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Abstract

Background

The role of high-resolution esophageal impedance manometry (HRIM) for establishing risk for dysphagia after anti-reflux surgery is unclear. We conducted a prospective study of children with primary gastroesophageal reflux (GER) disease, for whom symptoms of dysphagia were determined pre-operatively and then post-operatively and we examined for features that may predict post-operative dysphagia.

Methods

Thirteen children (aged 6.8–15.5 years) undergoing work-up prior to 360^o Nissen fundoplication were included in the study. A dysphagia score assessed symptoms at pre-operative study and post-operatively (mean 1.4 years). A HRIM procedure recorded 5-ml liquid, 5-ml viscous and 2-cm solid boluses. We assessed esophageal motility, esophago-gastric junction (EGJ) morphology, EGJ contractility and pressure-flow variables indicative of bolus distension pressures and bolus clearance pressures. A composite pressure-flow index score was also derived.

Results

Pre-operative pressure-flow index was positively correlated with post-operative dysphagia score (viscous bolus r = 0.771, p < 0.005). Of three variables that comprise the pressure-flow index, the ramp pressure measured during bolus clearance was the main driver of the effect seen (viscous bolus r = 0.819, p < 0.005).

Conclusions

In order to mitigate symptoms in relation to anti-reflux surgery, dysphagia symptoms and esophageal function need to be pre-operatively assessed. In patients with normal motility, an elevated pressure-flow index may predict post-operative dysphagia.

Keywords

Gastroesophageal reflux fundoplication dysphagia diagnosis

Key summary

The established knowledge on this subject:

Dysphagia can mar otherwise successful gastroesophageal reflux (GER) treatment.

The ability to accurately predict dysphagia risk would inform the choice of fundoplication over other treatments.

‘Pressure-flow’ anomalies may be predictors of dysphagia symptoms following anti-reflux surgery.

What are the significant and/or new findings of this study?

Dysphagia symptoms were common in pediatric GER disease patients prior to anti-reflux surgery.

In order to avoid symptom recurrence, re-investigations and further interventions, dysphagia symptoms should be attributed to GER.

In patients with normal motility, elevated clearance pressures and/or pressure-flow index may predict post-operative dysphagia.

Introduction

High-resolution esophageal impedance manometry (HRIM) derives biomechanical swallow measures which describe flow resistance and muscle contractility. These characterizations may guide clinical decisions around esophageal dysmotility.^1–3

Clinical guidelines now recommend pre-operative assessment of children with gastroesophageal reflux (GER) disease referred for anti-reflux surgery.⁴ HRIM can exclude a primary motor disorder, most importantly achalasia, which, while rare, causes symptoms of regurgitation, heartburn and chest pain in addition to dysphagia.^5,6 HRIM can determine hypomotility,^7–10 weak esophago-gastric junction (EGJ) contractility^10–13 and/or hiatus hernia subtype morphology,^3,14 which are features of primary GER disease.

The role of HRIM for establishing ‘risk’ of post-operative dysphagia is unclear. In pediatric series, dysphagia ranges from 12% to 40%.^15,16 Dysphagia can mar otherwise successful GER treatment. Prediction of dysphagia risk would inform the choice of other treatments over fundoplication.

We hypothesized that esophageal ‘pressure-flow’ anomalies may predict dysphagia.^17,18 We therefore investigated dysphagia and esophageal motor function in children with GER disease undergoing fundoplication.

Materials and methods

Children who had been referred for Nissen fundoplication surgery were included in the study. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Women's and Children's Hospital Human Research Ethical Committee (approval number REC 2345, February 2015). Informed consent was obtained.

Assessment of dysphagia symptoms

A dysphagia questionnaire modeled on the score of Dakkak and Bennett was used.¹⁹ This modified Dakkak score assessed dysphagia for nine different food consistencies (water to meat; scale 0–45; score > 10 = dysphagia)²⁰ and was mostly completed by patients with parental assistance.

Esophageal function testing

Esophageal function was assessed by HRIM catheter (25 1-cm-spaced pressure sensors and 12 impedance; Unisensor USA Inc, Portsmouth, NH). Data were recorded at 20 samples/s (Medical Measurement Systems, The Netherlands).

