Factors predicting successful endoscopic balloon dilatation of esophageal strictures in children - a retrospective study

Background & Aims: Endoscopic balloon dilatation has become the first line treatment for benign esophageal strictures; It is important to know the factors predicting successful outcome to assist in selecting optimal protocol to obtain the best outcome and avoid as many complication as possible. This study aimed to assess the factors predicting outcome of endoscopic balloon dilatation treatment for esophageal stricture in children. Methods: All the patients with benign esophageal stricture treated by endoscopic balloon dilatation from January 2010 to December 2014 were included. All procedures were performed under tracheal intubation and intravenous anesthesia using the 3rd grade controlled radial expansion balloon with the gastroscope. Outcomes were recorded and predictors for outcomes were analyzed. Results: A total of 170 dilations were completed in 64 patients. The success rate was 96.9%. The rates of response, complication, and recurrence were 96.77%, 8.06%, and 3.33%, respectively. The number of dilatation sessions and complications were significant higher in patients with smaller diameter strictures (P = 0.013, 0.023), and in patients with multiple structures (P = 0.014, 0.004); more complication and recurrences were seen in patients with longer strictures (P = 0.001, 0.012). The longer the interval between surgery and first dilatation the more sessions and the poorer the response in the patients with anastomotic esophageal strictures (p = 0.017, 0.024). Conclusions: The diameter, length and number of stricture were the most important risk factors for poor outcomes of endoscopic balloon dilatation treatment of esophageal stricture.

Benign esophageal strictures in children can be treated surgically or nonsurgically. Over the past 20 years, endoscopic balloon dilation (EBD) therapy has become a primary method. The advantages and safety of EBD was reported with high success and low complication and mortality rates (4)(5)(6)(7)(8)(9)(10)(11). However, few studies have focused on the factors such as the etiologies of stricture, the number of the stricture, the length of stricture, the interval between first EBD and surgery/injury/symptom onset, and sessions of EBD which affect the outcome of the treatment. Additionally, the sample size was relatively small and lack of studies on Chinese children was the limitation in the existing literatures. In this retrospective study of 64 Chinese children, we aimed to evaluate the response, safety and more important -the factors predicting outcome of EBD treatment for esophageal strictures.

Patients
The current study was a single-site retrospective study.

Endoscopic technique
After written consent was obtained from the children's parents, endoscopy and dilatation were present, after that the frequency was individualized to once every 4 -12 weeks according to stricture appearance at endoscopy or patient complaints.
The treatment effectiveness was judged based on improvement of symptoms. It was considered as effective response if a patient had disappearance or relief of dysphagia or dysphagia score of 1 for children older than 6 months for at least 1 year after last dilatation. We defined failure as resistance to EBD (no alteration of stricture diameter when dilated). The return of dysphagia more than 1 year after the last EBD was considered as recurrence.

Statistical Analysis
Statistical presentation and analysis was conducted using Statistical package SPSS 19.0 (SPSS Inc., Chicago, USA). Continuous variables are expressed as the mean ± SD. The Student's t-test was used for the comparison between groups; if the number of groups was 2 or more, the analysis of variance (ANOVA) was applied. Categorical variables were analyzed using the chi-square test. Spearman rank order correlations analysis, for nonparametric correlation, was applied to test correlations between variables. Two-tailed p-values less than 0.05 were considered statistically significant.

Demographic characteristics of patients
64 children were diagnosed with ES in this study (age range 1 -150 months, median age  Table 1.

Strictures
As shown in table 1, most cases had a single stricture site. The most frequently involvement was the lower third of the esophagus. The stricture was significantly greater after dilatation than it was before treatment ( Table 2).

Outcomes of treatment
A total of 170 dilations were done for the 64 patients, ranging from 1 to 6 sessions per patient. 2 cases failed and underwent surgery. 96.77% of the patients with successful management had symptom improvement. All the children with effective treatment were fed with solid or semi-liquid diet. Improvement in nutrition and failure to thrive was achieved. The relapse of symptoms occurred in 2 patients who received treatment with renewed EBD and are still being followed up. None of the patients died during the followup period after EBD. Outcomes of EBD procedure are presented in Table 2.
The most common complications in this study included esophageal perforation, bleeding, infection, and gastroesophageal reflux. Multiple complications occurred in 2 patients. One suffered perforation, aspiration, reflux esophagitis and infection, and the other one suffered perforation and infection. All the patients with complications recovered with conservative treatment as follows: pharyngeal suction, parenteral nutrition, systematic intravenous antibiotherapy and anti-reflux medications. The patients who suffered gastroesophageal reflux were treated with omeprazole for decrease production of HCl for 2 weeks to 2 months.

