A complex case of dysphagia with dual aetiology.

A woman in her early 60s was referred with dysphagia and chest pain to a tertiary referral centre specialising in oesophageal disorders. Cardiac symptom origin and sinister oesophageal pathology had been excluded at her local hospital in NHS Scotland. Under multidisciplinary team oversight, reinvestigation of mucosal pathology and oesophageal motility ultimately uncovered both Type III achalasia and eosinophilic oesophagitis. This case demonstrates the benefit of including provocative testing during high-resolution manometry to reproduce relevant dysphagia and the importance of stopping proton-pump inhibitors long enough to uncover excessive eosinophils which could otherwise be masked. Ultimately, tailored management for both conditions separately was required to achieve symptoms resolution.

Lymphocytic oesophagitis: diagnosis and management.

Lymphocytic oesophagitis is a rare inflammatory condition that was first described in 2006. Although it is being increasingly diagnosed, it remains poorly described and characterised. There is limited research on the natural history, diagnosis and management of this condition. The most common presenting symptoms are dysphagia, chest pain and heartburn. Endoscopic features can mimic eosinophilic oesophagitis. International consensus is needed to secure a histological definition, to agree on an endoscopic severity scoring system and to determine an appropriate management algorithm. This review summarises the main evidence for the diagnosis and management of lymphocytic oesophagitis, thus setting the scene for the future directions needed to improve the management of this condition.

Assessing the diagnostic yield of achalasia using provocative testing in high-resolution esophageal manometry: Serial diagnostic study.

BACKGROUND: Chicago Classification v4.0 recommends that if achalasia is demonstrated with single water swallows (SWS); provocative testing is not required. We determine whether provocative testing in patients with suspected achalasia can change manometric findings and reproduce symptoms. METHODS: Between 2016 and 2022, 127 consecutive manometry studies of patients with achalasia were retrospectively analyzed. All patients underwent SWS, a solid meal (SM) and/or a rapid drink challenge (RDC). Demographic data, fluoroscopy, gastroscopy, and pre-and post-treatment Eckardt scores were collated. KEY RESULTS: Of 127 achalasia patients (50.6 ± 16.6 years and 54.6% male), all completed a SM and 116 (91.3%) completed RDC; overall 83 were naïve (65.4%) to previous therapy. 15.4% patients with normal integrated relaxation pressure (IRP) on SWS demonstrated obstruction with RDC. SM gave a different achalasia phenotype in 44.9% of patients (p ⟨ 0.001). Twelve patients with normal IRP during SWS had persistent/recurrent obstruction during provocative testing; 83.3% had previous achalasia therapy. None of 13 patients with Type III (TIII) achalasia with SWS exhibited a change in manometric findings with provocative testing. Impedance bolus heights were lower in patients with TIII achalasia and those with normal IRP with SWS. During the SM, symptoms were reproduced in 56.7% of patients. Forty-six of 103 patients (44.7%) underwent therapy based upon the final achalasia subtype which was defined by the provocative test result of the high-resolution manometry (HRM) study. All treatments were effective, regardless of the achalasia subtype. CONCLUSIONS AND INFERENCES: Manometric findings remain unchanged when TIII achalasia is diagnosed with SWS. In patients with normal IRP, Type I, or Type II achalasia during SWS, provocative testing can alter achalasia phenotype or uncover achalasia where diagnosis is unclear. Further, it can reproduce symptoms. Such findings can personalize and guide effective therapeutic decisions.

Modern Achalasia: Diagnosis, Classification, and Treatment.

Achalasia is a major esophageal motor disorder featured by the altered relaxation of the esophagogastric junction in the absence of effective peristaltic activity. As a consequence of the esophageal outflow obstruction, achalasia patients present with clinical symptoms of dysphagia, chest pain, weight loss, and regurgitation of indigested food. Other less specific symptoms can also present including heartburn, chronic cough, and aspiration pneumonia. The delay in diagnosis, particularly when the presenting symptoms mimic those of gastroesophageal reflux disease, may be as long as several years. The widespread use of high-resolution manometry has permitted earlier detection and uncovered achalasia phenotypes which can have prognostic and therapeutic implications. Other tools have also emerged to help define achalasia severity and which can be used as objective measures of response to therapy including the timed barium esophagogram and the functional lumen imaging probe. Such diagnostic innovations, along with the increased awareness by clinicians and patients due to the availability of alternative therapeutic approaches (laparoscopic and robotic Heller myotomy, and peroral endoscopic myotomy) have radically changed the natural history of the disorder. Herein, we report the most recent advances in the diagnosis, classification, and management of esophageal achalasia and underline the still-grey areas that needs to be addressed by future research to reach the goal of personalizing treatment.

