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Is Tumor Detachment from Vascular Structures Equivalent to R0 Resection in Surgery for Colorectal Liver Metastases? An Observational Cohort. Viganò Luca,Procopio Fabio,Cimino Matteo Maria,Donadon Matteo,Gatti Andrea,Costa Guido,Del Fabbro Daniele,Torzilli Guido Annals of surgical oncology BACKGROUND:R0 resection is the standard for colorectal liver metastases (CLMs). Adequacy of R1 resections is debated. Detachment of CLMs from vessels has been proposed to prioritize parenchyma sparing and increase resectability, but outcomes are still to be elucidated. The present study aimed to clarify the outcomes of R1 surgery (margin <1 mm) in patients with CLMs, distinguishing standard R1 resection (parenchymal margin, R1Par) and R1 resection with detachment of CLMs from major intrahepatic vessels (R1Vasc). METHODS:All patients undergoing first resection between 2004 and June 2013 were prospectively considered. R0, R1Par, and R1Vasc were compared in per-patient and per-resection area analyses. RESULTS:The study included 627 resection areas in 226 consecutive patients. Fifty-one (8.1 %) resections in 46 (20.4 %) patients were R1Vasc, and 177 (28.2 %) resections in 107 (47.3 %) patients were R1Par. Thirty-two (5.1 %) surgical margin recurrences occurred in 28 (12.4 %) patients. Local recurrence risk was similar between the R0 and R1Vasc groups (per-patient analysis 5.3 vs. 4.3 %; per-resection area analysis 1.5 vs. 3.9 %, p = n.s.) but increased in the R1Par group (19.6 and 13.6 %, p < 0.05 for both). The R1Par group had a higher rate of hepatic-only recurrences (49.5 vs. 36.1 %, p = 0.042). On multivariate analysis, R1Par was an independent negative prognostic factor of overall survival (p = 0.034, median follow-up 33 months); conversely R1Vasc versus R0 had no significant differences. CONCLUSIONS:R1Par resection is not adequate for CLMs. R1Vasc surgery achieves outcomes equivalent to R0 resection. CLM detachment from intrahepatic vessels can be pursued to increase patient resectability and resection safety (parenchymal sparing). 10.1245/s10434-015-5009-y
The Prognostic Value of Varying Definitions of Positive Resection Margin in Patients with Colorectal Cancer Liver Metastases. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 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. 10.1007/s11605-018-3748-3
Surgical margin size in hepatic resections for colorectal metastasis: impact on recurrence and survival. Herman Paulo,Pinheiro Rafael S,Mello Evandro S,Lai Quirino,Lupinacci Renato M,Perini Marcos V,Pugliese Vincenzo,Andraus Wellington,Coelho Fabricio F,Cecconello Ivan,D'Albuquerque Luiz C Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery BACKGROUND:Approximately 50% of the patients with a colorectal tumor develop liver metastasis, for which hepatectomy is the standard care. Several prognostic factors have been discussed, among which is the surgical margin. This is a recurring issue, since no consensus exists as to the minimum required distance between the metastatic nodule and the liver transection line. AIM:To evaluate the surgical margins in liver resections for colorectal metastases and their correlation with local recurrence and survival. METHODS:A retrospective study based on the review of the medical records of 91 patients who underwent resection of liver metastases of colorectal cancer. A histopathological review was performed of all the cases; the smallest surgical margin was verified, and the late outcome of recurrence and survival was evaluated. RESULTS:No statistical difference was found in recurrence rates and overall survival between the patients with negative or positive margins (R0 versus R1); likewise, there was no statistical difference between subcentimeter margins and those greater than 1 cm. The disease-free survival of the patients with microscopically positive margins was significantly worse than that of the patients with negative margins. The uni- and multivariate analyses did not establish the surgical margin (R1, narrow or less than 1 cm) as a risk factor for recurrence. CONCLUSION:The resections of liver metastases with negative margins, independently of the margin width, had no impact on tumor recurrence (intra- or extrahepatic) or patient survival. 10.1590/s0102-67202013000400011
Extended resections of liver metastases from colorectal cancer. Jonas S,Thelen A,Benckert C,Spinelli A,Sammain S,Neumann U,Rudolph B,Neuhaus P World journal of surgery BACKGROUND:Indications for resection of liver metastases from colorectal cancer and surgical strategies are still under debate. METHODS:We have retrospectively reviewed the outcome of 660 patients after 685 liver resections for metastases of colorectal cancer in our institution from 1988 to 2004. All surviving patients have a minimum follow-up period of 1 year. The longest follow-up in these patients is 16 years. Three different time periods of 5 to 6 years each were analyzed. RESULTS:The 30- and 60-day mortality rates were 1.5% (n = 10) and 2.2 % (n = 15), respectively. The rate of formally curative (R0) resections was 84%. Five-year survival rates in all patients and in patients after R0 resection were 37% and 42%, respectively. If only resections from 1999 to 2004 were considered, 5-year survival in patients after R0 resection was 50%. In a multivariate analysis, surgical radicality, ligamental lymph node involvement, number of liver metastases, and time period, in which the liver resection had been performed, were independent prognostic parameters. CONCLUSIONS:Outcome after liver resection for metastases from colorectal cancer has constantly improved. A formally curative resection is the most relevant prognostic parameter. Number of liver metastases and, in the few patients concerned, lymph node infiltration of the hepatoduodenal ligament, were further prognostic parameters. 10.1007/s00268-006-0140-3
Resection margin in patients undergoing hepatectomy for colorectal liver metastasis: a critical appraisal of the 1cm rule. Hamady Z Z R,Cameron I C,Wyatt J,Prasad R K,Toogood G J,Lodge J P A European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology AIM:We undertook this study to evaluate the influence of resection margin distance from metastases on survival and post-operative disease recurrence after hepatectomy for colorectal liver metastasis. METHODS:Between January 1993 and December 2001, 293 consecutive patients underwent primary liver resection for colorectal metastasis. Clinical, pathological and outcome data were analysed using a prospectively collected database. Cases were stratified into those with involved and non-involved resection margins. Different non-involved margin widths were analysed against survival, recurrence rate and pattern (hepatic, extra hepatic) of recurrence. RESULTS:The 1, 3, 5 and 10 years actuarial survival rates were 82, 58, 44 and 36%, respectively. The median survival was 46 months. The histological liver resection margin involvement was a significant predictor of survival and disease free survival after surgery. One, two, five and 10 millimetres disease free resection margin widths were found not to be significant in influencing patients' survival or recurrence rate. CONCLUSION:A positive hepatic resection margin was associated with a higher incidence of post-operative recurrence and lower survival rate. The width of the resection margin did not influence the post-operative recurrence rate or pattern of recurrence. The '1 cm rule' should be abandoned. 10.1016/j.ejso.2006.02.001
Size of surgical margin does not influence recurrence rates after curative liver resection for colorectal cancer liver metastases. Bodingbauer M,Tamandl D,Schmid K,Plank C,Schima W,Gruenberger T The British journal of surgery BACKGROUND:The aim of this study was to examine the relationship between surgical margin status and site of recurrence after potentially curative liver resection for colorectal metastases using an ultrasonic dissection technique. METHODS:Between January 2000 and December 2003, 176 patients underwent liver resection with curative intent for colorectal metastases at a single institution. Demographics, operative data, pathological margin status, site of recurrence and long-term survival data were collected prospectively and analysed. RESULTS:On pathological analysis, resection margins were positive in 43 patients, negative by 1-9 mm in 110, and clear by more than 9 mm in 23 patients. At a median follow-up of 33 months, 133 of 176 patients had developed a recurrence, only five of whom had recurrence at the surgical margin. Recurrence at the surgical margin was not significantly related to the size of the margin. Overall, the median time to recurrence was 12.6 months, which was independent of surgical margin size, although there was a significantly higher proportion of patients with multiple metastases in the group with a positive margin (P = 0.008). Margin status did not correlate significantly with either recurrence-free or overall survival. CONCLUSION:The rate of recurrence at the surgical margin was low and a positive margin was not associated with an increased risk of recurrence either at the surgical margin or elsewhere. 10.1002/bjs.5762
Resection margin and recurrence-free survival after liver resection of colorectal metastases. Muratore Andrea,Ribero Dario,Zimmitti Giuseppe,Mellano Alfredo,Langella Serena,Capussotti Lorenzo Annals of surgical oncology BACKGROUND:Optimal margin width is uncertain because of conflicting results from recent studies using overall survival as the end-point. After recurrence, re-resection and aggressive chemotherapy heavily affect survival time; the potential confounding effect of such factors has not been investigated. Use of recurrence-free survival (RFS) may overcome this limitation. The aim of this study is to evaluate the impact of width of resection margin on RFS and site of recurrence after hepatic resection for colorectal metastases (CRM). METHODS:From a prospectively maintained institutional database (1/1999-12/2007) we identified 314 patients undergone hepatectomy for CRM (1/1999-12/2007) with detailed pathologic analysis of the surgical margin and complete follow-up imaging studies documenting disease status and site of recurrence, which was categorized as: resection margin (M(arg)), other intra-hepatic ((other)IH), lung (L) or other extra-hepatic ((other)EH). Recurrence-free estimation was the survival end-point. RESULTS:Median follow-up was 56.5 months. Two hundred and fifteen patients (68.8%) recurred at 288 sites after a mean of 15.5 months. A positive resection margin was associated with an increased risk of M(arg) recurrence (P < 0.001). The presence of >or=2 metastases was the only factor increasing the risk of positive margins (P < 0.05). The width of the negative resection margin (>or=1 cm versus >1 cm) was not a prognostic factor of worse RFS (30.2% versus 37.3%, P = 0.6). Node status of the primary tumour, and size and number of CRM were independent predictors of RFS. CONCLUSIONS:Tumour biology and not the width of the negative resection margin affect RFS. 10.1245/s10434-009-0770-4
Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Annals of surgery OBJECTIVE:To evaluate the influence of surgical margin status on survival and site of recurrence in patients treated with hepatic resection for colorectal metastases. METHODS: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. RESULTS: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 < 0.05). Median survival was 49 months in patients with positive margins and not yet reached in patients with negative margins (P = 0.01). After hepatic resection, 225 (40.4%) patients had recurrence: 21 at the surgical margin, 56 at another intrahepatic site, 82 at an extrahepatic site, and 66 at both intrahepatic and extrahepatic sites. Patients with negative margins of 1 to 4 mm, 5 to 9 mm, and > 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. CONCLUSIONS: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. 10.1097/01.sla.0000160703.75808.7d
Margin Status is Still an Important Prognostic Factor in Hepatectomies for Colorectal Liver Metastases: A Propensity Score Matching Analysis. Memeo Riccardo,de Blasi Vito,Adam Rene,Goéré Diane,Piardi Tullio,Lermite Emilie,Turrini Olivier,Navarro Francis,de'Angelis Nicola,Cunha Antonio Sa,Pessaux Patrick, World journal of surgery 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. 10.1007/s00268-017-4229-7
