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Diseases of the esophageal tract represent a heterogeneous class of pathological conditions for which diagnostic paradigms continue to emerge. In the last few decades, innovative diagnostic devices have been developed, and several attempts have been made to advance and standardize diagnostic algorithms to be compliant with medical procedures. To the best of our knowledge, a comprehensive review of the procedures and available technologies to investigate the esophageal tract was missing in the literature. Therefore, the proposed review aims to provide a comprehensive analysis of available endoluminal technologies and procedures to investigate esophagus health conditions. The proposed systematic review was performed using PubMed, Scopus, and Web of Science databases. Studies have been divided into categories based on the type of evaluation and measurement that the investigated technology provides. In detail, three main categories have been identified, i.e., endoluminal technologies for the (i) morphological, (ii) bio-mechanical, and (iii) electro-chemical evaluation of the esophagus.

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., (© 2021 John Wiley & Sons Ltd.)

Background: Postreflux swallow-induced peristaltic wave (PSPW) on pH-impedance monitoring and contraction vigor on high-resolution manometry (HRM) both assess esophageal peristaltic response. We aimed to evaluate relationships between PSPW and esophageal peristalsis on HRM in the context of reflux disease in this multicenter cohort study., Methods: pH-impedance and HRM studies performed on patients with persisting reflux symptoms were reviewed from 6 centers (5 in Europe and 1 in US). Total, upright and supine acid exposure time (AET) were evaluated from pH-impedance studies; PSPW index (PSPWI) and mean nocturnal baseline impedance (MNBI) were calculated using standard methodology. Esophageal body contraction vigor was analyzed using distal contractile integral (DCI), and DCI ratio > 1 between single swallows and multiple rapid swallows (MRS) defined presence of contraction reserve. Student's t test, ANOVA, and linear regression were utilized to investigate relationships between PSPW, contraction vigor, and contraction reserve., Key Results: Of 296 patients (52.8 ± 0.8 yr, 63% F), median PSPWI was 0.475. Only 24.0% had intact DCI; the remainder had varying degrees of hypomotility. As hypomotility increased, PSPWI and MNBI decreased significantly, while total AET and reflux episodes had an inverse response (P ≤ .002 for each). MRS data were available in 167 (56.4%), 72.5% had contraction reserve. MRS cohorts with normal PSPWI had significantly lower reflux burden compared to low PSPWI, regardless of presence or absence of contraction reserve (P ≤ .001)., Conclusions and Inferences: PSPWI correlates with esophageal hypomotility and reflux burden, and complements clinical reflux evaluation. Intact PSPW is more relevant to esophageal reflux clearance than contraction reserve., (© 2020 John Wiley & Sons Ltd.)

Objectives: To investigate the psychometric properties of the reflux symptom index (RSI) as short screening approach for the diagnostic of laryngopharyngeal reflux (LPR) in patients with confirmed diagnosed regarding the 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH)., Methods: From January 2017 to December 2018, 56 patients with LPR symptoms and 71 healthy individuals (control group) were prospectively enrolled. The LPR diagnosis was confirmed through MII-pH results. All subjects (n = 127) fulfilled RSI and the Reflux Finding Score (RFS) was performed through flexible fiberoptic endoscopy. The sensitivity and the specificity of RSI was assessed by ROC (Receiver Operating Characteristic) analysis., Results: A total of 15 LPR patients (26.8%) of the clinical group met MII-pH diagnostic criteria. Among subjects classified as positive for MII- pH diagnoses, RSI and RFS mean scores were respectively 20 (SD ± 10.5) and 7.1 (SD ± 2.5), values not significantly different compared to the negative MII-pH group. The metric analysis of the items led to the realization of a binary recoding of the score. Both versions had similar psychometric properties, α was 0.840 for RSI original version and 0.836 for RSI binary version. High and comparable area under curve (AUC) values indicate a good ability of both scales to discriminate between individuals with and without LPR pathology diagnosis. Based on balanced sensitivity and specificity, the optimal cut-off scores for LPR pathology were ≥ 5 for RSI binary version and ≥ 15 for RSI original version. Both version overestimated LPR prevalence. The original version had more sensitivity and the RSI Binary version had more specificity., Conclusions: It would be necessary to think about modifying the original RSI in order to improve its sensitivity and specificity (RSI binary version, adding or changing some items), or to introduce new scores in order to better frame the probably affected of LPR patient.

