Introduction

The post reflux swallow-induced peristaltic wave (PSPW) brings salivary bicarbonate via an esophago-salivary reflex to neutralize residual esophageal mucosal acidification after gastro-esophageal reflux episodes.

Aims & Methods

We hypothesized that reduced saliva in Sjogren’s syndrome and hypomotility in both Sjogren's syndrome and scleroderma/mixed connective tissue disease (MCTD) could compromise PSPW-induced pH recovery in the distal esophagus. Patients with confirmed Sjogren’s syndrome and scleroderma/MCTD (based on rheumatologic evaluation) who underwent high resolution manometry (HRM) and ambulatory pH-impedance monitoring off antisecretory therapy were retrospectively identified over a 5-year period at 2 motility centers. For comparison, patients without these disorders undergoing HRM and pH-impedance monitoring for GERD symptoms were identified from the same time-period, segregated into two groups based on presence or absence of ineffective esophageal motility (IEM). Patients with prior foregut surgery, studies with artifacts precluding reflux episode and PSPW identification, and unconfirmed rheumatologic diagnoses were excluded. Acid exposure time (AET), numbers of reflux episodes and PSPW (using Wingate Consensus criteria), pH recovery with PSPW, and HRM metrics were compared between Sjogren’s syndrome, scleroderma/MCTD and comparison groups. Univariate comparisons and multivariable analysis were performed to determine predictors of PSPW and pH recovery.

Results

We studied 34 patients with Sjogren’s syndrome, 14 with scleroderma/MCTD, 96 comparison patients with reflux symptoms (49 without IEM, and 47 with IEM, Table). Age and gender distribution were similar across groups. The scleroderma/MCTD group had higher AET, higher prevalence of hypomotility, lower detected reflux episodes from very low baseline impedance, and very low numbers of PSPW (p≤0.004 compared to other groups). There was no difference in pH impedance metrics between Sjogren’s syndrome, and comparison patients (p≥0.481), including between subsets of Sjogren’s and comparison patients with and without hypomotility (p≥0.116 for each comparison). In contrast, proportions with complete pH recovery with PSPW was lower in Sjogren’s patients compared to comparison reflux patients (p=0.009), predominantly in subsets with hypomotility (p<0.001). Within Sjogren’s syndrome, absent contractility was associated with rates of complete pH recovery with PSPW similar to scleroderma/MCTD (0.0% vs. 8.1% respectively, p=ns), while Sjogren’s with IEM resembled comparison patients with IEM (p=ns) although numbers were small. On multivariable analysis including variables of interest (total reflux episodes, PSPW index, AET, and diagnosis) only higher total reflux episodes (p=0.028) and diagnosis of Sjogren’s syndrome (p=0.034) independently predicted lack of complete pH recovery with PSPW, while failed and ineffective swallows and AET were not predictive.

	Sjogren’s syndrome n=34	Scleroderma/MCTD n=14	Comparison reflux patients n=96	p value across groups
Total AET (%)	3.2 (0.5-10.8)	13.2 (2.9-40.1)	3.5 (1.5-7.1)	0.017
Reflux episodes	26.5 (14.0-46.5)	9.5 (1.5-20.5)	34.5 (16.0-46.8)	0.003
PSPW	6.0 (3.0-11.0)	0.0 (0.0-6.0)	7.0 (2.0-12.0)	0.010
PSPWI (%)	21.7 (14.5-46.3)	8.3 (0.0-33.0)	21.2 (13.7-36.1)	0.160
Partial pH recovery (%)	11.3 (0.0-35.6)	11.1 (0.0-49.2)	10.7 (0.0-33.3)	0.765
Complete pH recovery (%)	38.1 (0.0-61.9)	8.1 (0.0-29.2)	55.6 (33.3-71.4)	0.002
Esophageal hypomotility	8 (23.6%)	11 (78.5%)	47 (49.0%)	<0.001
IEM	4 (11.8%)	1 (7.1%)	42 (43.8%)	<0.001
Absent contractility	4 911.8%)	10 (71.4%)	5 (5.2%)	<0.001

Values are described as median (interquartile range) or values (percent)

Conclusion

Saliva production may be more important than motor function in PSPW related pH recovery.

Introduction

Esophageal reflux burden can be quantified using acid exposure time (AET), mean nocturnal baseline impedance (MNBI) and numbers of reflux episodes (RE), each of which has identified thresholds for physiologic, borderline and pathologic reflux evidence. Alternate parameters such as reflux-symptom association on ambulatory reflux monitoring, hiatus hernia on high resolution manometry, and advanced esophagitis grade on endoscopy escalate confidence for reflux. Each of these parameters has varying importance in determining conclusive evidence of gastroesophageal reflux disease (GERD).

