Rapid drinking challenge during high-resolution manometry is complementary to timed barium esophagogram for diagnosis and follow-up of achalasia.

BACKGROUND: Esophageal stasis is a hallmark of achalasia. Timed barium esophagogram (TBE) is used to measure stasis but exposes patients to ionizing radiation. It is suggested that esophageal stasis can be objectified on high-resolution manometry (HRM) as well using a rapid drinking challenge test (RDC). We aimed to assess esophageal stasis in achalasia by a RDC during HRM and compare this to TBE. METHODS: Thirty healthy subjects (15 male, age 40 [IQR 34-49]) and 90 achalasia patients (53 male, age 47 [36-59], 30 untreated/30 treated symptomatic/30 treated asymptomatic) were prospectively included to undergo HRM with RDC and TBE. RDC was performed by drinking 200 mL of water. Response to RDC was measured by basal and relaxation pressure in the esophagogastric junction (EGJ) and esophageal pressurization during the last 5 seconds. KEY RESULTS: EGJ basal and relaxation pressure during RDC were higher in achalasia compared to healthy subjects (overall P < .01). Esophageal body pressurization was significantly higher in untreated (43 [33-35 mm Hg]) and symptomatic treated patients (25 [16-32] mm Hg) compared to healthy subjects (6 [3-7] mm Hg) and asymptomatic treated patients (11 [8-15] mm Hg, overall P < .01). A strong correlation was observed between esophageal pressurization during RDC and barium column height at 5 minutes on TBE (r = .75, P < .01), comparable to the standard predictor of esophageal stasis, IRP (r = .66, P < .01). CONCLUSIONS & INFERENCES: The RDC can reliably predict esophageal stasis in achalasia and adequately measure treatment response to a degree comparable to TBE. We propose to add this simple test to each HRM study in achalasia patients.

Incidence and costs of achalasia in The Netherlands.

BACKGROUND: Recent reports show increasing incidence of achalasia in some populations. The aim of this study was to estimate incidence, prevalence, and healthcare costs of achalasia in a large cohort in The Netherlands. METHODS: Data were obtained from the largest Dutch healthcare insurance company (±4.4 million insured). Adult achalasia patients were identified between 2006 and 2014 when having an achalasia diagnosis code registered. A total of 907 achalasia patients were identified and included in our database, along with 9068 control patients (non-achalasia patients), matched by age and gender. KEY RESULTS: The mean incidence over the 9-year period was 2.2 per 100 000 persons and the mean prevalence was 15.3 per 100 000 persons. Mean age of achalasia patients was 54 (range 18-98) years. Male to female ratio was 1:1. Socio-economic status distribution was similar in achalasia patients and controls. Prior to the diagnosis, 74% of achalasia patients received proton pump inhibitors and 26% received anti-emetic medication. The first year after diagnosis median total direct medical costs of achalasia patients were €2283 (IQR 969-3044) per year. Patients above the 90th percentile of €4717 were significantly older than other patients below the 90th percentile (mean age 63 vs 57); P = .005. CONCLUSION & INFERENCES: In this large study that used a database comprising about 25% of all inhabitants of The Netherlands, it is confirmed that achalasia affects individuals of both genders and all ages. The costs associated with diagnosis and treatment of new cases of achalasia increase with increasing age.

Evaluation of gastrointestinal motility with MRI: Advances, challenges and opportunities.

Dynamic magnetic resonance imaging (MRI) of gastrointestinal motility has developed rapidly over the past few years. The non-invasive and non-ionizing character of MRI is an important advantage together with the fact that it is fast and can visualize the entire gastrointestinal tract. Advances in imaging and quantification techniques have facilitated assessment of gastric, small intestinal, and colonic motility in a clinical setting. Automated quantitative motility assessment using dynamic MRI meets the need for non-invasive techniques. Recently, studies have begun to examine this technique in patients, including those with IBD, pseudo-obstruction and functional bowel disorders. Remaining challenges for clinical implementation are processing the large amount of data, standardization and validation of the numerous MRI metrics and subsequently assessment of the potential role of dynamic MRI. This review examines the methods, advances, and remaining challenges of evaluation of gastrointestinal motility with MRI. It accompanies an article by Khalaf et al. in this journal that describes a new protocol for assessment of pan-intestinal motility in fasted and fed state in a single MRI session.