Minimally invasive endoscopic therapies for gastro-oesophageal reflux disease.

The prevalence of the gastro-oesophageal reflux disease (GORD) in the western world is increasing. Uncontrolled GORD can lead to harmful long-term sequela such as oesophagitis, stricture formation, Barrett's oesophagus and oesophageal adenocarcinoma. Moreover, GORD has been shown to negatively impact quality of life. The current treatment paradigm for GORD consists of lifestyle modification, pharmacological control of gastric acid secretion or antireflux surgery. In recent years, several minimally invasive antireflux endoscopic therapies (ARET) have been developed which may play a role in bridging the unmet therapeutic gap between the medical and surgical treatment options. To ensure optimal patient outcomes following ARET, considered patient selection is crucial, which requires a mechanistic understanding of individual ARET options. Here, we will discuss the differences between ARETs along with an overview of the current evidence base. We also outline future research priorities that will help refine the future role of ARET.

How to effectively use and interpret the barium swallow: Current role in esophageal dysphagia.

BACKGROUND: The barium swallow is a commonly performed investigation, though recent decades have seen major advances in other esophageal diagnostic modalities. PURPOSE: The purpose of this review is to clarify the rationale for components of the barium swallow protocol, provide guidance on interpretation of findings, and describe the current role of the barium swallow in the diagnostic paradigm for esophageal dysphagia in relation to other esophageal investigations. The barium swallow protocol, interpretation, and reporting terminology are subjective and non-standardized. Common reporting terminology and an approach to their interpretation are provided. A timed barium swallow (TBS) protocol provides more standardized assessment of esophageal emptying but does not evaluate peristalsis. Barium swallow may have higher sensitivity than endoscopy for detecting subtle strictures. Barium swallow has lower overall accuracy than high-resolution manometry for diagnosing achalasia but can help secure the diagnosis in cases of equivocal manometry. TBS has an established role in objective assessment of therapeutic response in achalasia and helps identify the cause of symptom relapse. Barium swallow has a role in the evaluating manometric esophagogastric junction outflow obstruction, in some cases helping to identify where it represents an achalasia-like syndrome. Barium swallow should be performed in dysphagia following bariatric or anti-reflux surgery, to assess for both structural and functional postsurgical abnormality. Barium swallow remains a useful investigation in esophageal dysphagia, though its role has evolved due to advancements in other diagnostics. Current evidence-based guidance regarding its strengths, weaknesses, and current role are described in this review.

Esophagogastric junction contractile integral (EGJ-CI) complements reflux disease severity and provides insight into the pathophysiology of reflux disease.

BACKGROUND: Esophagogastric junction contractile integral (EGJ-CI) has not come into routine use due to methodological discrepancies and its unclear clinical utility. We aimed to determine which method of calculating EGJ-CI was best at discriminating between common reflux disease states. METHODS: High-resolution manometry (HRM) and pH-Impedance measurements were acquired for 100 patients; 25 Barrett's esophagus (>3 cm/acid exposure time (AET) > 6), 25 endoscopy-negative reflux disease (ENRD; AET >6), 25 borderline reflux (AET 4-6), 25 functional heartburn (FH; AET <4), constituting the developmental cohort. EGJ-CI was calculated at 20 mmHg, 2 mmHg, and 0 mmHg isobaric contour. Empirical associations, univariable, multivariable and ROC analyses were performed between EGJ-CI and manometric/pH-impedance metrics. A validation cohort (n = 25) was used to test the new EGJ-CI cutoff. KEY RESULTS: Significant correlations with AET were observed when EGJ-CI was calculated with an isobaric threshold of 20 mmHg (p < 0.001). Significant differences in EGJ-CI were observed between patients with FH and Barrett's esophagus (p = 0.004) and with ENRD (p = 0.01); however, LES basal pressure was unable to differentiate between these disease states (p = 0.09, p = 0.25, respectively). ROC analysis on the developmental cohort found that EGJ-CI 21.2 mmHg.cm demonstrated sensitivity 72% and specificity 72% between patients with reflux (Barrett's esophagus/ENRD) and FH. In the validation cohort, 92.8% with a low EGJ-CI had good/moderate improvement in symptoms following therapy compared to 54.5% with raised EGJ-CI (p = 0.026). CONCLUSIONS AND INFERENCES: This study re-affirms EGJ-CI as a reliable discriminator between reflux disease (Barrett's esophagus/ENRD) and FH. In borderline reflux patients, patients with a lower EGJ-CI score (<21.2 mmHg) appear to respond better to anti-reflux therapies compared to those with a higher value.