Patients were studied off proton pump inhibitors (PPI) (minimum 72 h) and in the semi-reclined position. The protocol was 5–10 × 5 ml boluses of liquid (saline) and viscous (‘EFT Viscous’, Sandhill Scientific, USA) and 3–5 × 2 cm solid (bread with saline topically added to increase conductivity).

Pressure topography

Motility disorders were diagnosed by Chicago Classification (V3.0).³ Esophageal pressure topography metrics were derived, namely: (i) 4s integrated relaxation pressure of the EGJ (IRP4s, mmHg); (ii) contractile front velocity of the distal esophagus (CFV, cm/s); (iii) distal contractile integral (DCI, mmHg cm/s); and (iv) distal latency (DL, s). EGJ barrier function was assessed using the EGJ contractile index (EGJ-CI).^12,13 EGJ morphology was defined as Type I (no lower esophageal sphincter (LES) to crural diaphragm (CD) separation), Type II (partial separation) or Type III (full separation).³

Pressure-flow analysis

Pressure-flow analysis (Figure 1) was applied using purpose designed software (AIMplot v8, copyright T Omari) programmed in MATLAB (version 7.9.0.529 R2009b, The MathWorks Inc., Natick, MA, USA).^17,20–22 The analyst selected key temporal and anatomical landmarks including: (i) swallow onset; (ii) esophageal proximal margin; (iii) transition zone; (iv) crural diaphragm and (v) stomach.

Figure 1.

Derivation of pressure-flow metrics. Automated analysis was applied to each swallow within a region of interest (see inset Clouse plot, lower right). (a) A pressure topography iso-contour plot with superimposed lines showing the position of the nadir impedance (thick purple line; indicating peak distension) and contractile peak (thick red line) over time. The analyst fine-adjusted the landmarks, paying particular attention to the transition zone (TZ), the contractile deceleration point (CDP; yellow star) and crural diaphragm (CD). (b) Intrabolus distension pressure during bolus transport was determined by pressure at nadir impedance which was measured along the esophagus. The average distension pressure (DP) was determined within three anatomical regions approximating the different phases of bolus transport. These were accommodation (DPA, pressures proximal to TZ), compartmentalized transport (DPCT, pressures TZ to CDP) and esophageal emptying (DPE, pressures from CDP to CD). (c) Effectiveness of bolus clearance was determined from TZ to CDP based on the impedance ratio (IR = nadir impedance divided by impedance at contractile peak). A higher IR equates to less effective bolus clearance. (c) Bolus flow latencies and clearance pressures were determined based on the pressure and impedance recordings at the CDP level. Swallow to distension latency (SDL) was measured from swallow onset to nadir impedance and distension to contraction latency (DCL) from NI to luminal clearance/closure corresponding to recovery of impedance to 50% from baseline (see plot lower left). The ramp pressure (RP) was determined within the distal esophagus (sensors within distal 25% of the TZ to CDP length) and defined by the mean gradient of pressure change over time from maximum distension (NI) to luminal closure (see plot lower middle, note impedance presented relative to baseline and reversed in direction). Variables DCL, DPE and RP were combined to derive the pressure-flow index (PFI) composite score.

Five classes of variable were then derived as described below (see Figure 1):

Intrabolus distension pressures (DP) during bolus transport were determined by pressure at nadir impedance. These were DP bolus accommodation (DPA, pressures UES to transition zone (TZ)), DP compartmentalized transport (DPCT, pressures TZ to contractile deceleration point (CDP)) and DP esophageal emptying (DPE, pressures CDP to CD; see Figure 1(b)).

Bolus clearance was determined by impedance ratio (IR = nadir impedance divided by contractile peak impedance). When bolus residual is present, then the impedance at the contractile peak has a lower value, hence IR becomes higher indicating less effective bolus clearance (see Figure 1(c)).²³

Bolus flow latencies were determined using pressure and impedance at the CDP level. These were swallow to distension latency (SDL) and distension to contraction latency (DCL) (Figure 1(c)).

Pressure generation during bolus clearance (or clearance pressures) was measured within the distal esophagus. The closure pressure (CP) was the pressure at luminal closure and the ramp pressure (RP) was the mean gradient of pressure during closure (Figure 1(c)). Timing of luminal closure was defined by the 50% impedance recovery, a validated criterion in widespread use.²⁴ A pressure-flow index (PFI) composite score was derived using the following formula:

PFI = (DPE * RP) / DCL

Trans EGJ bolus flow time (BFT) was estimated based on the method of Lin.²⁵ A shorter BFT indicates reduced esophageal emptying period.