Aims & Methods

Our aim was to determine if a novel reflux score (the Lyon Score) designed to quantify reflux burden can phenotype reflux syndromes and predict treatment outcome from medical or surgical anti-reflux therapy. Scores and ranges were assigned a priori to thresholds for each metric based on available research, the Lyon Consensus and ROME phenotypes (Table). An existing database of endoscopy-negative patients with typical reflux symptoms (heartburn, regurgitation, chest pain) evaluated off therapy for persisting reflux symptoms were reviewed from two centers (one each in Europe and US). Included patients were required to have completed high resolution manometry (Medtronic, Duluth, GA) and ambulatory pH-impedance monitoring (Diversatek, Boulder, CO) off antisecretory therapy. Symptom response was assessed using change in global symptom scores from validated symptom questionnaires over follow-up; a 50% reduction in global symptoms constituted a response to anti-reflux therapy, both medical management and anti-reflux surgery. Receiver operating characteristics (ROC) analysis determined performance of the scoring system in predicting overall response as well as within each distinct syndrome, and principal component analysis identified predictors of response within the scoring system.

Results

Data from 281 patients (median age 53 yr, 57.7% female) was analyzed, 71.9% with heartburn, 13.9% with regurgitation and 14.3% with chest pain. The median Lyon score was 4.0 (IQR 1.5-8.0, range 0.0-16.0). On ROC analysis, the Lyon score demonstrated an AUC of 0.816 in predicting 50% symptom improvement (p=0.026), with an optimal Lyon score threshold of 3.75 (sensitivity 81.2%, specificity 74.1%). The Lyon score performed better than any of the individual components of the score, and only AET (AUC 0.770, p=0.029), MNBI (AUC 0.747, p=0.030) and RE (AUC 0.728, p=0.030) approached the combined score. Using the Lyon score, patients were successfully phenotyped into distinct syndromes (Table), whereby proportions of patients with 50% response from anti-reflux therapy progressively increased across phenotypes with increasing reflux evidence: idiopathic heartburn: 6.1%, isolated permeability defect: 18.2%, reflux hypersensitivity: 27.7%, borderline GERD: 55.9%, conclusive GERD 76.6%, severe GERD 76.9% (Table, p<0.001 across groups). On principal component analysis, AET, MNBI and RE all demonstrated high values within the component matrix (≥0.80 for each), suggesting that each of these primary metrics carries independent weight in driving response to anti-reflux therapy.

Phenotype, score range	No GERD* (0-0.5)	Isolated permeability defect (0.5-2.0)	Reflux hypersensitivity (1.0-3.0)	Inconclusive or borderline GERD (≥3.0)	Conclusive GERD (≥5.0)	Severe GERD (≥10.0)
EGD	Normal: 0 LA A: 0.5	Normal-0 LA A: 0.5	Normal-0 LA A: 0.5	Normal- 0 LA A: 0.5	LA B: 5	LA C/D: 10
AET	< 4.0%: 0	< 4.0%: 0	< 4.0%: 0	4-6%: 2	>6.0%: 5	>10%: 10
RE (number)	<40: 0	<40: 0 40-80: 1	<40: 0 40-80:1	<40: 0 40-80: 1 >80: 2	<40: 0 40-80: 1 >80: 2	<40: 0 40-80: 1 >80: 2
MNBI (ohms)	>2500: 0	<1500: 1	<1500:1 1500-2499: 0.5 >2500: 0	<1500: 1 1500-2499 0.5 >2500- 0	< 1500: 1 1500-2499: 0.5 >2500: 0	<1500: 1 1500-2499: 0.5 >2500: 0
RSA	Negative: 0	Negative: 0	Positive:1	NA	Negative: 0 Positive: 1	Negative:0 Positive: 1
Hiatus Hernia	Negative: 0	Negative: 0	Negative: 0 <3 cm: 1 ≥3 cm: 2	Negative-0 <3 cm: 1 ≥3 cm: 2	Negative: 0 <3 cm: 1 ≥3 cm: 2	Negative: 0 <3 cm: 1 ≥3 cm: 2
Median score (IQR)	0.0 (0.0-0.0)	2.0 (1.0-2.0)	1.4 (0.5-2.3)	4.3 (2.8-4.7)	6.5 (5.5-8.0)	14.0 (12.0-15.0)
50% response**	3/49 (6.1%)	4/22 (18.2%)	13/47 (27.7%)	19/34 (55.9%)	59/77 (76.6%)	40/52 (76.9%)

