Publications by authors named "Serhat Bor"

74 Publications

In Vitro and In Vivo Effects of Nonsteroidal Anti-inflammatory Drugs and Aspirin on Rabbit Esophageal Epithelium.

Turk J Gastroenterol 2022 03;33(3):257-270

Department of Gastroenterology, Ege University Medical School Ege Reflux Study Group, İzmir, Turkey.

Background: Gastroesophageal reflux disease has a high incidence of 23%, with 29% of those with gastroesophageal reflux disease consuming nonsteroidal anti-inflammatory drugs. There are insufficient data concerning the effects of nonsteroidal anti-inflammatory drugs on the esophageal tissue. We aimed to examine the effects of well-known nonsteroidal anti-inflammatory drugs using electrophysiologic criteria on the rabbit esophageal epithelium.

Methods: Esophageal epithelium mounted on Ussing chambers enabled in vitro investigation of the electrophysiological properties. Doses of 1 mg/mL, 2.5 mg/mL, 5 mg/mL ibuprofen, naproxen, and aspirin were dissolved in dimethyl sulfoxide and added to the luminal side. Esophagi were cannulated from both sides for the administration of high-dose ibuprofen in vivo, and the potential difference was monitored.

Results: Ibuprofen and aspirin inhibited tissue transport functions in a dose-dependent manner. pH 4 acid and 0.1 mg/mL ibuprofen alone were not harmful; however, the combination of these agents had an additive and significance effect: 78% decrease in the potential difference and 85% decrease in the short-circuited current (Isc). The change in the potential difference in the in vivo experiments (5 mg/mL ibuprofen) was similar (52 ± 7% decrease) with in vitro experiments in the first 30 minutes.

Conclusion: Nonsteroidal anti-inflammatory drugs were harmful to the rabbit esophageal epithelium in both the in vitro and in vivo experiments. Even though aspirin and ibuprofen affected the transport mechanisms of the esophageal epithelium, the dose-dependent decrease of tissue potential difference and Isc with ibuprofen was more pronounced than those with aspirin. The combination of harmless doses of ibuprofen and acid demonstrated that even low acidic conditions can create a disruptive environment.
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http://dx.doi.org/10.5152/tjg.2022.201168DOI Listing
March 2022

Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study.

Am J Gastroenterol 2022 01;117(1):147-157

Ege University Department of Infectious Diseases, Izmir, Turkey.

Introduction: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month.

Methods: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire.

Results: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels.

Discussion: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection.
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http://dx.doi.org/10.14309/ajg.0000000000001541DOI Listing
January 2022

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

Neurogastroenterol Motil 2021 09;33(9):e14238

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1111/nmo.14238DOI Listing
September 2021

Efficacy of pinaverium bromide in the treatment of irritable bowel syndrome: a systematic review and meta-analysis.

Therap Adv Gastroenterol 2021 15;14:17562848211033740. Epub 2021 Sep 15.

TARGID, University of Leuven, Leuven, Belgium.

Background: Spasmolytic agents are an attractive first line treatment option for irritable bowel syndrome (IBS). Pinaverium bromide (pinaverium) has antispasmodic effects on gastrointestinal smooth muscle and can relieve major IBS symptoms, but an up-to-date meta-analysis comparing the efficacy of pinaverium with placebo is lacking. The aim is to perform a systematic review and meta-analysis to assess the efficacy of pinaverium compared with placebo for IBS treatment.

Methods: All placebo-controlled trials evaluating pinaverium for IBS treatment were included, up to October 2019. Treatment efficacy was evaluated by overall patient IBS symptoms. Individual symptoms were also evaluated. The effect of pinaverium placebo was expressed as standardized mean difference (SMD) and risk ratio (RR). Odds ratio (OR) and number needed to treat (NNT) were also calculated.

Results: Eight studies were included for analysis. Pinaverium treatment had a beneficial effect on overall IBS symptom relief with a positive SMD of 0.64 [95% confidence interval (CI) 0.45-0.82,  < 0.0001] and a positive RR of 1.75 (1.26-2.43,  < 0.0008). No significant difference was found by publication year, gender, age, methodological quality score (MQS), or sample size. No publication bias was detected. OR was 3.43 (2.00-5.88,  < 0.0001), and NNT was 4. Pinaverium also demonstrated a beneficial treatment effect for abdominal pain, stool change, and bloating improvement or resolution.