The Prognostic Impact of Determining Resection Margin Status for Multiple Colorectal Metastases According to the Margin of the Largest Lesion. Sasaki Kazunari,Margonis Georgios A,Maitani Kosuke,Andreatos Nikolaos,Wang Jaeyun,Pikoulis Emmanouil,He Jin,Wolfgang Christopher L,Weiss Matthew,Pawlik Timothy M Annals of surgical oncology BACKGROUND:Although the prognostic role of surgical margin status after resection of colorectal liver metastasis (CRLM) has been previously examined, controversy still surrounds the importance of surgical margin status in patients with multiple tumors. METHODS:Patients who underwent curative-intent surgery for CRLM from 2000 to 2015 and who presented with multiple tumors were identified. Patients with R1 resection status determined by the closest resection margin of the non-largest tumor were classified as R1-Type 1; patients with R1 status determined by the resection margin of the largest tumor were defined as R1-Type 2. Data regarding surgical margin status, size of tumors, and overall survival (OS) were collected and assessed. RESULTS:A total of 251 patients met inclusion criteria; 156 patients (62.2%) had a negative margin (R0), 50 had an R1-type 1 (19.9%), and 45 had an R1-type 2 (17.9%) margin. Median and 5-year OS in the entire cohort was 56.4 months and 48.0%, respectively. When all R1 (Type 1 + Type 2) patients were compared with R0 patients, an R1 was not associated with worse prognosis (P = 0.05). In contrast, when R1-type 2 patients were compared with R0 patients, an R1 was strongly associated with worse OS (P = 0.009). On multivariate analysis, although the prognostic impact of all R1 was not associated with OS (hazard ratio [HR] 1.56; P = 0.08), R1-Type 2 margin status independently predicted a poor outcome (HR 1.93; P = 0.03). CONCLUSIONS:The impact of margin status varied according to the size of the tumor assessed. While R1 margin status defined according to the non-largest tumor was not associated with OS, R1 margin status relative to the largest index lesion was associated with prognosis. 10.1245/s10434-017-5904-5
Prognostic influence of hepatic margin after resection of colorectal liver metastasis: role of modern preoperative chemotherapy. Makowiec Frank,Bronsert Peter,Klock Andrea,Hopt Ulrich T,Neeff Hannes P International journal of colorectal disease PURPOSE:Modern chemotherapy (CTX) increases survival in stage IV colorectal cancer. In colorectal liver metastases (CLM), neoadjuvant (neo) CTX may increase resectability and improve survival. Due to widespread use of CTX in CLM, recent studies assessed the role of the hepatic margin after CTX, with conflicting results. We evaluated the outcome after resection of CLM in relation to CTX and hepatic resection status. METHODS:Since 2000, 334 patients with first hepatic resection for isolated CLM were analyzed. Thirty-two percent had neoadjuvant chemotherapy (targeted therapy in 42%). Sixty-eight percent never had CTX before hepatectomy or longer than 6 months before resection. The results were gained by analysis of our prospective database. RESULTS:Positive hepatic margins occurred in 8% (independent of neoCTx). Patients after neoCTX had higher numbers of CLM (p < 0.01) and a longer duration of surgery (p < 0.03). After hepatectomy, 5-year survival was 45% and correlated strongly with the margin status (47% in R-0 and 21% in R-1; p < 0.001). Survival also correlated with margin status in the subgroups with neoCTX (p < 0.01) or without neoCTx (p < 0.01). In multivariate analysis of the entire group, hepatic margin status (RR 3.2; p < 0.001) and age > 65 years (RR 1.6; p < 0.01) were associated with poorer survival. In the subgroup of patients after neoCTX (n = 106), only the resection margin was an independent predictor of survival (p < 0.001). CONCLUSION:In patients with isolated colorectal liver metastases undergoing resection, the hepatic margin status was the strongest independent prognostic factor. This effect was also present after neoadjuvant chemotherapy for CLM. 10.1007/s00384-017-2916-3
Resection margin in laparoscopic hepatectomy: a comparative study between wedge resection and anatomic left lateral sectionectomy. Lee Kit-fai,Wong Jeff,Cheung Yue-sun,Ip Philip,Wong John,Lai Paul B S HPB : the official journal of the International Hepato Pancreato Biliary Association BACKGROUND:Experience from open hepatectomy shows that anatomic liver resection achieves a better resection margin than wedge resection. In recent years, laparoscopic hepatectomy has increasingly been performed in patients with liver pathology including malignant lesions. Wedge resection (WR) and left lateral sectionectomy (LLS), which also represent non-anatomic and anatomic resection respectively, are the two most common types of laparoscopic hepatectomy performed. The aim of the present study was to compare the two types of laparoscopic hepatectomy with emphasis on resection margin. METHODS:Between November 2003 and July 2009, 44 consecutive patients who underwent laparoscopic hepatectomy were identified and retrospectively reviewed. The WR and LLS group of patients were compared in terms of operative outcomes, pathological findings, recurrence patterns and survival. RESULTS:Out of the 44 patients, 21 underwent LLS and 23 a WR. The two groups of patients were comparable in demographics. The two groups did not differ in conversion rate, blood loss, blood transfusion, mortality, morbidity and post-operative length of stay. The LLS group patients had significantly larger liver lesions, wider resection margin and less sub-centimetre margins. In patients with malignant liver lesions, there was no difference between the two groups in incidence of intra-hepatic recurrence and 3-year overall and disease-free survival. CONCLUSION:Operative outcomes are similar between laparoscopic WR and LLS. However, WR is less reliable than LLS in achieving a resection margin of more than 1 cm. Larger studies involving more patients with longer follow-up are warranted to determine the impact of the resection margin on intra-hepatic recurrence and survival. 10.1111/j.1477-2574.2010.00221.x
Margin status after laparoscopic resection of colorectal liver metastases: does a narrow resection margin have an influence on survival and local recurrence? Postriganova Nadya,Kazaryan Airazat M,Røsok Bård I,Fretland Åsmund A,Barkhatov Leonid,Edwin Bjørn HPB : the official journal of the International Hepato Pancreato Biliary Association OBJECTIVES:Recent studies of margin-related recurrence have raised questions on the necessity of ensuring wide resection margins in the resection of colorectal liver metastases. The aim of the current study was to determine whether resection margins of 10 mm provide a survival benefit over narrower resection margins. METHODS:A total of 425 laparoscopic liver resections were carried out in 351 procedures performed in 317 patients between August 1998 and April 2012. Primary laparoscopic liver resections for colorectal metastases were included in the study. Two-stage resections, procedures accompanied by concomitant liver ablations and one case of perioperative mortality were excluded. A total of 155 eligible patients were classified into four groups according to resection margin width: Group 1, margins of < 1 mm [n = 33, including 17 patients with positive margins (Group 1a)]; Group 2, margins of 1 mm to < 3 mm (n = 31); Group 3, margins of ≥ 3 mm to <10 mm (n = 55), and Group 4, margins of ≥ 10 mm (n = 36). Perioperative and survival data were compared across the groups. Median follow-up was 31 months (range: 2-136 months). RESULTS:Perioperative outcomes were similar in all groups. Unfavourable intraoperative incidents occurred in 9.7% of procedures (including 3.2% of conversions). Postoperative complications developed in 11.0% of patients. Recurrence in the resection bed developed in three (1.9%) patients, including two (6.1%) patients in Group 1. Rates of actuarial 5-year overall, disease-free and recurrence-free survival were 49%, 41% and 33%, respectively. Median survival was 65 months. Margin status had no significant impact on patient survival. The Basingstoke Predictive Index (BPI) generally underestimated survival. This underestimation was especially marked in Group 1 when postoperative BPI was applied. CONCLUSIONS:Patients with margins of <1 mm achieved survival comparable with that in patients with margins of ≥ 10 mm. When modern surgical equipment that generates an additional coagulation zone is applied, the association between resection margin and survival may not be apparent. Further studies in this field are required. Postoperative BPI, which includes margin status among the core factors predicting postoperative survival, seems to be less precise than preoperative BPI. 10.1111/hpb.12204
Microscopic resection margins adversely influence survival rates after surgery for colorectal liver metastases: An open ambidirectional Cohort Study. Lee Keng Siang,Suchett-Kaye Ivo,Abbadi Reyad,Finch-Jones Meg,Pope Ian,Strickland Andrew,Rees Jonathan International journal of surgery (London, England) BACKGROUND:Liver resection is the most effective treatment for patients with colorectal liver metastases (CRLMs). Patients with tumour at the resection margin (R1) are reported to have worse survival compared to those with an uninvolved resection margin (R0). Recent data has questioned this finding. This study investigates whether R1 resections adversely influence survival when compared to R0 resections. MATERIAL AND METHODS:Patients undergoing surgery for CRLM, identified from a prospectively maintained database, from January 2007 to January 2017, were included. Univariate and multivariate survival analyses were performed. p < 0.05 was significant. RESULTS:282 patients were included. Median age 72 (32-90) years. 236 patients (83.7%) had chemotherapy and surgery, whilst 46 (16.3%) had surgery alone. 149 patients (52.8%) were alive at the end of the study period. R1 resection on univariate survival analysis was associated with better survival (HR 2.12, 95%CI 1.60-4.61, p = 0.0002). Multivariate analysis controlling for age and gender, identified presence of extrahepatic disease (HR 2.03, 95%CI 1.17-3.52, p < 0.001), R0 resection (HR 0.33, 95%CI 0.19-0.59, p = 0.003), primary tumour stage (HR 1.57, 95%CI 1.04-2.40, p = 0.034) and primary tumour differentiation (HR 2.56, 95%CI 1.01-6.46, p = 0.047), as prognostic factors for poorer survival. Five-year and 10-year survival were 54.3% and 41.7% respectively in patients with an R0 resection and, 25.8% and 17.2% in those with an R1 resection. CONCLUSION:The presence of extrahepatic disease, an R1 resection margin, advanced T-stage and poorer tumour differentiation were associated with worse survival in CRLM surgery and R0 resection is recommended. 10.1016/j.ijsu.2020.09.007
Preoperative Chemotherapy and Resection Margin Status in Colorectal Liver Metastasis Patients: A Propensity Score-Matched Analysis. Solaini Leonardo,Gardini Andrea,Passardi Alessandro,Mirarchi Maria Teresa,D'Acapito Fabrizio,La Barba Giuliano,Cucchi Michele,Casadei Gardini Andrea,Frassineti Giovanni L,Cucchetti Alessandro,Ercolani Giorgio The American surgeon In this article, we compared the early and long-term outcomes of patients with metastatic colorectal cancer treated with chemotherapy followed by resection with those of patients undergoing surgery first, focusing our analysis on resection margin status. Patients who underwent liver resection with curative intent for colorectal liver metastases from July 2001 to January 2018 were included in the analysis. Propensity score matching was used to reduce treatment allocation bias. The cohort comprised 164 patients; 117 (71.3%) underwent liver resection first, whereas the remaining 47 (28.7%) had preoperative chemotherapy. After a 1:1 ratio of propensity score matching, 47 patients per group were evaluated. A positive resection margin was found in 13 patients in the surgery-first group (25.5%) 4 (8.5%) in the preoperative chemotherapy group ( = 0.029). Postmatched logistic regression analysis showed that only preoperative chemotherapy was significantly associated with the rate of positive resection margin (odds ratio 0.24, 95% confidence interval 0.07-0.81; = 0.022). Median follow-up was 41 months (interquartile range 8-69). Cox proportional hazard regression analysis revealed that only positive resection margin was a significant negative prognostic factor (hazard ratio 2.2, 95% CI 1.18-4.11; = 0.014). Within the preoperative chemotherapy group, median overall survival was 40 months in R0 patients and 10 months in R1 patients ( = 0.016). Although preoperative chemotherapy in colorectal liver metastasis patients may affect the rate of positive resection margin, its impact on survival seems to be limited. In the present study, the most important prognostic factor was the resection margin status.
