Exertional esophageal pH-metry and manometry in recurrent chest pain

AIM: To investigate the diagnostic efficacy of 24-h and exertional esophageal pH-metry and manometry in patients with recurrent chest pain. METHODS: The study included 111 patients (54% male) with recurrent angina-like chest pain, non-respon- sive to therapy with proton pump inhibitors. Sixty-five (59%) had non-obstructive lesions in coronary artery angiography, and in 46 (41%) significant coronary artery narrowing was found. In all patients, 24-h esophageal pH-metry and manometry, and treadmill stress tests with simultaneous esophageal pH-metry and manometry monitoring were performed. During a 24-h examination the percentage of spontaneous chest pain (sCP) episodes associated with acid reflux or dysmotility (symptom index, SI) was calculated. Patients with SI > 50% for acid gastroesophageal reflux (GER) were classified as having GER-related sCP. The remaining symptomatic individuals were determined as having non-GER-related sCP. During the stress test, the occurrence of chest pain, episodes of esophageal acidification (pH < 4 for 10 s) and esophageal spasm with more than 55% of simultaneous contractions (exercise-provoked esophageal spasm or EPES) were noted. RESULTS: Sixty-eight (61%) individuals reported sCP during 24-h esophageal function monitoring. Eleven of these (16%) were classified as having GER-related sCP and 53/68 (84%) as having non-GER-related sCP. The exercise-provoked chest pain during a stress test occurred in 13/111 (12%) subjects. In order to compare the clinical usefulness of 24-h esophageal function monitoring and its examination limited only to the treadmill stress test, the standard parameters of diagnostic test evaluation were determined. The occurrence of GER- related or non-GER-related sCP was assumed as a "gold standard". Afterwards, accuracy, sensitivity and specificity were calculated. These parameters expressed a prediction of GER-related or non-GER-related sCP occurrence by the presence of chest pain, esophageal acidification and EPES. Accuracy, sensitivity and specificity of chest pain during the stress test predicting any sCP occurrence were 28%, 35% and 80%, respectively, predicting GER- related sCP were 42%, 0% and 83%, respectively, and predicting non-GER-related sCP were 57%, 36% and 83%, respectively. Similar values were obtained for exercise-related acidification with pH < 4 longer than 10 s in the prediction of GER-related sCP (44%, 36% and 92%, respectively) and EPES in relation to non-GER-related sCP (48%, 23% and 84%, respectively). CONCLUSION: The presence of chest pain, esophageal acidification and EPES had greater than 80% specificity to exclude the GER-related and non-GER-related causes of recurrent chest pain.

Prevalence of overweightedness in patients with gastro-esophageal reflux

AIM: To evaluate whether the prevalence of overweight and obese conditions is increased in gastro-esophageal reflux disease (GERD) patients (with 24-h pathological pH recordings) in comparison to general population. METHODS: A total of 196 consecutive patients (103 females, age range 18-83 years) with symptoms of gastro-esophageal reflux (GER) and 24-h pathological esophageal pH-metry. Body mass index (BMI) of the patients was calculated and its distribution (%) was compared with that of the Italian general population as assessed by National Bureau of Census (ISTAT). To evaluate the association of GERD with weight categories, the binomial test was employed. P < 0.05 was considered statistically significant. RESULTS: In males, overweightedness (BMI 25-25.9) was present in 43% of GERD patients vs 41.8% of Italian population (IP) (ns), obesity (BMI ≥ 30) in 10.9% vs 9.1% (ns). In females overweight was present in 34.9% of GERD patients vs 25.7% of IP (P < 0.01), obesity in 13.6% of GERD patients vs 9.1% of IP (P < 0.01). No statistically significant differences were noted in different age classes. CONCLUSION: In comparison to the Italian general population, the prevalence of overweightedness and obesity is increased in female but not in male patients with ascertained gastro-esophageal reflux disease.

