Keywords
esophageal atresia - outcome - surgical techniques - mortality rate - long-term morbidity
Introduction
Advances in surgical expertise, technical equipment as well as anesthetic and neonatal intensive care management, have contributed to decreased mortality and morbidity rates of patient with esophageal atresia (EA) in the last decades.[1]
[2]
[3]
Before gradual implementation of surgical management, the mortality rate of EA patients was 100%. The first survivors with the condition were independently reported by Leven and Ladd in 1939, who managed their cases with a staged approach consisting of initial gastrostomy, subsequent fistula ligation or division with cervical esophagostomy, and finally creation of an antethoracic skin tube conduit from the esophagostomy to the gastrostomy.[4]
[5]
[6]
[7] The first successful open end-to-end anastomosis and fistula ligation was reported in 1941 by Haight and Towsley.[8] At a later time, Haight revised his technique from a left extrapleural approach with single-layer anastomosis to two-layer anastomosis and a right extrapleural approach.[4] Many of Haight's initial techniques still guide our current management of neonates born with EA.[4]
Another milestone in EA surgery was achieved with the introduction of minimal invasive surgery. In 1999, the first successful thoracoscopic repair of a pure EA was performed.[9] One year later, Rothenberg reported the first thoracoscopic fistula ligation and primary anastomosis.[10] Since then, minimal invasive EA repair is deployed in increasing numbers worldwide.[11]
This report aims to elucidate and compare the outcome development of EA throughout the decades since the first end-to-end anastomosis to modern era. Besides mortality rates, we focused on common and severe postoperative complications after EA repair, such as occurrence of recurrent fistula, anastomotic leakage, and stricture.
Materials and Methods
In January 2018, a PubMed literature search was conducted for the years 1944 to 2017 using different combinations of the following keywords: “esophageal/oesophageal atresia,” “outcome,” “experience,” “management,” and “follow-up/follow up.” Additionally, reference lists of included papers were screened manually for further studies. Duplicates were deleted.
Selection Criteria and Data Extraction
Relevant articles were reviewed by title, abstract, and keywords, and full-text of selected articles were assessed by one of the authors (J.Z.). Only articles in English language were considered. Reports on long-gap EA only, case reports, and reviews without original patient data were excluded. We focused on mortality and rates of recurrent fistula, leakage, and stricture. The data were standardized extracted into an electronic database, containing the characteristics of the study (authors, publication year, time frame of the study, number of patients, age/mean follow-up time, mortality rate, and percentage of patients with recurrent fistula, leakage, and stricture).
Statistical Analysis
Microsoft Excel was used for data analysis. The percentage of patients with recurrent fistula, leakage, and stricture as well as the percentage of patients who died was compared between the different decades.
Results
A total of 747 articles were identified through literature search, of which 118 manuscripts met the inclusion criteria ([Fig. 1]). Included articles and their reported outcomes are shown in [Table 1]. An overview of the included study types is given in [Table 2]. All except for seven were retrospective studies.[3]
[12]
[13]
[14]
[15]
[16]
[17] One was a randomized controlled trial as reported by Upadhyaya et al.[18] It is notable that some reports comprise outcome data of several decades, which were matched to the related period.