Prognostic impact of margin status in liver resections for colorectal metastases after bevacizumab. Sasaki K,Margonis G A,Andreatos N,Wilson A,Weiss M,Wolfgang C,Sergentanis T N,Polychronidis G,He J,Pawlik T M The British journal of surgery BACKGROUND:Margin status with resection of colorectal liver metastasis (CRLM) was an important prognostic factor in the years before the introduction of biological chemotherapy. This study examined outcomes following CRLM resection in patients who received neoadjuvant chemotherapy with or without the monoclonal antiangiogenic antibody bevacizumab. METHODS:Patients who underwent surgery for CRLM at the Johns Hopkins Hospital between 2000 and 2015 were identified from an institutional database. Data regarding surgical margin status, preoperative bevacizumab administration and overall survival (OS) were assessed using multivariable analyses. RESULTS:Of 630 patients who underwent CRLM resection, 417 (66·2 per cent) received neoadjuvant chemotherapy with (214, 34·0 per cent) or without (203, 32·2 per cent) bevacizumab. The remaining 213 (33·8 per cent) did not receive neoadjuvant chemotherapy. Univariable analysis found that positive margins were associated with worse 5-year OS than R0 resection (36·2 versus 54·9 per cent; P = 0·005). After dichotomizing by the receipt of preoperative bevacizumab versus chemotherapy alone, the prognostic value of pathological margin persisted among patients who did not receive preoperative bevacizumab (5-year OS 53·0 versus 37 per cent after R0 versus R1 resection; P = 0·010). OS was not significantly associated with margin status in bevacizumab-treated patients (5-year OS 46·8 versus 33 per cent after R0 versus R1 resection; P = 0·081), in whom 5-year survival was slightly worse (presumably reflecting more advanced disease) than among patients treated with cytotoxic agents alone. Pathological margin status was not significantly associated with 5-year OS in patients with a complete or near-complete response to chemotherapy and bevacizumab (43 versus 30 per cent after R0 versus R1 resection; P = 0·917), but this may be due to a type II error. CONCLUSION:The impact of margin status varied according to the receipt of bevacizumab. Bevacizumab may have a role to play in improving outcomes among patients with more advanced disease. 10.1002/bjs.10510
Prognostic impact of positive surgical margins after resection of colorectal cancer liver metastases: reappraisal in the era of modern chemotherapy. Tranchart Hadrien,Chirica Mircea,Faron Matthieu,Balladur Pierre,Lefevre Leila Bengrine,Svrcek Magali,de Gramont Aimery,Tiret Emmanuel,Paye François World journal of surgery BACKGROUND:The purpose of the present study was to assess the prognostic impact of positive surgical margins (R1) after liver resection (LR) of colorectal liver metastases (CRLM) in the era of modern chemotherapy regimens. R1 resection is a negative prognostic factor after LR of CRLM. The significance of R1 margins in the era of effective chemotherapy is unknown. METHODS:From January 2000 to December 2009, 215 patients (177 men: 62 %; median age 60 years; range 30-84 years) underwent LR of CRLM. The LR was considered R1 (margin <1 mm) in 49 patients (23 %) and R0 in 166 patients (77 %). Overall, 108 (50 %) patients received preoperative chemotherapy and 156 (72 %) patients received postoperative chemotherapy. RESULTS:With a median follow-up of 36 months (range 1-141 months), the 5-year overall survival (OS) rate (47 vs 40 %; p = 0.05) and the disease-free survival (DFS) rate (36 vs 23 %; p = 0.006) were significantly lower in the R1 group. Recurrence developed in 152 patients (71 %) and the rate of recurrence was significantly higher (84 vs 67 %; p = 0.02) in the R1 group. On multivariate analysis, N+ status of the colorectal primary tumor (p = 0.008), presence of radiologically occult disease (p = 0.04), and R1 resection (p = 0.03) were independent adverse predictors of OS. The N+ status of the primary tumor (p = 0.003) and R1 resection (p = 0.02) were independent adverse predictors of DFS. On multivariate analysis use of postoperative chemotherapy was the only independent predictor of improved DFS (p = 0.02) in the R1 group. CONCLUSIONS:A positive resection margin remains a significant poor prognostic factor after LR of CRLM in the era of modern chemotherapy. Postoperative chemotherapy reduces recurrence rates after R1 resection of CRLM. 10.1007/s00268-013-2186-3
Margin status remains an important determinant of survival after surgical resection of colorectal liver metastases in the era of modern chemotherapy. Andreou Andreas,Aloia Thomas A,Brouquet Antoine,Dickson Paxton V,Zimmitti Giuseppe,Maru Dipen M,Kopetz Scott,Loyer Evelyne M,Curley Steven A,Abdalla Eddie K,Vauthey Jean-Nicolas Annals of surgery OBJECTIVE:To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases after modern preoperative chemotherapy. BACKGROUND:In the era of effective chemotherapy for colorectal liver metastases, the association between surgical margin status and survival has become controversial. METHODS:Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy. RESULTS:Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin <1 mm). The 5-year OS rates for patients with R0 resection (margin ≥1 mm) and R1 resection were 55% and 26%, respectively (P = 0.017). Multivariate analysis identified R1 resection (P = 0.03) and a minor pathologic response to chemotherapy (P = 0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs 11%; P = 0.007) than in patients with optimal response (3-year OS rate: 92% vs 88%; P = 0.917) and greater in patients with a minor pathologic response (5-year OS rate: 46% vs 0%; P = 0.002) than in patients with a major response (5-year OS rate: 63% vs 67%; P = 0.587). CONCLUSIONS:In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy. 10.1097/SLA.0b013e318283a4d1
Impact of surgical margins on overall and recurrence-free survival in parenchymal-sparing laparoscopic liver resections of colorectal metastases. Montalti Roberto,Tomassini Federico,Laurent Stéphanie,Smeets Peter,De Man Marc,Geboes Karen,Libbrecht Louis J,Troisi Roberto I Surgical endoscopy 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. 10.1007/s00464-014-3999-3
Long-Term Survival Benefit and Potential for Cure after R1 Resection for Colorectal Liver Metastases. Hosokawa Isamu,Allard Marc-Antoine,Gelli Maximiliano,Ciacio Oriana,Vibert Eric,Cherqui Daniel,Sa Cunha Antonio,Castaing Denis,Miyazaki Masaru,Adam René Annals of surgical oncology BACKGROUND:Although efficient chemotherapy regimens have improved outcomes after R1 resection (positive margins) for colorectal liver metastases (CLMs), the long-term survival benefit and potential for cure after R1 resection have not been clearly demonstrated. The aim of this study was to evaluate the long-term outcome after R1 resection for CLM, and to identify factors predictive of cure. METHODS:All resected CLM patients at our institution from 2000 to 2009 were prospectively evaluated. Cure was defined as a disease-free interval ≥5 years from the last hepatic or extrahepatic resection to last follow-up. RESULTS:Of 628 patients consecutively resected for CLM, 428 were eligible for the study, of whom 219 (51 %) underwent R0 resection (negative margins) and 209 (49 %) underwent R1 resection. Overall, 130 patients with R0 resection and 141 patients with R1 resection had more than 5 years of follow-up. Five- and 10-year overall survival rates were 56 and 34 % for R0 patients, and 48 and 36 % for R1 patients, respectively (p = 0.37). Of the 141 patients who underwent R1 resection, 26 patients (18 %) were considered 'cured', and 106 patients (75 %) were considered 'noncured'. Independent predictive factors of cure after R1 resection included ≤10 total cycles of preoperative chemotherapy and objective response to preoperative chemotherapy. CONCLUSIONS:Overall, potential cure can be achieved in 18 % of patients after R1 resection for CLM. The best conditions to achieve long-term survival after R1 resection rely on a good response to efficient and short first-line chemotherapy. 10.1245/s10434-015-5060-8
Significance of R1 Resection for Advanced Colorectal Liver Metastases in the Era of Modern Effective Chemotherapy. Laurent Christophe,Adam Jean-Philippe,Denost Quentin,Smith Denis,Saric Jean,Chiche Laurence World journal of surgery 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. 10.1007/s00268-016-3404-6
The prognostic impact of resection margin status varies according to the genetic and morphological evaluation (GAME) score for colorectal liver metastasis. Wang Hong-Wei,Wang Li-Jun,Jin Ke-Min,Bao Quan,Li Juan,Wang Kun,Xing Bao-Cai Journal of surgical oncology BACKGROUND:Surgical margin status remains a controversial factor in predicting the outcome of colorectal liver metastases (CRLM) resection. Our study aims to evaluate the effects of surgical margins on oncologic outcomes with regard to the genetic and morphological evaluation (GAME) score. METHODS:R1 resection was defined as having a less than 1 mm margin width. Patients who underwent surgery for CRLM from January 2005 to December 2018 were recruited. The patients were divided into two risk subgroups, namely, the low or medium risk (GAME 0-3) and high-risk (GAME score 4 or more) groups. The effects of margin status on overall survival (OS) and recurrence-free survival rate (RFS) were examined. RESULTS:In total, 661 patients were recruited, among which 159 (24.1%) had R1 resection. Before hepatectomy, 514 patients showed a low or medium risk (R1 resection: n = 124), while 147 patients demonstrated a high risk (R1 resection: n = 35). In the whole cohort, multivariable analysis did show that R1 resection was associated with worse RFS and OS. While further research only found that in the low or medium risk group, R1 resection was related to poor OS and RFS. Meanwhile, in the high risk group, no significant difference was found in the median OS and RFS among patients with R0 or R1 resection. CONCLUSION:The prognostic role of margin status varied according to the GAME score. Margin clearance only improved survival rates in patients with low or medium GAME score. In contrast, R1 resection demonstrated similar oncologic outcomes with R0 resection in patients with high GAME score. 10.1002/jso.26557
Influence of margins on overall survival after hepatic resection for colorectal metastasis: a meta-analysis. Dhir Mashaal,Lyden Elizabeth R,Wang Antai,Smith Lynette M,Ullrich Fred,Are Chandrakanth Annals of surgery OBJECTIVE:The aim of our study was to conduct a meta-analysis of reports published on hepatic resection for colorectal liver metastasis (CRLM) and determine whether a negative margin of 1 cm or more confers a survival advantage over subcentimeter negative margins. BACKGROUND:Surgical margin is an important prognostic factor in patients undergoing hepatic resection for CRLM. Although there is a consensus that positive margins portend a worse outcome than negative margins, the extent of negative margins remains controversial. METHODS:A PubMed search was conducted to identify articles on hepatic resection for CRLM. The 357 initially located articles were screened to identify 90 articles of interest. The texts of these 90 articles were completely reviewed to finalize 18 articles for inclusion in the study on the basis of absolute and relative inclusion criteria. Patients with positive margins were excluded from the meta-analysis. Meta-analysis was performed using STATA 9.2 statistical software. RESULTS:A total of 4821 patients with negative margins from the 18 studies were included in the meta-analysis. The overall 5-year survival for all patients was 41% [95% confidence interval (CI), 40%-43%]. The overall 5-year survival for the ≥1 cm negative margin subgroup was 46% (95% CI, 44%-48%) when compared with 38% (95% CI, 36%-40%) for less than 1 cm negative margin subgroup. The odds ratio for 1-cm or more negative margins was found to be 0.773 (95% CI, 0.638-0.938; P = 0.009) when compared with less than 1 cm negative margins. CONCLUSIONS:The results of this meta-analysis demonstrate that in patients undergoing hepatic resection for CRLM, a negative margin of 1 cm or more confers a survival advantage when compared with subcentimeter negative margins. 10.1097/SLA.0b013e318223c609