Other assessments

Information regarding clinical history was garnered from clinical notes and correspondence. Patients typically underwent 24-hour reflux monitoring (pH only, pH-MII probe), barium swallow radiology study and upper GI endoscopy. Available biopsy specimens were scored for presence of eosinophils. Eosinophilic esophagitis (EoE) was defined as ≥ 15 eosinophils per high power field (eos/hpf).²⁶

Post-operative assessments

The families of patients were contacted post-operatively and invited to complete a Dakkak questionnaire. Those who had not already undergone manometry investigation during the post-operative period were invited to repeat a HRIM. A medical record review was undertaken to determine post-operative therapy and investigations indicative of symptom recurrence.

Statistical analysis

Analysis was performed using SPSS (IBM Corporation, USA). Data are means (standard deviation) if normally distributed (passed Shapiro–Wilk normality testing) or median (interquartile range). Spearman's correlation rho investigated relationships between continuous variables and dysphagia scores. Group comparisons were performed using t-test or Mann–Whitney U-test. To compare pre- versus post-operative findings across consistencies, repeated measures ANOVA with logarithmic transformation was performed on data failing normality testing. Receiver operator curve analysis determined if larger PFI scores indicated evidence for a dysphagia using curve area, sensitivity and specificity. Only p-values ≤ 0.099 are reported.

Results

Patients

Twenty-seven children with GER disease (aged 0.8–16.1 years) were originally identified. However, 11 children were excluded due to missing assessments or they did not undergo surgery. Three had a poor quality HRIM; two, both aged one year, were unsettled rendering the measurement uninterpretable and one, aged 16 years, was not able to complete the protocol.

The final dataset included 13 children who were aged 6.8–15.5 years (average 12.5 years old) at initial investigation. The patients were between four months and 4.7 years (average 1.4 years) post-surgery when followed up symptomatically by Dakkak questionnaire; six patients were over one year post-op at follow-up.

Pre-operative clinical findings

Most patients had a history of typical symptoms of heartburn and/or regurgitation, 11 had one or more abnormal finding on 24-hour pH-MII probe (abnormal reflux index, abnormal reflux frequency and/or positive symptom association probability) and three had esophagitis (Table 1). Eosinophil counts ranged from 0 to 5 eos/hpf thus none met criteria for EoE (≥15 eos/hpf). Seven patients were investigated by barium swallow and all had normal esophageal bolus transit. EGJ barrier dysfunction was apparent in six patients; one had evidence of hiatus hernia (partial LES-CD separation consistent with a Type 2 EGJ Morphology). Two patients had a CC V3.0 diagnosis of ineffective esophageal motility (IEM).³ Five patients were on PPI therapy at follow-up.

Table 1.

Summary of clinical findings from 13 children who received gastroesophageal reflux (GER) diagnostic work-up and complete high-resolution esophageal impedance manometry (HRIM) protocol prior to receiving anti-reflux surgery and in whom followed up to assess bolus hold-up symptoms was achieved.

Age (yrs)	History & symptoms	pH-MII probe	Upper GI endoscopy		Barium radiology	HRM EGJ barrier	HRM motility	Post-Op symptom recurrence	Post-op PPI use	Modified Dakkak score (maximum 45)
Age (yrs)	History & symptoms	pH-MII probe	Endoscopic esophagitis	Eosinophils per hpf	Barium radiology	HRM EGJ barrier	HRM motility	Post-Op symptom recurrence	Post-op PPI use	Pre-op	Post-op	Post-op dysphagia
14	AB	AR	NO	0	n/a	Hypo.	Nor.	YES	Off	0.0	8.0	None or mild (Dakkak 0–10)
13	HB, RV	AR	NO	0	n/a	Hypo.	Nor.	NO	Off	3.5	4.5
14	RV	AR	NO	3	n/a	Hypo./HH	IEM	NO	On	7.0	0.0
11	RV	AR	NO	0	n/a	Hypo.	Nor.	YES	Off	8.0	8.0
12	HB, RV, RPPI	Nor.	NO	0	Nor.	Nor.	Nor.	NO	Off	10.5	0.0
13	HB, RV	AR	YES	1	Nor.	Hypo.	IEM	NO	On	12.0	0.0
14	HB, N	AR	NO	0	n/a	Hypo.	Nor.	NO	Off	13.5	0.0
9	RV	+SA	YES	3	Nor.	Nor.	Nor.	NO	On	20.0	0.0
12	Neuro, FT	AR	n/a	n/a	Nor.	Nor.	Nor.	NO	Off	29.0	4.5
14	Dys	AR, + SA	NO	1	Nor.	Nor.	Nor.	YES	On	26.0	12.0	New or persisting (Dakkak > 10)
7	RV	AR	NO	5	Nor.	Nor.	Nor.	YES	On	12.0	14.0
14	RV	Nor.	YES	2	Nor.	Nor.	Nor.	YES	Off	0.0	18.0
16	RV	AR, + SA	NO	1	n/a	Nor.	Nor.	YES	Off	41.5	39.5