GERD: gastroesophageal reflux disease; EGD: esophagogastroduodenoscopy; LA: Los Angeles grades (A/B/C/D); AET: acid exposure time; RE: reflux episodes: MNBI: mean nocturnal baseline impedance: RSA: reflux symptom association; IQR: interquartile range
*idiopathic heartburn, presumed esophageal chest pain; **improvement with medical or surgical anti-reflux therapy;

Conclusion

The novel Lyon score segregates reflux phenotypes, and identifies likelihood of symptom response from anti-reflux therapy. Prospective validation of the Lyon score is warranted.

Introduction

Gastroesophageal Reflux Disease (GERD) is a common condition diagnosed by endoscopy and/or pH monitoring. However, only high-resolution manometry (HRM) provides detailed assessment of the pathophysiology underlying reflux mechanisms and GERD symptoms. While it is widely accepted that esophago-gastric junction (EGJ) type 3 is a strong predictor of GERD, EGJ type 2 is less clearly implicated in GERD pathogenesis¹. This study aimed to investigate the clinical and physiological characteristics of patients with EGJ type 2 and to identify HRM variables that predict GERD in this category of patients.

Aims & Methods

535 patients with suspected GERD who underwent HRM and reflux monitoring were retrospectively analyzed. Patients were divided into three groups based on EGJ morphology (type 1, 2, or 3). Clinical data, HRM parameters, and reflux study results were compared among groups. The Milan Score², a novel metric that integrates ineffective esophageal motility (IEM), EGJ-contractile integral (EGJ-CI), EGJ morphology and straight leg raise (SLR) response, was applied to the EGJ type 2 group to identify patients at higher risk of developing GERD. Pathologic GERD was defined as AET >6% on pH-impedance monitoring and/or stricture, Barrett’s esophagus or Los Angeles grade B, C or D, or at endoscopy. As previously demonstrated, a Milan Score of 137 (risk rate 50%) or higher was considered pathologic. Receiver operating characteristic (ROC) analysis was performed to determine Milan score prediction of GERD within patients with EGJ type 2 morphology.

Results

Patients with EGJ type 3 had the highest rate of GERD diagnosis, followed by EGJ type 2 and type 1 (p <0.001). HRM showed differences in EGJ-CI, proportion of patients with IEM and positive SLR response among groups (p <0.001). Reflux monitoring revealed a stepwise increase in AET from type 1 to 3 (5.1±7.3 vs. 8.3±11.1 vs. 12.2±11.3, p <0.001). A pathologic Milan Score identified two subgroups of patients within the EGJ type 2 group: patients with a score below 137 resembled type 1, while those with a score of 137 or higher resembled type 3 in terms of pH monitoring characteristics (Table). On ROC analysis the area under the curve was 0.858, and the optimal threshold to identify pathologic GERD in this group was 137 points (sensitivity 77.3%, specificity 87.7%).

Conclusion

Our data suggests that EGJ type 2 encompasses a wide spectrum of disease severity. The Milan Score with a cut-off of 137 may help to identify patients with EGJ type 2 who are more likely to demonstrate pathologic GERD on reflux monitoring.

References

1. Tolone S, de Cassan C, de Bortoli N, et al. Esophagogastric junction morphology is associated with a positive impedance-pH monitoring in patients with GERD. Neurogastroenterol Motil. 2015 Aug;27(8):1175-82.
2. Siboni S, Sozzi M, Kristo I et al. The Milan score: A novel manometric tool for a more efficient diagnosis of gastro-esophageal reflux disease. United European Gastroenterol J. 2024 Mar 27. doi: 10.1002/ueg2.12565. Epub ahead of print. PMID: 38536701.

Introduction

Aging is associated with physiological changes in esophageal function, influencing motility and increasing susceptibility to dysphagia.

Aims & Methods

This study investigates esophageal peristaltic reserve across different age groups by employing multiple rapid swallow (MRS) during high-resolution manometry (HRM). A retrospective analysis was conducted on 331 patients presenting with dysphagia who underwent HRM between 2021 and 2023. Participants were stratified into four age groups: early adulthood (≤34 years, 12.1%), early middle-age (35–49 years, 12.7%), late middle-age (50–64 years, 45.3%), and late adulthood (≥65 years, 29.9%). Peristaltic reserve was assessed using MRS to evaluate esophageal contractile function.