Conclusion: Pinaverium is superior to placebo for the treatment of IBS symptoms, irrespective of patient age or gender, study publication year, sample size, or MQS. The NNT in this meta-analysis is amongst the lowest for studies and meta-analyses of antispasmodics placebo in IBS.
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http://dx.doi.org/10.1177/17562848211033740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447090PMC
September 2021

Validation of the Reflux Disease Questionnaire for a Turkish Population.

J Gastrointestin Liver Dis 2021 06 18;30(2):193-197. Epub 2021 Jun 18.

Department of Gastroenterology, Ege University School of Medicine, İzmir, Turkey.

Background And Aims: Achieving the correct diagnosis and therapeutic success in gastroesophageal reflux disease (GERD) depends on the patient's self-assessment. Therefore, valid and reliable patient-reported questionnaires are very important. When designing such measurement tools, researchers should focus on their validity, reliability, sensitivity, and, applicability. The reflux disease questionnaire (RDQ) largely meets these important requirements. This study aims to examine The RDQ's psychometric characteristics for the Turkish society (RDQ TR ) and its validity in symptoms' evaluation.

Methods: The sample of this study comprised 81 patients who were admitted to our institution, GERD study group outpatient clinic. The data collection forms used in the study were the case report forms and RDQ. Three weeks after the first interview, 30 patients were re-interviewed by the phone and the RDQ was re-administered. For the validity studies of the scale, language validity, content validity, and construct validity studies were used, and for the reliability studies, internal consistency and test-retest reliability methods were used.

Results: The content validity index of form was 0.95 (0.93-0.98). The performed factor analysis indicated 3 factors with an eigenvalue over 1.0. Those factors were responsible for 77.66% of the variance. The Cronbach's alpha values were 0.88 for regurgitation sub-dimension, 0.91 for dyspepsia sub-dimension, 0.86 for heartburn sub-dimension, and 0.92 overall. Intraclass correlation coefficient value of the scale was 0.94.

Conclusions: Our study highlights that the RDQ TR is reliable, valid, and responsive to change in Turkey patients with GERD symptomatology.
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http://dx.doi.org/10.15403/jgld-3309DOI Listing
June 2021

Pepsin and pH of Gastric Juice in Patients With Gastrointestinal Reflux Disease and Subgroups.

J Clin Gastroenterol 2021 May 28. Epub 2021 May 28.

Departments of Medical Biochemistry Medical Biology Ege Reflux Study Group, Division of Gastroenterology, Division of Internal Medicine, Ege Faculty of Medicine, Izmir, Turkey RD Biomed Limited, Castle Hill Hospital, Cottingham, UK.

Goal: The aim of this study was to investigate the pepsin values and pH results of gastric juice among the subtypes of gastroesophageal reflux disease (GERD) and functional heartburn.

Background: The major destructive agents of GERD on the esophageal epithelium are gastric acid and pepsin. No precise information about pepsin concentration in gastric juice exists.

Study: Ninety patients with GERD, 39 erosive reflux disease (ERD) Los Angeles (LA) grade A/B, 13 ERD LA grade C/D, 19 nonerosive reflux disease (NERD), 8 esophageal hypersensitivity, 11 functional heartburn, and 24 healthy controls were included in the study. During endoscopy gastric juices from the patients were aspirated and their pH readings immediately recorded. Gastric juice samples were analyzed using Peptest, a lateral flow device containing 2 unique human monoclonal antibodies to detect any pepsin present in the gastric juice sample.

Results: The highest mean gastric pepsin concentration (0.865 mg/mL) and the lowest median gastric pH (1.4) was observed in the LA grade C/D group compared with the lowest mean gastric pepsin concentration (0.576 mg/mL) and the highest median gastric pH (2.5) seen in the NERD group. Comparing pH, the NERD patient group was significantly higher (P=0.0018 to P=0.0233) when compared with all other GERD patient groups.

Conclusions: The basal gastric pepsin level in the healthy control group was comparable to literature values. There was good correlation and a significant linear relationship between the gastric pepsin level and gastric pH within the patient groups. The severity of the GERD disease is related to the lowest pH and the highest pepsin concentration in gastric juice.
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http://dx.doi.org/10.1097/MCG.0000000000001560DOI Listing
May 2021

Frequency of Irritable Bowel Syndrome in Patients with Brugada Syndrome and Drug-Induced Type 1 Brugada Pattern.

