or hepatic arterial infusion chemotherapy (P = .01). At multivariate analysis, only tumor size greater than 3 cm (P = .01) and margin size of 5 mm or less (P < .001) were independent predictors of shorter LTPFS. Median and 5-year OS were 36 months and 31%. At univariate analysis, predictors of shorter OS were tumor size larger than 3 cm (P = .005), carcinoembryonic antigen level greater than 30 ng/mL (P = .003), high modified CRS (P = .02), and extrahepatic disease (EHD) (P < .001). At multivariate analysis, tumor size greater than 3 cm (P = .006) and more than one site of EHD (P < .001) were independent predictors of shorter OS. CONCLUSION Tumor size of less than 3 cm and ablation margins greater than 5 mm are essential for satisfactory local tumor control. Tumor size of more than 3 cm and the presence of more than one site of EHD are associated with shorter OS.
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Affiliation(s)
- Waleed Shady
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Elena N. Petre
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Mithat Gonen
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Joseph P. Erinjeri
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Karen T. Brown
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Anne M. Covey
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - William Alago
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Jeremy C. Durack
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Majid Maybody
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Lynn A. Brody
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Robert H. Siegelbaum
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Michael I. D’Angelica
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - William R. Jarnagin
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Stephen B. Solomon
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Nancy E. Kemeny
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
| | - Constantinos T. Sofocleous
- From the Section of Interventional Radiology, Department of Radiology (W.S., E.N.P., J.P.E., K.T.B., A.M.C., W.A., J.C.D., M.M., L.A.B., R.H.S., S.B.S., C.T.S.), Department of Epidemiology and Biostatistics (M.G.), Department of Surgery (M.I.D., W.R.J.), and Department of Medicine (N.E.K.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-118, New York, NY 10065
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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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Tomassini F, Bonadio I, Smeets P, De Paepe K, Berardi G, Ferdinande L, Laurent S, Libbrecht LJ, Geboes K, Troisi RI. Safety analysis of the oncological outcome after vein-preserving surgery for colorectal liver metastases detached from the main hepatic veins. Langenbecks Arch Surg 2015; 400:683-691. [PMID: 26265280 DOI: 10.1007/s00423-015-1332-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2014] [Accepted: 08/02/2015] [Indexed: 12/14/2022]
Abstract
PURPOSE Recent studies have reported that margins alone do not predict survival in patients with a positive chemotherapy response. The aim of this retrospective study is to analyze the surgical and oncological outcomes of patients who underwent chemotherapy and liver resection for colorectal liver metastases (CRLM) with lesions detached from the main hepatic veins, comparing the vein-preserving (VP) approach with traditional surgery. METHODS Fourteen patients undergoing VP surgery from January 2006 to January 2013 were matched in a 1:2 ratio with a control group (CG) of 28 patients undergoing traditional resection. RESULTS The median follow-up was 43 months. The radiological response was classified as 'partial response' in eight VP patients and 11 controls (57 vs. 39 %, p = 0.249) and as 'stable disease' in three VP patients and 9 controls (21 vs. 32 %, p = 0.465). Ten VP (71.4 %) and twenty CG patients (71.4 %) experienced tumor relapse (p = 0.99). No venous edge recurrences were recorded in the VP group, whereas 1/13 (7.7 %) was observed in the control group (p = 0.99). The pathological response rate was 64 vs. 39 % (p = 0.037) in VP and CG patients, respectively. The 5-year recurrence-free survival rate was 24 % for VP patients and 25 % for CG patients (p = 0.431). CONCLUSION In patients with a positive CT response, CRLM can be detached from the hepatic veins, as the oncological outcome is similar to that of a larger resection. The VP approach offers the possibility to enlarge the surgical indications, thus optimizing future surgical treatment chances.
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Affiliation(s)
- Federico Tomassini
- Department of General and Hepato-Biliary Surgery, Liver Transplantation Service, Ghent University Hospital Medical School, De Pintelaan 185, Ghent, 9000, Belgium
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Aoki T, Murakami M, Koizumi T, Kusano T, Fujimori A, Enami Y, Matsuda K, Goto S, Watanabe M, Otsuka K. Preoperative Tattooing for Precise and Expedient Localization of Landmark in Laparoscopic Liver Resection. J Am Coll Surg 2015; 221:e97-e101. [PMID: 26278038 DOI: 10.1016/j.jamcollsurg.2015.07.444] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 07/06/2015] [Accepted: 07/16/2015] [Indexed: 12/01/2022]
Affiliation(s)
- Takeshi Aoki
- Department of Gastroenterological and General Surgery, School of Medicine, Showa University, Tokyo, Japan.
