Endoscopic postdilatation application of Mitomycin C in children with resistant esophageal strictures

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Korean J Pediatr. 2019;62(10):395-399

Publication date (electronic) : 2019 June 24

doi : https://doi.org/10.3345/kjp.2018.07157

Yasser K. Rashed, MD^,1, Mohamed El-Guindi, MD²

¹Department of Pediatric Hepatology, National Liver Institute, Menoufiya University, Menoufia, Egypt

²Department of Pediatric Hepatology, Gastroenterology and Nutrition, National Liver Institute, Menoufia University, Menoufia, Egypt

Corresponding author: Yasser K. Rashed, MD Department of Pediatric Hepatology, Gastroenterology and Nutrition, National Liver Institute, Menoufia University, 32511 Shebin El-koom, Menoufia, Egypt Tel: +2-048-222-2740 Fax: +2-048-223-4586 E-mail: yasserrashed79@yahoo.com

Received 2018 October 7; Revised 2019 June 17; Accepted 2019 June 22.

Abstract

Introduction

Esophageal strictures can occur in children, corrosives materials still the most important cause of stricture in children and constitute 80% of the cases [1]. Dysphagia occurs when stenosis constitutes half of the esophageal lumen [2].

Endoscopic conservative management of esophageal strictures has evolved first-line management, rather than more aggressive surgical substitution. Endoscopic dilatation of esophageal strictures is a successful method for treating such cases in more than 80% of cases [3].

Endoscopic balloon dilatation or bougies (Savary) are the initial step to treat esophageal strictures. Intraluminal stent is another endoscopic technique to treat esophageal strictures and to get patent esophageal lumen. Re stenosis still the main problem [4].

Mitomycin C has been well documented in various ophthalmologic procedures and laryngeal/tracheal conditions where it has been shown that Mitomycin C inhibited fibroblast proliferation. Use of Mitomycin C has been reported in caustic stricture of the esophagus [5].

The aim of this study was to evaluate the methodology, efficacy, and side effects of Mitomycin C application after GI endoscopic dilatation of resistant esophageal strictures in children.

Methods

This study included 30 children with one or more features of resistant esophageal stricture. Seventeen males and 13 females, their ages ranged from 16–168 months with a mean of 57.6 months. They were admitted to the Pediatric Endoscopy Unit in the Pediatric Hepatology Department - National Liver Institute – Menoufiya University – Egypt. The diagnosis of esophageal strictures based on clinical history, barium study and upper gastrointestinal (GI) endoscopy.

All patients in the study were subjected to full history taking including demographic data, the time of exposure, the nature of corrosives they ingested, and their dietary history. Thorough clinical examination was done with special interest in weight, height, and nutritional status. Laboratory investigations included full blood count, liver function tests, chest X-ray. Barium study and upper GI endoscopy were undergone aiming to diagnose the nature and extent of esophageal stricture.

Results

Caustic potash ingestion was the cause of esophageal stricture formation in 23 patients (76.66%) as shown in Table 1, which determined by careful history taking and/or observing the containing bottle by the family. Post reflux occurred in one patient, and post-sclerotherapy in another patient. The etiology was not discovered in 5 patients. Our results showed 80% of our patients were ≤5 years. Males were 17 while females were 13 of our patients. Twenty patients of our caustic ingestion patients had history of accidental ingestion of household cleaners (Potash).

Table 1.

Description of the studied cases

Upper endoscopy was performed in all of the patients and while Gastrografin/barium upper GI series was performed in 10 patients before endoscopy. The median diameter of the stricture was 1.5 mm (range, 1–5 mm) which determined by barium or by upper GI endoscope. The length of the stricture at diagnosis was ranged from 10–110 mm with the mean of 37.14 mm.

Before Mitomycin application, repeated dilation procedures in 21 patients ranging from 2–75 with the mean of 12 times. Nine patients had no history of previous dilatation while number of dilatation settings with Mitomycin applications ranged from one to 5 with the mean of 2.3 times

Before the application of Mitomycin C, endoscopic dilation setting repeated every 2 weeks (2.52±1.44 weeks), this duration was prolonged to 5.00±4.39 weeks after the application of Mitomycin C.