Am J Cardiol 2021 07 24;151:51-56. Epub 2021 May 24.

Department of Cardiology, Ege University School of Medicine, Izmir, Turkey. Electronic address:

Irritable bowel syndrome (IBS) is one of the most widely recognized functional bowel disorders (FBDs) with a genetic component. SCN5A gene and SCN1B loci have been identified in population-based IBS cohorts and proposed to have a mechanistic role in the pathophysiology of IBS. These same genes have been associated with Brugada syndrome (BrS). The present study examines the hypothesis that these two inherited syndromes are linked. Prevalence of FBDs over a 12 months period were compared between probands with BrS/drug-induced type 1 Brugada pattern (DI-Type 1 BrP) (n = 148) and a control group (n = 124) matched for age, female sex, presence of arrhythmia and co-morbid conditions. SCN5A/SCN1B genes were screened in 88 patients. Prevalence of IBS was 25% in patients with BrS/DI-Type 1 BrP and 8.1% in the control group (p = 2.34 × 10). On stepwise logistic regression analysis, presence of current and/or history of migraine (OR of 2.75; 95% CI: 1.08 to 6.98; p = 0.033) was a predictor of underlying BrS/DI-Type 1 BrP among patients with FBDs. We identified 8 putative SCN5A/SCN1B variants in 7 (12.3%) patients with BrS/DI-Type 1 BrP and 1 (3.2%) patient in control group. Five out of 8 (62.5%) patients with SCN5A/SCN1B variants had FBDs. In conclusion, IBS is a common co-morbidity in patients with BrS/DI-Type 1 BrP. Presence of current and/or history of migraine are a predictor of underlying BrS/DI-Type 1 BrP among patients with FBDs. Frequent co-existence of IBS and BrS/DI-Type 1 BrP necessitates cautious use of certain drugs among the therapeutic options for IBS that are known to exacerbate the Brugada phenotype.
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http://dx.doi.org/10.1016/j.amjcard.2021.04.010DOI Listing
July 2021

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

United European Gastroenterol J 2021 04;9(3):307-331

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1002/ueg2.12061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259261PMC
April 2021

Effectiveness of Biofeedback Therapy on Quality of Life in Patients with Dyssynergic Defecation Disorder.

Turk J Gastroenterol 2021 01;32(1):22-29

Division of Gastroenterology, Ege University School of Medicine, İzmir, Turkey.

Background: The first option to be considered in the treatment of functional defecation disorder is to correct the dyssynergia. However, limited studies exist to show the effectiveness of biofeedback.

Objective: We evaluated the effect of biofeedback on the severity of constipation, quality of life, and anorectal manometry in patients with dyssynergic defecation in which the biofeedback method was applied.

Methods: Effectiveness of biofeedback method on the quality of life of 24 dyssynergic defecation patients according to Rome III criteria after clinical and balloon expulsion tests (BETs) and colonic transit time was measured. Data were collected with patient identification form, Bristol Stool Chart, Constipation Quality of Life Scale forms, Visual Analogue Scale, diaphragmatic breathing exercises form, constipation diary, and constipation biofeedback monitoring form. Dyssnergic defecation cases received 6-week biofeedback training. For the same timeframe, the control group had a catheter into the rectum without any intervention.

Results: Constipation severity was reduced in both groups before biofeedback to post-biofeedback (P < .05). Anal canal pressure, BET, colonic transit time, and quality of life significantly improved in biofeedback patients compared with controls.

Conclusions: Biofeedback has a favorable effect on therapy and quality of life in dyssynergic defecation cases.
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http://dx.doi.org/10.5152/tjg.2020.19678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975507PMC
January 2021

Chicago Classification update (v4.0): Technical review of high-resolution manometry metrics for EGJ barrier function.

Neurogastroenterol Motil 2021 10 2;33(10):e14113. Epub 2021 Mar 2.

Department of Medicine, University of California, San Diego, California, USA.

