Obesity and GERD impair esophageal epithelial permeability through 2 distinct mechanisms.

BACKGROUND: The mechanism by which obesity leads to damage independent of reflux is unclear. We aimed to determine the influence of obesity on mean nocturnal baseline impedance (MNBI), a functional measure of the epithelial barrier, in the presence and absence of acid reflux, using ambulatory pH impedance measurements. METHODS: Twenty-four-hour pH impedance studies performed off medications in Caucasian men with a normal endoscopic examination were assessed for level of acid exposure and MNBI. Four patient groups were studied: Group 1, Not obese and normal acid exposure; Group 2, Obese and normal acid exposure; Group 3, Not obese and increased acid exposure; and Group 4, Obese with increased acid exposure. RESULTS: One hundred patients were studied (25 in each group). Mean esophageal mucosal impedance (MI) was substantially lower in obese patients without reflux (Group 2) and non-obese patients with reflux (Group 3) compared to normal controls (non-obese, no reflux, Group 1). MI was progressively lower in the distal (vs the proximal) esophagus in GER patients, compared to those without GER. This difference persisted in the presence or absence of obesity. In contrast, in obese patients, the mean MI was significantly lower throughout the esophagus when compared to the non-obese patients and also persisted in the presence and absence of accompanying reflux. Obesity and reflux were both independently negatively correlated with MI. CONCLUSION: Obesity is associated with abnormal esophageal MNBI. In contrast to gastro-esophageal reflux, this decrease is pan-esophageal. These data may support a systemic mechanism by which obesity alters the esophageal barrier function.

The clinical significance of esophagogastric junction outflow obstruction and hypercontractile esophagus in high resolution esophageal manometry.

BACKGROUND: Although major manometric abnormalities, the significance of esophagogastric junction outflow obstruction (EGJOO) and hypercontractile esophagus (HE) is poorly understood. We sought to determine long term outcomes for EGJOO and HE. METHODS: High-resolution impedance manometry (HRIM) studies conducted from 5/30/2012 to 8/1/2014 consistent with EGJOO and HE and normal studies from 5/30/12 to 11/1/12 were identified. Standardized follow up was conducted with a phone survey utilizing the impact dysphagia questionnaire (IDQ-10). KEY RESULTS: 56 EGJOO, 40 HE patients and 33 controls were identified. Structural evaluation with EGD and esophagram did not differ among groups. Use of opiates in EGJOO (P<.05) and of anticholinergics in EGJOO and HE patients was more prevalent than in controls (P<.005). Dysphagia was more common in EGJOO (P<.05) and chest pain more common in HE (P<.005) at presentation. While HE patients were more likely to be symptomatic (P<.05), the majority of EGJOO and HE patients overall were asymptomatic at a mean 2.8 years follow up without medical or procedural intervention in the majority (72.5%). Symptom persistence at follow up was predicted by maximum distal contractile integral (DCI) and IRP in both EGJOO and HE (P<.05). CONCLUSIONS & INFERENCES: The majority of patients with EGJOO and HE appear to have a benign clinical course similar to controls in the absence of specific treatment. However, the combination of abnormal IRP and DCI in both HE and EGJOO appears to discriminate an important subset of patients who may benefit from treatment. Further refinement of manometric criteria may therefore provide more useful clinical definitions of EGJOO and HE.

Presence of intraepithelial food antigen in patients with active eosinophilic oesophagitis.

BACKGROUND: Although eosinophilic oesophagitis (EoE) is putatively mediated by an abnormal response to food antigen, the oesophagus is considered relatively impermeable to large molecules. AIM: To assess whether food antigens penetrate the oesophageal mucosa in patients with EoE. METHODS: Anti-gliadin staining was performed in three groups: active EoE, inactive EoE and EoE patients on a low or gluten free diet. To appraise the specificity of our results, we also performed gliadin staining on six patients without oesophageal disease who were consuming gluten. The groups with EoE on gluten also underwent endoscopic infusion with gluten containing soy sauce and repeat biopsies during the endoscopy. We measured eosinophil density, dilated intercellular spaces (on a 0-4+ scale) and gliadin in oesophageal mucosa by immunofluorescence. RESULTS: Patients with active EoE had significantly greater epithelial density of anti-gliadin staining when compared to inactive EoE (P < 0.0065) and gluten-free patients (P < 0.0008) at baseline and after soy infusion. Gliadin was not detected in non-EoE control patients. The distribution of gliadin was both cytoplasmic and nuclear. There was good correlation of dilated intercellular spaces grade and total gliadin staining intensity (r = 0.577, P = 0.0077). Acute oesophageal perfusion of a commercial gliadin-rich soy sauce did not lead to an increase in gliadin staining in active or inactive EoE. CONCLUSION: These findings suggest, although do not prove, that antigen penetration in active eosinophilic oesophagitis might be facilitated by impairment of epithelial integrity.