Surgery for colorectal liver metastases: the impact of resection margins on recurrence and overall survival. Angelsen Jon-Helge,Horn Arild,Eide Geir Egil,Viste Asgaut World journal of surgical oncology BACKGROUND:Several reports have presented conflicting results regarding the association between resection margins (RMs) and outcome after surgery for colorectal liver metastases (CLM), especially in the era of modern chemotherapy. The purpose of this study was to evaluate the impact of RMs on overall survival (OS), time to recurrence (TTR) and local recurrence (LR) status, particularly for patients treated with preoperative chemotherapy. METHODS:A combined retrospective (1998 to 2008) and prospective (2008 to 2010) cohort study of consecutive patients with CLM without extrahepatic disease treated with primary resection at a medium volume centre. RESULTS:A total of 253 patients with known R status and 242 patients with defined margin width were included in the study. Patients were stratified according to margin width; A: R1, <1 mm (n=48, 19%), B: 1 to 4 mm (n=77), C: 5 to 9 mm (n=46) and D: ≥10 mm (n=71). Median time to recurrence was 12.8 months, and after five years 21.5% had no recurrence. LR (inclusive combined recurrence in other hepatic sites or extrahepatic) occurred in 40 (16.5%) cases, most frequently seen with RMs below 5 mm. Five-year OS was 42.5% in R0 and 16.1% in R1 resections (P=0.011). Patients were also stratified according to preoperative chemotherapy (n=88), and the difference in five-year OS between R0 (45.1%) and R1 (14.7%) was maintained (P=0.037). By multiple Cox regression analysis R1 resections tended to an adverse outcome (P=0.067), also when adjusting for preoperative chemotherapy (P=0.081). CONCLUSIONS:R1 resections for colorectal liver metastases predict adverse outcome. RMs below 5 mm increased the risk for LR and shortened the time to recurrence. Preoperative chemotherapy did not alter an adverse outcome in R1 vs. R0 patients. 10.1186/1477-7819-12-127
R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? de Haas Robbert J,Wicherts Dennis A,Flores Eduardo,Azoulay Daniel,Castaing Denis,Adam René Annals of surgery OBJECTIVE: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. SUMMARY BACKGROUND DATA: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. METHODS: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. RESULTS: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. CONCLUSIONS: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. 10.1097/SLA.0b013e31818a07f1
Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate? Sadot Eran,Groot Koerkamp Bas,Leal Julie N,Shia Jinru,Gonen Mithat,Allen Peter J,DeMatteo Ronald P,Kingham T Peter,Kemeny Nancy,Blumgart Leslie H,Jarnagin William R,DʼAngelica Michael I Annals of surgery OBJECTIVES:The impact of margin width on overall survival (OS) in the context of other prognostic factors after resection for colorectal liver metastases is unclear. We evaluated the relationship between resection margin and OS utilizing high-resolution histologic distance measurements. METHODS:A single-institution prospectively maintained database was queried for all patients who underwent an initial complete resection of colorectal liver metastases between 1992 and 2012. R1 resection was defined as tumor cells at the resection margin (0 mm). R0 resection was further divided into 3 groups: 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or greater. RESULTS:A total of 4915 liver resections were performed at Memorial Sloan Kettering Cancer Center between 1992 and 2012, from which 2368 patients were included in the current study. Half of the patients presented with synchronous disease, 43% had solitary metastasis, and the median tumor size was 3.4 cm. With a median follow-up for survivors of 55 months, the median OS of the R1, 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or more groups was 32, 40, 53, and 56 months, respectively (P < 0.001). Compared with R1 resection, all margin widths, including submillimeter margins correlated with prolonged OS (P < 0.05). The association between the margin width and OS remained significant when adjusted for all other clinicopathologic prognostic factors. CONCLUSIONS:Resection margin width is independently associated with OS. Wide margins should be attempted whenever possible. However, resection should not be precluded if narrow margins are anticipated, as submillimeter margin clearance is associated with improved survival. The prolonged OS observed with submillimeter margins is likely a microscopic surrogate for the biologic behavior of a tumor rather than the result of surgical technique. 10.1097/SLA.0000000000001427
Sub-millimeter surgical margin is acceptable in patients with good tumor biology after liver resection for colorectal liver metastases. Xu Da,Wang Hong-Wei,Yan Xiao-Luan,Li Juan,Wang Kun,Xing Bao-Cai European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology BACKGROUND:The definition of R1 resection in colorectal cancer liver metastases (CRLM) remains debatable. This retrospective study was conducted to clarify the impact of R1 margin on patient survival after liver resection for CRLM, taking into consideration tumor biology, including RAS status and chemotherapy response. METHODS:We retrospectively analysed the clinical and survival data of 214 CRLM patients with initially resectable liver metastases who underwent liver resection after receiving neoadjuvant chemotherapy between January 2006 and December 2016. RESULTS:R1 resection significantly impacted patients' overall survival (OS) and disease-free survival (DFS) in the overall patient cohort (5-year OS: 53.2% for R0 vs 38.2% for R1, P = 0.001; 5-year DFS: 26.5% for R0 vs 10.5% for R1, P = 0.002). In the RAS wild-type subgroup and respond to chemotherapy (RC) subgroup, R1 reached a similar OS to those who underwent R0 resection (RAS wild-type, P = 0.223; RC, P = 0.088). For the RAS mutated subgroup and no response to chemotherapy (NRC) subgroup, OS was significantly worse underwent R1 resection (RAS mutant, P = 0.002; NRC, P = 0.022). When considering tumor biology combining RAS and chemotherapy response status, R1 resection was only acceptable in patients with both RAS wild-type and RC (5-year OS: 66.4% for R0 vs 65.2% for R1, p = 0.884), but was significantly worse in those with either RAS mutation or NRC. CONCLUSIONS:Tumor biology plays an important role in deciding the appropriate resection margin in patients with CRLM undergoing radical surgery. R1 resection margin is only acceptable in RAS wild-type patients who respond to chemotherapy. 10.1016/j.ejso.2019.03.010
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. Ardito Francesco,Panettieri Elena,Vellone Maria,Ferrucci Massimo,Coppola Alessandro,Silvestrini Nicola,Arena Vincenzo,Adducci Enrica,Capelli Giovanni,Vecchio Fabio M,Giovannini Ivo,Nuzzo Gennaro,Giuliante Felice Surgery 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. 10.1016/j.surg.2018.09.005
Outcome of microscopic incomplete resection (R1) of colorectal liver metastases in the era of neoadjuvant chemotherapy. Ayez Ninos,Lalmahomed Zarina S,Eggermont Alexander M M,Ijzermans Jan N M,de Jonge Jeroen,van Montfort Kees,Verhoef Cornelis Annals of surgical oncology BACKGROUND:Data from patients with colorectal liver metastases (CRLM) who received neoadjuvant chemotherapy before resection were reviewed and evaluated to see whether neoadjuvant chemotherapy influences the predictive outcome of R1 resections (margin is 0 mm) in patients with CRLM. METHODS:Between January 2000 and December 2008, all consecutive patients undergoing liver resection for CRLM were analyzed. Patients were divided into those who did and did not receive neoadjuvant chemotherapy. The outcome after R0 (tumor-free margin >0 mm) and R1 (tumor-free margin 0 mm) resection was compared. RESULTS:A total of 264 were eligible for analysis. Median follow-up was 34 months. Patients without chemotherapy showed a significant difference in median disease-free survival (DFS) after R0 or R1 resection: 17 [95% confidence interval (CI) 10-24] months versus 8 (95% CI 4-12) months (P < 0.001), whereas in patients with neoadjuvant chemotherapy the difference in DFS between R0 and R1 resection was not significant: 18 (95% CI 10-26) months versus 9 (95% CI 0-20) months (P = 0.303). Patients without chemotherapy showed a significant difference in median overall survival (OS) after R0 or R1 resection: 53 (95% CI 40-66) months versus 30 (95% CI 13-47) months (P < 0.001). In patients with neoadjuvant chemotherapy, the median OS showed no significant difference: 65 (95% CI 39-92) months for the R0 group versus the R1 group, in whom the median OS was not reached (P = 0.645). CONCLUSIONS:In patients treated with neoadjuvant chemotherapy, R1 resection was of no predictive value for DFS and OS. 10.1245/s10434-011-2114-4
Impact of subcentimeter margin on outcome after hepatic resection for colorectal metastases: a meta-regression approach. Cucchetti Alessandro,Ercolani Giorgio,Cescon Matteo,Bigonzi Eleonora,Peri Eugenia,Ravaioli Matteo,Pinna Antonio D Surgery BACKGROUND:The optimal margin width and its influence on outcomes after hepatic resection for colorectal liver metastases is still controversial: a meta-analysis was conducted to analyze the impact of subcentimeter margin width on patient and disease-free survival after resection. METHODS:A systematic search was performed, covering the last decade, following the Meta-analysis Of Observational Studies in Epidemiology guidelines. Relative risks (RRs) for patient and disease-free survival (DFS) were calculated after resection in relationship to a margin width >1 cm (R0 > 1 cm) and between 1 mm and 1 cm (R0 < 1 cm) using the DerSimonian and Laird random-effects model. Meta-regression was applied for covariate adjustment. RESULTS:Eleven observational studies were identified involving 2823 patients. Overall, 59.1% of patients were R0 < 1 cm and 40.9% were R0 > 1 cm. Meta-analysis showed that compared with patients with margins R0 > 1 cm, a R0 < 1 cm margin lead to decreased 1-, 3-, and 5-year DFS with a RR of 1.17 (95% confidence interval [CI] 1.07-1.27), 1.38 (95% CI 1.16-1.65), and 1.55 (95% CI 1.25-1.91), respectively, but patient survival was obviously affected (P > .05 in all cases). Patients with margins of R0 < 1 cm differ from those with R0 > 1 cm for greater proportions of multiple metastases (RR 1.43; 95% CI 0.25-1.61) and synchronous bowel disease (RR 1.42; 95% CI 0.8-1.92). Meta-regression showed that these two covariates had a significant impact on DFS but not on patient survival. CONCLUSION:A resection margin width >1 cm is desirable even if patient survival is at best only slightly affected by subcentimeter margin as a consequence of a decreased DFS. The presence of multiple metastases and synchronous bowel neoplasm represent potential study selection biases that significantly decrease DFS; well-conducted, matched analyses consequently are essential to clarify the issue. 10.1016/j.surg.2011.12.009
