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Can the Risk of Lymph Node Metastases Be Gauged in Endoscopically Resected Submucosal Esophageal Adenocarcinomas? a Multi-Center Study
Joshua a. Boys1, Stephanie G. Worrell1, Parakrama Chandrasoma2, Christy M. Dunst3, Wayne L. Hofstetter4, Brian E. Louie5, Dipen Maru6, John G. Vallone2, Thomas J. Watson7, Steven R. Demeester*1
1Cardiothoracic Surgery, Univ. of Southern California, Los Angeles, CA; 2Pathology, Keck Medicine of USC, Los Angeles, CA; 3Surgery, Oregon Clinic, Portland, OR; 4Thoracic and Cardiovascular Surgery, MD Anderson, Houston, TX; 5Surgery, Swedish Hospital, Seattle, WA; 6Pathology, MD Anderson, Houston, TX; 7Surgery, University of Rochester, N.Y., New York, NY
Introduction: Endoscopic resection (ER) has revolutionized the therapy for esophageal adenocarcinoma. Intramucosal tumors rarely have node metastases, but the risk is 10-30% with submucosal (T1b) invasion. Factors reported to increase this risk are poor differentiation, lymphovascular invasion (LVI) and invasion >500 microns into the submucosa. Lesions without these factors have been labelled "low risk" and are potentially suitable for endoscopic therapy. The aim of this study was to evaluate whether it is possible to gauge the risk of lymph node metastases after endoscopic resection of a T1b adenocarcinoma based on differentiation, LVI and measured depth of submucosal invasion.
Methods: Patients with submucosal invasion on ER specimens who subsequently had an esophagectomy were identified at 5 US centers. The ER pathology slides were independently reviewed by 2-3 expert pathologists for differentiation, presence of LVI and depth of invasion. The pathologists collectively measured the depth of submucosal invasion, the width of invasion at the mucosal / submucosal interface, and the depth of uninvolved submucosa below the tumor to the resection margin. The esophagectomy pathology report was reviewed to determine the presence of lymph node metastases. Patients were excluded from analysis for other than T1b lesions, a poorly sectioned ER specimen or neoadjuvant therapy prior to esophagectomy.
Results: There were 20 patients with confirmed submucosal invasion. The median depth of invasion into the submucosa was 1360 microns, the median width was 2780 microns and the median depth of uninvolved submucosa below the lesion was 740 microns. Tumor characteristics and lymph node metastases are shown (Table). Overall 7 patients (35%) had lymph node metastases and the risk of node metastases could not be gauged using tumor differentiation, LVI or depth of submucosal invasion. The frequency of node metastases was similar between patients with "low risk" lesions and those with higher risk lesions (p=1). There were 9 patients with ≤ 500 microns of uninvolved submucosa between the tumor and the resection margin and 6 had node metastases. Residual tumor was present in the esophagectomy specimen in 8 patients.
Conclusions: Esophagectomy after an ER that showed submucosal invasion confirmed lymph node metastases in 35% of patients. There was no "safe" depth of submucosal invasion, nor was there a "low risk" lesion. Poor differentiation and LVI did not impact the risk, but 66% of patients with ≤ 500 microns of uninvolved submucosa below the tumor had node metastases. Endoscopic therapy would frequently be inadequate for T1b esophageal adenocarcinoma.
Submucosal adenocarcinoma and the risk of lymph node metastases.
| N (%) | Node positive | p-value | | Differentiation: | | | 1 | | -well/moderate* | 12 (60%) | 4 (33%) | | | -moderate/poor** | 8 (40%) | 3 (38%) | | | Lymphovascular Invasion: | | | 1 | | -absent* | 16 (80%) | 6 (38%) | | | -present** | 4 (20%) | 1 (25%) | | | Depth of SM Invasion (microns): | | | 0.6 | | ≤500* | 4 (20%) | 2 (50%) | | | ≥500** | 16 (80%) | 5 (31%) | | | * \"Low risk\" lesion | 2 (10%) | 1 (50%) | | | ** \"Highest risk\" lesion | 1 (5%) | 0 | |
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