Patients with esophageal symptoms potentially associated with gastroesophageal reflux disease such as heartburn, regurgitation, chest pain, or cough represent one of the most frequent reasons for referral to gastroenterological evaluation. The utility of esophageal reflux monitoring in clinical practice is: (1) to accurately define reflux burden, (2) to segregate patients according to reflux monitoring results as true GERD, reflux hypersensitivity and functional heartburn, and (3) to establish a treatment plan. With this in mind, in the last decade, investigations and technical advances, with the introduction of impedance-pH monitoring and wireless pH capsule, have enhanced our understanding and management of GERD. The following recommendations were discussed and approved after a comprehensive review of the medical literature pertaining to reflux testing techniques and their recent application. This review created under the auspices of the Società Italiana di Gastroenterologia ed Endoscopia Digestiva (SIGE), Società Italiana di Neuro-Gastro-Enterologia e Motilità (SINGEM) and Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) is intended to help clinicians in applying reflux studies in the most fruitful manner within the context of their patients with esophageal symptoms., Competing Interests: Conflict of interest Edoardo Savarino received lecture fee from Medtronic., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: The utilization of high-resolution manometry (HRM) has enhanced our understanding and assessment of esophageal motor disorders. Moreover, the combination of impedance technology with HRM (HRIM) has further improved our knowledge of esophageal physiology and the clinical evaluation of dysmotility, thanks to the addition of accurate measurement of bolus transit. Areas covered. This paper provides an overview of current knowledge in the use of HRIM for the study of esophageal functional disorders by reporting mainly the results of many publications and several systematic reviews in this field. Expert opinion. HRIM has represented a relevant improvement in the assessment of esophageal motility and has required the development of new metrics, such as the esophageal impedance integral ratio, the bolus flow time, the nadir impedance pressure and the impedance bolus height, which increase the evaluation of esophageal bolus transit. An extension of impedance is represented by functional lumen imaging probe (FLIP), which determines the biophysical properties and the distensibility of the esophagus and permits to detect contractility patterns not seen on HRM alone. We eagerly wait for a new and fruitful iteration of the Chicago Classification, now in version 3.0, which can cover the ongoing clinical experience of HRIM.

Jackhammer esophagus (JE) is a hypercontractile disorder, the pathogenesis of which is incompletely understood. Multiple rapid swallows (MRS) and rapid drink challenge (RDC) are complementary tests used during high-resolution manometry (HRM) that evaluate inhibitory and excitatory neuromuscular function and latent obstruction, respectively. Our aim was to evaluate esophageal pathophysiology using MRS and RDC in 83 JE patients (28 men; median age: 63 yr; IQR: 54-70 yr). Twenty-one healthy subjects (11 men; median age: 28 yr; range: 26-30 yr) were used as a control group. All patients underwent solid-state HRM with ten 5-ml single swallows (SS) and one to three 10-ml MRS; 34 patients also underwent RDC. Data are shown as median (interquartile range). Abnormal motor inhibition was noted during at least one MRS test in 48% of JE patients compared with 29% of controls ( P = 0.29). Mean distal contractile integral (DCI) after MRS was significantly lower than after SS [6,028 (3,678-9,267) mmHg·cm·s vs. 7,514 (6,238-9,197) mmHg·cm·s, P = 0.02], as was highest DCI ( P < 0.0001). Consequently, 66% of JE patients had no contraction reserve. At least one variable of obstruction during RDC (performed in 34 patients) was outside the normal range in 25 (74%) of JE patients. Both highest DCI after SS and pressure gradient across the esophagogastric junction (EGJ) during RDC were higher in patients with dysphagia versus those without ( P = 0.04 and 0.01, respectively). Our data suggest altered neural control in JE patients with heterogeneity in inhibitory function. Furthermore, some patients had latent EGJ obstruction during RDC, which correlated with the presence of dysphagia. NEW & NOTEWORTHY Presence of abnormal inhibition was observed during multiple rapid swallows (MRS) in some but not all patients with jackhammer esophagus (JE). Unlike healthy subjects, JE patients were more strongly stimulated after single swallows than after MRS. An obstructive pattern was frequently observed during rapid drink challenge (RDC) and was related to presence of dysphagia. MRS and RDC during high-resolution manometry are useful to show individual pathophysiological patterns in JE and may guide optimal therapeutic strategies.