Quantification of risk of a positive (R1) resection margin following hepatic resection for metastatic colorectal cancer: an aid to clinical decision-making. Welsh Fenella K S,Tekkis Paris P,O'Rourke Tom,John Timothy G,Rees Myrddin Surgical oncology BACKGROUND AND AIMS:Margin involvement following liver resection for colorectal cancer is associated with early disease recurrence and shorter long-term survival. This study aimed to develop a predictive index for quantifying the likelihood of a positive resection margin (R1) for patients undergoing hepatic resection for metastatic colorectal cancer. METHODS:Clinical, pathological and complete follow-up data were prospectively collected from 1005 consecutive liver resections performed in 929 patients for colorectal liver metastases with curative intent at a single centre between 1987 and 2005. Ninety-four resections in 81 patients with extra-hepatic disease were excluded, leaving 911 resections (844 primary and 67 repeat) in 848 patients for analysis. Multivariate logistic regression was used to identify independent predictors of margin involvement and from the beta-coefficients generated, develop a predictive model that was validated using measures of discrimination and calibration. RESULTS:There were 80 (8.8%) R1 resections, with a 5-year cancer-specific survival for R0 and R1 hepatic resections of 39.7% and 17.8%, respectively; p<0.001. On multivariate analysis, five risk factors were found to be independent predictors of an R1 resection: non-anatomical resection vs. anatomical resection (odds ratio (OR)=4.3, p=0.001), >3 hepatic metastases involving >50% of the liver vs. <3 metastases (OR=4.0, p<0.001); bilobar vs. unilobar disease (OR=2.9, p<0.001); repeat vs. primary hepatic resection (OR=3.1, p=0.006); abnormal vs. normal pre-operative liver function tests (OR=1.6, p=0.044). These five factors were used to develop a predictive model, which when tested, fitted the data well, with an area under the receiver operating characteristic curve of 78.1% (S.E.=2.7%). CONCLUSIONS:This study describes an accurate model for quantifying the risk of a positive margin following hepatic resection for liver metastases. It may be used pre-operatively by multi-disciplinary teams to identify patients who may benefit from neoadjuvant therapy prior to liver surgery, thus minimizing the risk of a positive resection margin. 10.1016/j.suronc.2007.12.003
Interaction of margin status and tumour burden determines survival after resection of colorectal liver metastases: A retrospective cohort study. Mao Rui,Zhao Jian-Jun,Bi Xin-Yu,Zhang Ye-Fan,Li Zhi-Yu,Zhou Jian-Guo,Zhao Hong,Cai Jian-Qiang International journal of surgery (London, England) PURPOSE:We sought to determine the impact of surgical margin status on overall survival (OS) and recurrence pattern stratified by tumor burden. MATERIALS AND METHODS:Data were collected from patients undergoing resection for colorectal liver metastases (CRLM). Tumor burden was calculated according to a newly proposed Tumor Burden Score (TBS) system, defined as the distance from the origin on a Cartesian plane that incorporated maximum tumor size and number of liver lesions. Patients were divided into low tumor burden group and high tumor burden group accordingly, and the impact of resection margin on overall survival was examined. RESULTS:A total of 286 patients were available, among which R1 resection was observed in 88 patients. The median TBS for the entire cohort was 3.84. Metastases in the R1 group were characterized by more advanced disease and more complex resections. Compared with a R0 resection, a R1 resection offered an lower 5-year overall survival rate (46.8% vs. 22.1%, p = 0.001). Multivariate analysis identified R1 resection (p = 0.03), high TBS (p = 0.002), lymph nodes metastases (p = 0.003) and lymphovascular invasion (p = 0.03) of the primary colorectal tumor as the factors independently associated with worse survival. The survival benefit associated with negative margins was greater in patients with low TBS (55.7% vs. 21.7%, p = 0.021) than in patients with high TBS (31.8% vs. 24.5%, p = 0.116). R1 resection was associated with an increased true margin recurrence rate in patients with low TBS (32.3% vs. 13.4%; p = 0.014) and an increased risk of new intrahepatic metastases in patients with high TBS (43.9% vs. 26.7%; p = 0.034). CONCLUSIONS:Negative margin is an important determinant of survival. The impact of positive margins is more pronounced in patients with low tumor burden. 10.1016/j.ijsu.2017.12.001
Impact of margin status and neoadjuvant chemotherapy on survival, recurrence after liver resection for colorectal liver metastasis. Pandanaboyana Sanjay,White Alan,Pathak Samir,Hidalgo Ernest L,Toogood Giles,Lodge J P,Prasad K R Annals of surgical oncology BACKGROUND:This study was designed to determine the impact of positive margin and neoadjuvant chemotherapy (NAC) on recurrence and survival after resection of colorectal liver metastasis (CRLM). METHODS:Prospective analysis of 1,255 patients undergoing resection of CLRM was undertaken. The impact of NAC, site of recurrence, and survival between R0 and R1 groups was analysed. RESULTS:The R0 and R1 resection rates were 68.9 % (n = 865) and 31.1 % (390). The median OS for R0 group was 2.7 years (95 % CI 2.56-2.85) and R1 group 2.28 years (CI 2.06-2.52; P < 0.001). The median DFS for R0 group was 1.52 years (CI 1.38-1.66) and R1 group 1.04 years (CI 0.94-1.19; P < 0.001). The intrahepatic recurrence was higher in R1 group 132 (33.8 %) versus 142 (16.4 %) [P = 0.0001]. A total of 103 (11.9 %) patients in R0 group underwent redo liver resection for recurrence compared with 66 (16.9 %) patients in R1 group (P = 0.016). NAC did not impact recurrence rate (57.8 % vs. 61.5 %, P = 0.187) and redo liver surgery between R0 and R1 groups (13 % vs. 17 %, P = 0.092). Within the R1 group, the intrahepatic recurrence rates were similar with and without NAC (33.9 % vs. 33.7 %, P = 0.669). However, DFS was longer in the no chemotherapy group than the chemotherapy group. CONCLUSIONS:R1 resections increase the likelihood of recurrence in the liver and redo liver surgery. NAC does not seem to improve survival in margin positive patients or have an impact on recurrence or reduce need for redo liver surgery for recurrence. In patients with R1 resection, neoadjuvant chemotherapy may have adverse outcome on disease free survival. 10.1245/s10434-014-3953-6
Influence of surgical margin on type of recurrence after liver resection for colorectal metastases: a single-center experience. Nuzzo Gennaro,Giuliante Felice,Ardito Francesco,Vellone Maria,Giovannini Ivo,Federico Bruno,Vecchio Fabio M Surgery BACKGROUND:Hepatectomy for colorectal liver metastases (CRLM) may offer good long-term survival. The impact of the tumor-free surgical margin on long-term results remains controversial, and we have assessed this component in 185 patients. METHODS:Between 1992 and 2005, 185 patients underwent primary hepatectomy with curative intent for CRLM (which originated from colon/rectum 133/52, synchronous/metachronous 66/119, and single/multiple 100/85). In this study, 105 major and 80 minor hepatectomies were evaluated; 133 hepatectomies had pedicle clamping. RESULTS:Operative mortality was 1.1%, morbidity was 25.7%, and blood transfusion requirement was 27.6%. Stratification of tumor-free margin in the patients with R0 liver resection was greater than or equal to 10 mm (63.0% of patients), 6-9 mm (11.4% of patients), 3-5 mm (16.5% of patients), and less than or equal to 2 mm (9.1% of patients), with infiltrated margin in the remainder (R1 liver resection 4.9% of the total number of patients). The 3-year, 5-year, and 10-year survival rates were 54.9%, 37.9%, and 22.9%, respectively. Global and surgical margin recurrence rates increased as the tumor-free margin decreased (P = .01 and P < .001, respectively). At univariate analysis, the width of surgical margin (P < .001), transfusion requirement, major hepatectomy, R1 resection, number of metastases, high preoperative CEA, and increasing tumor size (P value from .001 to .03) were associated with lesser rates of long-term survival. A similar association was found with disease-free survival. At multivariate analysis, width of surgical margin was the only independent predictor of both overall (P = .003) and disease-free (P < .001) survival. Although smaller margins were associated with synchronicity, increasing number of, and with bilobar distribution of, metastases which contributed to explain recurrences away from the margin), the width of surgical margin maintained the prominent impact on outcome. CONCLUSIONS:In our patients, the width of the surgical margin was a powerful prognostic factor after hepatectomy for CRLM. A resection margin less than or equal to 5 mm was associated with a greater risk of recurrence on the surgical margin, with a lesser rate of overall and disease-free survival. 10.1016/j.surg.2007.09.038
Negative surgical margin improved long-term survival of colorectal cancer liver metastases after hepatic resection: a systematic review and meta-analysis. Liu Wei,Sun Yi,Zhang Lei,Xing Bao-Cai International journal of colorectal disease 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. 10.1007/s00384-015-2323-6
Liver resection for colorectal liver metastases with peri-operative chemotherapy: oncological results of R1 resections. Eveno Clarisse,Karoui Mehdi,Gayat Etienne,Luciani Alain,Auriault Marie-Luce,Kluger Michael D,Baumgaertner Isabelle,Baranes Laurence,Laurent Alexis,Tayar Claude,Azoulay Daniel,Cherqui Daniel HPB : the official journal of the International Hepato Pancreato Biliary Association BACKGROUND:Retrospective analysis of outcomes of R0 (negative margin) versus R1 (positive margin) liver resections for colorectal metastases (CLM) in the context of peri-operative chemotherapy. METHODS:All CLM resections between 2000 and 2006 were reviewed. Exclusion criteria included: macroscopically incomplete (R2) resections, the use of local treatment modalities, the presence of extra-hepatic disease and no peri-operative chemotherapy. R0/R1 status was based on pathological examination. RESULTS:Of 86 eligible patients, 63 (73%) had R0 and 23 (27%) had R1 resections. The two groups were comparable for the number, size of metastases and type of hepatectomy. The R1 group had more bilobar CLM (52% versus 24%, P = 0.018). The median follow-up was 3.1 years. Five-year overall and disease-free survival were 54% and 21% for the R0 group and 49% and 22% for the R1 group (P = 0.55 and P = 0.39, respectively). An intra-hepatic recurrence was more frequent in the R1 group (52% versus 27%, P = 0.02) and occurred more frequently at the surgical margin (22% versus 3%, P = 0.01). DISCUSSION:R1 resections were associated with a higher risk of intra-hepatic and surgical margin recurrence but did not negatively impact survival suggesting that in the era of efficient chemotherapy, the risk of an R1 resection should not be considered as a contraindication to surgery. 10.1111/j.1477-2574.2012.00581.x
Survival and Prognostic Factors of Colorectal Liver Metastases After Surgical and Nonsurgical Treatment. Lemke Johannes,Cammerer Gregor,Ganser Johannes,Scheele Jan,Xu Pengfei,Sander Silvia,Henne-Bruns Doris,Kornmann Marko Clinical colorectal cancer OBJECTIVE:Colorectal cancer is one leading cause of cancer-related death worldwide, and distant metastases determine an unfavorable prognosis. Surgical resection of colorectal liver metastases (CRLM) improves survival and provides the chance for cure. The aim of this study was to prospectively analyze the outcome of patients with CRLM in a population-based manner, and thereby, to compare the prognosis of patients undergoing resection with those receiving nonsurgical treatment. Moreover, we set out to identify and confirm important prognostic factors after resection of CRLM. PATIENTS AND METHODS:We analyzed the outcome of 506 patients diagnosed with CRLM in our institution from 1996 to 2011. Survival and the impact of clinical and pathologic factors were analyzed by univariate analysis. Important independent prognostic factors were analyzed by multivariate analysis. RESULTS:The 5-year overall survival rate (5y-OSR) for patients receiving resection of CRLM (n = 152) was 46% (95% confidence interval (CI), 37%-54%) compared with a 5y-OSR of 6% (95% CI, 4%-9%) for patients treated nonsurgically (n = 354). There was no perioperative mortality. Multivariate analysis revealed, among other factors, good performance status of the patient (low American Society of Anesthesiologists score), the absence of extrahepatic metastases, < 5 metastatic lesions, and a tumor-free resection margin (R0) as important, independent prognostic factors. Importantly, repeated hepatic resections of CRLM performed in 13 patients were associated with an excellent outcome (5y-OSR, 47%; 95% CI, 17%-72%). CONCLUSION:Surgical resection, which can be performed with tolerable site-effects, is the first choice for patients diagnosed with metachronous and synchronous CRLM. Of note, repeated resections should be advised in recurrent intrahepatic colorectal cancer whenever possible. 10.1016/j.clcc.2016.04.007