Esophagogastric junction (EGJ) barrier function is of fundamental importance in the pathophysiology of gastroesophageal reflux disease. Impaired EGJ barrier function leads to excessive distal esophageal acid exposure or, in severe cases, esophagitis. Hence, proposed high-resolution manometry (HRM) metrics assessing EGJ integrity are clinically important and were a focus of the Chicago Classification (CC) working group for inclusion in CC v4.0. However, the EGJ is a complex sphincter comprised of both crural diaphragm (CD) and lower esophageal sphincter (LES) component, each of which is subject to independent physiological control mechanisms and pathophysiology. No single metric can capture all attributes of EGJ barrier function. The working group considered several potential metrics of EGJ integrity including LES-CD separation, the EGJ contractile integral (EGJ-CI), the respiratory inversion point (RIP), and intragastric pressure. Strong recommendations were made regarding LES-CD separation as indicative of hiatus hernia, although the numerical threshold for defining hiatal hernia was not agreed upon. There was no agreement on the significance of the RIP, only that it could localize either above the LES or between the LES and CD in cases of hiatus hernia. There was agreement on how to measure the EGJ-CI and that it should be referenced to gastric pressure in units of mmHg cm, but the numerical threshold indicative of a hypotensive EGJ varied widely among reports and was not agreed upon. Intragastric pressure was endorsed as an important metric worthy of further study but there was no agreement on a numerical threshold indicative of abdominal obesity.
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http://dx.doi.org/10.1111/nmo.14113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410874PMC
October 2021

Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0.

Neurogastroenterol Motil 2021 01;33(1):e14058

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.
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http://dx.doi.org/10.1111/nmo.14058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034247PMC
January 2021

High-Resolution Manometry Thresholds and Motor Patterns Among Asymptomatic Individuals.

Clin Gastroenterol Hepatol 2022 03 2;20(3):e398-e406. Epub 2020 Nov 2.

Division of Gastroenterology, Washington University School of Medicine in St Louis, St Louis, Missouri. Electronic address:

Objective: High-resolution manometry (HRM) is the current standard for characterization of esophageal body and esophagogastric junction (EGJ) function. We aimed to examine the prevalence of abnormal esophageal motor patterns in health, and to determine optimal thresholds for software metrics across HRM systems.

Design: Manometry studies from asymptomatic adults were solicited from motility centers worldwide, and were manually analyzed using integrated relaxation pressure (IRP), distal latency (DL), and distal contractile integral (DCI) in standardized fashion. Normative thresholds were assessed using fifth and/or 95th percentile values. Chicago Classification v3.0 criteria were applied to determine motor patterns across HRM systems, study positions (upright vs supine), ages, and genders.

Results: Of 469 unique HRM studies (median age 28.0, range 18-79 years). 74.6% had a normal HRM pattern; none had achalasia. Ineffective esophageal motility (IEM) was the most frequent motor pattern identified (15.1% overall), followed by EGJ outflow obstruction (5.3%). Proportions with IEM were lower using stringent criteria (10.0%), especially in supine studies (7.1%-8.5%). Other motor patterns were rare (0.2%-4.1% overall) and did not vary by age or gender. DL thresholds were close to current norms across HRM systems, while IRP thresholds varied by HRM system and study position. Both fifth and 95th percentile DCI values were lower than current thresholds, both in upright and supine positions.

Conclusions: Motor abnormalities are infrequent in healthy individuals and consist mainly of IEM, proportions of which are lower when using stringent criteria in the supine position. Thresholds for HRM metrics vary by HRM system and study position.
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http://dx.doi.org/10.1016/j.cgh.2020.10.052DOI Listing
March 2022

Esophagogastric junction morphology and contractile integral on high-resolution manometry in asymptomatic healthy volunteers: An international multicenter study.

Neurogastroenterol Motil 2021 06 23;33(6):e14009. Epub 2020 Oct 23.

Division of Gastroenterology, Washington University School of Medicine, St Louis, MO, USA.

Background: Esophagogastric junction contractile integral (EGJ-CI) and EGJ morphology are high-resolution manometry (HRM) metrics that assess EGJ barrier function. Normative data standardized across world regions and HRM manufacturers are limited.

Methods: Our aim was to determine normative EGJ metrics in a large international cohort of healthy volunteers undergoing HRM (Medtronic, Laborie, and Diversatek software) acquired from 16 countries in four world regions. EGJ-CI was calculated by the same two investigators using a distal contractile integral-like measurement across the EGJ for three respiratory cycles and corrected for respiration (mm Hg cm), using manufacturer-specific software tools. EGJ morphology was designated according to Chicago Classification v3.0. Median EGJ-CI values were calculated across age, genders, HRM systems, and regions.