Ambulatory pH-impedance-pressure monitoring as a diagnostic tool for the reflux-cough syndrome.

Gastroesophageal reflux is considered to be a significant contributing factor to chronic unexplained cough. Patients are often presumed to have reflux-induced cough and are exposed to high-dose and long-term empirical therapy with proton pump inhibitors (PPIs) despite the limited treatment efficacy in this population. We aimed to assess the diagnostic value of 24-hour ambulatory pH-impedance-pressure monitoring for the diagnosis of reflux-induced chronic cough. In this multicenter study, we evaluated 192 patients with chronic cough using 24-hour pH-impedance-pressure monitoring off PPIs. Manometry was used to detect all cough bursts while pH-impedance allowed for the evaluation of all reflux episodes, including weakly acidic reflux. The symptom association probability was used to determine a temporal relationship between reflux and cough. A diagnosis of reflux-induced cough was made in 25.5% of the patients. If only acid reflux episodes were used, 22.4% of those patients would not have been diagnosed. Significantly more patients with reflux-induced cough had typical reflux symptoms (P = 0.031) and a pathological distal acid exposure time (P = 0.025) in comparison to patients without the diagnosis. A diagnosis of cough-induced reflux was made in 24.0% of the patients. Only 59% of all cough bursts were registered by the patients. Overall, only approximately one quarter of patients with chronic unexplained cough have reflux-induced cough, explaining the observation that the vast majority of patients with chronic cough do not benefit from antireflux therapy. pH-impedance-pressure monitoring helps to identify patients who are likely to have reflux as a cause of their chronic cough.

Incidence of eosinophilic esophagitis in the Netherlands continues to rise: 20-year results from a nationwide pathology database.

BACKGROUND: The incidence of eosinophilic esophagitis (EoE) has increased rapidly. Most epidemiologic data were gathered in single-center studies over a short timeframe, possibly explaining the heterogeneous incidences. AIM: The aim of this study was to retrospectively estimate the Dutch nationwide incidence of EoE over the last 20 years. METHODS: The Dutch pathology registry (PALGA) was queried to identify pathology reports describing esophageal eosinophilia from 1996 to 2016. Cases were eligible if EoE was confirmed by the pathologist. Using the annual Dutch population data, the incidence of EoE was calculated. KEY RESULTS: The search yielded 11 288 reports of which 5080 described esophageal eosinophilia. Eosinophilic esophagitis was diagnosed in 2161 patients, 1574 (73%) males and 365 (17%) children. The incidence increased from 0.01 (95% CI 0-0.02) in 1996 to 2.07 (95% CI 2.05-2.23) per 100 000 inhabitants in 2015. The incidence was higher in males than in females, 3.02 (95% CI 2.66-3.41) vs 1.14 (95% CI 0.93-1.38), odds ratio (OR) 2.66 (95% CI 2.10-3.36) and higher in adults than in children, 2.23 (95% CI 1.99-2.49) vs 1.46 (95% CI 1.09-1.91), OR 1.78 (95% CI 1.32-2.40). Incidence of EoE increased more than 200-fold, whereas endoscopy rates only tripled, from 30 in 1996 to 105 per 100 000 inhabitants in 2015. We observed no seasonal variation. CONCLUSIONS AND INFERENCES: In the last decades, the Dutch EoE incidence has increased tremendously and still continues to rise. This expansion is only partially driven by increased endoscopy rates.

Subtle lower esophageal sphincter relaxation abnormalities in patients with unexplained esophageal dysphagia.