Background: Hypersensitive esophagus (HE) is defined by endoscopy-negative heartburn with a normal acid exposure time but positive symptom association probability (SAP) and/or symptom index (SI) on impedance-pH monitoring, and proton pump inhibitor (PPI) responsiveness. Functional heartburn (FH) is distinguished by negative SAP/SI and PPI refractoriness. The clinical value of SAP and SI has been questioned. We aimed to investigate whether impairment of chemical clearance and of mucosal integrity, expressed by the postreflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), characterize HE independently of SAP and SI., Methods: Impedance-pH tracings from PPI-responsive endoscopy-negative patients, 125 with nonerosive reflux disease and 108 with HE, distinguished by an abnormal and a normal acid exposure time, and from 70 patients with FH were retrospectively selected and blindly reviewed., Results: The mean PSPW index and MNBI were significantly lower in nonerosive reflux disease (30 %, 1378 Ω) than in HE (51 %; 2274 Ω) and in both of them as compared with FH (76 %; 3445 Ω) (P = 0.0001). Both the PSPW index (adjusted odds ratio 0.863, P = 0.001) and the MNBI (adjusted odds ratio 0.998, P = 0.001) were independent predictors of HE; with their combined assessment, the area under the curve on receiver operating characteristic analysis was 0.957. SAP and/or SI was positive in 67 of the 108 HE patients (62 %), whereas the PSPW index and/or MNBI was abnormal in 99 of the 108 HE patients (92 %; P < 0.0001)., Conclusions: HE is characterized by impairment of chemical clearance and mucosal integrity, which explains the increased reflux perception. When SAP and SI afford uncertain results, the PSPW index and MNBI should be analyzed.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized by symptoms related to esophageal dysfunction, as well as significant esophageal eosinophilia. The entity exists worldwide but has been most extensively studied in Western countries. However, a wide range of symptoms has been noticed such as chest pain or gastro-esophageal reflux disease-like symptoms. Upper gastro-intestinal endoscopy and esophageal biopsies are crucial for the diagnosis. Endoscopy might be normal or reveal typical patterns such as rings, furrows, exudates, edema, and stricture. Two to four biopsies should be performed both in the distal and in the proximal esophagus, and 15 eosinophils per high power field within the esophageal epithelium are the minimal threshold to diagnose eosinophilic esophagitis. Allergy testing is recommended, although its impact to orient treatment remains to be demonstrated. Eosinophilic esophagitis treatment includes medical treatment, diet and endoscopic dilation. Proton pump inhibitors are the first-line therapy as up to 50% of patients respond well to proton pump inhibitors irrespective of objective evidence of GERD. Topical viscous corticosteroids or elimination diet are the treatment of choice in case of unresponsiveness to proton pump inhibitors., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Patients with esophageal symptoms potentially associated to esophageal motor disorders such as dysphagia, chest pain, heartburn and regurgitation, represent one of the most frequent reasons for referral to gastroenterological evaluation. The utility of esophageal manometry in clinical practice is: (1) to accurately define esophageal motor function, (2) to identify abnormal motor function, and (3) to establish a treatment plan based on motor abnormalities. With this in mind, in the last decade, investigations and technical advances, with the introduction of high-resolution esophageal manometry, have enhanced our understanding and management of esophageal motility disorders. The following recommendations were developed to assist physicians in the appropriate use of esophageal manometry in modern patient care. They were discussed and approved after a comprehensive review of the medical literature pertaining to manometric techniques and their recent application. This position statement created under the auspices of the Gruppo Italiano di Studio per la Motilità dell'Apparato Digerente (GISMAD), Società Italiana di Gastroenterologia ed Endoscopia Digestiva (SIGE) and Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) is intended to help clinicians in applying manometric studies in the most fruitful manner within the context of their patients with esophageal symptoms., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Oesophageal clearance has been scarcely studied., Aims: Oesophageal clearance in endoscopy-negative heartburn was assessed to detect differences in bolus clearance time among patients sub-grouped according to impedance-pH findings., Methods: In 118 consecutive endoscopy-negative heartburn patients impedance-pH monitoring was performed off-therapy. Acid exposure time, number of refluxes, baseline impedance, post-reflux swallow-induced peristaltic wave index and both automated and manual bolus clearance time were calculated. Patients were sub-grouped into pH/impedance positive (abnormal acid exposure and/or number of refluxes) and pH/impedance negative (normal acid exposure and number of refluxes), the former further subdivided on the basis of abnormal/normal acid exposure time (pH+/-) and abnormal/normal number of refluxes (impedance+/-)., Results: Poor correlation (r=0.35) between automated and manual bolus clearance time was found. Manual bolus clearance time progressively decreased from pH+/impedance+ (42.6s), pH+/impedance- (27.1s), pH-/impedance+ (17.8s) to pH-/impedance- (10.8s). There was an inverse correlation between manual bolus clearance time and both baseline impedance and post-reflux swallow-induced peristaltic wave index, and a direct correlation between manual bolus clearance and acid exposure time. A manual bolus clearance time value of 14.8s had an accuracy of 93% to differentiate pH/impedance positive from pH/impedance negative patients., Conclusions: When manually measured, bolus clearance time reflects reflux severity, confirming the pathophysiological relevance of oesophageal clearance in reflux disease., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Recently, it has been suggested that low esophageal basal impedance may reflect impaired mucosal integrity and increased acid sensitivity. We aimed to compare baseline impedance levels in patients with heartburn and pathophysiological characteristics related to functional heartburn (FH) divided into two groups on the basis of symptom relief after proton pump inhibitors (PPIs)., Methods: Patients with heartburn and negative endoscopy were treated with esomeprazole or pantoprazole 40 mg daily for 8 weeks. According to MII-pH (off therapy) analysis, patients with normal acid exposure time (AET), normal reflux number, and lack of association between symptoms and refluxes were selected; of whom 30 patients with a symptom relief higher than 50% after PPIs composed Group A, and 30 patients, matched for sex and age, without symptom relief composed Group B. A group of 20 healthy volunteers (HVs) was enrolled. For each patient and HV, we evaluated the baseline impedance levels at channel 3, during the overnight rest, at three different times., Key Results: Group A (vs Group B) showed an increase in the following parameters: mean AET (1.4 ± 0.8% vs 0.5 ± 0.6%), mean reflux number (30.4 ± 8.7 vs 24 ± 6.9), proximal reflux number (11.1 ± 5.2 vs 8.2 ± 3.6), acid reflux number (17.9 ± 6.1 vs 10.7 ± 6.9). Baseline impedance levels were lower in Group A than in Group B and in HVs (p < 0.001)., Conclusions & Inferences: Evaluating baseline impedance levels in patients with heartburn and normal AET could achieve a better understanding of pathophysiology in reflux disease patients, and could improve the distinction between FH and hypersensitive esophagus., (© 2014 John Wiley & Sons Ltd.)