The impact of subdivisions of microscopically positive (R1) margins on patterns of relapse in stage III colorectal cancer - A retrospective cohort study. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland AIM:Microscopically positive (R1) margins are associated with poorer outcomes in patients with colorectal cancer. However, the impact of subdivisions of R1 margins, be they to the primary tumour (R1 tumour) or to lymph node metastases (R1LNM), on patterns of relapse is unknown. METHODS:Patients treated for stage III colorectal cancer from 01 January 2016 to 31 December 2019 in four specialist centres were identified from the Danish national cancer registry. Patients were stratified into three groups according to margin status (R0 vs. R1 tumour vs. R1LNM). The primary outcomes were local recurrence-free survival (LRFS), distant metastases-free survival (DMFS) and disease-specific survival (DSS). RESULTS:A total of 1,164 patients were included, with R1 margins found in 237 (20.4%). Irrespective of tumour location, R1 tumour and R1LNM margins were independent prognostic factors for systemic relapse (R1 tumour HR 1.84, CI: 1.17-2.88, p = 0.008; R1LNM HR 1.59, CI: 1.12-2.27, p = 0.009) and disease-related death (R1 tumour HR 2.08, CI: 1.12-3.85, p = 0.020; R1LNM HR 1.84, CI: 1.12-3.02, p = 0.016). Whereas R1 tumour margins were associated with poorer 3-year LRFS in both colon and rectum cancer, R1LNM margins only reduced LRFS in patients with rectal cancer. Patterns of relapse differed between R1 subdivisions, with R1 tumour margins more likely to affect multiple anatomical sites, with a predilection for extra-hepatic/pulmonary metastases. CONCLUSION:Subdivisions of R1 margins have a distinct impact on the oncological outcomes and patterns of disease relapse in patients with stage III colorectal cancer. 10.1111/codi.16121
Impact of Surgical Margin Width on Recurrence and Overall Survival Following R0 Hepatic Resection of Colorectal Metastases: A Systematic Review and Meta-analysis. Margonis Georgios A,Sergentanis Theodoros N,Ntanasis-Stathopoulos Ioannis,Andreatos Nikolaos,Tzanninis Ioannis-Georgios,Sasaki Kazunari,Psaltopoulou Theodora,Wang Jaeyun,Buettner Stefan,Papalois Αpostolos E,He Jin,Wolfgang Christopher L,Pawlik Timothy M,Weiss Matthew J Annals of surgery OBJECTIVE:To examine the impact of surgical margin width on survival following R0 hepatic resection for colorectal metastases (CRLM). SUMMARY OF BACKGROUND DATA:Although negative resection margin is considered of paramount importance for the prognosis of patients with colorectal liver metastases, optimal resection margin width remains controversial. METHODS:Eligible studies examining the association between margin status after R0 hepatic resection for CRLM and survival, including overall survival (OS) and disease-free survival (DFS) were sought using the Medline, Cochrane, and EMBASE databases. Random-effects models were used for the calculation of pooled relative risks (RRs) with their 95% confidence intervals (95% CIs). RESULTS:Thirty-four studies were deemed eligible for inclusion representing a cohort of 11,147 hepatic resections. Wider resection margin (>1 vs <1 cm) was significantly associated with improved OS at 3 years (pooled RR = 0.86, 95% CI: 0.79-0.95), 5 years (pooled RR = 0.91, 95% CI: 0.85-0.97), and 10 years (pooled RR = 0.94, 95% CI: 0.88-1.00). Similarly, DFS was positively associated with >1 cm resection margin at 3, 5, and 10 years. Interestingly, >1 mm (vs <1 mm) resection margin was significantly associated with improved OS at all-time points. Meta-regression analyses did not reveal any significant modifying role of the study features under investigation, such as the administration of neoadjuvant/adjuvant therapy. CONCLUSIONS:Importantly, our findings suggest that while a >1 mm margin is associated with better prognosis than a submillimeter margin, achieving a margin >1 cm may result in even better oncologic outcomes and should be considered if possible. 10.1097/SLA.0000000000002552
Intraoperative surgical margin re-resection for colorectal liver metastasis: is it worth the effort? Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 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. 10.1007/s11605-014-2710-2
Resection of liver metastases from colorectal cancer. Indications and results. Pedersen I K,Burcharth F,Roikjaer O,Baden H Diseases of the colon and rectum PURPOSE:This study was undertaken to determine the indications for and value of liver resection for metastases from colorectal cancer. METHODS:From 1978 through 1991, 66 patients were operated on for liver metastases from colorectal cancer. All patients had had a curative resection of their colorectal cancer. Forty resections of the liver were major anatomic resections. RESULTS:Five patients died in the postoperative period. All resections were intended to be curative, but in 16 of the patients the resection became noncurative. None of these patients lived more than two years after liver resection. Fifty patients with a curative resection had a three-year survival rate of 36 percent, postoperative death included. Recurrence in the liver was observed in 30 patients (60 percent) from 3 to 33 (median, 11) months after the liver resection. Four patients had repeated resections performed. Two of them are alive without recurrences 34 and 60 months after the first liver resection, respectively. The difference in survival between curative and noncurative liver resection was highly significant (P = 0.01). CONCLUSIONS:Sex, age, Dukes stage of primary colorectal cancer, synchronous or metachronous appearance of metastases, or number of metastases could not predict long-term prognosis. The only factors of predictive value were tumor size less than 4 cm in diameter, a free resection margin, and no extrahepatic tumor. If it is possible to do a curative resection, there should be few contraindications against liver surgery as it is the only treatment that can demonstrate long-term survival for approximately one-third of the patients, and it is the only possibility of a cure. 10.1007/bf02049807
Perioperative and long-term outcomes of laparoscopic liver resections for non-colorectal liver metastases. Triantafyllidis Ioannis,Gayet Brice,Tsiakyroudi Sofia,Tabchouri Nicolas,Beaussier Marc,Bennamoun Mostefa,Sarran Anthony,Lefevre Marine,Louvet Christophe,Fuks David Surgical endoscopy BACKGROUND:Liver is a common metastatic site not only of colorectal but of non-colorectal neoplasms, as well. However, resection of non-colorectal liver metastases (NCRLMs) remains controversial. The aim of this retrospective study was to analyze the short- and long-term outcomes of patients undergoing laparoscopic liver resection (LLR) for NCRLMs. METHODS:From a prospectively maintained database between 2000 and 2018, patients undergoing LLR for colorectal liver metastases (CRLMs) and NCRLMs were selected. Clinicopathologic, operative, short- and long-term outcome data were collected, analyzed, and compared among patients with CRLMs and NCRLMs. RESULTS:The primary tumor was colorectal in 354 (82.1%), neuroendocrine in 21 (4.9%), and non-colorectal, non-neuroendocrine in the remaining 56 (13%) patients. Major postoperative morbidities were 12.7%, 19%, and 3.6%, respectively (p = 0.001), whereas the mortality was 0.6% for patients with CRLMs and zero for patients with NCRLMs. The rate of R surgical margin was comparable (p = 0.432) among groups. According to the survival analysis, 3- and 5-year recurrence-free survival (RFS) rates were 76.1% and 64.3% in the CRLM group, 57.1% and 42.3% in the neuroendocrine liver metastase (NELM) group, 33% and 20.8% in the non-colorectal, non-neuroendocrine liver metastase (NCRNNELM) group (p = 0.001), respectively. Three- and 5-year overall survival (OS) rates were 88.3% and 82.7% in the CRLM group, 85.7% and 70.6% in the NELM group, 71.4% and 52.9% in the NCRNNELM group (p = 0.001), respectively. In total, 113 out of 354 (31.9%) patients with CRLMs, 2 out of 21(9.5%) with NELMs, and 8 out of 56 (14.3%) patients with NCRNNELMs underwent repeat LLR for recurrent metastatic tumors. CONCLUSION:LLR is safe and feasible in the context of a multimodal management where an aggressive surgical approach, necessitating even complex procedures for bilobar multifocal metastases and repeat hepatectomy for recurrences, is the mainstay and may be of benefit in the long-term survival, in selected patients with NCRNNELMs. 10.1007/s00464-019-07148-4
Preventing Futile Liver Resection: A Risk-Based Approach to Surgical Selection in Major Hepatectomy for Colorectal Cancer. Annals of surgical oncology BACKGROUND:Early recurrence following liver resection for metastatic colorectal cancer generally portends poor survival. We sought to identify factors associated with early disease recurrence after major hepatectomy for metastatic colorectal cancer in order to improve patient selection and prevent futile hepatectomy. METHODS:Sequential major (four or more segments) liver resections performed for metastatic colorectal cancer between 1995 and 2019 were selected from our prospectively maintained database. Univariate analyses, multivariable regression modelling, and survival analyses were used to identify predictors of futile resection (recurrence within 6 months of hepatectomy). RESULTS:Of 259 patients included, the median age was 61.3 years (interquartile range [IQR] 15.3) and the median number of liver tumors was 3.0 (IQR 2.0); 78.0% of patients received prehepatectomy chemotherapy. Surgeries were right (56.4%), left (19.3%), and extended hepatectomy (24.3%). Futile resection occurred in 26 (12.6%) patients. Margin positivity was similar in the futile resection group compared with the non-futile resection group (11.5% vs. 11.4%). Extrahepatic disease that disappeared with chemotherapy was present in 23.1% of patients with a futile resection and 7.2% of those without (p = 0.019). After multivariable regression, the factors predictive of futile resection were extrahepatic disease (odds ratio [OR] 5.6; p = 0.004), more than three liver lesions (OR 4.9; p = 0.001), and extended hepatectomy (OR 2.6; p = 0.038). Notably, 70.8% of futile recurrences occurred within the liver remnant and 20.8% were pulmonary metastases. Overall survival was 11.7 months (95% confidence interval [CI] 7.1-16.2) for the futile resection cohort versus 45.6 (95% CI 39.1-52.1) for non-futile hepatectomies (p < 0.001). CONCLUSIONS:Futile hepatic resection can be predicted based on preoperative factors and carries a poor prognosis. Improved risk stratification for futility will aid in patient selection and treatment discussions. 10.1245/s10434-021-10761-0
Effect of Time to Surgery of Colorectal Liver Metastases on Survival. Chen Emerson Y,Mayo Skye C,Sutton Thomas,Kearney Matthew R,Kardosh Adel,Vaccaro Gina M,Billingsley Kevin G,Lopez Charles D Journal of gastrointestinal cancer PURPOSE:Resection of liver-only colorectal liver metastases (CRLM) with perioperative chemotherapy is potentially curative. Specific primary tumor and liver metastasis characteristics have been validated to estimate the risk of recurrence. We hypothesize that the time interval from diagnosis of CRLM to surgery, or time to surgery (TTS), is clinically prognostic. METHODS:Patients from a prospectively maintained institutional database at a Comprehensive Cancer Center from May 2003 to January 2018 were reviewed. Clinicopathologic, perioperative treatment, and TTS data were collected. TTS was categorized into short (< 3 months), intermediate (3-6 months), and long (> 6 months) intervals. RESULTS:Two hundred eighty-one patients were identified. While overall survival (OS) was similar across TTS, postoperative overall survival (postoperative OS) of long TTS was associated with worse survival, 44 months (95% CI, 34-52) compared to short TTS, 59 months (95% CI, 43-79), and intermediate TTS, 63 months (95% CI, 52-108), both p < 0.01. With regard to long-term OS, intermediate TTS had 5-year OS of 59% and 8-year OS of 43% compared to long TTS (5-year OS 53% and 8-year OS 18%) and short TTS (5-year OS 54% and 8-year OS 29%). Long TTS was negatively associated with postoperative OS on multivariate analysis (HR 1.6, p < 0.01) when adjusting for resection margin, CRLM size, age, and use of postoperative chemotherapy. CONCLUSION:Short and intermediate TTS had similar survival although patients with intermediate TTS may have better odds of long-term OS. While long TTS was associated with worse survival, likely due to higher disease burden, long-term survivors were still observed. 10.1007/s12029-020-00372-5
