Prognostic significance of cancer within 1 mm of the circumferential resection margin in oesophageal cancer patients following neo-adjuvant chemotherapy

Department of Upper GI Surgery, St James's University Hospital, Leeds, UK.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery (Impact Factor: 3.3). 06/2012; 43(3). DOI: 10.1093/ejcts/ezs331
Source: PubMed


The prognostic significance of the circumferential resection margin (CRM) status in oesophageal cancer patients treated with neo-adjuvant chemotherapy and radical resection is controversial. Furthermore, it is currently unclear whether patients with cancer located at the CRM have a prognosis different from that of those with cancer within 1 mm of the CRM. This is the first study aiming to establish the optimal tumour-free distance from the CRM of an oesophagectomy in patients who have undergone neo-adjuvant chemotherapy.

The clinicopathological data of 232 oesophageal cancer patients from two UK centres were analysed. The CRM status was classified as Group A (cancer at the CRM), Group B (cancer within 1 mm but not at the CRM) and Group C (no cancer within 1 mm from the CRM). The relationship between the CRM status and patient survival was investigated.

Thirty-eight specimens were classified as Group A, 89 as Group B and 105 as Group C. CRM status was related to the depth of tumour invasion (P < 0.001) and lymph node status (P < 0.001). The prognoses of the Group A and the Group B patients were similar. Both were poorer than that of the Group C patients (P = 0.008). Lymph node status was the only independent prognostic marker in multivariate analysis.

Oesophageal cancer patients treated with preoperative chemotherapy with cancer cells at the CRM or within 1 mm of the CRM of the resected specimen have a significantly worse survival than patients with no cancer cells within 1 mm of the margin. However, this study suggests that the overall prognostic significance of the CRM status is limited in this cohort and the postoperative lymph node status is the most important prognostic factor in oesophageal cancer patients treated with neo-adjuvant chemotherapy and surgery.

