Rapid Drink Challenge During High-resolution Manometry for Evaluation of Esophageal Emptying in Treated Achalasia.

BACKGROUND & AIMS: Incomplete esophageal emptying is a key variable predicting symptom relapse after achalasia treatment. Although optimally evaluated using the timed barium esophagogram (TBE), incomplete esophageal emptying can also be identified on rapid drink challenge (RDC) performed during high-resolution manometry. METHODS: We evaluated if RDC differentiates complete from incomplete esophageal emptying in treated patients with achalasia, against a TBE gold standard. Unselected treated patients with achalasia with both TBE (200 mL of low-density barium suspension) and RDC (200 mL of water in sitting position) were enrolled in 5 tertiary referral centers. TBE barium column height at 1, 2, and 5 minutes were compared with RDC variables: pressurizations >20 mmHg, maximal RDC pressurization, proportion of RDC time occupied by pressurizations, trans-esophagogastric junction gradient, and integrated relaxation pressure. RESULTS: Of 175 patients recruited (mean age, 59 years; 47% female), 138 (79%) were in clinical remission. Complete TBE emptying occurred in 45.1% at 1 minute, 64.0% at 2 minutes, and 73.1% at 5 minutes. RDC integrated relaxation pressure correlated strongly with TBE column height, and a 10-mmHg threshold discriminated complete from incomplete emptying at all 3 TBE time points with area under receiver operating characteristic curves of 0.85, 0.87, and 0.85, respectively. This threshold had high negative predictive values for complete emptying (88% at 2 minutes, 94% at 5 minutes), and modest positive predictive values for incomplete emptying (77% at 2 minutes, 62% at 5 minutes). CONCLUSIONS: RDC during high-resolution manometry is an effective surrogate for TBE in assessing esophageal emptying in treated patients with achalasia.

The role of endoscopy in eosinophilic esophagitis: from diagnosis to therapy.

Endoscopy plays an important role in the management of eosinophilic esophagitis (EoE), since it is involved in the diagnosis, follow-up and treatment of this condition. In patients presenting with food impaction, dysphagia and other symptoms of suspected EoE, esophago-gastric-duodenoscopy (EGD) with multiple esophageal biopsies should be performed to confirm or rule out the diagnosis of EoE. The EREFS system, a validated instrument for assessment of the endoscopically-identified esophageal features in EoE (edema, rings, exudates, longitudinal furrows and strictures), is currently used in the clinical practice for the evaluation of the macroscopic aspects of esophageal mucosa during EGD. Multiple esophageal biopsies are mandatory to further confirm EoE diagnosis and subsequent response to treatment, since symptoms reported by patients do not always correlate with histological activity, and considering the low sensitivity of endoscopic assessment; a cut-off of ≥15 eosinophils in at least one high power field is the density threshold considered the standard for diagnosis (sensitivity 100%, specificity 96%). Other histological features, included in the EoE histologic scoring system (EoEHSS), are supportive for the diagnosis and for the assessment of inflammatory activity during follow-up. Esophageal dilation, performed either with Savary dilators/bougie or hydrostatic balloon, is an effective and safe treatment in both adult and pediatric EoE patients with fibrostenotic features, mainly in association with other therapeutic strategies which can control eosinophilic inflammation.

Reflux characteristics triggering post-reflux swallow-induced peristaltic wave (PSPW) in patients with GERD symptoms.

BACKGROUND: Esophageal chemical clearance has been evaluated with the post-reflux swallow-induced peristaltic wave (PSPW) index. The factors triggering PSPW in Gastro-esophageal reflux disease (GERD) have not yet been investigated. This multicenter study was aimed at evaluating the characteristics of reflux episodes associated with PSPW occurrence in patients with typical GERD symptoms. METHODS: Impedance-pH tracings from patients with typical reflux symptoms were analyzed. Sixteen healthy subjects were included for comparison. Multivariate analysis was performed to determine predictors of PSPW events. KEY RESULTS: Impedance-pH tracings from 60 patients and 16 healthy subjects were evaluated. A total of 3454 refluxes were recorded. In patients, comparing reflux episodes followed with those not followed by a PSPW, significantly higher proportions of acid (79% vs. 74%, p: 0.02), mixed (47% vs. 32%, p: 0.0001) and proximal refluxes (34% vs. 20%, p: 0.0001) were observed. A multivariate analysis, acid (OR: 1.3, 95% CI: 1.05-1.6), mixed (OR: 2, 95% CI: 1.6-2.3), and proximal (OR: 2.1, 95% CI: 1.7-2.5) refluxes were independently associated with PSPWs. Reflux episodes followed by a PSPW were characterized by a significantly higher bolus clearing time [(mean ± SD) 41 s ± 6 s vs. 30 s ± 5 s, p < 0.05] whereas nadir pH value of reflux events preceding PSPWs was tangentially but not significantly lower [(mean ± SD) 2.61 ± 1.22 vs. 2.74 ± 1.26, p: 0.057]. CONCLUSIONS AND INFERENCES: Acid, mixed and proximal refluxes, and their duration are key factors in eliciting PSPWs. PSPW represents a response to reflux directly related to the potential harmfulness of reflux contents.