Repeat hepatectomy for recurrent colorectal liver metastases is associated with a high survival rate. Andreou Andreas,Brouquet Antoine,Abdalla Eddie K,Aloia Thomas A,Curley Steven A,Vauthey Jean-Nicolas HPB : the official journal of the International Hepato Pancreato Biliary Association BACKGROUND:The outcome after a repeat hepatectomy for recurrent colorectal liver metastases (CLM) is not well defined. The present study examined the morbidity, mortality and long-term survivals after a repeat hepatectomy for recurrent CLM. METHODS:Data on patients who underwent surgery for recurrent CLM between 1993 and 2009 were retrospectively evaluated. Patients who underwent radiofrequency ablation at the time of first treatment or at recurrence of CLM were excluded. RESULTS:Forty-three patients underwent a repeat hepatectomy for recurrent CLM. At the time of recurrence, patients had a median of 1 (1-3) lesions and the median tumour size was 2 (0.5-8.7) cm. The post-operative morbidity and mortality rates were 12% and 0%, respectively. After a median follow-up of 33 months from a repeat hepatectomy, 5-year overall and progression-free survival rates were 73% and 22%, respectively. Using multivariate analysis, the largest initial CLM ≥5 cm and positive surgical margins at initial resection were independently associated with a worse survival after surgery for recurrent CLM. Positive surgical margins at repeat hepatectomy were a predictive factor for an increased risk of further recurrence. DISCUSSION:A repeat hepatectomy for recurrent CLM was associated with excellent survival, low morbidity and no mortality. Surgeon-controlled variables, including margin-negative resection at first and repeat hepatectomy, contribute to good oncological outcome. 10.1111/j.1477-2574.2011.00370.x
Recurrence at surgical margin following hepatectomy for colorectal liver metastases is not associated with R1 resection and does not impact survival. Andreou Andreas,Knitter Sebastian,Schmelzle Moritz,Kradolfer Daniel,Maurer Martin H,Auer Timo Alexander,Fehrenbach Uli,Lachenmayer Anja,Banz Vanessa,Schöning Wenzel,Candinas Daniel,Pratschke Johann,Beldi Guido Surgery BACKGROUND:Resection margin status has traditionally been associated with tumor recurrence and oncological outcome following liver resection for colorectal liver metastases. Previous studies, however, did not address the impact of resection margin on the site of tumor recurrence and did not differentiate between true local recurrence at the resection margin and recurrence elsewhere in the liver. This study aimed to determine whether positive resection margins determine local recurrence and whether recurrence at the surgical margin influences long-term survival. METHODS:Clinicopathological data and oncological outcomes of patients who underwent curative resection for colorectal liver metastases between 2012 and 2017 at 2 major hepatobiliary centers (Bern, Switzerland, and Berlin, Germany) were assessed. Cross-sectional imaging following hepatectomy was reviewed by radiologists in both centers to distinguish between recurrence at the resection margin, defined as hepatic local recurrence, and intrahepatic recurrence elsewhere. The association between surgical margin status and location of tumor recurrence was evaluated, and the impact on overall survival was determined. RESULTS:During the study period, 345 consecutive patients underwent hepatectomy for colorectal liver metastases. Histologic surgical margins were positive for tumor cells (R1) in 63 patients (18%). After a median follow-up time of 34 months, tumor recurrence was identified in 154 patients (45%). Hepatic local recurrence was not detected more frequently after R1 than after R0 resection (P = .555). Hepatic local recurrence was not associated with worse overall survival (P = .436), while R1 status significantly impaired overall survival (P = .025). Additionally, overall survival was equivalent between patients with hepatic local recurrence and patients with any intrahepatic and/or extrahepatic recurrence. In patients with intrahepatic recurrence only, oncological outcomes improved if local hepatic therapy was possible (resection or ablation) in comparison to patients treated only with chemotherapy or best supportive care (3-year overall survival: 85% vs 39%; P < .0001). CONCLUSION:The incidence of hepatic local recurrence after hepatectomy for colorectal liver metastases is independent of R1 resection margin status. Additionally, hepatic local recurrence at the resection margin is not associated with worse overall survival compared with any other intra- or extrahepatic recurrence. Therefore, R1 status at hepatectomy seems to be a surrogate factor for advanced disease without influencing location of recurrence and thereby oncological outcome. This finding may support decision-making when extending the indication for surgery in borderline resectable colorectal liver metastases. 10.1016/j.surg.2020.11.024
Hepatic resection for colorectal metastases: can preoperative scoring predict patient outcome? World journal of surgery A retrospective study was performed to define patient selection, safety, and efficacy of hepatic resection for colorectal metastases. The recently proposed preoperative clinical risk score (CRS) for selection of patients for surgery was also assessed. In all, 146 consecutive hepatic resections in 137 patients operated in the period between 1977 and 1999 were studied. Of these patients, 113 were classified into five CRS groups. Perioperative mortality was 1.4% (2 patients; no death in 120 patients operated after 1985) and morbidity was 38%. Five-year actuarial survival (perioperative mortality included) was 29% (median 37 months), and actual 5-year survival was 25% (17/69 patients). Patients operated after 1995 lived longer than those operated before 1995. Multiple regression analyses identified preoperative carcinoembryonic antigen CEA <100 mg/L, nodal status at resection of primary tumor, and R0 vs. R1/R2 resection as prognostic parameters. CRS grouping had prognostic importance. The relative risk (hazard rate) of tumor recurrence in patients with CRS 3-4 was 2.1, compared to that of patients with CRS 0-2. Five-year actuarial survival in the two groups was 12% and 40%, respectively. Fourteen of 15 long-term survivors (>5 years) classified by the CRS system had CRS of 2 or less. Resection for colorectal liver metastases is safe, and long-term survival rates are acceptable. CRS predicts patient outcome, but the clinical role in patient selection will have to be defined in prospective studies. 10.1007/s00268-002-6231-x
Oncological safety of ultrasound-guided laparoscopic liver resection for colorectal metastases: a case-control study. Langella Serena,Russolillo Nadia,D'Eletto Marco,Forchino Fabio,Lo Tesoriere Roberto,Ferrero Alessandro Updates in surgery Laparoscopic liver surgery has gained widespread acceptance and nowadays it is suggested even for malignant disease. Although the benefits on short-term outcomes have been proven, data on oncological safety are still lacking. The aim of this study is to assess oncologic results after ultrasound-guided laparoscopic liver resection (LLR) or open liver resection (OLR) for colorectal metastases. 37 consecutive patients undergoing LLR between 01/2004 and 03/2014 were matched at a ratio of 1:1 with 37 OLR. Matching criteria were male sex, number and diameter of liver metastases, segment location, synchronous presentation, site and stage of primary tumor, positive lymph nodes of the primary, and concomitant extrahepatic disease. Demographic characteristics were similar among groups. Parenchymal transection time was longer in the LLR group (68 ± 38.2 SD vs 40 ± 33.7 SD, p = 0.01). Mortality was nil in LLR and OLR. Overall morbidity was significantly lower in LLR (13.5 vs 37.8%, p = 0.02), although severe complications were similar among the two groups. Patients undergoing LLR were discharged earlier (5 ± 2.3 SD vs 8 ± 6.6 SD days, p < 0.001). The median margin width was 5 (0-40) mm in LLR vs 8 (0-25) mm in OLR, p = 0.897. R1 resection was recorded in four LLR and three OLR (p = 1). Overall recurrences were similar among groups. Eight patients with hepatic or extrahepatic recurrence among LLR underwent surgery vs four of OLR (p = 0.03). After a median follow-up of 35.7 months in LLR and 47.9 months in OLR, 3-year overall survival was 91.8% LLR and 74.8% OLR (p = 0.14). 3-year disease-free survival was 69.1% LLR and 65.9% OLR (p = 0.53). Multivariate analysis showed that postoperative complications [HR 3.42 (95% CI 1.32-8.89)] and multiple metastases [HR 3.84 (95% CI 1.34-10.83)] were independent predictors of worse survival (p = 0.01). Ultrasound-LLR for colorectal hepatic metastases is safe, ensuring oncologic outcomes comparable to OLR. 10.1007/s13304-015-0325-0
Resection of colorectal liver metastases: is a resection margin of 3 mm enough? : a multicenter analysis of the GAST Study Group. Konopke Ralf,Kersting Stephan,Makowiec Frank,Gassmann Peter,Kuhlisch Eberhard,Senninger Norbert,Hopt Ulrich,Saeger Hans Detlev World journal of surgery BACKGROUND:A safety margin of > or =10 mm is generally accepted in surgery for colorectal metastases. It is reasonable that modern methods of liver parenchyma dissection may allow for a reduction in this distance. METHODS:A total of 333 patients were included in a multicenter trial after resection of colorectal liver metastases. Dissection of the liver had been performed with a CUSA, UltraCision, or water-jet dissector. The size of the resection margin was correlated with recurrence risk and survival. RESULTS:The median hepatic recurrence-free survival reached 35 months for all patients; median recurrence-free survival was 24 months and overall survival was 41 months. Univariate analysis of different groups denoting the extent of resection margin (> or =10 mm, 6-9 mm, 3-5 mm, 1-2 mm, 0 mm (R1)) indicated that a margin of 1-2 mm leads to a significantly reduced median hepatic recurrence-free survival of 20 months (p = 0.004) and recurrence-free survival of 19 months (p = 0.011). Patients with R1 resection had the worst prognosis. Overall survival was not influenced by the size of the resection margin. Surgical margins were significantly reduced in simultaneous resections of four or more liver metastases and in cases in which metastatic infiltration of central liver segments was present. At multivariate analysis, resection margins of 1-2 mm and 0 mm were independent predictors of hepatic recurrence and overall recurrence. CONCLUSION:The indication for resection of metastases can be safely extended to cases in which tumors sit closer than 1 cm to nonresectable structures. 10.1007/s00268-008-9629-2
Hepatic resection after neoadjuvant chemotherapy for patients with liver metastases from colorectal cancer: need for cautious planning. Annals of surgical treatment and research 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. 10.4174/astr.2019.97.5.245