Low prevalence of positive hydrogen breath tests in patients with functional gastrointestinal conditions and hypermobile Ehlers-Danlos syndrome.

BACKGROUND: Using hydrogen breath testing (HBT) to diagnose small intestinal bacterial overgrowth (SIBO) remains controversial in patients with functional gastrointestinal (GI) disorders, and unknown in those with hypermobility Ehlers-Danlos syndrome (hEDS). We assessed prevalence of positive HBTs in these groups, evaluated the predictive value of GI symptoms and the potential role of proton pump inhibitors (PPIs) on test results. METHODS: Sequential patients referred for HBT to a tertiary unit were classified into the following groups: GI maldigestion/malabsorption, GI sensorimotor disorders, hEDS, and functional GI disorders. All underwent standardized HBT, and the yield was assessed against symptoms and PPI use. KEY RESULTS: A total of 1062 HBTs were performed over 3 years (70% female, mean age 48 ± 16 years). Overall, 7.5% (80/1062) patients had a positive HBT. Prevalence of positive HBT was highest in patients with GI maldigestion/malabsorption (17.9%; DOR 16.16, p < 0.001), GI sensorimotor disorders (15.9%; DOR 8.84, p < 0.001), compared to functional GI disorders (1.6%; DOR 1.0) (p < 0.0001). None of the hEDS patients tested positive for HBT. A positive HBT was independently associated with increased age (DOR 1.03; p < 0.001) and symptoms of diarrhea (DOR 3.95; p < 0.0001). Patients on PPIs tended towards a positive HBT than patients off PPIs (16.1% vs 6.9%; DOR 2.47; p < 0.0001). CONCLUSIONS & INFERENCES: Less than 2% of patients with functional GI disorders, and none of the patients with hEDS had a positive HBT. Pre-test probability was higher in patients with: GI structural or neurological disorders; use of long-term PPIs and symptoms of diarrhea. These criteria may be helpful in making appropriate therapeutic decisions and avoiding unnecessary hydrogen breath testing.

Assessment of Esophageal Motility in Patients With Eosinophilic Esophagitis: A Scoping Review.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated condition causing esophageal symptoms, particularly dysphagia. Despite the important progress in the treatment of EoE, a significant proportion of patients continue to report symptoms that negatively impact quality of life. Esophageal manometry is used to assess motility and function, but is not routinely used in EoE. We aimed to systematically review and describe current literature evaluating esophageal manometry in EoE. Forty-eight studies meeting the criteria were identified, describing 802 patients. Using standard water swallow protocols, the proportion of abnormalities detected was not dissimilar to other populations, apart from disorders of esophago-gastric outflow, which were found in 5%. Twelve studies described pretreatment and posttreatment manometry, with motility normalization after pharmacological therapy reported in 20%. Early, brief panesophageal pressurization was described in a number of studies and was more prevalent in the few studies utilizing additional provocation testing. Reports in the literature regarding temporal relationships between manometric findings and symptoms are variable. Esophageal manometry may be capable of detecting clinically relevant changes to esophageal function in EoE. Possible mechanisms are altered neuromuscular function because of secretory products of EoE and/or fibroinflammatory processes, manifesting as pressurization because of altered esophageal compliance. Some changes may be reversible with therapy. Drawing strong conclusions from the literature is difficult, with bias toward case reports and retrospective observation. Adaptations to assessment protocols to include provocation testing may provide more robust evaluation and detect clinically relevant, subtle changes in esophageal function, earlier within the patient pathway.

How provocative tests in addition to wet swallows during high-resolution manometry can direct clinical management.