BACKGROUND: Esophageal dysphagia is a relatively common symptom. We aimed to evaluate whether subtle, presently not acknowledged forms of dysfunction of the lower esophageal sphincter (LES) could explain dysphagia in a subset of patients with normal findings at high-resolution manometry (HRM) according to the Chicago classification v3.0. METHODS: We used HRM to compare LES relaxation characteristics in 97 patients with unexplained dysphagia with those in 44 healthy subjects. In addition, normative values for time to LES relaxation and completeness of LES relaxation were calculated. Patients with delayed or incomplete LES relaxation were compared with patients with normal relaxation. KEY RESULTS: Dysphagia patients had a higher nadir LES pressure (P=.001) and a longer time to LES relaxation (P=.012) than healthy subjects. Based on the findings in healthy subjects, normal values of LES relaxation were defined as: ≥50% of swallows with normal LES relaxation time (<5 seconds) and ≤20% of swallows with incomplete LES relaxation (not reaching a value below 10 mm Hg). Dysphagia patients had significantly more often >50% swallows with delayed and/or incomplete LES relaxation than healthy controls (25% vs 4.5%; P=.004). Dysphagia patients with >50% delayed and/or incomplete LES relaxation had a significantly higher LES resting pressure (P<.001) and a significantly higher intrabolus pressure (P<.001) than dysphagia patients who did not fulfill the criteria. CONCLUSIONS AND INFERENCES: Subtle LES relaxation abnormalities, such as a delayed relaxation of the LES and/or incomplete LES relaxation, could be a cause of dysphagia in approximately one quarter of the patients with otherwise unexplained esophageal dysphagia.

Reflux-cough syndrome: Assessment of temporal association between reflux episodes and cough bursts.

BACKGROUND: Gastro-esophageal reflux can be the cause of chronic cough. In the assessment of the temporal association between reflux and cough, previous studies have used a two-minute time window, based on studies in patients with heartburn. However, it remains unclear whether the optimal time window duration for the evaluation of reflux-induced cough is two minutes as well. Therefore, we aimed to determine whether a two-minute time window is optimal to diagnose reflux-induced cough. METHODS: In this multicenter study, 137 patients with chronic cough were evaluated using 24-h pH-impedance-pressure monitoring. Repetitive symptom association analysis was employed using an array of time windows of various duration. For each time window, the symptom association probability (SAP) and symptom index (SI) were calculated. KEY RESULTS: A total of 4377 cough burst episodes and 5074 reflux episodes were detected. The number of patients with a positive SAP increased with increasing window duration until a plateau was reached around a time window duration of 1.5 min. Similarly, the SI increased steeply until a window duration of about 2 min, after which a linear increase was seen. CONCLUSIONS AND INFERENCES: A two-minute time window seems appropriate for evaluation of the relationship between reflux and chronic cough using 24-h pH-impedance-pressure monitoring. A time window duration of 30 s or 1 min is too short to diagnose patients with reflux-induced cough accurately.

Esophageal sensitivity to acid in patients with Barrett's esophagus is not related to preserved esophageal mucosal integrity.

BACKGROUND: Patients with Barrett's esophagus (BE) usually have severe gastroesophageal reflux. However, they often have surprisingly few reflux symptoms. We hypothesized that BE patients are less sensitive to acid than gastroesophageal reflux disease (GERD) patients without Barrett and that this is due to an unusual preservation of mucosal integrity of the squamous epithelium prohibiting transepithelial acid diffusion. METHODS: We prospectively analyzed esophageal sensitivity and esophageal mucosal integrity in GERD patients with and without BE and healthy subjects. An acid perfusion test was performed and mucosal integrity was assessed in vivo by electrical tissue impedance spectroscopy and ex vivo by Ussing chamber experiments with biopsy specimens. KEY RESULTS: Gastroesophageal reflux disease patients with BE were less sensitive to acid than GERD patients without BE, but more sensitive to acid than healthy controls (time to perception Barrett's 14.0 minutes, GERD 4.6 minutes, controls 17.5 minutes). However, extracellular impedance (6.2 and 5.7 vs 8.4×103  Ω/m) and transepithelial resistance (94.0 and 89 vs 118 Ω/cm2 ) was similar in BE and GERD patients and significantly lower than in healthy subjects. Transepithelial fluorescein flux was equally increased in GERD patients with and without BE (1.6 and 1.7×103 vs 0.6×103  nmol/cm2 /h). CONCLUSIONS & INFERENCES: Esophageal hypersensitivity to acid is less pronounced in BE patients than in GERD patients without Barrett. However, mucosal integrity of the squamous epithelium is equally impaired in GERD patients with and without Barrett, indicating that factors other than esophageal mucosal barrier integrity explain the difference in acid sensitivity between those with BE and those without.