Oropharyngeal acid reflux and motility abnormalities of the proximal esophagus

AIM To investigate the relationship between pathological oropharyngeal(OP) acid exposure and esophageal motility in patients with extra-esophageal syndromes.METHODS In this prospective study we enrolled consecutive outpatients with extra-esophageal symptoms suspected to be related to gastroesophageal reflux disease(GERD). We enrolled only patients with a reflux symptom index(RSI) score-higher than 13 and with previous lung, allergy and ear, nose and throat evaluations excluding other specific diagnoses. All patients underwent 24-h OP pH-metry with the Dx probe and esophageal highresolution manometry(HRM). Patients were divided into two groups on the basis of a normal or pathological p H-metric finding(Ryan Score) and all manometric characteristics of the two groups were compared.RESULTS We examined 135 patients with chronic extra-esophageal syndromes. Fifty-one were considered eligible for the study. Of these, 42 decided to participate in the protocol. Patients were divided into two groups on the basis of normal or pathological OP acid exposure. All the HRM parameters were compared for the two groups. Significant differences were found in the median upper esophageal sphincter resting pressure(median 71 mmH g vs 126 mmH g, P = 0.004) and the median proximal contractile integral(median 215.5 cm·mmH g·s vs 313.5 cm·mmH g·s, P = 0.039), both being lower in the group with pathological OP acid exposure, and the number of contractions with small or large breaks, which were more frequent in the same group. This group also had a larger number of peristaltic contractions with breaks in the 20 mm Hg isobaric contour(38.7% vs 15.38%, P < 0.0001).CONCLUSION In patients with suspected GERD-related extraesophageal syndromes pathological OP acid exposure was associated with weaker proximal esophageal motility.

Effects of refluxate pH values on duodenogastroesophageal reflux-induced esophageal adenocarcinoma

AIM： To determine the effects of duodenogastric juice pH on the development of esophageal adenocarcinoma （EAC）. METHODS： An animal model of duodenogastroesophageal reflux was established using Sprague-Dawley （SD） rats undergoing esophagoduodenostomy （ED）. The development of EAC was investigated in rats exposed to duodenogastric juice of different pH. The rats were di- vided into three groups： Iow-pH group （group A）, high- pH group （group B） and a sham-operated group as a control （group C） （n = 30 rats in each group）. The inci- dence of esophagitis, Barrett＇s esophagus （BE）, intestinal metaplasia with dysplasia and EAC was observed 40 wk after the treatment. RESULTS： The incidence rate of esophagitis, BE, intestinal metaplasia with dysplasia and EAC was higher in groups A and B compared with the control group after 40 wk （P 〈 0.01）, being 96% and 100% （P 〉 0.05）, 88% and 82.4% （P 〉 0.05）, 20% and 52.1% （P 〈 0.05）, and 8% and 39% （P 〈 0.05）, respectively. CONCLUSION： Non-acidic refluxate increases the occurrence of intestinal metaplasia with dysplasia and EAC while the Iow-pH gastric juice exerts a protective effect in the presence of duodenal juice. The non-acid reflux is particularly important in the progression from BE to cancer. Therefore, control of duodenal reflux may be an important prophylaxis for EAC.

Gastrointestinal function testing model using a new laryngopharyngeal pH probe(Restech)in patients after Ivor-Lewis esophagectomy

BACKGROUND There is no established correlation between 24-h esophageal pH-metry(Eso-pH)and the new laryngopharyngeal pH-monitoring system(Restech)as only small case series exist.Eso-pH was not designed to detect laryngopharyngeal reflux(LPR)and Restech may detect LPR better.We have previously published a dataset using the two techniques in a large patient collective with gastroesophageal reflux disease.Anatomically,patients after esophagectomy were reported to represent an ideal human reflux model as no reflux barrier exists.AIM To use a human reflux model to examine our previously published correlation in these patients.METHODS Patients after Ivor Lewis esophagectomy underwent our routine follow-up program with surveillance endoscopies,computed tomography scans and further exams following surgery.Only patients with a complete check-up program and reflux symptoms were offered inclusion into this prospective study and evaluated using Restech and simultaneous Eso-pH.Subsequently,the relationship between the two techniques was evaluated RESULTS A total of 43 patients from May 2016-November 2018 were included.All patients presented with mainly typical reflux symptoms such as heartburn(74%),regurgitation(84%),chest pain(58%),and dysphagia(47%).Extraesophageal symptoms such as cough,hoarseness,asthma symptoms,and globus sensation were also present.Esophageal 24-hour pH-metry was abnormal in 88%of patients with a mean DeMeester Score of 229.45[range 26.4-319.5].Restech evaluation was abnormal in 61%of cases in this highly selective patient cohort.All patients with abnormal supine LPR were also abnormal for supine esophageal reflux measured by conventional Eso-pH.CONCLUSION Patients following esophagectomy and reconstruction with gastric interposition can ideally serve as a human reflux model.Interestingly,laryngopharyngeal reflux phases occur mainly in the upright position.In this human volume-reflux model,results of simultaneous esophageal and laryngopharyngeal(Restech)pHmetry showed 100%correlation as being explicable by one of our reflux scenarios.

