Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: a systematic review

Abstract

Aim: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/T1b esophageal neoplasms.

Methods: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. "Neural networks" as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial submucosal esophageal carcinoma. Another data mining technique, the "feature selection and root cause analysis", was used to identify the most important predictors of local recurrence and metachronous cancer development in endoscopically resected patients, and lymph node positivity in squamous carcinoma (SCC) and adenocarcinoma (ADC) separately in surgically resected patients.

Results: Endoscopically resected patients: Low grade dysplasia was observed in 4% of patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer in 54%, and submucosal cancer in 16% of patients. There were no significant differences between endoscopic mucosal resection and endoscopic submucosal dissection (ESD) for the following parameters: complications, patients submitted to surgery, positive margins, lymph node positivity, local recurrence and metachronous cancer. With regard to piecemeal resection, ESD performed better since the number of cases was significantly less [coefficient: -7.709438, 95%CI: (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559), P < 0.01]. A higher rate of esophageal stenosis was observed following ESD [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A significantly greater number of SCC patients were submitted to surgery (log-odds, ADC: -2.1206 ± 0.6249 vs SCC: 4.1356 ± 0.4038, P < 0.05). The odds for re-classification of tumor stage after endoscopic resection were 53% and 39% for ADC and SCC, respectively. Local tumor recurrence was best predicted by grade 3 differentiation and piecemeal resection, metachronous cancer development by the carcinoma in situ component, and lymph node positivity by lymphovascular invasion. With regard to surgically resected patients: Significant differences in patients with positive lymph nodes were observed between ADC and SCC [coefficient: 1.889569, 95%CI: (0.3945146, 3.384624), P < 0.01). In contrast, lymphovascular and microvascular invasion and grade 3 patients between histologic types were comparable, the respective rank order of the predictors of lymph node positivity was: Grade 3, lymphovascular invasion (L+), microvascular invasion (V+), submucosal (Sm) 3 invasion, Sm2 invasion and Sm1 invasion. Histologic type (ADC/SCC) was not included in the model. The best predictors for SCC lymph node positivity were Sm3 invasion and (V+). For ADC, the most important predictor was (L+).

Conclusion: Local tumor recurrence is predicted by grade 3, metachronous cancer by the carcinoma in-situ component, and lymph node positivity by L+. T1b cancer should be treated with surgical resection.

Keywords: Adenocarcinoma; Controversies in treatment; Deep third submucosal layer; Dysplasia; Endoscopic gastrointestinal surgery; Endoscopic gastrointestinal surgical procedures; Endoscopic resection; Esophageal cancer; Lymph node dissection; Lymphatic invasion; Middle third submucosal layer; Mucosal infiltration; Recurrent tumor; Squamous cell carcinoma; Submucosal involvement; Submucosal layer; Superficial esophageal cancer; Superficial submucosal layer; Vascular invasion.

Figure 1

Progress through the stages of study review included. SCC: Squamous cell carcinoma; ADC: Adenocarcinoma; EMR: Endoscopic mucosal resection; ESD: Endoscopic submucosal dissection.

Figure 2

Forest plot of log-odds in both groups (endoscopic mucosal resection and endoscopic submucosal dissection): No statistically significant differences were observed. A: Forest plot of log-odds patients submitted to surgery; B: Forest plot of log-odds of piecemeal resected patients; C: Forest plot of log-odds of positive resection margins patients; D: Forest plot of log-odds of local recurrence in both groups [endoscopic mucosal resection and endoscopic submucosal dissection (EMR-ESD)]: No statistically significant differences were observed, with the exception of piecemeal resected patients. In this last instance ESD was more efficient; E: Forest plot of log-odds of metachronous cancer development; F: Forest plot of log-odds of esophageal stenosis in both groups (EMR-ESD): EMR was less destructive.