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Available from: Jeremy David Hayden, Apr 21, 2014
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    • "Sagar et al (1993) first reported an association between CRM+ and local recurrence after oesophagectomy, and several studies have since examined the influence of CRM+ on survival (Dexter et al, 2001; Khan et al, 2003; Griffiths et al, 2006; Sujendran et al, 2008; Thompson et al, 2008; Deeter et al, 2009; Saha et al, 2009; Scheepers et al, 2009; Mirnezami et al, 2010; Pultram et al, 2010; Chao et al, 2011; Verhage et al, 2011; Harvin et al, 2012; Rao et al, 2012; Salih et al, 2012). Although some report an independent negative association between CRM+ and survival (Dexter et al, 2001; Griffiths et al, 2006; Sujendran et al, 2008; Deeter et al, 2009; Saha et al, 2009; Scheepers et al, 2009; Pultram et al, 2010; Verhage et al, 2011), others have not (Khan et al, 2003; Thompson et al, 2008; Mirnezami et al, 2010; Chao et al, 2011; Harvin et al, 2012; Rao et al, 2012; Salih et al, 2012). "
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    ABSTRACT: Background: The optimum multimodal treatment for oesophageal cancer, and the prognostic significance of histopathological tumour involvement of the circumferential resection margin (CRM+) are uncertain. The aims of this study were to determine the prognostic significance of CRM+ after oesophagectomy and to identify endosonographic (endoluminal ultrasonography (EUS)) features that predict a threatened CRM+. Methods: Two hundred and sixty-nine consecutive patients underwent potentially curative oesophagectomy (103 surgery alone, 124 neoadjuvant chemotherapy (CS) and 42 chemoradiotherapy (CRTS)). Primary outcome measures were disease-free survival (DFS) and overall survival (OS). Results: CRM+ was reported in 98 (38.0%) of all, and in 90 (62.5%) of pT3 patients. Multivariate analysis of pathological factors revealed: lymphovascular invasion (HR 2.087, 95% CI 1.396–3.122, P<0.0001), CRM+ (HR 1.762, 95% CI 1.201–2.586, P=0.004) and lymph node metastasis count (HR 1.563, 95% CI 1.018–2.400, P=0.041) to be independently and significantly associated with DFS. Lymphovascular invasion (HR 2.160, 95% CI 1.432–3.259, P<0.001) and CRM+ (HR 1.514, 95% CI 1.000–2.292, P=0.050) were also independently and significantly associated with OS. Multivariate analysis revealed EUS T stage (T3 or T4, OR 24.313, 95% CI 7.438–79.476, P<0.0001) and use or not of CRTS (OR 0.116, 95% CI 0.035–0.382, P<0.0001) were independently and significantly associated with CRM+. Conclusion: A positive CRM was a better predictor of DFS and OS than standard pTNM stage.
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    ABSTRACT: Background: Differences in the extent and quality of surgical resection for esophageal cancer may influence the pathological staging and patient outcome. There are no data in the literature qualitatively and/or quantitatively characterizing esophagectomy specimens. Methods: Macroscopic images of 161 esophagectomy specimens were analyzed retrospectively. The extent of resection was qualitatively classified as "muscularis propria," "intra-meso-esophageal," or "meso-esophageal." The volume of meso-esophageal tissue was quantified morphometrically. The number of muscle defects per specimen was counted. Results were related to clinicopathological variables, including survival. Results: Sixty-two (39%) specimens were classified as "muscularis propria," 65 (40%) as "intra-meso-esophageal," and 34 (21%) as "meso-esophageal." The morphometrically measured meso-esophageal tissue volume was different between the three types (P < 0.001). The specimen type was related to the total number of lymph nodes (P = 0.02), number of metastatic lymph nodes (P = 0.024), and depth of tumor invasion (P = 0.013), but not related to extramural tumor volume, circumferential resection margin status, or the surgeon performing the resection. The number of muscle defects per specimen was similar in all resection types. The resection specimen classification was related to survival in patients treated by surgery alone (P = 0.027). Conclusions: This is the first study to quantify and classify the volume of tissue resected during esophagectomy. Our study shows significant variation of the resected tissue volume impacting pathological tumor staging. This variation was not associated with individual surgeon performance. A prospective, multicenter study is needed to validate our results and to investigate the potential biological mechanisms influencing the resectable volume of meso-esophageal tissue in cancer patients.
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    ABSTRACT: The prognostic role and definition of circumferential resection margin (CRM) involvement in operable oesophageal cancer remain controversial. The College of American Pathologists (CAP) and Royal College of Pathologists (RCP) define CRM involvement as tumour found at the cut resection margin and within 1 mm of the cut margin respectively. This systematic review and meta-analysis was performed to determine the influence of CRM involvement on survival in operable oesophageal cancer. PubMed, MEDLINE and the Cochrane Library (January 1990 to June 2012) were searched for studies correlating CRM involvement with 5-year mortality. Statistical analysis of dichotomous variables was performed using the odds ratio (OR) as the summary statistic. Fourteen studies involving 2433 patients with oesophageal cancer who had undergone potentially curative oesophagectomy were analysed. Rates of CRM involvement were 15·3 per cent (173 of 1133) and 36·5 per cent (889 of 2433) according to the CAP and RCP criteria respectively. Overall 5-year mortality rates were significantly higher in patients with CRM involvement compared with CRM-negative patients according to both CAP (OR 4·02, 95 per cent confidence interval (c.i.) 2·25 to 7·20; P < 0·001) and RCP (OR 2·52, 1·96 to 3·25; P < 0·001) criteria. CRM involvement between 0·1 and 1 mm was associated with a significantly higher 5-year mortality rate than CRM-negative status (involvement more than 1 mm from CRM) (OR 2·05, 95 per cent c.i. 1·41 to 2·99; P < 0·001). CRM involvement is an important predictor of poor prognosis. CAP criteria differentiate a higher-risk group than RCP criteria, but overlook a patient group with similar poor outcomes. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
    Full-text · Article · Mar 2013 · British Journal of Surgery
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