Modified Dakkak scores, which define bolus hold-up perception, are shown in the far-right columns. The four patients reporting new or ongoing swallowing difficulties are ranked by their post-operative Dakkak score, other patients ranked by pre-operative Dakkak score.

Abbreviations: n/a: not available; Nor.: normal findings.

History: Neuro, neurological patient; HB, heartburn; RV, regurgitation and/or vomiting; N, nausea; Dys, dysphagia; FT, failure to thrive; IC, irritability and crying; AB, acid brash; RPPI, refractory to PPI.

pH-MII GER: AR, abnormal acid GER; NAR, abnormal non-acid GER; + SA, positive symptom association probability.

HRM: Hypo, hypotensive EGJ; HH, hiatus hernia morphology; IEM, ineffective esophageal motility.

Pre-operative dysphagia questionnaire

Eight children returned a pre-operative Dakkak score > 10 indicative of pre-operative dysphagia (Table 1). During liquid swallows, higher proximal distension pressure (DPA) and longer BFT correlated with Dakkak score (Table 2). However, neither parameter was significantly different based on grouped analyses of patients with/without dysphagia. Pre-operative EGJ-CI did not correlate with pre-operative Dakkak score (r = 0.463, ns); however, it was associated with dysphagia on grouped analysis (dysphagia 30.9 (15.1) mmHg.cm vs. no dysphagia 13.3 (11.9) mmHg.cm, t = 2.201, p = 0.050).

Table 2.

Correlation esophageal function variables recorded pre-operatively with dysphagia symptoms reported pre-operatively and post-operatively.

	Metric vs. pre-op Dakkak score			Metric vs. post-op Dakkak score
Pre-op metric	LIQ	VIS	Solid	LIQ	VIS	Solid
Esophageal pressure topography
DCI	0.085	−0.028	0.069	0.402	0.445	0.465
CFV	−0.094	−0.240	0.118	0.235	0.173	0.060
DL	−0.247	−0.413	−0.198	−0.270	−0.088	−0.150
IRP4s	−0.342	−0.455	0.273	0.235	0.204	0.235
Intrabolus distension pressures
DPA	0.554(0.05)	0.336	0.047	−0.167	0.249	0.221
DPCT	0.314	0.229	0.190	−0.040	−0.119	0.380
DPE	−0.008	0.160	0.248	−0.028	−0.062	0.116
Intrabolus clearance pressures
RP	0.336	0.179	−0.212	0.230	0.819***	0.709**
CP	0.466	0.287	−0.402	0.337	0.802***	0.261
Flow/distension timing
SDL	0.074	−0.264	−0.259	−0.261	−0.023	−0.207
DCL	−0.234	−0.163	−0.377	0.014	−0.145	−0.201
Composite measures
Pressure-flow index	0.369	0.309	0.182	0.366	0.771***	0.757***
Impedance ratio	0.094	0.163	−0.006	−0.184	−0.028	0.028
Bolus flow time	0.617*	−0.074	−0.524(0.066)	0.584*	0.527(0.064)	0.068

Spearman's correlation rho based on data from 13 patients with complete HRIM studies for all consistencies.