Results

Among the 311 patients included, 195 (58.9%) were male, with a median age of 57 years (IQR 45–66). The prevalence of normal esophageal motility was highest in early adulthood (67.5%) and early middle-age (78.6%) but declined significantly in late middle-age (48.7%; p=0.014) and late adulthood (44.4%; p<0.001). Late adulthood was also characterized by lower median upper esophageal sphincter (UES) pressure (101 mmHg) and reduced UES length (3 cm; p<0.05). Additionally, esophagogastric junction (EGJ) type II and III morphology was more frequently observed in late adulthood (52.5%; p<0.05). In patients with normal motility (n=177), MRS motor wave transmission was lower in late adulthood (75%, p<0.05) compared to early adulthood (96.3%), early middle age (88.1%) and late middle age (93.2%), and the prevalence of incomplete MRS inhibition was higher in late adulthood (79.5%, p<0.05) compared to early adulthood (11.1%), early middle age (21.2%) and late middle age (46.6%). The DCI-MRS and DCI wet ratio were significantly lower in late adulthood (0.51, IQR 0.13 – 0.88; p<0.01).

Conclusion

Peristaltic reserve declines with advancing age, which may contribute to dysphagia. MRS proves to be a useful diagnostic tool for detecting subtle motility impairments related to aging.

Introduction

Gastro-esophageal reflux disease (GERD) is a multifactorial disease that manifests in patients with different degrees of anti-reflux barrier impairment. GERD significantly impacts quality of life despite the fact that symptom burden may not always correlate with disease severity. Precise pathophysiologic evaluation can identify patients with actionable GERD who may benefit from anti-reflux surgery or escalation of medical therapy. The Milan Score, a novel high-resolution manometry (HRM) metric, numerically quantifies the degree of anti-reflux barrier disruption¹. While the Milan Score has been proven to predict pathologic GERD, its ability to distinguish non-severe from severe GERD and to identify patients with a higher grade of anti-reflux barrier disruption requires further study.

Aims & Methods

A database of prospectively collected data from a cohort of patients undergoing HRM and pH-study for persistent GERD symptoms was queried. Using Lyon 2.0 consensus, pathologic GERD was defined as AET >6%, grade B-C-D esophagitis or Barrett’s esophagus on endoscopy. Severe reflux was defined as AET >12%, DeMeester score >50, grade C-D esophagitis or Barrett’s esophagus². Demographic, HRM and pH data were extracted, classified and compared between groups with varying GERD severity (no GERD, non-severe GERD, severe GERD). The Milan Score integrates the main manometric parameters related with the pathophysiology of GERD (ineffective esophageal motility, esophago-gastric junction (EGJ) contractile integral, EGJ morphology and straight leg raise maneuver response). In order to simplify the use of the Milan Score, risk rates have been classified into six categories, from extremely unlikely to extremely likely. A cumulative odds ordinal logistic regression was run to determine the independent effect of HRM variables on reflux severity. The ability of the Milan Score to predict severe reflux was assessed, as well as its association with the pH-study criteria proposed by Lyon 2.0 as adjunctive evidence for pathologic GERD (>80 reflux episodes, mean nocturnal baseline impedance (MNBI) <1500 W or positive reflux-symptom association).

Results

Among 603 patients enrolled (median age 49.9 years, median body mass index (BMI) 25.3 Kg/m², 50.5% males), 124 (20.6%) had non-severe and 142 (23.5%) had severe GERD. Non-severe and severe GERD patients had similar demographic and clinical characteristics, but were significantly different from the no-GERD group (Table). On univariate analysis, presence and size of hiatal hernia, Milan Score and Milan Score categories were significantly different among the groups (p <0.001). On ordinal logistic regression, hiatal hernia size and Milan Score category were found to be independent predictors of GERD severity (OR 1.28, 95% CI, 1.04-1.57, p=0.018 and OR 2.92, 95% CI, 2.47-4.45, p=<0.001 respectively). A significantly higher Milan Score (p <0.001) was found in patients with >80 reflux episodes, MNBI <1500 W, positive reflux-symptom association and any criteria of severe GERD.

Conclusion

Hiatal hernia size and Milan Score assessed at HRM are independent factors associated with severe GERD. The Milan Score is significantly higher in patients with pathologic adjunctive pH-impedance metrics and in patients with severe GERD.

