Esophageal strictures after extensive endoscopic submucosal dissection: Steroid gel application, the ideal choice?

Today, strategies to prevent significant esophageal stricture after extensive endoscopic submucosal dissection (ESD) could be generally divided into three categories: mechanical treatments, drug therapies, and regenerative medicine (Table 1). Mechanical treatments do not target pathophysiological mechanisms of artificial ulcer healing process, so it is understandable that refractory stenosis sometimes occurs and additional endoscopic interventions are needed, which result in excess cost, patient inconvenience, and increased complication risks. Drug therapies, which take antiinflammatory, antifibrotic formation, or antiscar formation effects, have been demonstrated effective by several studies, but systematic or procedure-related side-effects should not be neglected. Because drug therapy alone can seldom prevent stricture in cases of circumferential esophageal resection, combination methods are selected, commonly steroid use and preventive endoscopic balloon dilatation (EBD). In patients with recalcitrant esophageal stricture with large post-ESD mucosal defect, combination methods may diminish both the need for repeat dilation and average time to repeat dilation. Regenerative medicine usher an exciting era. For instance, endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets has been used safely and effectively to promote re-epithelialization of the esophagus and prevent stricture formation following ESD. It is a landmark study of connection between endoscopy and regenerative medicine, and may be a trend of individualized therapy. But a cell-processing center with clean rooms continuously monitored according to the good manufacturing practice guideline and skilled operators following the standard operation procedures of regenerative medicine are both indispensable, which can hardly be obtained in overwhelming majority of hospitals. Although the safety and validity of tissue-engineering cell sheets has been preliminary demonstrated by a series of patients, wide clinical application may not be available in the near future. The ideal intervention should be safe, effective, controllable, and simple; none of the previously listed strategies can meet the standard. We read with interest the article by Hirohito Mori et al., which described an innovative therapeutic intervention using combined steroid gel application and planned balloon dilatation in the prevention of esophageal strictures after ESD. From April 2009 to July 2012, they involved 43 patients who underwent two-thirds to entire circumferential esophageal mucosa resection into this sealed-envelope randomized prospective study, and divided them into two groups: 23 patients were treated with local steroid injection and balloon dilatation, and 20 patients were treated with steroid gel application and balloon dilatation. These interventions were performed mandatorily in each group on postoperative days (PODs) 5, 8, 12, and 15. After comparing stricture rate in different check points, additional costs, and bleeding risk between groups, they concluded that steroid gel application was more effective compared with local injection. Is steroid gel the ideal choice we are waiting for? To answer this question, there are concerns regarding their study design, data description, and results explanation. Precise data are basis of a credible research. In their study, no significant intergroup difference was observed in the stricture rate on PODs 5, 8, 12, 15, 20, 30, and 60 by using unpaired t-test, which graphically displayed in Figure 4. In the result part, we saw that except for POD 8, the stricture rate of the gel application group was greater than or equal to the local injection group. But it was confused that the two broken lines in Figure 4 showed the