Radiofrequency ablation for early esophageal squamous cell neoplasia

Abstract

Esophageal cancer is the sixth most common cause of cancer death in the world [1]. Over 80% of esophageal cancers occur in developing countries [1], and in these areas, 90% of these cancers are esophageal squamous cell carcinoma (ESCC) [2]. The precursor lesion of ESCC is squamous intraepithelial neoplasia (squamous dysplasia), defined histologically as nuclear atypia (enlargement, pleomorphism and hyperchromasia), loss of normal cellular polarity, and abnormal tissue maturation [3,4]. WHO subclassifies squamous intraepithelial neoplasia into low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN), depending on the extent of the nuclear atypia and the involvement of the epithelium [4]. In China, where ESCC and its precursors are very common in some areas, a three-tier system is used, including LGIN (mild dysplasia, involving the lower third of the epithelium), medium-grade intraepithelial neoplasia (MGIN, moderate dysplasia, involving the lower two-thirds of the epithelium), and HGIN (severe dysplasia, involving the full thickness of the epithelium) [3]. Follow-up studies in China have shown that the rate of progression to ESCC differs significantly between LGIN (5.3% over 3.5 years), MGIN (26.7%), and HGIN (65.2%), and because of their significant risk of progression, MGIN and HGIN are targets for screening and therapy [5,6]. Current treatment of esophageal squamous cell neoplasia (ESCN, including squamous intraepithelial neoplasia and invasive squamous cell carcinoma) involves surgery for lesions invading into the deep submucosa or beyond and endoscopic treatment for lesions restricted to the epithelial layer (intraepithelial neoplasia; m1) or the lamina propria (m2). Lesions invading into the muscularis mucosae (m3) or superficial submucosa (sm1) are considered the “grey zone” between endoscopic and surgical treatment. One option for endoscopic treatment of early ESCN involves endoscopic resection (ER) of unstained lesions (USLs) after Lugol’s chromoscopy, as USLs are predictive for the presence of neoplasia. ER allows for histological staging of infiltration depth, tumor differentiation, lymph-vascular invasion, while completely removing the visible lesion. USLs larger than 15 mm require either piecemeal resection with the standard cap-based ER techniques or endoscopic submucosal dissection (ESD) for complete resection. Widespread ER/ESD, however, is technically demanding, with procedure times of many hours, and is associated with severe esophageal stenosis for lesions that encompass >75% of the circumference and a significant risk for esophageal perforation and bleeding. Complete endoscopic resection is also not necessarily the best approach for all patients with early ESCN. Large flat type lesions (i.e. type 0-IIb), which carry a very low risk for deeper invasion, can be effectively treated by an endoscopic ablation technique that is much easier to apply and is associated with a very low rate of complications, such as esophageal stenosis. A safe, effective and technically easy to administer ablation method is especially attractive for geographic areas where ESCN is endemic and most endoscopists have a lower level of expertise in ER/ESD. In China, there are many high-risk areas for ESCN, such as the Taihang mountain range in North-central China and areas in Sichuan, Shandong, Jiangsu and Fujian Provinces and the Xinjiang Uygur Autonomous Region [7]. These high-risk areas in China are estimated to include a total of over 100 million people, and invasive ESCN occurs here at rates approaching or surpassing 100/100,000 people per year [2], an incidence approximately 30-fold of that of Barrett’s related esophageal adenocarcinoma in the Western world [8]. The Chinese government is supporting widespread endoscopic screening using Lugol’s chromoscopy in these high-risk areas and in 2010 it is estimated that 57,000 subjects will undergo such a screening endoscopy. From this screening process, it is estimated that 5% of patients will have MGIN, HGIN, or early cancer limited to the epithelium and will be eligible for endoscopic therapy.