PURPOSE OF REVIEW: Provocative tests have been advocated to address limitations of high-resolution manometry (HRM) with wet swallows. We describe the commonly used provocative manometric manoeuvres [rapid drink challenge (RDC), multiple rapid swallows (MRS), solid swallows and the solid test meal (STM)], compare their diagnostic yield and accuracy to wet swallows, and outline their role in directing clinical management. RECENT FINDINGS: Provocative testing with RDC and STM identifies a proportion of achalasia cases missed by standard testing, and RDC can play a similar role to radiology in the evaluation of treatment response. In EGJOO, provocative testing with RDC and STM not only increase the diagnostic yield, but can also help differentiate between spurious cases and those representing true outflow obstruction likely to respond to achalasia-type therapies. MRS and STM can help determine the clinical relevance (or otherwise) of ineffective oesophageal motility, and in this setting, MRS may predict the likelihood of postfundoplication dysphagia. RDC and STM can help identify cases of postfundoplication dysphagia more likely to respond to dilatation. SUMMARY: Provocative testing has been shown to increase diagnostic yield of HRM, clarify inconclusive diagnoses, allows corroboration of dysmotility with patient symptoms and helps direct clinical management.

British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults.

BACKGROUND: Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. METHODS: The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. RESULTS: Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. CONCLUSIONS: These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.

British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults

Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.

Timed barium swallow: Esophageal stasis varies markedly across subtypes of esophagogastric junction obstruction.

BACKGROUND: Timed barium swallow (TBS) is a recommended ancillary investigation in evaluation of esophagogastric junction (EGJ) obstruction, yet there are little data comparing esophageal stasis across subtypes. METHODS: A retrospective cohort study was performed. All type III achalasia diagnosed between November 2016 and November 2020 were included, along with matched numbers of consecutive types I and II and conclusive EGJOO cases with concurrent TBS evaluation. Co-primary outcomes were TBS retention at 1 and 5 min. Secondary outcomes were symptoms and manometric metrics of EGJ function and peristaltic integrity. KEY RESULTS: One hundred patients were included (25 each of types I-III and conclusive EGJOO). TBS retention measured by height and width at 1 and 5 min differed significantly across the four subtypes (p < 0.0001 all comparisons), with esophageal stasis tending to be significantly greater for types I and II achalasia (88% and 84% with >5 cm column at 5 min) compared to type III and EGJOO (24% and 8% with >5 cm column; p < 0.0001). Eckardt symptom severity was similar across subtypes (p = 0.30). Magnitude of esophageal stasis and integrated relaxation pressure (IRP) were uncorrelated (R = 0.21). In EGJOO, the number of swallows with intact peristalsis inversely correlated with barium column height (R = -0.49) and those with disordered peristalsis were more likely to have any residual barium at 5 min compared to those without disordered peristalsis (43% vs. 0%; p = 0.02). CONCLUSIONS & INFERENCES: Timed barium swallow findings differed markedly with significantly less esophageal stasis in type III achalasia and EGJOO, despite similar symptom severity and no correlation between degree of emptying and IRP. Preservation of peristalsis may underlie this finding in EGJOO.

An investigation into the effect of nasogastric intubation on markers of autonomic nervous function.

BACKGROUND: Nasogastric (NG) intubation for esophageal manometry can be traumatic and may be associated with a temporary reduction/absence in esophageal peristalsis. This study explored the prevalence and effect on esophageal motor function. We also hypothesized that baseline anxiety as well as markers of autonomic nerve function were correlated to attenuated esophageal peristalsis. METHODS: Twenty-seven patients with esophageal symptoms referred for esophageal manometry investigation (mean age 56.8 ± 16.7 years, range 23-85 years) reported baseline anxiety score (Likert scale) preintubation. Patients had continuous heart rate and blood pressure measured prior to intubation and until 10 min after catheter withdrawal. Quality of motility was assessed for each 5 ml water swallow using standard Chicago Classification metrics. KEY RESULTS: Nasogastric-intubation elicited a significant increase in heart rate (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.001) blood pressure, which was in part anticipatory. The median time taken for patients' first hypotensive peristalsis (Distal Contractile Integral; DCI ≥100 mmHg s cm) was 130 s (Interquartile range; 47-242 s) and for their first normal peristalsis (DCI ≥450 mm Hg s cm) was 150 s (IQR 61-320 s), with improvement and consistent stabilization in DCI there onward. This corresponded closely to the time for initial recovery of heart rate and systolic and diastolic blood pressure postintubation. CONCLUSIONS AND INFERENCES: Nasogastric intubation resulted in heightened sympathetic responses and/or dampened parasympathetic responses, and an associated temporary reduction or absence in esophageal peristalsis.

The natural history of low-grade dysplasia in Barrett's esophagus and risk factors for progression.