Results: Of 484 studies (28.0 years, 56.2% F, 60.7% Medtronic studies, 26.0% Laborie, and 13.2% Diversatek), EGJ morphology was type 1 in 97.1%. Median EGJ-CI was similar between Medtronic (37.0 mm Hg cm, IQR 23.6-53.7 mm Hg cm) and Diversatek (34.9 mm Hg cm, IQR 22.1-56.1 mm Hg cm, P = 0.87), but was significantly higher using Laborie equipment (56.5 mm Hg cm, IQR 35.0-75.3 mm Hg cm, P < 0.001). 5 percentile EGJ-CI values ranged from 6.9 to 12.1 mm Hg cm. EGJ-CI values were consistent across world regions, but different between manufacturers even within the same world region (P ≤ 0.001). Within Medtronic studies, EGJ-CI and basal LESP were similar in younger and older individuals (P ≥ 0.3) but higher in women (P < 0.001).

Conclusions: EGJ morphology is predominantly type 1 in healthy adults. EGJ-CI varies widely in health, with significant gender influence, but is consistent within each HRM system. Manufacturer-specific normative values should be utilized for clinical HRM interpretation.
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http://dx.doi.org/10.1111/nmo.14009DOI Listing
June 2021

Normal values and regional differences in oesophageal impedance-pH metrics: a consensus analysis of impedance-pH studies from around the world.

Gut 2020 Oct 9. Epub 2020 Oct 9.

Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA.

Objective: Limitations of existing impedance-pH thresholds include small sample size of normative studies, inclusion of artefactual pH drops and incorrect identification of impedance reflux events. We aimed to obtain new impedance-pH thresholds from expert consensus analysis of tracings from a large number of healthy subjects.

Design: Of 541 studies performed worldwide using two different systems (Diversatek, USA, and Laborie, Netherlands), 150 tracings with oesophageal diagnoses, behavioural disorders and study-related artefacts were excluded. The remainder studies were subject to two reviewer consensus analysis, in-person or through video conference, consisting of editing meals and pH drops, identification of impedance reflux and postreflux swallow-induced peristaltic wave (PSPW) using strict pre-established criteria and measurement of distal mean nocturnal baseline impedance (MNBI).

Results: Consensus analysis was performed in 391 tracings (age 32.7 years, range 18-71, 54.2% female). Normative thresholds were significantly different between Diversatek and Laborie (total acid exposure time: 2.8% and 5%; reflux episodes: 55 and 78; MNBI at 3 cm: 1400 and 1500 ohms, at 5 cm: 1400 and 1800 ohms). Males had higher acid exposure, more reflux episodes and lower MNBI. Significant regional differences were identified, including higher PSPW scores in Western countries, and higher MNBI in Asia using Diversatek, and higher acid exposure in the Netherlands, higher MNBI in Asia and South Africa, and lower MNBI in Turkey using Laborie.

Conclusion: Normal impedance-pH monitoring thresholds have regional and system-related differences. Clinical interpretation needs to use normal thresholds valid for the system used and world region, following careful editing of the tracings.
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http://dx.doi.org/10.1136/gutjnl-2020-322627DOI Listing
October 2020

Trimebutine Maleate Monotherapy for Functional Dyspepsia: A Multicenter, Randomized, Double-Blind Placebo Controlled Prospective Trial.

Medicina (Kaunas) 2020 Jul 8;56(7). Epub 2020 Jul 8.

Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 54642 Thessaloniki, Macedonia, Greece.

Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders; it has a great impact on patient quality of life and is difficult to treat satisfactorily. This study evaluates the efficacy and safety of trimebutine maleate (TM) in patients with FD. : Α multicenter, randomized, double-blind, placebo controlled, prospective study was conducted, including 211 patients with FD. Participants were randomized to receive TM 300 mg twice per day (BID, 108 patients) or placebo BID (103 patients) for 4 weeks. The Glasgow Dyspepsia Severity Score (GDSS) was used to evaluate the relief of dyspepsia symptoms. Moreover, as a pilot secondary endpoint, a substudy (eight participants on TM and eight on placebo) was conducted in to evaluate gastric emptying (GE), estimated using a 99mTc-Tin Colloid Semi Solid Meal Scintigraphy test. : Of the 211 patients enrolled, 185 (87.7%) (97 (52.4%) in the TM group and 88 (47.6%) in the placebo group) completed the study and were analyzed. The groups did not differ in their demographic and medical history data. Regarding symptom relief, being the primary endpoint, a statistically significant reduction in GDSS for the TM group was revealed between the first (2-week) and final (4-week) visit (-value = 0.02). The 99 mTc-Tin Colloid Semi Solid Meal Scintigraphy testing showed that TM significantly accelerated GE obtained at 50 min (median emptying 75.5% in the TM group vs. 66.6% in the placebo group, = 0.036). Adverse effects of low to moderate severity were reported in 12.3% of the patients on TM. : TM monotherapy appears to be an effective and safe approach to treating FD, although the findings presented here warrant further confirmation.
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http://dx.doi.org/10.3390/medicina56070339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404657PMC
July 2020