Factors predicting the outcomes of EBD
The predictive factors are summarized in Table 3

Discussion
In this study, we found that stricture length was an import risk factor of EBD treatment for ES in children, which has a significant impact on the complications of EBD. 2 (14.3%) children with 2 -5 cm stricture and 3 (37.5%) children with stricture longer than 5 cm suffered complication. The results were similar to the previous observations in which the complication rates were very high in cases that had strictures longer than 5 cm (4).
Previous studies also state that treatment results are better in patients with shorter stricture lengths (13,14). The short stricture treatment was also of significantly shorter duration than the long stricture treatment (15). However, we did not find the association of the length of stricture with success rate and EBD sessions. This is in contrast to the studies which reported that patients with long strictures (>5 cm) required a significantly higher number of sessions than those with shorter strictures (1,5). We considered that lumen tortuosity, deformation and diverticulization due to long stricture, which contributed to the adverse impact on endoscopic procedures and resulted in more complications.
The diameter and number of strictures was also an important predicting factor in this study, which significantly affected the complication rate and number of EBD sessions needed for all patients, but this did not affected the rate of success, response and recurrence. The present results were in agreement with other observations in which more complications and more sessions were seen in the patients with multiple strictures (5,16).
Though in cases with small and/or multiple stricture, EBD was performed in combination with fluoroscopy to avoid the complication as possible, for advancing a balloon without guidewire leads to fibrotic or ulcer, leads to direct perforation as a result of hooking of the tip to the stricture (6), and for a wrong passage that the esophageal diverticulum was mistaken for a stricture to be dilated, which leads to perforation after the balloon is blown in cases of multiple stricture. Moreover, It was likely that substantially higher shear force was necessary to achieve the same expected diameter using a small size of balloon than a larger one, for example, 10 atm force was needed to get the same diameter of 8 mm with the use of 6-7-8 mm balloon while just 3 atm force by using 8-9-10 mm balloon. More shearing force was exerted on the esophagus in patients with smaller stricture diameter.
Whether some alternative methods are better than endoscopic balloon dilatation remains an issue in management of pediatric patients with multiple esophageal strictures and needs to be investigated further.
Number of EBD sessions was not a predictive factor of clinical outcomes in this study.
When we compared the failure and complication rates of the first two EBD procedures with those of subsequent dilatations in patients requiring more than two procedures we did not find any higher risk of failure or complication in the subsequent procedures. It was reported that the recurrence and complications were more frequent in patients who underwent a higher number of dilatations and steroid injection (4), use of multiple dilations led to increased perforation risk (17).
Etiology of esophageal strictures was reported to be a crucialy important factor determining the outcome of EBD. But we did not find that etiology affected the clinical outcomes in this study. There are some reports revealing that the results are less satisfactory in cases of corrosive injury than with other etiologies for more dilatation sessions (1,16,18), lower effectiveness rates (4), and higher complication and failure rates (19)(20)(21), possibly because of the rapid restenosis due to formation of fibrous tissue after dilatation (13,(22)(23)(24). On the contrary, we found that the EBD sessions, complication and success rate were not significant higher in patients with caustic esophageal strictures than those with other etiologies in this study. However, a lower success rate was in patients with congenial esophageal stricture compared with the other patients, but it was not significant. The results of this study indicated that EBD should be the first line of treatment in cases of corrosive injury, as well as of other etiologies.
Specifically, the time of first EBD after surgery finding in this study was a major predictor of treatment outcome in the patients with anastomotic esophageal strictures. The interval between surgery and the first EBD was significant associated with the number of EBD sessions. Early EBD was related to fewer EBD sessions. This finding is similar to the previous reports of different series in which time to diagnosis or onset of stricture is the most important factor affecting recurrence after dilation (25,26). The observations on adult patients with gastrectomy for gastric cancer indicated balloon dilations earlier than 90 days after surgery require careful observation for restenosis (27). Early EBD has a positive impact on treatment success in patients with caustic esophageal strictures (28).
However, the optimal time of initial dilation remains to be determined, because there is always concern that performing dilation 2-3 weeks after surgery might be too early in the healing process and would put the anastomosis at risk for perforation (29). We suggest the time of initial EBD not exceeding 2 months after surgery.
The shortcomings to our study include the relatively short follow-up period and a small sample size resulting in small subgroup size.

Conclusions
This study indicated that the length, diameter and number of the strictures were the most crucial predictive factors for treatment outcome. Early EBD after surgery was related to better response and fewer EBD sessions in the patients with anastomotic esophageal stricture.

Declarations
Ethical approval: The Ethics Committees of Shenzhen Children's Hospital approved this current study.
Informed consent statement: The informed consent was waived due to the retrospective nature of this study.

Consent for publication: Not applicable
Availability of data and material: All data analyzed during the current study are included in this published article.    Interval † : Interval between first EBD and surgery/injury/symptom onset. * P < 0.05