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      Prognostic Impact of Surgical Margin Width in Hepatectomy for Colorectal Liver Metastasis

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          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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          Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases.

          To evaluate the influence of surgical margin status on survival and site of recurrence in patients treated with hepatic resection for colorectal metastases. Using a multicenter database, 557 patients who underwent hepatic resection for colorectal metastases were identified. Demographics, operative data, pathologic margin status, site of recurrence (margin, other intrahepatic site, extrahepatic), and long-term survival data were collected and analyzed. On final pathologic analysis, margin status was positive in 45 patients, and negative by 1 to 4 mm in 129, 5 to 9 mm in 85, and > or =1 cm in 298. At a median follow-up of 29 months, the 1-, 3-, and 5-year actuarial survival rates were 97%, 74%, and 58%; median survival was 74 months. Tumor size > or =5 cm, >3 tumor nodules, and carcinoembryonic antigen level >200 ng/mL predicted poor survival (all P or =1 cm had similar overall recurrence rates (P > 0.05). Patients with positive margins were more likely to have surgical margin recurrence (P = 0.003). Adverse preoperative biologic factors including tumor number greater than 3 (P = 0.01) and a preoperative CEA level greater than 200 ng/mL (P = 0.04) were associated with an increased risk of positive surgical margin. A positive margin after resection of hepatic colorectal metastases is associated with adverse biologic factors and increased risk of surgical-margin recurrence. The width of a negative surgical margin does not affect survival, recurrence risk, or site of recurrence. A predicted margin of <1 cm after resection of hepatic colorectal metastases should not be used as an exclusion criterion for resection.
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            R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery?

            To compare long-term outcome of R0 (negative margins) and R1 (positive margins) liver resections for colorectal liver metastases (CLM) treated by an aggressive approach combining chemotherapy and repeat surgery. Complete macroscopic resection with negative margins is the gold standard recommendation in the surgical treatment of CLM. However, due to vascular proximity or multinodularity, complete macroscopic resection can sometimes only be performed through R1 resection. Increasingly efficient chemotherapy may have changed long-term outcome after R1 resection. All resected CLM patients (R0 or R1) at our institution between 1990 and 2006 were prospectively evaluated. Exclusion criteria were: macroscopic incomplete (R2) resection, use of local treatment modalities, and presence of extrahepatic disease. We aimed to resect all identified metastases with negative margins. However, when safe margins could not be obtained, resection was still performed provided complete macroscopic tumor removal. Overall survival (OS) and disease-free survival were compared between groups, and prognostic factors were identified. Of 840 patients, 436 (52%) were eligible for the study, 234 (28%) of whom underwent R0 resection, and 202 (24%) underwent R1 resection. Number and size of CLM were higher, and distribution was more often bilateral in the R1 group. After a mean follow-up of 40 months, 5-year OS was 61% and 57% for R0 and R1 patients (P = 0.27). Five-year disease-free survival was 29% in the R0 group versus 20% in the R1 group (P = 0.12). In the R1 group, intrahepatic (but not surgical margin) recurrences were more often observed (28% vs. 17%; P = 0.004). Preoperative carcinoembryonic antigen level > or =10 ng/mL and major hepatectomy, but not R1 resection, were independent predictors of poor OS. Size > or =30 mm, bilateral distribution, and intraoperative blood transfusions independently predicted positive surgical margins. Despite a higher recurrence rate, the contraindication of R1 resection should be revisited in the current era of effective chemotherapy because survival is similar to that of R0 resection.
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              Two-stage hepatectomy: A planned strategy to treat irresectable liver tumors.

              To assess feasibility, risks, and patient outcomes in the treatment of colorectal metastases with two-stage hepatectomy. Some patients with multiple hepatic colorectal metastases are not candidates for a complete resection by a single hepatectomy, even when downstaged by chemotherapy, after portal embolization, or combined with a locally destructive technique. In two-stage hepatectomy, the highest possible number of tumors is resected in a first, noncurative intervention, and the remaining tumors are resected after a period of liver regeneration. In selected patients with irresectable multiple metastases not amenable to a single hepatectomy procedure, two-stage hepatectomy might offer a chance of long-term remission. Of consecutive patients with conventionally irresectable colorectal metastases treated by chemotherapy, 16 of 398 (4%) became eligible for curative two-stage hepatectomy combined with chemotherapy and adjuvant nonsurgical interventions as indicated. Two-stage hepatectomy was feasible in 13 of 16 patients (81%). There were no surgical deaths. The postoperative death rate (2 months or less) was 0% for the first-stage procedure and 15% for the second-stage one. Postoperative complication rates were 31% and 45%, respectively, with only one complication leading to reoperation. The 3-year survival rate was 35%, with four patients (31%) disease-free at 7, 22, 36, and 54 months. Median survival was 31 months from the second hepatectomy and 44 months from the diagnosis of metastases. Two-stage hepatectomy combined with chemotherapy may allow a long-term remission in selected patients with irresectable multiple metastases and increases the proportion of patients with resectable disease.
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                Author and article information

                Journal
                J Clin Transl Hepatol
                J Clin Transl Hepatol
                JCTH
                Journal of Clinical and Translational Hepatology
                XIA & HE Publishing Inc.
                2225-0719
                2310-8819
                28 June 2023
                17 January 2023
                : 11
                : 3
                : 705-717
                Affiliations
                [1 ]Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
                [2 ]Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
                Author notes
                [* ] Correspondence to: Katsunori Sakamoto, Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, 454 Kou, Shitsukawa, Toon Ehime 791-0295, Japan. ORCID: https://orcid.org/0000-0002-6431-0011. Tel: +81-89-9605327, Fax: +81-89-9605329, E-mail: sakamoto.katsunori.gq@ 123456ehime-u.ac.jp

                None to declare.

                The authors have no conflict of interests related to this publication.

                Study concept and design (KS, TB), acquisition of data (KS), analysis and interpretation of data (KS, TB), drafting of the manuscript (KS), critical revision of the manuscript for important intellectual content (TB, KO, KT, MH, NF, YT), administrative, technical, or material support (KS, TB), and study supervision (TB). All authors have made a significant contribution to this study and have approved the final manuscript.

                Author information
                https://orcid.org/0000-0002-6431-0011
                https://orcid.org/0000-0001-6076-6516
                Article
                JCTH.2022.00383
                10.14218/JCTH.2022.00383
                10037520
                36969881
                982e6628-65dc-4f8a-9340-a2fbe78f6c11
                © 2023 Authors.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 August 2022
                : 1 October 2022
                : 6 November 2022
                Categories
                Review Article

                surgical margin,colorectal liver metastasis,chemotherapy

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