| | - Masahiko Murakami
- Department of Gastroenterological and General Surgery, School of Medicine, Showa University, Tokyo, Japan
| | - Tomotake Koizumi
- Department of Gastroenterological and General Surgery, School of Medicine, Showa University, Tokyo, Japan
| | - Tomokazu Kusano
- Department of Gastroenterological and General Surgery, School of Medicine, Showa University, Tokyo, Japan
| | - Akira Fujimori
- Department of Gastroenterological and General Surgery, School of Medicine, Showa University, Tokyo, Japan
| | - Yuta Enami
- Department of Gastroenterological and General Surgery, School of Medicine, Showa University, Tokyo, Japan
| | - Kazuhiro Matsuda
- Department of Gastroenterological and General Surgery, School of Medicine, Showa University, Tokyo, Japan
| | - Satoru Goto
- Department of Gastroenterological and General Surgery, School of Medicine, Showa University, Tokyo, Japan
| | - Makoto Watanabe
- Department of Gastroenterological and General Surgery, School of Medicine, Showa University, Tokyo, Japan
| | - Koji Otsuka
- Department of Gastroenterological and General Surgery, School of Medicine, Showa University, Tokyo, Japan
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Oh SY, Kim DY, Suh KW. Oncologic outcomes following metastasectomy in colorectal cancer patients developing distant metastases after initial treatment. Ann Surg Treat Res 2015; 88:253-9. [PMID: 25960988 PMCID: PMC4422878 DOI: 10.4174/astr.2015.88.5.253] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Revised: 11/20/2014] [Accepted: 11/26/2014] [Indexed: 12/27/2022] Open
Abstract
Purpose We performed a comparative analysis of the clinicopathologic features and oncologic outcomes of colorectal cancer patients with metachronous versus synchronous metastasis, according to the prognostic factors. Methods Ninety-three patients who underwent curative resection for distant metastatic colorectal cancer were included in the study between December 2001 and December 2011. We assessed recurrence-free survival and overall survival in patients with distant metastasis who underwent curative surgery. Results The most common site of distant metastasis was lung alone (n = 19, 51.4%) in patients with metachronous metastasis, while liver alone was most common in those with synchronous metastasis (n = 40, 71.4%). Overall survival rate was significantly different between patients with synchronous metastasis and metachronous metastasis (34.0% vs. 53.7%; P = 0.013). Incomplete resection of the metastatic lesion was significantly related to poor overall survival in both, patients with synchronous metastasis, and metachronous metastasis. Conclusion Our study indicates that patients developing distant metastasis after initial treatment show a different metastatic pattern and better oncologic outcomes, as compared to those presenting with distant metastasis. Resection with tumor free margins significantly improves survival in patients with metachronous as well as synchronous metastasis.
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Affiliation(s)
- Seung Yeop Oh
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Do Yoon Kim
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Kwang Wook Suh
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
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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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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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Ardito F, Arena V, Vellone M, Grande G, Pennacchia I, Majellaro F, Giovannini I, Vecchio FM, Nuzzo G, Giuliante F. Strong YB-1 expression predicts liver recurrence following resection for colorectal metastases. J Gastrointest Surg 2014; 18:1987-93. [PMID: 25231080 DOI: 10.1007/s11605-014-2657-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2014] [Accepted: 09/02/2014] [Indexed: 01/31/2023]
Abstract
INTRODUCTION The Y-box binding protein-1 (YB-1) is a multifunctional oncoprotein involved in the proliferation and aggressiveness of cancer cells. The aim of this study was to determine whether strong YB-1 expression in neoplastic cells of colorectal liver metastases (CRLM) may have an impact on liver disease-free survival following liver resection. MATERIALS AND METHODS Immunohistochemistry was performed to evaluate YB-1 in 66 patients who underwent liver resection for CRLM. YB-1 expression was classified as weak (low-staining intensity) and strong (high-staining intensity). RESULTS YB-1 expression was observed in the cytoplasm of all CRLM. YB-1 expression was weak in 17 patients (25.8%) and strong in 49 patients (74.2%). Liver recurrence rate was significantly higher in the strong than in the weak expression group: 55.1 vs. 23.5% (p = 0.023). Multivariable logistic regression analysis showed that YB-1 strong expression was the only independent risk factor for liver recurrence. The 5-year specific liver disease-free survival rate was 76.0% in the weak expression group and 41.5% in the strong expression group (p = 0.034). These results were not influenced by clinical prognostic factors of tumor recurrence. CONCLUSIONS This is the first study showing that the degree of YB-1 expression in tissue specimens of CRLM predicts liver recurrence following liver resection.
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Affiliation(s)
- Francesco Ardito
- Hepatobiliary Surgery Unit, Department of Surgery, School of Medicine, Catholic University of the Sacred Heart, L.go A. Gemelli, 8, I-00168, Rome, Italy,
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