Table 1
Included articles and their characteristics for this study (chronological order)
Author and year
|
Study period
|
Study type
|
No. of patients
|
Anastomotic leak
|
Recurrent fistula
|
Stricture rate
|
Mortality
|
Donoso and Lilja 2017[53]
|
1994–2013
|
Retrospective
|
129
|
Yes
|
No
|
Yes
|
Yes
|
Tröbs et al 2017[54]
|
2006–2013
|
Retrospective
|
24
|
N/R
|
N/R
|
N/R
|
Yes
|
Long et al 2017[15]
|
2008–2009
|
Prospective
|
21
|
Yes
|
No
|
Yes
|
N/R
|
Acher et al 2016[17]
|
Not specified
|
Prospective
|
445
|
Yes
|
N/R
|
Yes
|
N/R
|
Bakal et al 2016[55]
|
1996–2011
|
Retrospective
|
51
|
Yes
|
N/R
|
Yes
|
Yes
|
Bradshaw et al 2016[56]
|
2004–2013
|
Retrospective
|
58
|
Yes
|
N/R
|
Yes
|
Yes
|
Dingemann et al 2016[25]
|
2007–2012
|
Retrospective
|
75
|
Yes
|
Yes
|
Yes
|
No
|
Donoso et al 2016[57]
|
1994–2013
|
Retrospective
|
129
|
Yes
|
Yes
|
Yes
|
Yes
|
Hannon et al 2016[27]
|
1993–2015
|
Retrospective
|
9
|
N/R
|
Yes
|
N/R
|
Yes
|
Hartley et al 2016[58]
|
1996–2014
|
Retrospective
|
120
|
Yes
|
N/R
|
N/R
|
Yes
|
Malakounides et al 2016[35]
|
2001–2011
|
Retrospective
|
200
|
N/R
|
N/R
|
N/R
|
Yes
|
Okata et al 2016[59]
|
2000–2015
|
Retrospective
|
28
|
Yes
|
No
|
Yes
|
N/R
|
Tong et al 2016[60]
|
2008–2014
|
Retrospective
|
35
|
Yes
|
N/R
|
N/R
|
N/R
|
Okuyama et al 2015[21]
|
Not specified
|
Retrospective
|
58
|
Yes
|
Yes
|
Yes
|
Yes
|
Pini Prato et al 2015[14]
|
2011–2013
|
Prospective
|
146
|
Yes
|
Yes
|
Yes
|
Yes
|
Uygun et al 2015[61]
|
2009–2013
|
Retrospective
|
6
|
Yes
|
N/R
|
Yes
|
Yes
|
Allin et al 2014[12]
|
2008–2009
|
Prospective
|
151
|
Yes
|
Yes
|
Yes
|
Yes
|
Dunkley et al 2014[52]
|
1990–2007
|
Retrospective
|
66
|
Yes
|
Yes
|
Yes
|
Yes
|
Fallon et al 2014[62]
|
2002–2012
|
Retrospective
|
91
|
Yes
|
Yes
|
Yes
|
Yes
|
Lee et al 2014[63]
|
2008–2013
|
Retrospective
|
23
|
Yes
|
Yes
|
Yes
|
N/R
|
Schneider et al 2014[13]
|
2008–2009
|
Prospective
|
307
|
Yes
|
Yes
|
Yes
|
Yes
|
Sulkowski et al 2014[48]
|
1999–2012
|
Retrospective
|
3479
|
N/R
|
Yes
|
N/R
|
Yes
|
Wang et al 2014[1]
|
2000–2009
|
Retrospective
|
4168
|
N/R
|
N/R
|
N/R
|
Yes
|
Yamato et al 2014[29]
|
2001–2012
|
Retrospective
|
26
|
Yes
|
Yes
|
Yes
|
No
|
Burge et al 2013[16]
|
2008–2009
|
Prospective
|
151
|
Yes
|
N/R
|
N/R
|
Yes
|
Dingemann et al 2013[26]
|
2001–2011
|
Retrospective
|
44
|
Yes
|
Yes
|
No
|
No
|
Koivusalo et al 2013[37]
|
1991–2001
|
Retrospective
|
130
|
Yes
|
Yes
|
Yes
|
Yes
|
Niramis et al 2013[64]
|
2003–2010
|
Retrospective
|
132
|
Yes
|
Yes
|
Yes
|
Yes
|
Rothenberg 2013[24]