Diagnostic features of malignancy-associated pseudoachalasia.

BACKGROUND: Pseudoachalasia is a condition in which clinical and manometric signs of achalasia are mimicked by another abnormality, most often a malignancy. AIM: To identify risk factors that suggest presence of malignancy-associated pseudoachalasia. METHODS: In this retrospective cohort study, achalasia patients newly diagnosed by manometry were included. Patients with a normal initial endoscopy, clinical and manometric signs of achalasia who were afterwards found to have an underlying malignant cause were classified as pseudoachalasia. Clinical and diagnostic findings were compared between malignant pseudoachalasia and achalasia. RESULTS: We included 333 achalasia patients [180 male, median age 50 (38-62)]. Malignant pseudoachalasia was diagnosed in 18 patients (5.4%). Patients with malignancy-associated pseudoachalasia were older at time of diagnosis [67 (54-71) vs. 49 (37-60) years], had a shorter duration of symptoms [6 (5-10) vs. 25 (11-60) months] and lost more weight [12 (9-17) vs. 5 (0-12) kg). In 61% of the pseudoachalasia patients, the oesophagogastric junction (OGJ) was difficult or impossible to pass during endoscopy, compared to 23% in achalasia. Age ≥55 years (OR 5.93), duration of symptoms ≤12 months (OR 14.5), weight loss ≥10 kg (OR 6.73) and difficulty passing the OGJ during endoscopy (OR 6.06) were associated with a higher risk of malignant pseudoachalasia. CONCLUSIONS: Advanced age, short duration of symptoms, considerable weight loss and difficulty in passing the OGJ during endoscopy, are risk factors that suggest potential malignancy-associated pseudoachalasia. To exclude pseudoachalasia, additional investigations are warranted when two or more risk factors are present.

Esophageal stasis in achalasia patients without symptoms after treatment does not predict symptom recurrence.

BACKGROUND: After achalasia treatment, a subset of patients has poor esophageal emptying without having symptoms. There is no consensus on whether to pre-emptively treat these patients. We hypothesized that, if left untreated, these patients will experience earlier symptom recurrence than patients without stasis. METHODS: 99 treated achalasia patients who were in clinical remission (Eckardt ≤3) at 3 months after treatment were divided into two groups, based on presence or absence of esophageal stasis on a timed barium esophagogram performed after 3 months. KEY RESULTS: Two years after initial treatment, patients with stasis after treatment still had a wider esophagus (3 cm; IQR: 2.2-3.8) and more stasis (3.5 cm; IQR: 1.9-5.6) than patients without stasis (1.8 cm wide and 0 cm stasis; both P<.001). In patients with stasis, the esophageal diameter had increased from 2.5 to 3.0 cm within 2 years of follow-up. The symptoms, need for and time to retreatment were comparable between the two groups. Quality of life and reflux symptoms were also comparable between the two groups. CONCLUSIONS & INFERENCES: Although patients with stasis initially had a wider esophagus and 2 years after treatment also had a higher degree of stasis and a more dilated esophagus, compared to patients without stasis, they did not have a higher chance of requiring retreatment. We conclude that stasis in symptom-free achalasia patients after treatment does not predict treatment failure within 2 years and can therefore not serve as a sole reason for retreatment.

Elemental diet decreases inflammation and improves symptoms in adult eosinophilic oesophagitis patients.