International consensus on the diagnosis and management of dumping syndrome.

Nat Rev Endocrinol 2020 08 26;16(8):448-466. Epub 2020 May 26.

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), Catholic University of Leuven, Leuven, Belgium.

Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose.
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http://dx.doi.org/10.1038/s41574-020-0357-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351708PMC
August 2020

Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.

Gastroenterology 2021 01 12;160(1):99-114.e3. Epub 2020 Apr 12.

Dhaka Medical College & Hospital, Dhaka, Bangladesh.

Background & Aims: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents.

Methods: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately.

Results: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%).

Conclusions: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.
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http://dx.doi.org/10.1053/j.gastro.2020.04.014DOI Listing
January 2021

Oropharyngeal swallowing functions are impaired in patients with naive-achalasia.

Eur Arch Otorhinolaryngol 2020 Apr 24;277(4):1219-1226. Epub 2020 Jan 24.

Division of Gastroenterology, Ege Reflux Study Group, Ege University School of Medicine, Bornova, Turkey.

Background: It is generally accepted that achalasia is limited to the pathology of the esophageal body and lower esophageal sphincter. However, patients with achalasia still have symptoms such as aspiration and weight loss after even a succesfull treatment, suggesting that additional oropharyngeal pathologies may be frequent in patients with achalasia.

Objective: The aim of the study was to assess the oropharyngeal/hypopharyngeal swallowing functions of patients with naive-achalasia.

Methods: We evaluated the oropharyngeal functions with fiberoptic endoscopic evaluation of swallowing (FEES) and high-resolution manometry (HRM) in 36 patients with naive-achalasia(mean age 47.8 ± 14.7; 20F, 20M) diagnosed with and upper gastrointestinal endoscopy, HRM, radiology compared the results with 40 healthy volunteers (mean age 48.25 ± 12.37; 23F, 17M) as controls. The Beck Depression Inventory (BDI) and the MD Anderson Dysphagia Inventory (MDADI) were used for psychological analysis and to assess quality of life.

Results: Mean integrated relaxation pressure (IRP) values were significantly higher (12.7 ± 10.9) for all patients compared to controls (0 ± 4.40). In the presence of pharyngeal residue IRP was 18.6 ± 11.8 mmHg compare to patients without pharyngeal residue which was 7.2 ± 6.4 mmHg (p < 0.05). Resting pressures were 105.7 ± 60.4 mmHg in study group vs 116 ± 55.1 mmHg in the control group (NS). In the study group we determined that residues of semisolid and liquid food were significantly higher in the vallecula, retrocricoid region, pharyngeal wall, and piriform sinuses with FEES. The average MDADI score was 58.1 ± 19.8 and 87.6 ± 10.7 in the study and control groups, respectively (p < 0.05). Depression may be significantly higher in achalasia patients based on the BDI.

Conclusion: Relaxation of the upper esophageal sphincter is insufficient especially in patient with residue. This finding is supported by the presence of residue during FEES evaluation. In the assessment of patients with achalasia, in the presence of residue symptoms,oropharyngeal phases of swallowing should be examined with FEES. Furthermore, the effect of exercises to improve the pathological findings should be evaluated.
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http://dx.doi.org/10.1007/s00405-020-05800-7DOI Listing
April 2020

Population-based assessment of gastrointestinal symptoms and diseases: Cappadocia Cohort, Turkey.

Turk J Gastroenterol 2019 Dec;30(12):1009-1020

Department of Gastroenterology, Ege University School of Medicine, İzmir, Turkey.

