A long time ago in a galaxy far far away, I was taught that children with esophageal atresia would have reflux for life due to dysmotility following repair. Thus, these children presumably should remain on acid blockers indefinitely. It turns out that this was fiction (just like Star Wars).
In this retrospective study with 48 children, the authors had the following key points:
Microscopic esophagitis was found in 33 (69%)
Pathological esophageal acid exposure on MII-pH was detected in 12 (25%)
The presence of long-gap esophageal atresia was associated with abnormal MII-pH.
The authors conclude that “histological esophagitis is highly prevalent at 1 year after esophageal atresia repair, but our results do not support a definitive causative role of acid-induced GERD. Instead, they support the hypothesis that chronic stasis in the dysmotile esophagus might lead to histological changes.”
My take: Along with endoscopy, pH probe testing can be helpful in selecting which children with esophageal atresia should continue with PPI therapy.
A recent retrospective study (PD Ngo et al. JPGN 2020; 70: 462-7) describes the largest published experience with intralesional steroid injection (ISI) for esophageal anastomotic strictures; the population studied in this report were strictures associated with esophageal atresia (EA) repair.
158 patients, 2010-2017, were included
1055 balloon dilatations and 452 ISI+
Triamcinolone acetate (10 mg/mL) was injected into the scar tissue “at a typical doses of 1 to 2 mg/kg with a weight-based maximum of 20mg and not >40 mg per procedure (typically 10-20 mg). The total injected dose was divided into 4 or more injection sites.”
Dilatation was performed with controlled radial expansion (CRE) balloons.
Prior to dilatation, a brief intraoperative contrast esophagram with half-strength ioversol 68% (Optiray 320) was performed. This allowed estimation of the anastomotic diameters. In some cases with poor contrast distention, the estimation was completed using the endoscope diameter or biopsy forceps size.
The median change in stricture diameter was significantly greater in the ISI+ group compared to the ISI-neg group with stricture dilatation, with an adjusted odds ratio of 3.24
The likelihood of ISI injection being helpful was more pronounced with the first three sessions, with a median change of 1 mm compared to 0.5mm (after the first three). The authors note that after the first 3 ISI+-dilatations, there was not a statistically-significant difference in stricture dilatation between those receiving ISI and those with balloon alone
There was no difference in perforation rates with ISI than without
The authors noted that patients who received ISI were less likely to be subsequently characterized as refractory
The study has a number of limitations including lack of precision/reproducibility with stricture diameter with dilatation; in addition, it was non-randomized and retrospective.
My take: This study, completed in a highly-specialized center, provides evidence that stricture dilatation following esophageal atresia repair is likely to be more successful with steroid injection.
” I will argue that the cumulative deaths from COVID19 will not be reduced significantly by flatten-the-curve policies. And that this virus will be as dangerous to vulnerable patients in 6 months to a year. We should be allowed to debate this.”
Key points: flattening of the curve does not mean that we will substantially lower the total mortality related to COVID-19 –though hospitals now have had time to avoid being overwhelmed. The virus is not contained, tests will underperform, new treatments do not help much (thus far), the overall mortality is ~1%, it may be difficult for a vaccine to prove its effectiveness, and COVID-19 (& our response) will likely lead to a large number of deaths not due to COVID-19.
In 8th grade, our English teacher would say ‘Esophagus, recite that poem.’ He would say this to everybody. It is possible that the flask that he carried could have influenced his word choice.
That anecdote came to mind as reading a recent article (K Birketvedt et al. J Pediatr 2020; 218: 130-7) which showed that a large number of adolescents with history of esophageal disease (esophageal atresia [EA]) had a high likelihood of suboptimal nutritional parameters. In this study with 68 pediatric subjects, extensive investigations including 4-day diet records, blood tests, pH measuring, EAT (eating assessment test) questionnaire, and interviews. Median age at follow-up was 16 years.
Median height-for-age Z score was -0.6. 10 patients (15%) were considered stunted (height-for-age Z score <-2).
More than two-thirds reported symptoms of dysphagia (EAT score ≥3) and avoided specific foods.
48 (71%) had suboptimal energy intake on diet records –intake below age-appropriate recommendations. Many had low vitamin D and iron intake.
13 of 68 patients had VACTERL association and 17 (25%) had congenital heart disease
My take: If your esophagus is not working right, it definitely can impair one’s nutritional status. Some patients have other reasons (other comorbidities) that could influence these reported results.
As for the anecdote, I still remember some of the poems we had to recite. The one I remember best:
A recent retrospective study (FWT Vergouwe et al. JPGN 2019; 69: 515-22) with 57 children with esophageal atresia (EA) found most children have a normal reflux index.