BACKGROUND: Eosinophilic oesophagitis (EoE) is a chronic disease, driven by food allergens. Elemental diets are effective for the management of children with EoE, but studies on the effect of elemental diets in adults are scarce and poor palatability challenges dietary adherence. AIM: To assess the effects of an elemental diet (Neocate, Nutricia, Utrecht, the Netherlands) on the inflammation, symptoms and endoscopic signs in adult EoE patients. METHODS: In this prospective study, 21 patients with active EoE, confirmed by biopsies showing ≥15 eosinophils per microscopic high power field (HPF) and symptoms of oesophageal dysfunction were included. Patients underwent endoscopy before and 4 weeks after diet. Histological disease activity (peak eosinophil count/HPF), and endoscopic signs were scored by physicians. Symptoms and adherence to the diet were evaluated by questionnaires. Serum total IgE levels and total eosinophil counts were determined and the expression of inflammatory cytokines was analysed by qPCR. RESULTS: In total, 17 (81%) of the patients completed the diet, of whom 12 (71%) showed complete histological response (≤15 eosinophils/HPF) and 4 (24%) showed partial histological response (≥50% reduction of baseline eosinophil count). Peak eosinophil counts decreased significantly after the diet from 40 to 9 per HPF (P ≤ 0.001). A marked improvement in endoscopic signs was observed. Symptoms decreased significantly in all subjects, and 15 patients (88%) became completely asymptomatic (P ≤ 0.001). In 14 patients (82%), blood eosinophil count and serum IgE decreased (P ≤ 0.05). CONCLUSION: Elemental diet reduces eosinophilic inflammation and induces clinical remission in adult patients with eosinophilic oesophagitis.

Esophagogastric junction distensibility identifies achalasia subgroup with manometrically normal esophagogastric junction relaxation.

BACKGROUND: Manometric criteria to diagnose achalasia are absent peristalsis and incomplete relaxation of the esophagogastric junction (EGJ), determined by an integrated relaxation pressure (IRP) >15 mm Hg. However, EGJ relaxation seems normal in a subgroup of patients with typical symptoms of achalasia, no endoscopic abnormalities, stasis on timed barium esophagogram (TBE), and absent peristalsis on high-resolution manometry (HRM). The aim of our study was to further characterize these patients by measuring EGJ distensibility and assessing the effect of achalasia treatment. METHODS: Impedance planimetry (EndoFLIP) was used to measure EGJ distensibility and compared to previous established data of 15 healthy subjects. In case the EGJ distensibility was impaired, achalasia treatment followed. Eckardt score, HRM, TBE, and EGJ distensibility measurements were repeated >3 months after treatment. KEY RESULTS: We included 13 patients (5 male; age 19-59 years) with typical symptoms of achalasia, Eckardt score of 7 (5-7). High-resolution manometry showed absent peristalsis with low basal EGJ pressure of 10 (5.8-12.9) mm Hg and IRP of 9.3 (6.1-12) mm Hg. Esophageal stasis was 4.6 (2.7-6.9) cm after 5 minutes. Esophagogastric junction distensibility was significantly reduced in patients compared to healthy subjects (0.8 [0.7-1.2] mm2 /mm Hg vs 6.3 [3.8-8.7] mm2 /mm Hg). Treatment significantly improved the Eckardt score (7 [5-7] to 2 [1-3.5]) and EGJ distensibility (0.8 [0.7-1.2] mm2 /mm Hg to 3.5 [1.5-6.1] mm2 /mm Hg). CONCLUSIONS & INFERENCES: A subgroup of patients with clinical and radiological features of achalasia but manometrically normal EGJ relaxation has an impaired EGJ distensibility and responds favorably to achalasia treatment. Our data suggest that this condition can be considered as achalasia and treated as such.

Jackhammer esophagus: Observations on a European cohort.