|
2000–2012
|
Retrospective
|
61
|
Yes
|
No
|
Yes
|
No
|
Sfeir et al 2013[3]
|
2008–2009
|
Prospective
|
307
|
N/R
|
Yes
|
Yes
|
Yes
|
Sfeir et al 2013[65]
|
2008–2009
|
Retrospective
|
307
|
N/R
|
N/R
|
N/R
|
Yes
|
Huang et al 2012[46]
|
2007–2012
|
Retrospective
|
33
|
Yes
|
Yes
|
Yes
|
Yes
|
Jawaid et al 2012[66]
|
1999–2009
|
Retrospective
|
119
|
Yes
|
Yes
|
Yes
|
Yes
|
Oddsberg et al 2012[47]
|
1964–2007
|
Retrospective
|
1126
|
N/R
|
N/R
|
N/R
|
Yes
|
Rothenberg 2012[30]
|
N/R
|
Retrospective
|
49
|
Yes
|
No
|
Yes
|
No
|
Spoel et al 2012[50]
|
2005–2009
|
Retrospective
|
37
|
N/R
|
N/R
|
Yes
|
N/R
|
Burford et al 2011[67]
|
1993–2008
|
Retrospective
|
72
|
Yes
|
Yes
|
Yes
|
N/R
|
Sistonen et al 2011[68]
|
1947–1985
|
Retrospective
|
101
|
Yes
|
Yes
|
Yes
|
Yes
|
Szavay et al 2011[22]
|
2002–2010
|
Retrospective
|
68
|
Yes
|
N/R
|
N/R
|
No
|
Zhao et al 2011[69]
|
2000–2009
|
Retrospective
|
85
|
Yes
|
N/R
|
Yes
|
N/R
|
Jong et al 2010[70]
|
2000–2006
|
Retrospective
|
59
|
Yes
|
Yes
|
Yes
|
Yes
|
Lacher et al 2010[36]
|
1988–2009
|
Retrospective
|
111
|
Yes
|
Yes
|
Yes
|
Yes
|
Serhal et al 2010[71]
|
2000–2005
|
Retrospective
|
62
|
Yes
|
N/R
|
N/R
|
N/R
|
MacKinlay 2009[72]
|
N/R
|
Retrospective
|
36
|
Yes
|
Yes
|
Yes
|
Yes
|
Patkowsk et al 2009[73]
|
2005–2008
|
Retrospective
|
23
|
Yes
|
No
|
Yes
|
Yes
|
Petrosyan et al 2009[2]
|
1987–2009
|
Retrospective
|
25
|
Yes
|
No
|
Yes
|
Yes
|
Tandon et al 2009[74]
|
2007–2008
|
Retrospective
|
98
|
Yes
|
N/R
|
N/R
|
Yes
|
Lilja et al. 2008[38]
|
1986–2005
|
Retrospective
|
147
|
Yes
|
Yes
|
Yes
|
Yes
|
Lugo et al 2008[23]
|
2000–2006
|
Retrospective
|
33
|
Yes
|
N/R
|
Yes
|
No
|
Sri Paran et al 2007[75]
|
1977–2004
|
Retrospective
|
26
|
N/R
|
N/R
|
Yes
|
Yes
|
Upadhyaya et al 2007[18]
|
2004–2006
|
RCT
|
50
|
Yes
|
N/R
|
Yes
|
Yes
|
van der Zee and Bax 2007[76]
|
2000–2006
|
Retrospective
|
51
|
Yes
|
Yes
|
Yes
|
Yes
|
Al-Salem et al 2006[33]
|
1989–2004
|
Retrospective
|
94
|
Yes
|
Yes
|
Yes
|
Yes
|
Sugito et al 2006[34]
|
1975–2003
|
Retrospective
|
24
|
Yes
|
Yes
|
Yes
|
Yes
|
Uchida et al 2006[77]
|
1979–2003
|
Retrospective
|
42
|
Yes
|
Yes
|
Yes
|
Yes
|
Yang et al 2006[31]
|
1994–2003
|
Retrospective
|
15
|
Yes
|
No
|
Yes
|
Yes
|
Al-Malki et al 2005[78]
|
1990–2000
|
Retrospective
|
101
|
N/R
|
N/R
|
N/R
|
Yes
|
Holcomb et al 2005[39]
|
N/R
|
Retrospective
|
104
|
Yes
|
Yes
|
Yes
|
N/R
|
Calisti et al 2004[79]
|
1999–2002
|
Retrospective
|
75
|
Yes
|
Yes
|
Yes
|
Yes
|
Deurloo et al 2004[80]
|
1982–2002
|
Retrospective