This study, analyzing data between 2012-2017, reviewed all 24-hour pH-impedance (MII) studies in children at ≤18 months and 8 year olds with EA. “All children with EA born in our hospital are offered a 24-hour pH-MII study at the age of 0.5 years and 8 years.” In this institution, PPI treatment is given for at least 6 months after surgery. Of the 57 in the cohort, 20 had completed pH-MII at <18 months of age and 32 at age 8 years.
In children ≤18 months of age, median reflux index was 2.6% (abnormal in 2), median number of retrograde boluses was 61 (62% nonacid, 58% mixed)
In the older cohort (~8 years of age), median reflux index was 0.3% (abnormal in 4) and median number of retrograde boluses was 21 (64% nonacid, 75% mixed)
Overall, 10 of 57 children (17.5%) had GERD with reflux index >7% (n=6) or positive SI/SAP (n=4). The authors note that much higher rates of GERD have been found in prior studies. If they included children with fundoplication who were considered as having GERD (prior to fundoplication), then the GERD rate was 32%.
My take: This study showed that reflux in this cohort of children with EA was similar to the general population and likely indicates that a substantial portion of patients with EA do not need indefinite PPI therapy. In children with more complex EA, PPI therapy is likely to be more beneficial.
At our recent national meeting, Dr. Peter Kahrilas indicated that POEM (Per-oral Endoscopic Myotomy) was now the treatment of choice for most adults with achalasia (#NASPGAN19 Postgraduate Course -Part 3).
A Chone et al (JPGN 2019; 69: 523-7) provide recent multicenter retrospective data on POEM in the pediatric agegroup (mean age 14 years), n=117.
Clinical success, defined as Eckardt score ≤3 during followup, was achieved in 90.6% of cases. The Eckardt score was >3 in 5 (4.3%) and data was missing in 6 (5.1%)
Adverse events included 1 case with significant bleeding, 2 cases of aspiration pneumonia (related to anesthesia), 1 esopleural fistula (managed endoscopically), and 6 mild AEs (4 mucosomtomies, 2 subcutaneous emphysema)
D Ley et al (JPGN 2019; 69: 528-32) provide retrospective data on 39 patients, median age 19 months, with refractory esophageal strictures which were treated with mitomycin C. The authors considered mitomycin C after a minimum of two previous dilatations.
Etiology: The majority had strictures/stenosis associated with esophageal atresia (n=25) followed by caustic ingestion in 9.
Number of stenosis: The majority (n=35) had a single stenosis.
In 26 patients (67%), topical application of mitomycin C was considered a success based on a reduction in the number of dilatations. In this group, the number of dilatations dropped from 102 to 17 over a comparable period.
16 (41%) never required further dilatation following mitomycin C application
My take: This study provides some of the best evidence that mitomycin C may be helpful. Long-term followup and more studies are needed.
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A recent study (JL Yasuda et al. JPGN 2019; 69: 163-70) shows that esophagitis is common with and without proton pump inhibitor (PPI) therapy in children with esophageal atresia (EA).
Background: This study encompassed 310 patients (34% long gap EA) and 576 endoscopies (median age 3.7 years)
Erosive esophagitis was found in 8.7% of patients.
15.2% of patients had esophagitis with >15 eos/hpf; 49% of patients had ≥1 eos/hpf (histologic eosinophilia)
87% of endoscopies were preceded by acid suppression therapy; being on acid suppression reduced the odds for abnormal esophageal biopsy (P=0.011).
Histologic esophagitis was “highly prevalent even with high rates of acid suppressive medications use.”
For example, among those receiving PPI monotherapy, 150 had normal biopsy and 136 had abnormal biopsy. Among those off all acid suppression, 30 had normal biopsy and 45 had abnormal biopsy.
For erosive esophagitis, this occurred in 12 on PPI and was not present in 274 on PPI therapy. Among those off all acid suppression, 4 had erosive esophagitis and 70 did not.
Presence or integrity of fundoplication was not significantly associated with esophagitis.
While this is a large study, the findings have several limitations. This is a single center retrospective study and this center attracts highly complex cases of EA.
My take: In addition to fairly high rates of erosive esophagitis and eosinophilic esophagitis, this study shows a high incidence of microscopic esophagitis, the significance of this is unclear. This study supports the current recommendations of 3 endoscopies in childhood and perhaps more frequent surveillance in those with more complex EA.
A recent study (FR Grunder et al. JPGN 2019; 69: 45-51) examines the use of proton pump inhibitor use after surgical repair of esophageal atresia; this involved a longitudinal cohort (n=73) with prospectively collected data over 11 years.
Background: While PPIs have been used for long-term treatment due to the high frequency of reflux and concerns regarding anastomotic strictures, the authors note that data on long-term outcomes/natural history and benefits/risks of this approach are lacking.
48% of patients had PPIs discontinued at followup.