Baseline impedance measured during high-resolution esophageal impedance manometry reliably discriminates GERD patients.

BACKGROUND: Baseline impedance measured with ambulatory impedance pH monitoring (MII-pH) and a mucosal impedance catheter detects gastroesophageal reflux disease (GERD). However, these tools are limited by cost or patient tolerance. We investigated whether baseline impedance measured during high-resolution impedance manometry (HRIM) distinguishes GERD patients from controls. METHODS: Consecutive patients with clinical HRIM and MII-pH testing were identified. Gastroesophageal reflux disease was defined by esophageal pH <4 for ≥5% of both the supine and total study time, whereas controls had an esophageal pH <4 for ≤3% of the study performed off PPI. Baseline impedance was measured over 15 seconds during the landmark period of HRIM and over three 10 minute intervals during the overnight period of MII-pH. KEY RESULTS: Among 29 GERD patients and 26 controls, GERD patients had a mean esophageal acid exposure time of 22.7% compared to 1.2% in controls (P<.0001). Mean baseline impedance during HRIM was lower in GERD (1061 Ω) than controls (2814 Ω) (P<.0001). Baseline mucosal impedance measured during HRIM and MII-pH correlated (r=0.59, P<.0001). High-resolution esophageal manometry baseline impedance had high diagnostic accuracy for GERD, with an area under the curve (AUC) of 0.931 on receiver operating characteristics (ROC) analysis. A HRIM baseline impedance threshold of 1582 Ω had a sensitivity of 86.2% and specificity of 88.5% for GERD, with a positive predictive value of 89.3% and negative predictive value of 85.2%. CONCLUSIONS & INFERENCES: Baseline impedance measured during HRIM can reliably discriminate GERD patients with at least moderate esophageal acid exposure from controls. This diagnostic tool may represent an accurate, cost-effective, and less invasive test for GERD.

The course of achalasia one to four decades after initial treatment.

BACKGROUND: Most follow-up studies of achalasia are limited to <5 years. AIM: To study the long-term efficacy of pneumatic dilation (PD) and myotomy in achalasia at least 10 years after treatment. METHODS: We performed a retrospective cohort study of achalasia patients with >10 years follow-up after initial myotomy or pneumatic dilation. Symptom recurrence which required repeat dilation or surgery was compared between pneumatic dilation and myotomy. RESULTS: One hundred and fifty patients (112 myotomy, 38 pneumatic dilation) of similar characteristics were studied. The mean duration of follow-up after initial treatment was 17.5 ± 7.2 years (10-40 years). Symptoms recurrence rate was 60.7% (100% pneumatic dilation patients vs. 47.3% myotomy), hazard ratio 0.24 demonstrating a lower need for repeat dilation or surgery with myotomy than pneumatic dilation (P = 0.008). All pneumatic dilation patients underwent myotomy in 4 ± 4 (0-16 years). Forty of 53 myotomy patients had symptom recurrence prompting further treatment: 16 pneumatic dilation, 11 myotomy and 13 both. The mean time to repeat procedure was 6.9 years (0-40). The myotomy group required fewer dilations and/or surgeries than the pneumatic dilation group (1.6 vs. 3.6, P < 0.001). 13 patients (10.1%) progressed to end-stage achalasia (five myotomy, eight pneumatic dilation) over 40 years. At last follow-up, 57/62 (92%) patients had absent or mild dysphagia, 53/62 (85%) patients had regurgitation less than once per week and 37 (60.7%) had heartburn episodes <1/week similar for pneumatic dilation and myotomy (P = 0.27). CONCLUSION: Although the majority of patients treated for achalasia do well after decades of treatment, most patients may need a series of endoscopic and/or surgical procedures to maintain effective symptom control.

Achalasia and chronic opiate use: innocent bystanders or associated conditions?

High-resolution manometry identifies three subtypes of achalasia. However, type 3 differs from classic achalasia. Although opiates affect esophageal motility, opiate use and achalasia have not been studied. Patients with a new diagnosis of achalasia at Mayo Clinic Rochester between June 1, 2012 and January 3, 2014 were identified. Clinical records were reviewed to assess symptoms, opiate use, and therapy. Fifty-six patients with achalasia were identified, 14 (25%) were on opiates. Opiate prescription was unrelated to achalasia in all cases, with chronic back and joint pain constituting the majority. Of patients on opiates, five (36%) had type 3 achalasia compared with four (10%) not on opiates (P = 0.02). No patients on opiates had type 1 achalasia. Clinical presentation did not differ with opiates, although those on opiates were more likely to report chest pain (39 vs. 14%, P = 0.05) and less likely to have esophageal dilation (62 vs. 82%, P = 0.13), none with greater than 5-cm diameter. Contractile vigor was greater with opiate use, with distal contractile integral of 7149 versus 2615.5 mmHg/cm/second (P = 0.08). Treatment response was inferior on opiates, with persistent symptoms in 22% compared with 3% without opiates (P = 0.06). Opiate use is common in type 3 achalasia, with the majority of patients on opiates. No patients on opiates were diagnosed with type 1 achalasia. Manometric findings of type 3 achalasia mimic those induced by opiates, suggesting a physiologic mechanism for opiate induced type 3 achalasia. Treatment outcome is inferior with opiates, with opiate cessation perhaps preferable. Further studies assessing opiate use and achalasia are needed.