|
197
|
Yes
|
Yes
|
N/R
|
Yes
|
Orford et al 2004[81]
|
1970–2000
|
Retrospective
|
152
|
Yes
|
N/R
|
Yes
|
Yes
|
Tonz et al 2004[82]
|
1973–1999
|
Retrospective
|
104
|
Yes
|
Yes
|
Yes
|
Yes
|
Touloukian, Seashore[83]
|
1968–2003
|
Retrospective
|
143
|
Yes
|
Yes
|
Yes
|
Yes
|
Konkin et al 2003[84]
|
1984–2000
|
Retrospective
|
144
|
Yes
|
Yes
|
Yes
|
Yes
|
Little et al 2003[43]
|
1972–1990
|
Retrospective
|
69
|
Yes
|
N/R
|
Yes
|
N/R
|
van der Zee and Bax 2003[85]
|
2002
|
Retrospective
|
13
|
Yes
|
N/R
|
Yes
|
N/R
|
Deurloo et al 2002[86]
|
1947–2000
|
Retrospective
|
371
|
Yes
|
Yes
|
Yes
|
Yes
|
Sharma et al 2000[32]
|
1972–1996
|
Retrospective
|
585
|
Yes
|
Yes
|
Yes
|
Yes
|
Sparey et al 2000[87]
|
1985–1997
|
Retrospective
|
120
|
N/R
|
N/R
|
Yes
|
Yes
|
Nawaz et al 1998[88]
|
1981–1996
|
Retrospective
|
41
|
Yes
|
No
|
Yes
|
Yes
|
Somppi et al 1998[89]
|
1963–1993
|
Retrospective
|
60
|
N/R
|
N/R
|
N/R
|
Yes
|
Okada et al 1997
|
1957–1995
|
Retrospective
|
159
|
Yes
|
Yes
|
Yes
|
Yes
|
Tsai et al 1997[90]
|
1957–1995
|
Retrospective
|
81
|
Yes
|
N/R
|
Yes
|
Yes
|
Engum et al 1995[91]
|
1971–1993
|
Retrospective
|
227
|
N/R
|
Yes
|
Yes
|
Yes
|
Rokitansky et al 1994[92]
|
1960–1991
|
Retrospective
|
309
|
N/R
|
N/R
|
N/R
|
Yes
|
Spitz et al 1994[28]
|
1980–1992
|
Retrospective
|
372
|
N/R
|
N/R
|
N/R
|
Yes
|
Alexander et al 1993[93]
|
1966–1986
|
Retrospective
|
25
|
Yes
|
Yes
|
Yes
|
Yes
|
Rokitansky et al 1993[45]
|
1975–1991
|
Retrospective
|
223
|
Yes
|
Yes
|
Yes
|
Yes
|
Touloukian 1992[94]
|
1968–1990
|
Retrospective
|
68
|
Yes
|
Yes
|
Yes
|
Yes
|
Poenaru et al 1991[95]
|
1962–1988
|
Retrospective
|
131
|
Yes
|
Yes
|
Yes
|
Yes
|
McKinnon and Kosloske 1990[96]
|
1976–1989
|
Retrospective
|
64
|
Yes
|
Yes
|
Yes
|
Yes
|
Adebo 1990[97]
|
1977–1987
|
Retrospective
|
11
|
Yes
|
N/R
|
Yes
|
Yes
|
Chittmittrapap et al 1990[98]
|
1980–1987
|
Retrospective
|
199
|
Yes
|
Yes
|
Yes
|
N/R
|
Randolph et al 1988[99]
|
1966–1988
|
Retrospective
|
118
|
Yes
|
N/R
|
Yes
|
Yes
|
Pohlsen et al 1988[100]
|
1980–1986
|
Retrospective
|
70
|
Yes
|
N/R
|
N/R
|
Yes
|
Sillen et al 1988[101]
|
1967–1984
|
Retrospective
|
110
|
Yes
|
N/R
|
Yes
|
Yes
|
Biller et al 1987[102]
|
1950–1960
|
Retrospective
|
12
|
No
|
N/R
|
Yes
|
N/R
|
Connolly and Guiney 1987[103]
|
1974–1983
|
Retrospective
|
139
|
Yes
|
Yes
|
Yes
|
Yes
|
Spitz et al 1987[104]
|
1980–1985
|
Retrospective
|
148
|
Yes
|
Yes
|
Yes
|
Yes
|
Manning et al 1986[4]
|
1935–1985
|
Retrospective
|
426
|
Yes
|
Yes
|
Yes
|
Yes
|
Bishop et al 1985[105]