Synthesis, Characterization and Biological Activity Studies on Novel 4-Chloro-2- [(1-Phenyl-1H-Tetrazol-5-Ylimino)-Methyl] Phenol and Its Metal Complexes

Novel 4-Chloro-2-[(1-phenyl-1H-tetrazol-5-ylimino)-methyl] phenol (Cl-PTMP) and its transition metal complexes were synthesized and characterized by FT-IR, 1H-NMR, UV-Vis spectroscopy, Mass spectrometry, TGA and SEM. The pH-metric technique was applied to get an insight of the number of dissociable protons and protonation sites in candidate compound. The pH-Metric studies were also carried out in presence of metal ions to establish the formation of corresponding metal complexes in solution. Further, the metal ligand compositions of Cu (II) and Co (II) complexes were determined spectrophotometrically by employing Job’s continuous variation method. To know the molecular properties in title imine compound suitable for metal ion coordination, the computational studies were carried out by employing HyperChem 7.5 tools. The energies of HOMO and LUMO frontier orbitals and their electron density contour maps were generated with geometry optimized molecule. Biological activity of Cl-PTMP and its metal complexes was investigated by disc diffusion method.

Alginate controls heartburn in patients with erosive and nonerosive reflux disease

AIM:To evaluate the effect of a novel alginate-based compound,Faringel,in modifying reflux characteristics and controlling symptoms.METHODS:In this prospective,open-label study,40 patients reporting heartburn and regurgitation with proven reflux disease(i.e.,positive impedance-pH test/evidence of erosive esophagitis at upper endoscopy) underwent 2 h impedance-pH testing after eating a refluxogenic meal.They were studied for 1 h under basal conditions and 1 h after taking 10 mL Faringel.In both sessions,measurements were obtained in right lateral and supine decubitus positions.Patients also completed a validated questionnaire consisting of a 2-item 5-point(0-4) Likert scale and a 10-cm visual analogue scale(VAS) in order to evaluate the efficacy of Faringel in symptom relief.Tolerability of the treatment was assessed using a 6-point Likert scale ranging from very good(1) to very poor(6).RESULTS:Faringel decreased significantly(P < 0.001),in both the right lateral and supine decubitus positions,esophageal acid exposure time [median 10(25th75th percentil 6-16) vs 5.8(4-10) and 16(11-19) vs 7.5(5-11),respectively] and acid refluxes [5(3-8) vs 1(1-1) and 6(4-8) vs 2(1-2),respectively],but increased significantly(P < 0.01) the number of nonacid reflux events compared with baseline [2(1-3)vs 3(2-5) and 3(2-4) vs 6(3-8),respectively].Percentage of proximal migration decreased in both decubitus positions(60% vs 32% and 64% vs 35%,respectively;P < 0.001).Faringel was significantly effective in controlling heartburn,based on both the Likert scale [3.1(range 1-4) vs 0.9(0-2);P < 0.001] and VAS score [7.1(3-9.8) vs 2(0.1-4.8);P < 0.001],but it had less success against regurgitation,based on both the Likert scale [2.6(1-4) vs 2.2(1-4);P = not significant(NS)] and VAS score [5.6(2-9.6) vs 3.9(1-8.8);P = NS].Overall,the tolerability of Faringel was very good 5(2-6),with only two patients reporting modest adverse events(i.e.,nausea and bloating).CONCLUSION:Our findings demonstrate that Faringel is well-tolerated and effective in reducing heartburn by modifying esophageal acid exposure time,number of acid refluxes and their proximal migration.