Among the 43 with PPI discontinuation, 40 had endoscopy results available. Histologic abnormalities were noted in 8 (19%) which was lower than in the group receiving ongoing PPI use (n=19, 63%).. These 8 patients had PPI restarted.
Among patients unable to discontinue PPI therapy, there was a higher rate of prior anti-reflux surgical procedure, 27% compared to 5% who had anti-reflux procedure among group who were able to discontinue PPI therapy.
Patients more likely to remain on PPIs more frequently had a prior anastomotic leak and/or moderate to severe tracheomalacia.
The authors state that among patients receiving PPIs, there was more frequent recurrent pneumonia as well as more frequent use of inhaled beta-adrenergic agonists and steroids. However, this was not shown to be a causal association. It is unclear whether these patients had more severe esophageal dysfunction or whether PPI use contributed to this outcome.
In their discussion, the authors note that PPIs have not been shown to reduce the rate of anastomotic strictures. They argue that “PPI could be used more selectively in the following: in children with long-gap EA or anastomotic tension or anastomotic leak; after a first dilatation for anastomotic stricture rather than systematically, given the lack of preventive effect of PPI; and in children whose esophagoscopy demonstrates peptic esophagitis, eosinophilic esophagitis, or gastric metaplasia.”
My take: The authors are probably right that a large fraction of EA patients may not need long-term PPI use. Selecting which patients will benefit will remain a challenge. Published guidelines recommend monitoring for GERD complications in EA, especially after stopping PPIs.
Related blog posts:
Guidelines for esophageal atresia-TEF “Endoscopy with biopsies is mandatory for routine monitoring of GERD in patients with EA.” The authors recommend evaluation (pH, impedance, and/or endoscopy) at time of stopping anti-acid treatment and during long-term follow-up. Specifically, with low level of evidence, the authors advocate for one endoscopy after stopping PPI therapy, one before age 10 years, and one at transition to adulthood.”
This retrospective, single-center study examined 4 eosinophilic esophagitis (EoE) study cohorts and identified EoE in 20 of 110 patients (18%) who had surgically-repaired esophageal atresia.
This association has been seen previously: World J Gastroenterol. 2014 Dec 21; 20(47): 18038–18043. This case study stated ” We are suggesting that EoE is a frequent concomitant problem in patients with history of congenital esophageal deformities, and for this reason any of these patients with refractory reflux symptoms or dysphagia (with or without anastomotic stricture) may benefit from an endoscopic evaluation with biopsies to rule out EoE.”
A recent commentary (JM Hauer JAMA Pediatrics; 2018. doi: 10.1001/jamapediatrics.2018.1531) addresses a common misconception regarding children with severe neurologic impairment (SNI):
“we don’t think she experiences pain”
She notes that literature since 2002 has challenged this assumption and that this is addressed in a new AAP clinical report as well (Hauer J, Houtrow AJ. Pediatrics 2017; 139: e20171002).
Children with SNI may have moaning, grimacing, changes in tone/body position in reaction to pain and treatment can make them comfortable.
“We can never prove that such a child does not feel pain…When parents of children with hydranencephaly were asked whether their child felt pain, 96% indicated yes.”
Pain can trigger changes in catecholamines, cortisol and stress hormones. “These considerations suggest that untreated chronic pain is more harmful to the well-being of children with SNI than is treatment used for pain.”
Sometimes no source for pain is identified. This may be related to a CNS etiology (alteration of CNS) and may benefit from treatment.
“It is time to do away with the question of whether these children feel pain and focus on how we as individuals” identify/consider pain
My take: Reframing this issue is important; pain can occur in children with SNI. At the same time, we have to be careful that some “palliative” measures could paradoxically prolong suffering in some children.
A recent study (SA Pellegrino et al. J Pediatr 2018; 198: 60-6) examines the likelihood of redo fundoplication for esophageal atresia (EA) in comparison to redo fundoplication for other indications.
Among all EA cases, n=344 (1994-2013), 85 underwent fundoplication (single-center study from Melbourne)
Rates of fundoplication were declining over study period: there was a 37% drop from 2010-2013 compared to 1994-97.
Overall, 767 patients had a fundoplication (n=682 without EA). The rates of redo fundoplication were similar 11/85 compared with 53/682, despite the fact that EA patients had earlier surgery with median ages of 7.2 months versus 23 months, respectively.
Factors leading to fewer fundoplications:
Improving medical therapies, including proton pump inhibitors and use of jejunal feedings
Awareness that fundoplication may not be curative and is associated with significant morbidity
Anecdotally, I have had some EA patients whose lives were transformed positively by fundoplication, though many are difficult operations due to anatomic factors like small gastric volumes and pulmonary issues. Careful selection and surgical expertise are essential to good outcomes.
My take: The authors note that “this study challenges the assertion that fundoplicaiton is less successful in patients with EA.”