BACKGROUND: With the advent of high-resolution manometry (HRM), a new diagnosis, jackhammer esophagus, was introduced. Little is known about this rare condition, and the relationship between symptoms and hypercontractility is not always straightforward. The aim of our study was to describe a large cohort of patients with jackhammer esophagus and to investigate whether manometric findings are associated with the presence of symptoms. METHODS: All patients from 06, 2014 until 12, 2015 seen at two tertiary centers with at least one hypercontractile swallow (distal contractile integral [DCI] >8000 mm Hg/s/cm) on HRM were analyzed. Patients with ≥20% premature swallows, or patients with another diagnosis explaining their symptoms were excluded. KEY RESULTS: Of the 34 patients identified with jackhammer esophagus, most suffered from dysphagia (67.6%) and/or chest pain (47.1%). The symptom chest pain was not associated with any of the manometric findings, whereas dysphagia was associated with the DCI of the hypercontractile swallows and with intrabolus pressure. In addition, all patients who had an isolated DCI of the lower esophageal sphincter (LES) zone >2000 mm Hg/s/cm had dysphagia. The differences in HRM and clinical characteristics between subgroups based on the contraction type (single- or multi-peaked) or based on meeting criteria of the Chicago Classification v3.0 and v2.0 were limited. CONCLUSIONS & INFERENCES: The symptom dysphagia is accompanied with strong contractions of the LES, signs of a possible outflow obstruction, and a very high DCI. The presence of a multipeaked contraction seems to be of limited relevance, and caution is warranted in labeling patients with one hypercontractile swallow as normal.

Efficacy of pneumodilation in achalasia after failed Heller myotomy.

BACKGROUND: Heller myotomy is an effective treatment for the majority of achalasia patients. However, a small proportion of patients suffer from persistent or recurrent symptoms after surgery and they are usually subsequently treated with pneumodilation (PD). Data on the efficacy of PD as secondary treatment for achalasia are scarce. Therefore, this study aimed to investigate the efficacy of PD as treatment for achalasia patients suffering from persistent or recurrent symptoms after Heller myotomy. METHODS: Patients with recurrent or persistent symptoms (Eckardt score >3) after Heller myotomy were selected. Patients were treated with PD, using a graded distension protocol with balloon sizes ranging from 30 to 40 mm. After each dilation symptoms were assessed to evaluate whether a subsequent dilation with a larger balloon size was required. Patients with recurrent or persistent symptoms (Eckardt score >3) after treatment with a 40-mm balloon were identified as failures. KEY RESULTS: Twenty-four patients were included in total; 15 patients with achalasia type I, seven with achalasia type II and two with achalasia type III. Median relapse time was 2.5 years after Heller myotomy (IQR: 9 years and 3 months). Three patients were not suitable for PD; one patient was morbidly obese and not fit for any form of sedation and two had a siphon-shaped esophagus leaving 21 patients to treat. Eight patients were successfully treated with a single 30-mm balloon dilation (median follow-up time: 6.5 years; IQR: 7.5 years). Four patients required dilations with 30- and 35-mm balloons (median follow-up time: 11 years; IQR: 3 years). Nine patients failed on the 35-mm balloon dilation and underwent a subsequent dilation with a 40-mm balloon, and all failed on this balloon as well. Thus, PD was successful in 12 of the 21 treatable patients, resulting in a success rate of 57% for treatable patients or 50% for all patients. Baseline Eckardt scores were also higher in those that failed (median: 8; IQR: 2) than those that were treated successfully (median: 5.5; IQR: 2) treated (p = 0.009). Furthermore, baseline barium column height at 5 min was higher in patients with failed (median: 6 cm; IQR: 6 cm) treatment than in patients with successful (median: 2.6 cm; IQR: 4.7 cm) treatment (p = 0.016). Baseline lower esophageal sphincter pressure was not different between patients who were treated successfully (median: 11 mmHg; IQR: 5 mmHg) and those that failed on PD (median: 17.5 mmHg; IQR: 10.8 mmHg) treatment (p > 0.05). Baseline symptom pattern was also not a predictor of successful treatment. No adverse events were recorded during or after PD. CONCLUSIONS & INFERENCES: Pneumodilation for recurrent symptoms after previous Heller myotomy is safe and has a modest success rate of 57%, using 30- and 35-mm balloons. Patients with recurrent symptoms after PD with 35-mm balloon are likely to also fail after subsequent dilation with a 40-mm balloon.