CFV: contractile front velocity; CP: clearance pressure; DCI: distal contractile integral; DCL: distension to contraction latency; DL: distal latency; DPA: DP bolus accommodation; DPCT: DP compartmentalized transport; DPE: DP esophageal emptying; IRP4s: 4s integrated relaxation pressure; RP: ramp pressure; SDL: swallow to distension latency.

*Indicates significant correlation (two-tail; *p < 0.05, **p < 0.01, ***p < 0.005).

Post-operative dysphagia questionnaire

The severity of post-operative dysphagia symptoms was not significantly correlated with the time of follow-up (r = –0.084). Six patients were assessed >1 year post-operatively and their dysphagia scores were not different from those of patients surveyed at earlier time points (Dakkak 2 [0, 23] > 1 year vs. 8 [0, 12] < 1 year, t = –0.221, p = n.s.).

Five of eight patients with pre-operative dysphagia improved post-operatively decreasing their Dakkak scores to <10 (Table 1). However, four patients reported significant dysphagia post-operatively; three with persisting dysphagia and one with ‘new’ dysphagia (a 14-year-old boy with Dakkak 0 pre-operatively increasing to Dakkak 18 post-operatively).

Surgery reduced esophageal acid exposure in six patients investigated by pH-probe after surgery on grounds of symptom recurrence (Figure 2). These patients had greater dysphagia post-operatively than other patients (Dakkak 13[8, 23] in refractory patients vs. 0[0, 2.2] in others, t = 3.095, p = 0.001), suggesting that post-operative dysphagia may have contributed to post-operative investigation.

Figure 2.

Reflux monitoring findings in six patients investigated by pH or pH-MII probe pre- and post-operatively due to symptom recurrence. a) Total number of acid GER episodes, b) reflux index (%time pH<4) and c) total number of impedance detected liquid GER episodes Wilcoxon Signed Rank Test standardized t- and p-value shown. Total liquid GER data (in c) are incomplete for four patients due to pH-MII not being performed pre-operatively.

Pre-operative findings associated with symptoms of post-operative dysphagia

Routine reflux investigations did not discriminate post-operative dysphagia. However, manometric features that would normally corroborate a diagnosis of primary GER disease, such as evidence of IEM or EGJ barrier dysfunction, were never seen in the patients reporting dysphagia (Table 1). No patients raised clinical suspicion of rumination syndrome.

Of the parameters measured pre-operatively, higher RP, CP and PFI were correlated with post-operative Dakkak score and, for these variables, correlations using viscous consistency were superior (Table 2). Viscous bolus correlations were similarly apparent within patient sub-groups that were assessed < 1year post-op (RP: r = 0.764, p = 0.046; CP: r = 0.764, p = 0.046; PFI: r = 0.837, p = 0.019) and >1 year post-op (RP: r = 0.820, p = 0.046; CP: r = 0.942, p = 0.005; PFI: r = 0.880, p = 0.021). Grouped analysis showed that pre-operative viscous bolus clearance pressures were higher in those who had post-operative dysphagia compared with those who did not have post-operative dysphagia (RP: 47 [27, 71] mmHg/s vs. 13 [10, 18] mmHg/s, respectively, p = 0.002; CP: 72 [48, 100] mmHg vs. 31 [25, 38] mmHg, respectively, p = 0.002). BFT was longer pre-operatively in patients with post-operative dysphagia (Table 2).

To clarify and explain our main results we provide two case examples that are illustrative of our findings.

Case 1: A child with pre-operative dysphagia that resolved (Figure 3(a) to (d))

A nine-year-old female with regurgitation, esophagitis and a positive SAP to heartburn. Pre-operative HRIM was considered normal (no hiatus hernia, EGJ-CI 43 mmHg.cm, mean liquid DCI 1960 mmHg.cm.s and IRP4s 12 mmHg). The patient reported dysphagia pre-operatively (Dakkak 20), which resolved following fundoplication (Dakkak 0). The patient was successfully treated.

Figure 3.