|
1951–1983
|
Retrospective
|
240
|
Yes
|
Yes
|
Yes
|
Yes
|
Louhimo and Lindahl 1983[106]
|
1947–1978
|
Retrospective
|
500
|
Yes
|
Yes
|
Yes
|
Yes
|
O'Neill et al 1982[107]
|
1971–1980
|
Retrospective
|
53
|
Yes
|
N/R
|
Yes
|
Yes
|
Lindahl et al 1982[108]
|
1949–1955
|
Retrospective
|
54
|
Yes
|
Yes
|
N/R
|
Yes
|
Touloukian 1981[109]
|
1968–1979
|
Retrospective
|
38
|
Yes
|
Yes
|
Yes
|
Yes
|
Atwell et al 1980[110]
|
1967–1976
|
Retrospective
|
6
|
N/R
|
N/R
|
Yes
|
Yes
|
Strodel et al 1979[42]
|
N/R
|
Retrospective
|
365
|
Yes
|
Yes
|
Yes
|
Yes
|
Hrabovsky and Boles 1978[111]
|
1961–1973
|
Retrospective
|
135
|
Yes
|
N/R
|
Yes
|
Yes
|
Fasting and Winther 1978[112]
|
1952–1976
|
Retrospective
|
86
|
Yes
|
N/R
|
Yes
|
Yes
|
Pietsch et al 1978[113]
|
1962–1977
|
Retrospective
|
52
|
Yes
|
Yes
|
Yes
|
Yes
|
Exarhos et al1977[114]
|
N/R
|
Retrospective
|
16
|
N/R
|
N/R
|
Yes
|
Yes
|
Orringer et al 1977[115]
|
N/R
|
Retrospective
|
22
|
N/R
|
N/R
|
Yes
|
N/R
|
Ein and Themann 1973[49]
|
2,5 years
|
Retrospective
|
38
|
Yes
|
Yes
|
Yes
|
Yes
|
Laks et al 1972[116]
|
1945–1955
|
Retrospective
|
45
|
N/R
|
N/R
|
Yes
|
N/R
|
Battersby et al 1971[117]
|
1940–1969
|
Retrospective
|
210
|
N/R
|
N/R
|
N/R
|
Yes
|
Ferguson et al 1970[118]
|
1954–1969
|
Retrospective
|
69
|
N/R
|
N/R
|
N/R
|
Yes
|
Holden and Wooler 1970[119]
|
1939–1967
|
Retrospective
|
116
|
Yes
|
N/R
|
Yes
|
Yes
|
Krishinger et al 1969[120]
|
1944–1968
|
Retrospective
|
30
|
Yes
|
Yes
|
Yes
|
Yes
|
Romsdahl et al 1966[121]
|
1949–1965
|
Retrospective
|
34
|
N/R
|
Yes
|
Yes
|
Yes
|
Wayson et al 1965[41]
|
1940–1965
|
Retrospective
|
89
|
Yes
|
Yes
|
Yes
|
Yes
|
Waterston et al 1962[122]
|
1946–1959
|
Retrospective
|
218
|
N/R
|
N/R
|
N/R
|
Yes
|
Hays 1962[123]
|
1950–1960
|
Retrospective
|
110
|
N/R
|
N/R
|
N/R
|
Yes
|
Rehbein and Yanagiswa 1958[124]
|
1951–1958
|
Retrospective
|
84
|
Yes
|
Yes
|
Yes
|
Yes
|
Parish and Cummings 1958[5]
|
N/R
|
Retrospective
|
17
|
N/R
|
N/R
|
Yes
|
Yes
|
Ashe and Seibold 1949[125]
|
N/R
|
Retrospective
|
8
|
Yes
|
N/R
|
Yes
|
Yes
|
Ladd and Swenson 19947[126]
|
1940–1946
|
Retrospective
|
75
|
N/R
|
N/R
|
N/R
|
Yes
|
Daniel 1944[127]
|
1941–1944
|
Retrospective
|
7
|
N/R
|
N/R
|
N/R
|
Yes
|
Haight 1944[128]
|
1935–1944
|
Retrospective
|
28
|
N/R
|
N/R
|
N/R
|
Yes
|
Abbreviations: N/R, mortality or morbidity not reported; No, no mortality or morbidity occurred during the study period; RCT, randomized controlled trial; Yes, rate for mortality or morbidity is mentioned in the paper.