The Endoscopic Reference Score shows modest accuracy to predict histologic remission in adult patients with eosinophilic esophagitis.

BACKGROUND: The relationship between the severity of endoscopic signs scored according to the Endoscopic Reference Score (EREFS) and histopathologic signs of eosinophilic esophagitis (EoE) has not been sufficiently explored. We aimed to determine if the EREFS system predicts histopathologic activity in EoE patients. METHODS: We included 69 patients with EoE (age 35 [IQR 29-48] years; 80% male) who, between 2006 and 2014, underwent esophagogastroduodenoscopy (EGD) during which high-quality endoscopic images were taken and esophageal biopsy specimens were obtained. Per EGD, three or more depersonalized images were scored by an expert endoscopist, and histopathologic signs were scored by a pathologist with gastrointestinal expertise; both in a blinded fashion. The predictive values of endoscopic signs for disease activity (peak eosinophil count) were calculated. In addition, we measured the utility of the EREFS in the follow-up of 35 EoE patients. KEY RESULTS: Individual endoscopic signs did not correspond to the peak eosinophil count or other histopathologic signs. Although the composite fibrotic signs score, inflammatory signs score, and total EREFS correlated weakly to moderately with the peak eosinophil count, none of these scores had both high positive and negative predictive values for histopathologic disease activity. In the follow-up of 35 patients, lower peak eosinophil counts were not associated with a decrease in endoscopic abnormalities. CONCLUSIONS & INFERENCES: In adult patients with EoE, the EREFS system correlates with peak eosinophil counts, but their predictive value for disease activity is insufficient for clinical use. Therefore, biopsies remain indispensable for the assessment of disease activity.

Esophageal acid sensitivity and mucosal integrity in patients with functional heartburn.

BACKGROUND: Patients with functional heartburn (FH) experience troublesome heartburn that is not related to gastroesophageal reflux. The etiology of the heartburn sensation in FH patients is unknown. In patients with reflux disease, esophageal hypersensitivity seems associated with impaired mucosal integrity. We aimed to determine esophageal sensitivity and mucosal integrity in FH and non-erosive reflux disease (NERD) patients. METHODS: In this prospective experimental study, we performed an acid perfusion test and upper endoscopy with biopsies in 12 patients with NERD and nine patients with FH. Mucosal integrity was measured during endoscopy using electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance and transepithelial permeability. KEY RESULTS: Lag time to heartburn perception was significantly longer in FH patients (median 12 min) than in NERD patients (median 3 min). Once perceived, intensity of heartburn was scored equal with median visual analog scale 6.5 and 7.1 respectively. Esophageal mucosal integrity was also comparable between FH and NERD patients, both in vivo extracellular impedance and ex vivo transepithelial resistance and permeability were similar. CONCLUSIONS & INFERENCES: Patients with FH did not show acid hypersensitivity as seen in patients with NERD. However, once perceived, intensity of heartburn is similar. Esophageal mucosal integrity is similar between NERD and FH patients, and is therefore unlikely to be the underlying cause of the observed difference in esophageal acid perception.

Diagnostic yield of 24-hour esophageal manometry in non-cardiac chest pain.

BACKGROUND: In the past, ambulatory 24-h manometry has been shown useful for the evaluation of patients with non-cardiac chest pain (NCCP). With the diagnostic improvements brought by pH-impedance monitoring and high-resolution manometry (HRM), the contribution of ambulatory 24-h manometry to the diagnosis of esophageal hypertensive disorders has become uncertain. Our aim was to assess the additional diagnostic yield of ambulatory manometry to HRM and ambulatory pH-impedance monitoring in this patient population. METHODS: All patients underwent 24-h ambulatory pressure-pH-impedance monitoring and HRM. Patients had retrosternal pain as a predominant symptom and no explanation after cardiologic and digestive endoscopic evaluations. Diagnostic measurements were analyzed by two independent physicians. KEY RESULTS: Fifty-nine patients met the inclusion criteria; 37.3% of the patients had their symptoms explained by abnormalities on pH-impedance monitoring and 6.8% by ambulatory manometry. Functional chest pain was diagnosed in 52.5% of the patients. High-resolution manometry, using the Chicago Classification v3.0 criteria alone, did not identify any of the four patients with esophageal spasm on ambulatory manometry. However, taking into account other abnormalities, such as simultaneous (rapid) or repetitive contractions, HRM had a sensitivity of 75% and a specificity of 98.2% for the diagnosis of esophageal spasm. CONCLUSIONS & INFERENCES: In the work-up of NCCP, ambulatory 24-h manometry has a low additional diagnostic yield. However, it remains the best technique to identify esophageal spasm as the cause of symptoms. This is particularly useful when an unequivocal diagnosis is needed before treatment.