Pre-operative recordings and pressure-flow data from example cases: Case 1 with pre-operative dysphagia that resolved post-operatively and Case 2 with significant persisting dysphagia. Tracings are based on recordings of 5-ml viscous bolus swallows. (a–e) Esophageal pressure topography of the distal esophagus with axial location of contractile deceleration point (CDP) marked. (b and f) Pressure (black) and impedance (purple) profiles over time at the level of the CDP. (c and g) Pressure (black) and the impedance relative to baseline (purple) for the period 1 s before to 0.5 s after the 30-mmHg iso-contour (the direction of impedance change is reversed compared to b and f; 100% is pre-swallow baseline, 0% is maximum distension and 50% defines luminal closure). Note that the impedance-defined luminal closure (50%) occurs relatively later in time for Case 2, resulting in greater clearance pressures being generated as the lumen closes. (d and h) The relationship between relative impedance (x axis) and pressure (y axis) over time. As seen in d, from Case 1, the lumen opens and then closes without any change in clearance pressure (known as isotonic contraction). As seen in h, from Case 2, the lumen opens and then closes with clearance pressures increasing (known as auxotonic contraction). (i) Bar charts of patient Dakkak scores and the average data for the relevant pressure-flow metrics derived for liquid and viscous bolus swallows. Note, markedly higher clearance pressures (RP and CP) for Case 2.

Case 2: A child with pre-operative dysphagia that did not resolve (Figure 3(e) to (h))

A 16-year-old female with regurgitation, abnormal reflux index (19.2%) and positive SAP to regurgitation. Pre-operative HRIM was considered normal (no hiatus hernia, EGJ-CI 32 mmHg.cm, mean liquid DCI 2541 mmHg.cm.s, IRP4s 10 mmHg). The patient reported significant dysphagia pre-operatively (Dakkak 41.5), which did not resolve following fundoplication (Dakkak 39.5). Repeat pH-probe demonstrated normalization of reflux parameters.

When Case 1 and Case 2 were compared (Figure 3), clearance pressures (CP and RP) were much higher pre-operatively for the viscous swallows in Case 2 (Figure 3(i)). In Case 2, luminal closure occurred later in time (compare Figure 3(b) vs. Figure 3(f)) and auxotonic contraction was observed (Figure 3(h)).

Effects of surgery on biomechanical measures

Post-operative HRIM data were complete for liquid and viscous boluses for seven patients who had received manometry post-fundoplication (four months to four years, average 1.4 years). The main effects of fundoplication surgery were investigated by repeated measures ANOVA. Despite the small sample, anticipated trends were revealed (Table 3), namely increased distension pressures in the distal esophagus and EGJ (higher DPE and IRP4). The PFI, which includes DPE in its calculation, was higher post-operatively.

Table 3.

Effect of fundoplication surgery on esophageal function variables. Data from seven patients participating in repeat study. Data are estimated marginal mean (95% confidence interval of difference). Statistics for RM-ANOVA shown.

	Time point		Main effects RM-ANOVA
Metric	Pre-op Mean (CI)	Post-op Mean (CI)	Surgery (F, p)	Consistency (F, p)
Esophageal pressure topography
DCI (mmHg.cm.s)	1214 (643, 1784)	1102 (454, 1751)	−	−
CFV (cm/s)	3.8 (2.9, 4.7)	4.1 (2.2, 6.1)	−	−
DL (s)	6.8 (6.0, 7.6)	7.3 (5.9, 8.8)	−	↑F 3.919, p 0.095
IRP4s (mmHg)	9.0 (5.9, 12.1)	13.5 (7.7, 19.3)	↑F 4.811, p 0.071	−
Intrabolus distension pressures
DPA (mmHg)	3.7 (1.1, 6.3)	0.4 (−1.2, 2.0)	↓F 6.233, p 0.047	↑F 33.488, p 0.001
DPCT (mmHg)	6.3 (2.6, 10.1)	7.1 (3.5, 10.7)	−	↑F 22.502, p 0.003
DPE (mmHg)	14.2 (8.8, 19.5)	19.9 (12.2, 27.6)	↑F 3.979, p 0.093	↑F 31.103, p 0.001
Intrabolus clearance pressures
RP (mmHg/s)	19.0 (4.4, 33.6)	15.9 (8.4, 23.4)	−	↑F 7.526, p 0.034
CP (mmHg)	40.0 (21.6, 58.4)	38.1 (27.5, 48.8)	−	↑F 12.144, p 0.013
Flow/distension timing
SDL (s)	3.9 (2.9, 4.8)	4.6 (3.2, 5.9)	↑F 5.797, p 0.053	↑F 13.298, p 0.011
DCL (s)	2.5 (1.9, 3.1)	1.6 (1.2, 1.9)	−	↓F 38.956, p 0.001
Composite measures
Pressure-flow index	69.7 (25.5, 114.0)	428 (26.1, 830.8)	↑F 5.173, p 0.063	↑F 25.865, p 0.002
Impedance ratio	0.29 (0.22, 0.37)	0.34 (0.27, 0.41)	−	↑F 27.932, p 0.001
Bolus flow time (s)	2.2 (1.2, 3.2)	2.0 (1.2, 2.7)	−	−

Main effects in relation to surgery and bolus type on swallow function variables are indicated; – indicates no effects; ↑↓ indicates the directionality of the effects.

