Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures

Abstract

Background Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and transforming growth factor β3 (TGF-β3) exhibits antiscarring effects that may prevent post-ESD stricture formation. Methods Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n = 6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2); Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-β3 2 μg (n = 2), 0.5 μg (n = 2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80 % or the animals were unable to maintain weight. Results The control group had a luminal diameter reduction of 78.2 ± 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks, the Hal group showed a decrease in mean stricture formation (68.4 % low dose, 57.7 % high dose), while both TGF-β3 dosage groups showed no significant change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-β3 and Hal treated areas appeared re-epithelialized and healthy. Conclusions Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formation after EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy.

Systematic review: the prevention of oesophageal stricture after endoscopic resection

“…One study of our team included nine pigs and did not show any benefit on oesophageal stricture occurrence . Another study reported two animals treated with low dose mitomycin, finding a moderate, non statistically significant increase in the oesophageal lumen compared to the controls, as well as two premature deaths attributable to the local toxicity of high doses of mitomycin . Anti‐inflammatory molecules with supposed anti‐fibrotic properties have been assessed in animal studies.…”

“…Anti‐inflammatory molecules with supposed anti‐fibrotic properties have been assessed in animal studies. Halofugidone was poorly effective in a controlled study involving four pigs and six controls with no statistically significant differences in terms of oesophageal diameter reduction . As fibrotic processes involve oxidative stress, N‐acetylcysteine as an anti‐oxidant may exert an anti‐fibrotic activity.…”

Tissue and Organ Regeneration in Adults

“…Examples of organ deformation following trauma in experimental animal models are the observation of contraction of the ureter following resection of a portion of the circumference (Oppenheimer and Hinman 1955;Kiviat et al 1973) and the contraction of the transected ligament (Dahners et al 1986;Wilson and Dahners 1988). In humans, the narrowing (stricture) of the urethra that follows trauma (Rudolph et al 1992;Wong et al 2012;Lee and Kim 2013); narrowing of the esophagus (esophageal stricture) after swallowing a corrosive agent (Peacock 1984) or after surgery (Singhal et al 2013;Wu et al 2013); and contraction of a defect in the upper eyelid (ectropion) after radiotherapy (Tarallo et al 2012), have been usually attributed to the same contractile process that leads to closure of skin defects. Biologically inert implants, inserted inside an organ in a space that has been prepared by tissue excision, are typically covered by a capsule of contractile tissue; examples are silicone breast implants and cardiac pacemakers (Rudolph et al 1992).…”

Intramuscular injection of mitomycin C combined with endoscopic dilation for benign esophageal strictures

“…In recent studies, mitomycin C has also been used for the treatment of esophageal strictures after ESD in adults . Furthermore, previous studies have supported the application of mitomycin C in combination with endoscopic dilation as an alternative option that is both effective and safe for treating benign esophageal strictures.…”