Objectives: To assess the correlation between delayed oro-cecal transit time (OCTT) and esophageal motility abnormalities in a cohort of systemic sclerosis (SSc) patients., Methods: We prospectively enrolled 50 consecutive SSc patients and 60 healthy volunteers (HVs) as controls. Both groups underwent glucose breath test (GBT) to exclude small intestine bacterial overgrowth, lactulose hydrogen, and octanoic acid breath tests (LHBT and OBT) to measure OCTT and gastric emptying (GE), respectively, and manometry to assess esophageal motility., Results: Thirty-one (63%) SSc patients presented ineffective esophageal motility (IEM) compared with 3 HVs (5%; P<0.01), 37 (74%) had an abnormal OCTT compared with 4 HVs (7%; P <0.01), and 16 (32%) had an altered GE compared with 4 HVs (7%; P <0.01). The median OCTT and gastric t½ were longer in SSc than in HVs (165 min vs. 101 min and 125 min vs. 78 min, respectively; P <0.01). A delayed GE was present in 12/37 (32%), whereas IEM in 27/37 (73%) SSc patients with prolonged OCTT. The prevalence of IEM increased in parallel with the prolongation of OCTT (31% when OCTT<150 min, 73% when OCTT≥150 min, and up to 85% when OCTT>180 min, P<0.01)., Conclusions: Abnormalities of both esophageal and small intestine motility are frequent in SSc patients and esophageal motility is altered in most cases with small bowel involvement. Delayed GE plays a limited role in prolonging OCTT. LHBT is a non-invasive, cheap, well-tolerated diagnostic tool that may be useful to estimate intestinal involvement and also to estimate a higher risk of esophageal hypomotility in SSc patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Gastroesophageal reflux disease (GERD) is a common disorder of the upper gastrointestinal tract which is typically characterized by heartburn and acid regurgitation. These symptoms are widespread in the community and range from 2.5% to more than 25%. Economic analyses showed an increase in direct and indirect costs related to the diagnosis, treatment and surveillance of GERD and its complications. The aim of this review is to provide current information regarding the natural history of GERD, taking into account the evolution of its definition and the worldwide gradual change of its epidemiology. Present knowledge shows that there are two main forms of GERD, that is erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter comprises the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, which is considered as a pre-cancerous lesion. Although data from medical literature on the natural history of this disease are limited and mainly retrospective, they seem to indicate that both NERD and mild esophagitis tend to remain as such with time and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barrett's esophagus may occur in a small proportion of patients, ranging from 0 to 30%, 10 to 22% and 1 to 13% of cases, respectively. It is necessary to stress that these data are strongly influenced by the use of powerful antisecretory drugs (PPIs). Further studies are needed to better elucidate this matter and overcome the present limitations represented by the lack of large prospective longitudinal investigations, absence of homogeneous definitions of the various forms of GERD, influence of different treatments, clear exclusion of patients with functional disorders of the esophagus. [ABSTRACT FROM AUTHOR]