Distal esophageal spasm and the Chicago classification: is timing everything?

BACKGROUND: According to the Chicago classification of esophageal motility disorders, distal esophageal spasm (DES) is defined as premature esophageal contractions (distal latency [DL] <4.5 s) for ≥20% of swallows, in the presence of a normal mean integral relaxation pressure (IRP). However, some patients with symptoms of DES have rapid contractions with a normal DL. The aim of this study was to characterize these patients and compare their clinical characteristics to those of patients classified as DES. METHODS: We retrospectively compared clinical characteristics and high-resolution manometry findings of patients with rapid contractions with normal latency to those meeting the Chicago classification criteria for DES. KEY RESULTS: Over a 3-year period, nine patients were diagnosed with DES and 14 showed rapid contractions in the distal esophagus with normal latency. The latter were younger than DES patients (60 ± 4 vs 72 ± 3 years, p < 0.05). Dysphagia and retrosternal pain occurred to a similar degree in both groups. Weight loss and abnormal barium esophagogram tended to be more frequent in DES patients. There was no difference in contractile front velocity (CFV) and in distal contractile integral (DCI) between patients with DES and rapid contractions with normal latency. Lower esophageal sphincter pressures were not different between groups. However, IRP was significantly higher in DES compared to rapid contractions with normal latency (11.7 ± 0.6 mmHg vs 7.6 ± 1.2 mmHg, p < 0.05), albeit still within the normal range. CONCLUSIONS & INFERENCES: These data suggest that patients with simultaneous contractions with normal latency represent a group of patients with many features similar to DES.

A pregnant patient with excessive belching.

We present a patient that developed severe belching during pregnancy. Esophageal pH-impedance monitoring revealed frequent supragastric belching, but not gastroesophageal reflux disease (GERD). Thus, severe belching during pregnancy can be due to a behavioral disorder in the absence of GERD. Belching complaints during pregnancy should therefore not always be treated as GERD.

Assessment of bolus transit with intraluminal impedance measurement in patients with esophageal motility disorders.

BACKGROUND: The clinical management of patients with non-obstructive dysphagia is notoriously difficult. Esophageal impedance measurement can be used to measure esophageal bolus transit without the use of radiation exposure to patients. However, validation of measurement of bolus transit with impedance monitoring has only been performed in healthy subjects with normal motility and not in patients with dysphagia and esophageal motility disorders. The aim was, therefore, to investigate the relationship between transit of swallowed liquid boluses in healthy controls and in patients with dysphagia. METHODS: Twenty healthy volunteers and 20 patients with dysphagia underwent concurrent impedance measurement and videofluoroscopy. Each subject swallowed five liquid barium boluses. The ability of detecting complete or incomplete bolus transit by means of impedance measurement was assessed, using radiographic bolus transit as the gold standard. KEY RESULTS: Impedance monitoring recognized stasis and transit in 80.5% of the events correctly, with 83.9% of bolus transit being recognized and 77.2% of stasis being recognized correctly. In controls 79.8% of all swallows were scored correctly, whereas in patients 81.3% of all swallows were scored correctly. Depending on the contractility pattern, between 77.0% and 94.3% of the swallows were scored correctly. CONCLUSIONS & INFERENCES: Impedance measurement can be used to assess bolus clearance patterns in healthy subjects, but can also be used to reliably assess bolus transit in patients with dysphagia and motility disorders.