Discussion

Dysphagia and esophageal function were investigated in children undergoing fundoplication surgery. Our findings were: (i) patients reported symptoms of dysphagia pre-operatively; (ii) fundoplication surgery decreased dysphagia in most; however (iii) some had post-operative dysphagia and were distinguishable by elevated bolus clearing pressures.

When assessed pre-operatively, dysphagia was common. Improvement after surgery suggests GER was a causal factor. Few parameters were linked to pre-operative dysphagia before reflux, as an influencer of symptoms, was mitigated. Patients with manometry evidence of primary GER disease (low EGJ-CI, hiatus hernia EGJ morphology and/or an IEM subtype) did not have post-operative dysphagia. While those with a normal motility diagnosis and higher clearing pressures had higher post-operative dysphagia scores. This association has been previously reported in post-operative^17,18 and non-obstructive dysphagia^2,27,28 (note, defined by the parameter ‘intrabolus pressure slope’).

Using the data available, fundoplication increased esophageal emptying resistance (DPs and IRP4) but not clearance pressures. The PFI composite score, being calculated based on a formula which includes both distension pressures (DPE) and clearance pressures (RP), was found to be increased by surgery and was also higher in relation to post-operative dysphagia and may be a useful clinical measure particularly in the context of findings of otherwise ‘normal’ peristalsis. The optimal PFI cut-off criteria suggested by this study are provided in Table 4.

Table 4.

Prognostic value of the pressure-flow index score to predict levels of dysphagia.

ROC parameters	Dakkak score used to define post-operative dysphagia
ROC parameters	Dakkak > 0	Dakkak > 5	Dakkak > 10
Patients: positive/negative	8/5	6/7	4/9
ROC area (p-value)
Liquid	0.775 (ns)	0.667 (ns)	0.556 (ns)
Viscous	0.950 (0.008)	0.857 (0.032)	0.833 (0.064)
Solid	0.875 (0.028)	0.905 (0.015)	0.833 (0.064)
Optimal PFI cut-off (sens, spec)
Liquid	32 (0.75, 0.80)	32 (0.83, 0.74)	38 (0.75, 0.67)
Viscous	151 (1.00, 0.80)	221 (0.83, 0.86)	280 (1.00, 0.78)
Solid	1240 (0.75, 1.00)	1240 (0.83, 0.86)	1629 (0.75, 0.89)

Receiver operator curve analysis determining if larger values of the PFI result indicate stronger evidence for a dysphagia.

Esophageal resistance to bolus flow during bolus transport occurs on a continuum from unimpeded flow at one extreme, to totally obstructed flow at the other extreme. Obstructed luminal flow can be deduced by the presence of high compartmentalized DPs (for example, in relation to focal strictures and EGJ outflow obstruction). However, if bolus flow of a viscous or solid bolus is impeded rather than obstructed, then clearance pressures that quantify bolus pressurization superior to the bolus midpoint (i.e. toward and at the bolus tail) are important because they drive the bolus movement. A high clearance pressure suggests that the contraction, rather than being isometric (pressure rise occurs with a closed lumen after the bolus has passed), is instead auxotonic (pressure increases with a closing lumen as the bolus passes, see Figure 3(h)).^29,30 The recording of auxotonic pressure-flow phenomena demonstrates that the demands placed on the esophageal muscles to do mechanical work (expend energy) during bolus clearance are greater because the bolus is, for one or more reasons, less easily transportable. Various intrinsic and extrinsic factors to the bolus material influence this. Bolus rheology (resistance to flow) is important; solids resist flow. Additionally, other superimposed factors may be relevant, namely: (i) the size of luminal aperture; (ii) the stiffness of the esophageal wall; and (iii) the surface ‘tackiness’ of the mucosal lining due to the presence/absence of luminal secretions which influence surface interaction and lubrication.