References

1. Siboni S, Sozzi M, Kristo I et al. The Milan score: A novel manometric tool for a more efficient diagnosis of gastro-esophageal reflux disease. United European Gastroenterol J. 2024 Mar 27. doi: 10.1002/ueg2.12565. Epub ahead of print. PMID: 38536701.
2. Horvath KD, Jobe BA, Herron DM et al. Laparoscopic Toupet fundoplication is an inadequate procedure for patients with severe reflux disease. J Gastrointest Surg. 1999 Nov-Dec;3(6):583-91. doi: 10.1016/s1091-255x(99)80079-1. PMID: 10554364.

Introduction

Gastroesophageal reflux disease (GERD) presents with typical and atypical symptoms of varying frequency and severity. We compared 5-point Likert scales assessing symptom burden to validated GERD questionnaires, and to outcome following reflux management.

Aims & Methods

We analyzed pooled data from patients undergoing pH-impedance testing for reflux symptoms from two tertiary care centers. All patients completed pre-procedure questionnaires assessing typical (heartburn, regurgitation, esophageal chest pain) and atypical symptoms (cough, belching, wheezing, dysphagia). Symptom severity and frequency were scored on 5-point Likert scales (0=not severe, infrequent; 4=extremely severe, multiple daily episodes); the product of severity and frequency for the highest scoring symptom constituted the dominant symptom intensity (DSI). Patients reported global symptom severity (GSS) on 100 mm visual analog scales (VAS) anchored by 0=no symptoms and 100=severe symptoms. Spearman correlation, general linear regression and receiver operating characteristic (ROC) analyses were performed to compare DSI with validated instruments including GSS, gastroesophageal reflux disease questionnaire (GERDQ) and reflux symptom index (RSI), and pH-impedance parameters per Lyon Consensus 2.0. In a subset, change in DSI after medical and surgical GERD management was compared against symptom burden (GSS) and satisfaction with therapy on 100 mm VAS.

Results

808 patients (mean age 53.8±1.44 years, 65.2% female) were included, 499 (61.8%) with dominant typical symptoms. DSI significantly correlated with GSS (R=0.682), GERDQ (R=0.414), RSI (R=0.577), acid exposure time (AET) (R=0.175), total reflux episodes (R=0.194) and mean nocturnal baseline impedance (R=-0.157)(p<0.0001 for each comparison). DSI remained significantly correlated with GERDQ, GSS, RSI, AET and reflux episodes in both typical and atypical symptom subgroups. Mean DSI was higher with abnormal GERDQ, RSI, and conclusive GERD per Lyon Consensus (p<0.0001 each comparison). On ROC analyses, DSI (AUROC=0.60) was non-inferior to GSS, GERDQ, and RSI in predicting pathologic AET and total reflux episodes, and conclusive GERD. Percentage improvement in DSI after antireflux treatment significantly correlated overall with GSS change (R=0.632, p<0.0001) and treatment satisfaction (R=0.513, p<0.0001), and in both typical and atypical symptom subgroups. On multivariable linear regression analyses, percentage change in DSI remained an independent predictor of GSS change (β=0.302, p<0.0001), and satisfaction with anti-reflux therapy (β=0.833, p=0.011). On ROC analyses, DSI change (AUROC=0.730) was non-inferior to GSS change in predicting satisfaction with therapy.

	Overall	Typical, n=499	Atypical, n=309
Age (years)	53.8±1.44	51.0±2.28	58.2±0.79*
Gender (female)	527 (65.2%)	356 (71.3%)	171 (56.3%)*
Body mass index (kg/m2)	27.4±0.25	27.6±0.32	27.1±0.39
Mean baseline DSI	9.37±0.21	10.6±0.25	7.34±0.33*
Mean baseline GSS	50.1±1.15	60.4±1.28	33.7±1.82*
Mean AET (%)	3.29±0.18	3.63±0.23	2.67±0.26*
Number of reflux events	46.9±1.31	50.3±1.78	40.6±1.62*
MNBI (ohms)	1743±83	1667±106	1864±134
Conclusive GERD	177 (21.9%)	125 (25.1%)	52 (16.8%)

GSS: global symptom severity; AET: acid exposure time; MNBI: mean nocturnal baseline impedance; GERD: gastroesophageal reflux disease;
*p<0.05 compared to typical group

Conclusion

DSI correlates with validated reflux questionnaires, discriminates abnormal from normal reflux burden, and DSI change reflects reflux treatment outcome and satisfaction. DSI is a useful addition to reflux symptom assessment.