Decellularized and matured esophageal scaffold for circumferential esophagus replacement: Proof of concept in a pig model.

Surgical resection of the esophagus requires sacrificing a long portion of it. Its replacement by the demanding gastric pull-up or colonic interposition techniques may be avoided by using short biologic scaffolds composed of decellularized matrix (DM). The aim of this study was to prepare, characterize, and assess the in vivo remodeling of DM and its clinical impact in a preclinical model. A dynamic chemical and enzymatic decellularization protocol of porcine esophagus was set up and optimized. The resulting DM was mechanically and biologically characterized by DNA quantification, histology, and histomorphometry techniques. Then, in vitro and in vivo tests were performed, such as DM recellularization with human or porcine adipose-derived stem cells, or porcine stromal vascular fraction, and maturation in rat omentum. Finally, the DM, matured or not, was implanted as a 5-cm-long esophagus substitute in an esophagectomized pig model. The developed protocol for esophageal DM fulfilled previously established criteria of decellularization and resulted in a scaffold that maintained important biologic components and an ultrastructure consistent with a basement membrane complex. In vivo implantation was compatible with life without major clinical complications. The DM's scaffold in vitro characteristics and in vivo implantation showed a pattern of constructive remodeling mimicking major native esophageal characteristics.

Lymph node invasion might have more prognostic impact than R status in advanced esophageal adenocarcinoma.

BACKGROUND: Advanced esophageal adenocarcinomas are associated with 5-year survival rates ranging from 14% to 35%. Nodal status and tumor clearance are the main prognostic factors. However, their respective prognostic values have not been compared to date. METHODS: Seventy consecutive patients with stage T3 adenocarcinomas of the esophagus or gastric cardia were retrospectively assessed. Neoadjuvant therapy was indicated in all cases. Prognostic values of R0 resection and nodal status were evaluated using univariate and multivariate analyses. RESULTS: Neoadjuvant therapy was achieved in 62 patients, 41 with radiochemotherapy and 21 with perioperative chemotherapy. Transthoracic esophagectomy and transhiatal esophagectomy were performed in 54 and 15 patients, respectively. Clavien-Dindo grade III or IV complications occurred in 16 patients (23%). Two patients died in the hospital (3%). In univariate and multivariate analyses, nodal status was the main independent factor predicting overall survival; tumor clearance (R0 or R1) had less prognostic impact and was not statistically significant. Furthermore, R1 resection was a prognostic indicator for metastatic recurrence. CONCLUSIONS: These results indicate that nodal status has more prognostic impact than R status in stage T3 adenocarcinomas of the esophagus or gastric cardia. Thus, local control in R1 patients by postoperative radiotherapy is not justified.