The mechanism(s) by which higher clearance pressures may directly lead to bolus perception are unclear. Sensory afferent mechanisms are largely insensitive to common isotonic and isometric wall states.²⁹ However, the active tension produced in relation to a prolonged auxotonic state may generate wall tension sufficient to produce a noxious stimulus. In other words, a bolus being transported that has been orally processed to be soft, moist and slippery (via saliva coating and mucosal secretions lining the esophagus all the way down) should not be felt. Conversely, a bolus that is hard, dry and resistive should be felt in order to generate alarm sensations that will alter eating behavior. However, in certain pathophysiological situations, a soft, moist and slippery bolus may be rendered less easy to transport. If so, this will lead to the bolus being felt because its transport is being impeded changing the wall state.

Elevated clearance pressures may indicate dysregulated bolus transport, due to changes to the enteric nervous system (ENS) and/or the muscle layers. Muscle relaxation ahead and then contraction behind the moving bolus are dependent upon normal functioning of the ENS.^31,32 Rapid swallow testing reveals aberrant ENS inhibition and may predict dysphagia risk.³³ Esophageal distension in-vivo can reveal abnormal intramural motor patterns in dysphagic patients with otherwise normal primary peristalsis.³⁴ Contractile decoupling and selective contractile dysfunction(s) of the circular and longitudinal muscle layers are reported in various disorders³⁵ and may perturb the normal ability of the esophagus to biomechanically distend.³⁵ Hence, contractile decoupling can produce a motor pattern suggestive of impaired inhibition, even though the inhibitory apparatus is functioning normally. Irrespective of the underlying mechanism(s), the lack of ability of the lumen to distend would impede normal bolus flow leading to high clearance pressures.

Strengths of our study are the detailed characterizations of symptoms, reflux, and motility and pressure-flow phenomena. Our data support the findings from previous studies;^17,18 however, the variation of follow-up time is a significant limitation. A larger prospective study, including longitudinal measurements at fixed early and long-term post-operative time points, is clearly needed. Data from very young patients were not included limiting generalizability to all pediatric GER disease. There are challenges for generating quality HRIM data in the very young because patients must tolerate the procedure and repeat-swallow boluses on command.

In conclusion, dysphagia symptoms were common in pediatric GER disease patients prior to anti-reflux surgery. In order to avoid symptom recurrence, re-investigations and further interventions, dysphagia symptoms should be attributed to GER. In patients with normal motility, elevated clearance pressures and/or PFI may predict post-operative dysphagia.

Footnotes

Acknowledgements

We thank Mrs G Seiboth, Mrs K Lowe and Ms S Kritas for assistance with performance of HRIM studies, Dr Kyra Sierakowski for assistance with obtaining patient histories and Dr Junko Fujino for assistance with reviewing endoscopy images.

Declaration of conflicting interests

Omari holds inventorship of patents that cover some of the analytical methods described. The other authors have no conflicts of interest relevant to this article to disclose.

Funding

Supported by The Women’s & Children’s Hospital Foundation.

Ethics approval

The study protocol was approved by the Women s and Children’s Hospital Human Research Ethical Committee (approval number REC 2345, February 2015).

Informed consent

Informed consent was obtained from each patient’s parent or guardian.

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A study of dysphagia symptoms and esophageal body function in children undergoing anti-reflux surgery

Abstract

Background

Methods

Results

Conclusions

Keywords

Key summary

Introduction

Materials and methods

Assessment of dysphagia symptoms

Esophageal function testing

Pressure topography

Pressure-flow analysis

Other assessments

Post-operative assessments

Statistical analysis

Results

Patients

Pre-operative clinical findings

Pre-operative dysphagia questionnaire

Post-operative dysphagia questionnaire

Pre-operative findings associated with symptoms of post-operative dysphagia

Case 1: A child with pre-operative dysphagia that resolved (Figure 3(a) to (d))

Case 2: A child with pre-operative dysphagia that did not resolve (Figure 3(e) to (h))

Effects of surgery on biomechanical measures

Discussion

Footnotes

Acknowledgements

Declaration of conflicting interests

Funding

Ethics approval

Informed consent

References