Esophageal cancer screening in achalasia: is there a consensus?

Achalasia is an important but relatively uncommon disorder. While highly effective therapeutic options exist, esophageal cancer remains a long-term potential complication. The risk of esophageal cancer in achalasia remains unclear, with current guidelines recommending against routine endoscopic screening. However, given limited data and conflicting opinion, it is unknown whether consensus regarding screening practices in achalasia among experts exists. A 10-question survey to assess screening practices in achalasia was created and distributed to 28 experts in the area of achalasia. Experts were identified based on publications and meeting presentations in the field. Survey responses were received from 17 of 28 (61%) experts. Wide geographic distribution was seen among respondents, with eight (47%) from Europe or Australia, seven (41%) from the United States, and two (12%) from Asia. Screening for esophageal cancer was inconsistent, with nine (53%) experts endorsing the practice and eight (47%) not. Screening practices did not differ among geographic regions. No consensus regarding the risk for esophageal cancer in achalasia was seen, with three experts reporting no increased risk compared with the general population, eight experts a lifetime risk of 0.1-0.5%, three experts a 0.5-1% risk, two experts a 1-2% risk, and one expert a 3-5% risk. However, these differences in perception of risk did not influence screening practices. Upper endoscopy was utilized among all experts who endorsed screening. However, practices still varied with screening commencing at or within 1 year of diagnosis in two practices compared with 5 and 10 years in three respective practices each. Surveillance intervals also varied, performed every 2 years in four practices, every 3 years in four practices, and every 5 years in one practice. Practice variation in the management of achalasia itself was also seen, with initial treatment with Heller myotomy endorsed by eight experts, pneumatic dilation by five experts, and two each endorsing peroral endoscopic myotomy or no specific preference. In addition, while 82% (14/17) of experts endorsed long-term follow up of patients, no consensus regarding long-term follow up existed, with annual follow up in eight practices, every 3-6 months in three practices, and every 2 years in three practices. Large practice variation in the long-term management of achalasia exists among experts in the field. Only a slight majority of experts endorse screening for esophageal cancer in achalasia, and no consensus exists regarding how surveillance should be structured even among this group. Interestingly, the lack of consensus on cancer screening parallels a lack of agreement on initial treatment of achalasia. These findings suggest a need for greater homogeneity in the management of longstanding achalasia and cancer screening. Further, this study highlights the need for more data on this topic to foster greater agreement.

The effects of a weakly acidic meal on gastric buffering and postprandial gastro-oesophageal reflux.

BACKGROUND: Exclusion of the meal during ambulatory pH monitoring presumes that a meal completely buffers gastric acid and reflux of acidic food content cannot be distinguished from gastric acid. However, the ability of a meal to completely buffer gastric acid remains unclear. AIM: To determine the effect of a weakly acid meal on gastric buffering and oesophageal acid exposure. METHODS: Patients undergoing multichannel intraluminal impedance pH studies were given a standard weakly acidic meal (pH = 5.9). Gastric and oesophageal pH was measured during the meal and in 15 min intervals for 2 h postprandially. RESULTS: The study included 30 patients, with pathological acid reflux detected in 18 patients. Complete gastric buffering occurred in seven patients (23%) and was lost in all patients within 75 min of the meal. Oesophageal acid was detected in 33% of patients within 30 min of the meal and 81% of patients during the 2 h postprandial period. Postprandial oesophageal acid exposure was greater in patients with pathological acid reflux (9 ± 2.7% vs. 1.7 ± 0.8% P = 0.05) with a trend towards more incomplete gastric acid buffering and significant differences when measuring weak acid reflux (pH 4-5). Acid reflux rarely occurred in the absence of gastric acid, with gastric acid present in 74 of 79 (94%) fifteen minute postprandial intervals with acid reflux. CONCLUSIONS: The ability of a meal to buffer gastric acid is poor. Early postprandial oesophageal acid reflux occurs in a substantial proportion of patients. Addition of a weakly acidic or pH neutral meal to ambulatory pH monitoring may unmask early postprandial acid reflux and provide data on gastric acid buffering.