Resection strategy for colorectal liver metastasis focusing on intrahepatic vessels and resection margins. Iwaki Kentaro,Kaihara Satoshi,Kitamura Koji,Uryuhara Kenji Surgery today PURPOSE:We analyzed the impact of surgical margins and vessel preservation on the oncological outcomes of patients with colorectal liver metastases (CRLM). METHODS:In this retrospective study, resected CRLM (n = 242) from 116 patients were assigned to one of the following groups: Group A, apart from vessels (n = 201); Group B, hepatic vein contact (n = 27); or Group C, Glissonean pedicle contact (n = 25). We analyzed the local recurrence rates (LRR) in each group. RESULTS:The total LRR and that in Groups A, B, and C were 11.6%, 10.4%, 7.4%, and 20%, respectively. In group A, R1 resections were associated with a significantly higher LRR than R0 resections (27.6% vs 7.6%, respectively; P = 0.001); however, the margin widths were not related to the LRR. In group B, the LRR for hepatic vein preservation and resection did not differ. In group C, the Glissonean pedicle preservation group had a higher LRR than the Glissonean pedicle resection group (66.7% vs 5.3%, respectively; P = 0.001). The 5-year overall survival rate of the local recurrence group (25%) was significantly lower than that of the no recurrence group (84%, P < 0.001) and the intrahepatic recurrence group (60%, P = 0.026). CONCLUSION:R0 resections for CRLM, apart from those involving vessels, can achieve local control. While preserving hepatic vein contact with CRLM is acceptable, the Glissonean pedicle should be resected because of the higher LRR. 10.1007/s00595-021-02254-0
Colorectal Cancer Liver Metastases: Is an R1 Hepatic Resection Accepted? Clinics and practice Metastatic colorectal cancer is associated with a rather dismal 5-year overall survival. The liver is the most commonly affected organ. Improved 5-year survival rates after successful hepatic resections for metastases confined to the liver have been reported. Certainly, a hepatectomy that results in an incomplete tumor resection, in terms of leaving macroscopic residual tumor in the future liver remnant, is not associated with survival benefits. However, the prognostic implications of a microscopically positive surgical margin or a clear margin of less than 1 mm (R1) on pathology are debatable. Although it has been a field of extensive research, the relevant literature often reports contradictory results. The purpose of the present study was to define, assess the risk factors for, and, ultimately, analyze the effect that an R1 hepatic resection for colorectal cancer liver metastases might have on local recurrence rates and long-term prognosis by reviewing the relevant literature. Achieving an R0 hepatic resection, optimally with more than 1 mm of clear margin, should always be the goal. However, in the era of the aggressive multimodality treatment of liver metastatic colorectal cancer, an R1 resection might be the cost of increasing the pool of patients finally eligible for resection. The majority of literature reports have highlighted the detrimental effect of R1 resections on local recurrence and overall survival. However, there are indeed studies that degraded the prognostic handicap as a consequence of an R1 resection in selected patients and highlighted the presence of RAS mutations, the response to chemotherapy, and, in general, factors that reflect the biology of the disease as important, if not the determinant, prognostic factors. In these patients, the aggressive disease biology seems to outperform the resection margin status as a prognostic factor, and the recorded differences between R1 and R0 resections are equalized. Properly and accurately defining this patient group is a future challenge in the field of the surgical treatment of colorectal cancer liver metastases. 10.3390/clinpract12060112
Prognostic impact of R1 resection margin in synchronous and simultaneous colorectal liver metastasis resection: a retrospective cohort study. World journal of surgical oncology BACKGROUND:A margin ≥ 1 mm is considered a standard resection margin for colorectal liver metastasis (CRLM). However, microscopic incomplete resection (R1) is not rare since aggressive surgical resection has been attempted in multiple and bilobar CRLM. This study aimed to investigate the prognostic impact of resection margins and perioperative chemotherapy in patients with CRLM. METHODS:A total of 368 of 371 patients who underwent simultaneous colorectal and liver resection for synchronous CRLM between 2006 and June 2017, excluding three R2 resections, were included in this study. R1 resection was defined as either abutting tumor on the resection line or involved margin in the pathological report. The patients were divided into R0 (n = 304) and R1 (n = 64) groups. The clinicopathological characteristics, overall survival, and intrahepatic recurrence-free survival were compared between the two groups using propensity score matching. RESULTS:The R1 group had more patients with ≥ 4 liver lesions (27.3 vs. 50.0%, P < 0.001), higher mean tumor burden score (4.4 vs. 5.8%, P = 0.003), and more bilobar disease (38.8 vs. 67.2%, P < 0.001) than the R0 group. Both R0 and R1 groups showed similar long-term outcomes in the total cohort (OS, P = 0.149; RFS, P = 0.414) and after matching (OS, P = 0.097, RFS: P = 0.924). However, the marginal recurrence rate was higher in the R1 group than in the R0 group (26.6 vs. 16.1%, P = 0.048). Furthermore, the resection margin did not have a significant impact on OS and RFS, regardless of preoperative chemotherapy. Poorly differentiated, N-positive stage colorectal cancer, liver lesion number ≥ 4, and size ≥ 5 cm were poor prognostic factors, and adjuvant chemotherapy had a positive impact on survival. CONCLUSIONS:The R1 group was associated with aggressive tumor characteristics; however, no effect on the OS and intrahepatic RFS with or without preoperative chemotherapy was observed in this study. Tumor biological characteristics, rather than resection margin status, determine long-term prognosis. Therefore, aggressive surgical resection should be considered in patients with CRLM expected to undergo R1 resection in this multidisciplinary approach era. 10.1186/s12957-023-03042-5
Risk factors for cancer recurrence or death within 6 months after liver resection in patients with colorectal cancer liver metastasis. Jung Sung Won,Kim Dong-Sik,Yu Young Dong,Han Jae Hyun,Suh Sung-Ock Annals of surgical treatment and research PURPOSE:The aim of this study was to find risk factors for early recurrence (ER) and early death (ED) after liver resection for colorectal cancer liver metastasis (CRCLM). METHODS:Between May 1990 and December 2011, 279 patients underwent liver resection for CRCLM at Korea University Medical Center. They were assigned to group ER (recurrence within 6 months after liver resection) or group NER (non-ER; no recurrence within 6 months after liver resection) and group ED (death within 6 months after liver resection) or group NED (alive > 6 months after liver resection). RESULTS:The ER group included 30 patients (10.8%) and the NER group included 247 patients (89.2%). The ED group included 18 patients (6.6%) and the NED group included 253 patients (93.4%). Prognostic factors for ER in a univariate analysis were poorly differentiated colorectal cancer (CRC), synchronous metastasis, ≥5 cm of liver mass, ≥50 ng/mL preoperative carcinoembryonic antigen level, positive liver resection margin, and surgery alone without perioperative chemotherapy. Prognostic factors for ED in a univariate analysis were poorly differentiated CRC, positive liver resection margin, and surgery alone without perioperative chemotherapy. Multivariate analysis showed that poorly differentiated CRC, ≥5-cm metastatic tumor size, positive liver resection margin, and surgery alone without perioperative chemotherapy were independent risk factors related to ER. For ED, poorly differentiated CRC, positive liver resection margin, and surgery alone without perioperative chemotherapy were risk factors in multivariate analysis. CONCLUSION:Complete liver resection with clear resection margin and perioperative chemotherapy should be carefully considered when patients have the following preoperative risk factors: metastatic tumor size ≥ 5 cm and poorly differentiated CRC. 10.4174/astr.2016.90.5.257
Real-time surgical margin assessment using ICG-fluorescence during laparoscopic and robot-assisted resections of colorectal liver metastases. Achterberg Friso B,Sibinga Mulder Babs G,Meijer Ruben P J,Bonsing Bert A,Hartgrink Henk H,Mieog J Sven D,Zlitni Aimen,Park Seung-Min,Farina Sarasqueta Arantza,Vahrmeijer Alexander L,Swijnenburg Rutger-Jan Annals of translational medicine Background:Almost a third of the resections in patients with colorectal liver metastases (CRLM) undergoing curative surgery, end up being tumor-margin positive (≤1 mm margin). Near-infrared fluorescent (NIRF) imaging using the fluorescent contrast agent indocyanine green (ICG) has been studied for many different applications. When administered in a relatively low dose (10 mg) 24 hours prior to surgery, ICG accumulated in hepatocytes surrounding the CRLM. This results in the formation of a characteristic fluorescent 'rim' surrounding CRLM when located at the periphery of the liver. By resecting the metastasis with the entire surrounding fluorescent rim, in real-time guided by NIRF imaging, the surgeon can effectively acquire margin-negative (>1 mm) resections. This pilot study aims to describe the surgical technique for using near-infrared fluorescence imaging to assess tumor-margins in patients with CRLM undergoing laparoscopic or robot-assisted resections. Methods:Out of our institutional database we selected 16 CRLM based on margin-status (R0; n=8, R1; n=8), which were resected by a minimally-invasive approach using ICG-fluorescence. NIRF images acquired during surgery, from both the resection specimen and the wound bed, were analysed for fluorescent signal. We hypothesized that a protruding fluorescent rim at the parenchymal side of the resection specimen could indicate a too close proximity to the tumor and could be predictive for a tumor-positive surgical margin. NIRF images were correlated to final histopathological assessment of the resection margin. Results:All lesions with a NIRF positive resection plane were reported as having a tumor-positive margin. Lesions that showcased no protruding rim in the wound bed were diagnosed as having a tumor-negative margin in 88% of cases. A 5-step surgical workflow is described to document the NIRF signal was used assess the resection margin for future clinical studies. Conclusions:The pilot study shows that image-guided surgery using real-time ICG-fluorescence has the potential to aid surgeons in achieving a tumor-negative margin in minimally invasive liver metastasectomies. The national multi-centre MIMIC-Trial will prospectively study the effect of this technique on surgical tumor-margins (Dutch Trial Register number NL7674). 10.21037/atm-20-1999
Prognostic Impact of Surgical Margin Width in Hepatectomy for Colorectal Liver Metastasis. Journal of clinical and translational hepatology 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. 10.14218/JCTH.2022.00383
Risk and prognostic factors in patients with colon cancer with liver metastasis. The Journal of international medical research OBJECTIVE:The most common site of metastasis in patients with colon cancer is the liver. This study aimed to identify patients with colon cancer at high risk of developing liver metastasis and to explore their prognosis. METHODS:The clinical characteristics, treatment methods and survival outcomes of patients diagnosed with colon cancer from 2010 to 2015 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Patients were divided into two groups according to the presence of liver metastasis, and multivariate logistic and Cox regression models were used to identify risk and prognostic factors. RESULTS:A total of 60,018 patients with colon cancer were selected from the SEER database. The incidence of liver metastasis was 9.2%. African American ethnicity, poor differentiation, higher tumor stage, higher lymph node ratio, and lung metastases were common factors associated with both liver metastasis risk and prognosis. CONCLUSIONS:Metastasectomy might improve survival among patients with colon cancer with resectable liver metastasis lesions and no other organ involvement. 10.1177/03000605231191580