Esophageal atresia (EA) is a common congenital anomaly of the digestive tract, with a prevalence of 1 in 3,500 births (1). EA with tracheoesophageal fistula (EA/TEF) accounts for ~70–90% of cases of EA (2, 3). Operation is indispensable to save the patient's life. The azygos vein is usually ligated and divided to facilitate operation during the repair procedure of EA/TEF (4).

The azygos vein is an important vein that ascends in the posterior region of the right thorax and next to the vertebral column. It drains blood from all of the posterior intercostal veins but the first intercostal vein in the right thorax into the superior vena cava. Some investigators maintain that the azygos vein is a major vessel and should be preserved if preservation does not augment the incidence of postoperative complications (5). Anastomotic leakage is one of the most frequent postoperative complications and significantly increases postoperative hospitalization time and cost (6, 7). Some researchers believe that ligation of the azygos vein will aggravate postoperative edema at the anastomosis and chest congestion and consequently lead to higher incidences of complications, including anastomotic leakage and pneumonitis (5, 8). Although a series of studies have been performed to verify this assumption, those studies have failed to achieve consistent conclusions (5, 8–11). Concerns are raised regarding whether azygos vein preservation will increase the difficulty or time of operation and reduce the quality of anastomosis. A longer operative time results in longer anesthetic exposure. Longer anesthetic exposure may augment the risk of impairment in neural development (12). With the view that more than 90% of pediatric surgeons preferring thoracotomy to thoracoscopy to deal with EA, (13) in the present study, we conducted this meta-analysis to investigate whether azygos vein preservation would be feasible with no increased risks or even reduced risks of postoperative complications in patients undergoing thoracotomy.

Study selection and the results of selection are shown in Figure 1. Forty-eight potentially eligible records were identified by using the search strategy. After carefully reviewing the titles and abstracts of these publications, the full texts and reference lists of 7 records were scrutinized, and 4 articles meeting the inclusion criteria were ultimately included in the final analyses (5, 8, 10, 11). Table 1 summarizes the baseline characteristics and Jadad scores of these four studies. A total of 286 patients were assigned to the preservation group (n = 164) or the ligation group (n = 122). Table 2 reports the exact case numbers of each outcome in each study. There was no evidence of obvious publication bias in each analysis, based on funnel-plot symmetry.

EA is the most frequent congenital malformation of the esophagus, which is supposed to emerge as a consequence of the abnormal development of the foregut (16). The first successful end-to-end anastomosis and fistula ligation to treat EA/TEF was presented in 1941, (17) and currently, surgery is considered to be inevitable to save life.

In the standard operation procedure of repair surgery of EA/TEF, the azygos vein would be ligated and divided to provide a clear operation field and facilitate identification of the distal esophagus and fistula to conduct esophageal anastomosis. It was worrisome whether preservation of the azygos vein would prolong operative time. A longer duration of surgery means a longer duration of general anesthesia. Some studies have indicated that prolonged anesthesia might affect neurodevelopmental outcomes (18). Harmsen et al. reported that the duration of anesthetic exposure was negatively correlated with motor developmental outcome in patients with EA (19). Our study found that the preservation group might not need a longer operative time than the ligation group. The results of four studies were not consistent. The differences in the mean operative times in the two groups were small. Further large trials are needed to clarify this question.

The azygos vein drains deoxygenated blood from the ascending lumbar veins and the right subcostal veins into the superior vena cava, which means that the azygos vein also drains the esophagus and bronchus. Compared with ligation of the azygos vein, preservation of the azygos vein possibly lowered the degree of esophageal anastomotic edema and postoperative congestion of the lung. It might be reasonably deduced that preservation of the azygos vein could reduce the risks of anastomotic complications and pneumonias.

Anastomotic leak was a main early postoperative complication in EA patients, with an estimated prevalence of 20% (20). Patients with long gap EA had a higher risk of anastomotic leakage, which might be attributed to high tension on the anastomosis (20, 21). Minor leaks might heal spontaneously by managing conservatively with drainage. Nevertheless, major leakage might be life-threatening, and reoperation may be needed. Some researchers supposed that ligation of the azygos vein would aggravate postoperative edema at the anastomosis and consequently increase the risk of anastomotic leakage in patients (8). Our study demonstrated that preservation of the azygos vein could reduce the prevalence of anastomotic leakage. Nevertheless, whether the decrease in anastomotic leakage is related to the relief of postoperative edema by draining blood remains to be clarified.

Although mortality after EA repair remarkably dropped from 81% in the 1940s to 9% in the 2010s with the development of equipment and perioperative management 26, death is still a threat to patients with EA. In this study, we found that preservation of the azygos vein could significantly lower mortality. Approximately half of patients with EA have associated anomalies (3, 22). Cardiac defects were the most common associated anomaly, with a prevalence of 26.7% (22). It was reported that cardiac defects were related to mortality (22, 23). Preservation of the azygos vein might have less of an effect on the circulatory system than ligation of the azygos vein. In addition, preservation of the azygos vein was able to reduce the risk of postoperative pneumonitis (8, 11). These advantages might contribute to the lower mortality.

Some limitations should be noted in this study. Although only RCTs were included in this meta-analysis, which maximally reduced potential biases, the number of included studies was limited. Many postoperative complications, including anastomotic stricture, recurrent TEF and gastroesophageal reflux disease, were not compared owing to a lack of relevant data. Thus, we were not able to evaluate the preservation of azygos veins in all aspects, and more studies are needed to assess the preservation of azygos veins in those aspects to provide a further understanding.

This study offers distinguished evidence regarding the safety and benefit of preservation of the azygos vein in patients with EA/TEF. Our research demonstrates that preservation of the azygos vein is able to reduce the prevalence of anastomotic leakage and mortality compared with ligation of the azygos vein. Further studies are needed to evaluate the preservation of the azygos vein in other aspects, including anastomotic stricture, recurrent TEF and gastroesophageal reflux disease.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

XM contributed to the design of the study. CW and JZ performed the literature search and extracted the data. XM and CW analyzed the data and interpreted the statistical analysis. XM, CW, and JZ drafted the manuscript. All authors read and approved the final manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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