Patient No. 1 required 75 dilatation settings before the application of Mitomycin C. This patient was 5 years female child presented with severe dysphagia, the length of stricture was 11 cm, which diagnosed with barium and upper GI endoscope, with repeated dilatation the length of stricture improved, but only 1 cm resist further dilatation, and we tried Mitomycin C application, and then started the idea to extent the study.

Excellent improvement regarding both clinical and endoscopic findings seen in 28 patients (93.3%) while partly improving seen in 2 (6.7%), we did not find any patient with poor response in this study. There were no complications related to the Mitomycin application in both studied group.

Follow-up of our patients for 3–5 years did not show any complications related to the procedures itself or to Mitomycin C, the results of both pledget and spray methods nearly the same without any difference regarding the side effects which encourage the use of spray method as it easier for the endoscopist and shorter in duration.

Discussion

Repeated sessions of dilatation required in severe esophageal strictures due to restenosis. The cause of restenosis can be explained by intense fibrogenesis during healing and after the traumatic dilatation procedure, making repeated dilatations necessary with an increased risk of complications and perforation.

Failure of dilatation of long and resistant strictures with repeated dilatation has been associated with psychological problems, withdrawal from school, hospital fears, and familial problems. In our center, trials to decrease the number of dilatations started with trial of steroid injection in localized strictures to increase the intervals but appeared not effective [6].

Trial of Mitomycin C (MMC) application on localized strictures has shown better outcome with less number of dilatation sessions. In our center, the first MMC application done in a very resistant case described above, whose stricture started as 11 cm long and esophageal lumen was very tight, and then showed marked improvement of the dysphagia with a decrease in the number of dilatations after MMC application.

The data published in children, most cases of esophageal strictures caused by ingestion of caustic substances, peptic esophagitis, or after anastomotic surgery done for EA [7]. this run in harmony with our results as 76.66% of our patients got esophageal stricture due to accidental caustic ingestion.

The majority of patients were under the age of 5 years and boys are more often affected than girls, this in agreement with most of the studies done on children [8].

Corrosives may be either acidic or alkaline substances. The most common corrosive caused caustic esophageal injuries were household cleaners, mostly alkaline. In children, ingestions are often accidental; the severity of injury depends upon amount, type and concentration of the ingested corrosive substance.

Alkaline agents leading to rapid liquefaction necrosis and persistent ulceration and fibrosis for months, contiguous damage occurs from the esophagus to the stomach and beyond while acidic agents cause more superficial coagulation necrosis with scarring that may limit the extent of injury, and the stomach is more affected than the esophagus [9]. Mitomycin C tried in extra gastrointestinal lesions after internal optical urethrotomy, Mitomycin C is effective in preventing recurrence of urethral stricture [10].

In our study, gastro-esophageal reflux disease (GERD) with resultant peptic injury was the cause of esophageal stricture in only one patient (Table 1). This was different from that reported by El-Serag [11] and Spechler et al. [12] who they found GERD with resultant peptic injury is the most common cause of benign esophageal strictures. The difference with our results may be because he studied different age group or different number of patients. Typically, these strictures are located near the gastro-esophageal junction and are relatively short (1–2 cm) in length.

Mitomycin C applied to stricture mucosa after dilatation. Various techniques have been used to topically deliver Mitomycin C to the anastomotic stricture. Mucosal application of Mitomycin C has been shown to be an effective and safe treatment without complications detected in our patients. This in agreement with Heran et al. [13], who studied 2 cases and used Mitomycin C to the disrupted stricture through the gastrostomy tract, and used a 12F to 16F semirigid sheath introduced over a guide wire and passed retrograde up the esophagus to the stricture. Also Rosseneu et al. [14] found that postdilation application of topical Mitomycin C had major success in 62.5% of patients and partial success in 18.7%.

Gusmon-Oliveira et al. [15] concluded that the repeated injection in the short interval of MMC in refractory pharyngoesophageal stenosis in patients after head and neck cancer is not recommended, this finding was in great difference with our results, this can be easily explained by different age group and different nature of both diseases.

Finally, we can conclude that Mitomycin C topical application can be safely tried for patients with caustic esophageal stricture, reducing the number of required dilatation sessions. It should be considered as an adjunct new modality before decision of more invasive therapeutic modalities. However, more studies on larger number of patients will be needed to prove the efficacy of MMC in these patients.

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