Lessons from pathological analysis of recurrent early esophageal squamous cell neoplasia after complete endoscopic radiofrequency ablation
submitted 17 August 2017
accepted after revision 10 December 2017
15 February 2018 (eFirst)
Background Endoscopic radiofrequency ablation (RFA) is a treatment option for early esophageal squamous cell neoplasia (ESCN); however, long-term follow-up studies are lacking. The risks of local recurrence and “buried cancer” are also uncertain.
Methods Patients with flat-type ESCN who were treated with balloon-type ± focal-type RFA were consecutively enrolled. Follow-up endoscopy was performed at 1, 3, and 6 months, and then every 6 months thereafter. Endoscopic resection was performed for persistent and recurrent ESCN, and the histopathology of resected specimens was assessed.
Results A total of 35 patients were treated with RFA, of whom 30 (86 %) achieved a complete response, three were lost to follow-up, and five (14 %) developed post-RFA stenosis. Two patients had persistent ESCN and received further endoscopic resection, in which the resected specimens all revealed superficial submucosal invasive cancer. Six of the 30 patients with successful RFA (20 %) developed a total of seven episodes of local recurrence (mean size 1.4 cm) during the follow-up period (mean 40.1 months), all of which were successfully resected endoscopically without adverse events. Histological analysis of the resected specimens revealed that six (86 %) had esophageal glandular ductal involvement, all of which extended deeper than the muscularis mucosae layer. Immunohistochemistry staining for P53 and Ki67 suggested a clonal relationship between the ductal involvement and epithelial cells. None of the tumors extended out of the ductal structure; no cases of cancer buried beneath the normal neosquamous epithelium were found.
Conclusions Because ductal involvement is not uncommon and may be related to recurrence, the use of RFA should be conservative and may not be the preferred primary treatment for early ESCN.
- 1 Shaheen NJ, Sharma P, Overholt BF. et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. NEJM 2009; 360: 2277-2288
- 2 Phoa KN, van Vilsteren FG, Weusten BL. et al. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial. JAMA 2014; 311: 1209-1217
- 3 Bergman JJ, Zhang YM, He S. et al. Outcomes from a prospective trial of endoscopic radiofrequency ablation of early squamous cell neoplasia of the esophagus. Gastrointest Endosc 2011; 74: 1181-1190
- 4 He S, Bergman J, Zhang Y. et al. Endoscopic radiofrequency ablation for early esophageal squamous cell neoplasia: report of safety and effectiveness from a large prospective trial. Endoscopy 2015; 47: 398-408
- 5 Wang WL, Chang IW, Chang CY. et al. Circumferential balloon-based radiofrequency ablation for ultralong and extensive flat esophageal squamous neoplasia. Gastrointest Endosc 2014; 80: 1185-1189
- 6 Ganz RA, Utley DS, Stern RA. et al. Complete ablation of esophageal epithelium with a balloon-based bipolar electrode: a phased evaluation in the porcine and in the human esophagus. Gastrointest Endosc 2004; 60: 1002-1010
- 7 Dunkin BJ, Martinez J, Bejarano PA. et al. Thin-layer ablation of human esophageal epithelium using a bipolar radiofrequency balloon device. Surg Endosc 2006; 20: 125-130
- 8 Nomura T, Miyashita M, Makino H. et al. Argon plasma coagulation for the treatment of superficial esophageal carcinoma. J Nippon Med Sch 2007; 74: 163-167
- 9 Min BH, Kim ER, Lee JH. et al. Feasibility and efficacy of argon plasma coagulation for early esophageal squamous cell neoplasia. Endoscopy 2013; 45: 575-578
- 10 Tanaka T, Matono S, Nagano T. et al. Photodynamic therapy for large superficial squamous cell carcinoma of the esophagus. Gastrointest Endosc 2011; 73: 1-6
- 11 Ono S, Fujishiro M, Niimi K. et al. Long-term outcomes of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms. Gastrointest Endosc 2009; 70: 860-866
- 12 Wang WL, Chang IW, Chen CC. et al. Radiofrequency ablation versus endoscopic submucosal dissection in treating large early esophageal squamous cell neoplasia. Medicine 2015; 94: e2240
- 13 Tajima Y, Nakanishi Y, Tachimori Y. et al. Significance of involvement by squamous cell carcinoma of the ducts of esophageal submucosal glands. Analysis of 201 surgically resected superficial squamous cell carcinomas. Cancer 2000; 89: 248-254
- 14 Takubo K, Takai A, Takayama S. et al. Intraductal spread of esophageal squamous cell carcinoma. Cancer 1987; 59: 1751-1757
- 15 Jansen M, Scholvinck DW, Kushima R. et al. Is it justified to ablate flat-type esophageal squamous cancer? An analysis of endoscopic submucosal dissection specimens of lesions meeting the selection criteria of radiofrequency studies. Gastrointest Endosc 2014; 80: 995-1002
- 16 Kumagai Y, Inoue H, Nagai K. et al. Magnifying endoscopy, stereoscopic microscopy, and the microvascular architecture of superficial esophageal carcinoma. Endoscopy 2002; 34: 369-375
- 17 Ohashi S, Miyamoto S, Kikuchi O. et al. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology 2015; 149: 1700-1715
- 18 Fagundes RB, Melo CR, Putten AC. et al. p53 immunoexpression: an aid to conventional methods in the screening of precursor lesions of squamous esophageal cancer in patients at high-risk?. Cancer Detect Prev 2005; 29: 227-232
- 19 Chen M, Huang J, Zhu Z. et al. Systematic review and meta-analysis of tumor biomarkers in predicting prognosis in esophageal cancer. BMC Cancer 2013; 13: 539
- 20 Swager AF, Boerwinkel DF, de Bruin DM. et al. Detection of buried Barrett's glands after radiofrequency ablation with volumetric laser endomicroscopy. Gastrointest Endosc 2016; 83: 80-88
- 21 van Vilsteren FG, Alvarez Herrero L, Pouw RE. et al. Radiofrequency ablation for the endoscopic eradication of esophageal squamous high grade intraepithelial neoplasia and mucosal squamous cell carcinoma. Endoscopy 2011; 43: 282-290
- 22 Scholvinck DW, Alvarez Herrero L, Visser M. et al. Effects of Lugol staining on stenosis formation induced by radiofrequency ablation of esophageal squamous epithelium: a study in a porcine model. Dis Esophagus 2015; 28: 603-611