BACKGROUND AND AIM: Barrett's esophagus is associated with increased risk of esophageal adenocarcinoma. The optimal management of low-grade dysplasia arising in Barrett's esophagus remains controversial. We performed a retrospective study from a tertiary referral center for Barrett's esophagus neoplasia, to estimate time to progression to high-grade dysplasia/esophageal adenocarcinoma in patients with confirmed low-grade dysplasia compared with those with downstaged low-grade dysplasia from index presentation and referral. We analyzed risk factors for progression. METHODS: We analyzed consecutive patients with low-grade dysplasia in Barrett's esophagus referred to a single tertiary center (July 2006-October 2018). Biopsies were reviewed by at least two expert pathologists. RESULTS: One hundred and forty-seven patients referred with suspected low-grade dysplasia were included. Forty-two of 133 (32%) of all external referrals had confirmed low-grade dysplasia after expert histopathology review. Multivariable analysis showed nodularity at index endoscopy (P < 0.05), location of dysplasia (P = 0.05), and endoscopic therapy after referral (P = 0.09) were associated with progression risk. At 5 years, 59% of patients with confirmed low-grade dysplasia had not progressed versus 74% of patients in the cohort downstaged to non-dysplastic Barrett's esophagus. CONCLUSION: Our data show variability in the diagnosis of low-grade dysplasia. The cumulative incidence of progression and time to progression varied across subgroups. Confirmed low-grade dysplasia had a shorter progression time compared with the downstaged group. Nodularity at index endoscopy and multifocal low-grade dysplasia were significant risk factors for progression. It is important to differentiate these high-risk subgroups so that decisions on surveillance/endotherapy can be personalized.

Characterisation of patients with supine nighttime reflux: observations made with prolonged wireless oesophageal pH monitoring.

BACKGROUND: Although nighttime reflux symptoms are common, the presence of nocturnal reflux is seldom confirmed with a standard 24 hours pH study. AIM: To study patients with supine nighttime reflux symptoms using prolonged wireless pH monitoring. METHODS: In this retrospective study, patients with typical acid reflux symptoms were studied using 96-h pH monitoring. Patients with nighttime reflux symptoms were compared to those without. Night-to-night variability and diagnostic accuracy of 24-, 48- and 72-hours pH studies compared to the 96-hours "gold standard" were evaluated. RESULTS: Of the 105 included patients (61.9% females; mean age 46.8 ± 14.4 years), 86 (81.9%) reported nighttime reflux symptoms, of which 67.4% had pathological supine nocturnal acid exposure in at least one night. There was high variance in night-to-night acid exposure (94% [IQR0-144]), which was larger than the variance in upright acid exposure (58% [IQR32-88]; P < 0.001). When analysing the first 24 hours of the pH study, 32% of patients were diagnosed with pathological supine nighttime acid exposure versus 51% of patients based upon the 96-hours pH-test. The diagnostic accuracy and yield improved with study duration (P < 0.001). Reflux episodes with a lower nadir pH or longer acid clearance time were more prone to provoke nightly symptoms. CONCLUSIONS: The majority of patients with nocturnal reflux symptoms had pathological acid exposure in at least one night of the prolonged pH recording. A high night-to-night variability in acid exposure reduces the clinical value and diagnostic yield of pH monitoring limited to 24 hours. Prolonged testing is a more appropriate diagnostic tool for patients with nocturnal reflux symptoms.

Advances and caveats in modern achalasia management.

Achalasia is a rare esophageal motility disorder characterized by the incomplete relaxation of the lower esophageal sphincter (LES) and impaired peristaltic activity. The advent of high-resolution manometry (HRM) and the rapidly evolving role of therapeutic endoscopy have revolutionized the approach to the diagnosis and management of achalasia patients in the last decade. With advances in HRM technology and methodology, fluoroscopy and EndoFlip, achalasia can be differentiated into therapeutically meaningful phenotypes with a high degree of accuracy. Further, the newest treatment option, per-oral endoscopic myotomy (POEM), has become a staple therapy following the last 10 years of experience, and recent randomized trials appear to show no difference between POEM, graded pneumatic dilatation and surgical Heller myotomy in terms of short- and long-term efficacy or complication rate. On the other hand, how treatment outcomes are measured as well as the risk of reflux following therapy remain areas of contention. This review aims to summarize the recent advancements in achalasia testing and therapy, describes the recent randomized clinical trials as well as their potential setbacks, and touches on the future of personalizing achalasia treatment.