Note: For reasons of clarity, this table gives only a brief overview of the recorded data of included papers. The extended table with staggered outcome regarding the different decades can be requested from the authors.
Table 2
Overview of included study types (multiple selections possible)
Study type
|
Number of studies
|
Randomized controlled trials
|
1
|
Prospective studies
|
7
|
Retrospective studies
|
110
|
Multicenter studies
|
10
|
Single-center studies
|
100
|
Comparative Studies
|
7
|
Fig. 1 PRISMA flow chart for data extraction. EA, esophageal atresia; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
A total of 102 (86%) of the included studies reported on mortality. Reported mortality rate after EA repair decreased markedly over time. It dropped from 100% in the presurgical era to 81% in the 1940s and to 54% in the 1950s. Further reduction followed in the next decades with 36% in 1960 to 1969, 28% in 1970 to 1979, and 16% in 1980 to 1989 and 1990 to 1999. In the postmillennial era, mortality rate after EA repair decreased further to 12% in 2000 to 2009, and in the current decade, it is 9% ([Fig. 2]).
Fig. 2 Reported mortality rate decreased from 100% before 1941 to 54% in 1950 to 1959, 28% in 1970 to 1979, 16% in 1990 to 1999, and 9% nowadays. Rates of recurrent fistula varied over time between 4 and 9% and leakage rate varied between 11 and 16%. However, stricture rate increased from 25 to 38%.
Reported rates of recurrent fistula varied over time between 4 and 9%, and leakage rate varied between 11 and 16% ([Fig. 2]). The number of studies reporting on recurrent fistula and leakage rate were 67 (56%) and 89 (75%), respectively, in this study.
Ninety-one (77%) out of 118 included papers reported on stricture rate. Stricture rate showed a substantial increase in the last decade. Between 1940 and 2009, the reported rate varied between 25 and 31%, whereas the average stricture rate was 38% in 2010 to 2017 ([Fig. 2]).
Discussion
“To anastomose the ends of an infant's esophagus, the surgeon must be as delicate and precise as a skilled watchmaker. No other operation offers a greater opportunity for pure technical artistry.”[19] This statement made by Dr. Willis J. Potts in the 1950s has lost none of its relevance.[19] In addition to surgery and refinement of surgical technique, newly developed drugs and equipment and continuous optimization of treatment strategies has led to constantly improved survival rates of neonates born with EA over time. Before the era of surgical correction, the diagnosis of EA was a death sentence, but overall mortality reached a single-digit rate in the last decade. There is an ongoing discussion for surgical best practice: open or thoracoscopic technique.[20] Several authors postulated that both approaches have a comparable perioperative outcome,[21]
[22]
[23] while others rate minimal invasive repair superior.[24] Careful patient selection and the case load per center may influence surgical outcome after EA correction.[25]
[26] Additionally, there seems to be a considerable variability in technical aspects of the operation as well as the postoperative management of patients with EA.[11]
[21] Examples are intrapleural versus extrapleural approaches, choice of suturing and surgical sewing material, and application of chest drains or transanastomotic tubes.[11] Furthermore, use and duration of paralysis, mechanical ventilation, antibiotic treatment, as well as antacid therapy vary widely among different centers worldwide.[11]
Even high-risk groups (very-low-birth-weight infants/extremely premature babies) present currently with acceptable survival rates. Hannon et al demonstrated 50% survival in EA patients with a birth weight below 1 kg.[27] However, in their study, all infants below 800 g body weight had poor outcome.[27] In contrast, there is 95% expected survival in babies of more than 1500 g body weight, depending on their comorbidites.[27]
[28]
Although several authors published a survival rate of 100% in their center,[22]
[23]
[24]
[26]
[29]
[30] the overall mortality found in this study was between 9 and 11% in the last two decades. This is due to the fact that we also included studies with very-low-birth-weight infants and articles from third world countries in this report.[27]
[31]
[32]
[33]
[34] However, it has been suggested that birth weight is nowadays not an important factor as it was previously, although major cardiac anomalies are still of poor prognostic aspect.[35]
In our report, leakage rate remained stable over time between 11 and 16%, suggesting that surgical variations do not have any substantial influence on this complication. Likewise, neither open nor thoracoscopic technique seems to markedly affect the rate of recurrent fistula.[36]
[37]
[38]
[39]
[40]
[41]
[42] Although, there are minor variations between 4 and 9% over time course, there was no further improvement since introduction of the minimal invasive technique. It remains elusive, why we observed a drop to 4% rate of recurrent fistula in the 1950s compared with high rates up to 9% in the following two decades.