Diagnostic delay and misdiagnosis in eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis (EoE) may lead to severe complications if not promptly recognised. AIMS: To assess the diagnostic delay in patients with EoE and to explore its risk factors. METHODS: EoE patients followed-up at eight clinics were included via retrospective chart review. Diagnostic delay was estimated as the time lapse occurring between the appearance of the first likely symptoms indicative of EoE and the final diagnosis. Patient-dependent and physician-dependent diagnostic delays were assessed. Multivariable regression models were computed. RESULTS: 261 patients with EoE (mean age 34±14 years; M:F ratio=3:1) were included. The median overall diagnostic delay was 36 months (IQR 12-88), while patient- and physician-dependent diagnostic delays were 18 months (IQR 5-49) and 6 months (IQR 1-24). Patient-dependent delay was greater compared to physician-dependent delay (95% CI 5.1-19.3, p<0.001). A previous misdiagnosis was formulated in 109 cases (41.8%; gastro-oesophageal reflux disease in 67 patients, 25.7%). The variables significantly associated with greater overall diagnostic delay were being a non-smoker, >1 episode of food impaction, previous endoscopy with no biopsies, regurgitation, and ≥2 assessing physicians. Being single was significantly associated with lower overall and patient-dependent diagnostic delay. CONCLUSION: EoE is burdened by substantial diagnostic delay, depending on both patient-related and physician-related factors.

Response of eosinophilic oesophagitis to proton pump inhibitors is associated with impedance-pH parameters implying anti-reflux mechanism of action.

BACKGROUND: Proton pump inhibitors (PPIs) are effective therapies for eosinophilic oesophagitis (EoE), but the mechanism of action is uncertain. At on-PPI impedance-pH monitoring, improvement in oesophageal chemical clearance assessed with post-reflux swallow-induced peristaltic wave (PSPW) index characterises PPI-responsive EoE and reflux disease. Off-PPI, higher efficacy of the oesophago-salivary reflex as measured with PSPW-associated pH increments characterises PPI-responsive reflux disease and could typify PPI-responsive EoE as well. AIM: To establish whether PPI responsiveness in EoE is associated with higher efficacy of the oesophago-salivary reflex. METHODS: Prospective multicentre study in EoE patients investigated with impedance-pH monitoring before starting PPI. Impedance-pH parameters in PPI-responsive and PPI-refractory cases were compared. PPI response was defined histologically. RESULTS: Considerable PSPW-associated pH increments (median 1.4 units) were found in 80 EoE patients, with significantly higher values in 48 PPI-responsive than in 32 PPI-refractory cases (1.8 vs 1.0, P = 0.02). Mucosal integrity, as measured with mean nocturnal baseline impedance was more severely impaired in the distal oesophagus in PPI-responsive cases, the gradient between mid and distal oesophagus being significantly higher (546 vs 137 Ω, P = 0.0002). PSPW-associated pH increments and the baseline impedance gradient between mid and distal oesophagus were independently associated with histological response at multivariable logistic regression; at receiver operating characteristic analysis, the area under the curve of PPI response calculated by combined assessment was 0.88. CONCLUSION: Higher efficacy of oesophago-salivary reflex and more severe mucosal damage in the distal oesophagus are associated with EoE response to PPIs, implying an anti-reflux mechanism of action as most likely.

Esophageal pH increments associated with post-reflux swallow-induced peristaltic waves show the occurrence and relevance of esophago-salivary reflex in clinical setting.

BACKGROUND: Following acid perfusion, esophageal pH is restored by swallowed bicarbonate-containing saliva secreted in response to a vagal esophago-salivary reflex. At impedance-pH monitoring, the post-reflux swallow-induced peristaltic wave (PSPW) index puts into relationship timely post-reflux swallows with the number of reflux events: Low values typify reflux-related heartburn (RRH) and lack of on-therapy improvement characterizes proton pump inhibitor (PPI) failure. Considerable esophageal pH increments associated with PSPWs could demonstrate the occurrence of esophago-salivary reflex in clinical setting, while its relevance could be shown by lower esophageal pH increments in PPI-refractory RRH. METHODS: Prospective multicenter study in patients with PPI-refractory or PPI-responsive RRH evaluated with off-PPI impedance-pH monitoring. Increments in pH associated with PSPWs were measured and the mean calculated to obtain the PSPW-associated ∆pH. KEY RESULTS: The mean PSPW-associated ∆pH in 294 RRH patients was 1.2 ± 0.7 and was lower in 137 PPI-refractory (1.0 ± 0.6) than in 157 PPI-responsive (1.5 ± 0.6) cases (p < 0.0001). Lower PSPW-associated ∆pH was independently related to PPI failure at multivariable logistic regression analysis (OR 0.16, 95% CI 0.09-0.26). At ROC analysis, comparing PPI-refractory to PPI-responsive cases the AUC for PSPW-associated ∆pH was 0.76 (95% CI 0.71-0.82), the best cutoff value being 1.2. CONCLUSIONS AND INFERENCES: Considerable PSPW-associated pH increments demonstrate the occurrence of esophago-salivary reflex in clinical setting. Lower increments in PPI-refractory RRH cases show the clinical relevance of esophago-salivary reflex, confirming that PSPW represents a defense mechanism against reflux. PSPW-associated ∆pH can efficiently predict PPI response in patients undergoing off-therapy impedance-pH monitoring.