Background The role of esophagogastric junction contractile integral ( EGJ- CI) as assessed by high-resolution manometry ( HRM) is unclear. We aimed to correlate the EGJ- CI with impedance-pH findings in gastro-esophageal reflux disease ( GERD) patients. Methods Consecutive patients with GERD symptoms were enrolled. All patients underwent upper endoscopy, HRM, and impedance-pH testing. The EGJ- CI was calculated using the distal contractile integral tool box during three consecutive respiratory cycles. The value was then divided by the duration of these cycles. A value below 13 was considered as a defective EGJ- CI. We also assessed EGJ morphology, esophageal acid exposure time ( AET), number of reflux episodes ( NRE), and symptom association analysis ( SAA). A positive impedance-pH monitoring was considered in case of abnormal AET and/or NRE and/or positive SAA. Key Results Among 130 patients we enrolled, 91 had GERD (abnormal AET and/or elevated NRE and/or positive SAA) and 39 had functional heartburn ( FH) (negative endoscopy, normal AET, normal NRE, and negative SAA). The GERD patients had a lower median value of EGJ- CI (11 [3.1-20.7] vs 22 [9.9-41], p < 0.02) compared to FH patients. Patients with a defective EGJ- CI had, more frequently, a positive impedance-pH monitoring or esophageal mucosal lesions at endoscopy ( p < 0.05 and p < 0.05, respectively) than patients with a normal EGJ- CI. An EGJ- CI cut-off value of 5 mmHg cm yielded the optimal performance in identifying GERD at impedance-pH (sensitivity 89%-specificity 63%). Conclusions & Inferences A defective EGJ- CI at HRM is clearly associated with evidence of GERD at impedance-pH monitoring. Evaluating EGJ- CI may be useful to predict an abnormal impedance-pH testing. [ABSTRACT FROM AUTHOR]

Background Barrett's oesophagus is regarded as the most important risk factor for development of oesophageal adenocarcinoma. According to current guidelines, treatment should be limited to symptomatic Barrett's oesophagus. Aim To evaluate the expression of Ki67, cyclooxygenase-2 (COX-2) and apoptosis in Barrett's oesophagus after 12 months of double-dose proton pump inhibitor therapy. The effectiveness of esomeprazole and pantoprazole was also compared. Methods Seventy-seven nondysplastic Barrett's oesophagus patients underwent baseline upper endoscopy. Patients were then randomised into two groups: one group was allocated to receive esomeprazole 40 mg b.d. and the other group pantoprazole 40 mg b.d. for 12 months. A follow-up endoscopy was performed at the end of treatment. Sixty-five of 77 patients agreed to undergo oesophageal manometry and 24-h pH-metry. Barrett's oesophagus biopsies, obtained at baseline and after treatment, were analysed using immunohistochemistry to assess Ki67 and COX-2 expression; apoptosis was evaluated using TUNEL. Results In the esomeprazole group, a significant decrease in Ki67 and COX-2 expression, as well as an increase in apoptosis, were observed (P < 0.05). By contrast, in the pantoprazole group Ki67, COX-2 and apoptosis did not vary significantly from baseline. By 24-h oesophageal pH-monitoring, a normal acid exposure time was recorded in patients treated with esomeprazole, while those allocated to pantoprazole displayed abnormal acid exposure (P < 0.05). Conclusions Treatment of Barrett's oesophagus patients with high-dose esomeprazole, but not pantoprazole, promoted a decrease in proliferative markers, concomitantly with a decrease in apoptotic cell death. Moreover, esomeprazole allowed a better oesophageal acid control than pantoprazole. [ABSTRACT FROM AUTHOR]