Surprisingly, we found that stricture rate after EA repair increased in the last decade. A recent survey admonishes that retrospective studies of EA may underestimate long-term esophageal complications, such as strictures.[17] It is debatable, whether pediatric surgeons have become more aware of this complication during follow-up appointments over time and may therefore indicate endoscopic diagnostic including balloon dilatation or bougienage more generously. On the other hand, there is no uniform definition for “stricture” and indication of therapeutic interventions, which might explain the observed stricture rate variation between 4 and almost 90%. Additionally, thoracoscopic technique and its associated learning curve might also affect anastomotic narrowing. Correspondingly, Rothenberg described stricture rates of almost 50% in their initial minimal invasive series, decreasing later to 20%.[24] Furthermore, babies less than 1500 g of body weight have been found to have an increased risk of stricturing with primary EA repair.[2] In several long-term analyses, dysphagia and swallow difficulties have been shown to be common problems.[36]
[43]
[44] However, they seem to occur mainly in the first years of life and become clinically less relevant thereafter as most children learn coping mechanisms over the years.[43]
[44] Nonetheless, the continuously high complication rates demonstrate that close interdisciplinary long-term follow-up is more important than ever. It is crucial to detect and treat the complications accordingly, and patients born with EA must be assisted for transition to adult care by their pediatric surgeon.
Remarkably, only one randomized control trial[18] and seven prospective studies[3]
[12]
[13]
[14]
[15]
[16]
[17] could be included in this study. A limited number of multicenter studies[1]
[3]
[12]
[13]
[21]
[39]
[45]
[46]
[47]
[48] reported on their experiences, whereas the majority presented single center data. Likewise, also comparative studies were rare.[22]
[23]
[29]
[49]
[50]
[51]
[52] Therefore, the current level of evidence in EA treatment is very low, and reference networks such as The European Reference Network on Rare inherited and congenital anomalies (ERNICA), which aims to assure quality treatment with high levels of evidence for EA in the future, are urgently needed.
The authors are aware of study limitations. A key point is the heterogeneity of included EA cases. No distinction was made between different types of EA (gap length, existence of a tracheoesophageal fistula). As we aimed to show the worldwide overall outcome of morbidity and mortality over time course, the articles were not extracted for surgical technique (open vs. minimal invasive, anastomotic technique, and primary vs. staged repair), birth weight/age, associated anomalies, time of follow-up, or country of origin (industrial states vs. third world countries). There is also a potential bias in study selection for the current manuscript. Amount of accessibility of papers from the early decades was restricted. Furthermore, there is a considerable variety of therapeutic regimen and treatment strategies among the different centers involved in EA treatment as well as the possibility of selection bias in the included studies themselves.
Conclusion
This article reflects the heterogeneity of EA, its patients, and its repair modalities during the course of 80 years. The worldwide mortality rate decreased from 100% in the presurgical era to a single-digit range in the last decade. Along with the decrease in mortality, there is a shift to the importance of major postoperative complications and long-term morbidity regardless of surgical technique. Therefore, close and regular follow-up of EA patients must be mandatory to assure health and normal development not only during childhood, but also for transition into adult care. Further studies, particularly prospective or randomized controlled trials, or at least consensus conferences, are needed to achieve higher levels of evidence and quality improvement for current therapeutic strategies for EA treatment.