Background/aims: The aim of this study was to determine the prevalence of symptoms and diseases of the lower and upper gastrointestinal system (GIS) in a population-based sample.

Materials And Methods: The cross-sectional cohort study was conducted in Cappadocia cohort comprising the Gülşehir and Avanos districts. The "Gastrointestinal Symptom Questionnaire" was applied to persons over the age of 18 years.

Results: The GI Symptom Questionnaire was applied to 3369 subjects, and height and body weight were measured in 2797 consenting subjects. Of the participants, 61% were female and the mean patient age was 50±15 years. At least one GI symptom was present in 70.6% of the cohort. The most common upper GI symptoms were gastric bloating (31.0%) and heartburn (29.1%). The most common lower GI symptom was abnormal defecation (33.5). The prevalence of upper GIS and lower GIS diseases was 32.7% and 12.9%, respectively, and the prevalence of togetherness of upper and lower GIS diseases was 9.9%. Prevalence of GIS disease was approximately 3 times higher in females (p<0.001). All of the upper and lower GI symptoms and the prevalence of upper GIS disease increased in line with Body mass index (BMI).

Conclusion: This first population-based, cross-sectional cohort study revealed that the prevalence of GIS diseases is critically high for optimal public health. Special attention must be paid to these diseases while planning health policies and reimbursements.
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http://dx.doi.org/10.5152/tjg.2019.19882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924608PMC
December 2019

Validation of Peptest™ in Patients with Gastro-Esophageal Reflux Disease and Laryngopharyngeal Reflux Undergoing Impedance Testing.

J Gastrointestin Liver Dis 2019 Dec 9;28(4):383-387. Epub 2019 Dec 9.

RD Biomed Limited, Castle Hill Hospital, United Kingdom.

Background And Aims: Pepsin in the gastric refluxate is a marker for a prior reflux event and rapid detection might be achieved using the Peptest™, an in vitro diagnostic medical device. The aim of this study was to validate the use of Peptest™ to reliably diagnose reflux in patients with gastro-esophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) disease diagnosed with multichannel intraluminal impedance/ pHmetry (MII-pH).

Methods: 20 reflux patients were recruited of whom 10 had classical GERD and 10 had LPR. All patients underwent MII-pH and provided expectorated saliva samples when a MII-pH reflux event was observed, or reflux symptoms were experienced, and all were tested for the presence of pepsin using the Peptest™.

Results: Pepsin was detected in 31 out of 45 samples (68.9%). At least 1 positive pepsin result was seen in 16 patients (80%) and this was the same, irrespective of the GERD or LPR diagnosis. Peptest™ had a positive predictive value of 69% to detect MII-pH reflux events.

Conclusions: Peptest™ is a good first-line diagnostic procedure to use in reflux sufferers to confirm the presence of reflux.
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http://dx.doi.org/10.15403/jgld-335DOI Listing
December 2019

Alginates: From the ocean to gastroesophageal reflux disease treatment.

Turk J Gastroenterol 2019 09;30(Suppl2):109-136

Department of Pediatrics, Hacettepe University School of Medicine, Ankara, Turkey.

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http://dx.doi.org/10.5152/tjg.2019.19677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836317PMC
September 2019

Reflux esophagitis, functional and non-functional.

Authors:
Serhat Bor

Best Pract Res Clin Gastroenterol 2019 Jun - Aug;40-41:101649. Epub 2019 Sep 17.

Professor in Gastroenterology, Ege University, School of Medicine, Division of Gastroenterology, Ege Reflux Group, Izmir, Turkey. Electronic address:

The pathogenesis of gastroesophageal reflux disease has been explained by acid-peptic model. However, related with the progress of the diagnostic modalities, another phenotypical group of patients were defined and called "functional disorders of the esophagus". These patients are important because diagnosis is particularly difficult, co-morbid disorders especially psychiatric diseases are common, proton pump inhibitor response is low, and surgical results are very poor. Simpler and translational science studies are required in functional groups in order to differentiate from acid-peptic disorders. New and more accurate diagnostic modalities as well as therapeutic approaches are strongly needed in this particularly new and exciting era, especially in the effect of neuromodulators. Current diagnostic modalities should also be evaluated and in fact, normal values should be established. New medications, especially acting at the level of esophageal epithelium and intercellular spaces, might shift the paradigm.
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http://dx.doi.org/10.1016/j.bpg.2019.101649DOI Listing
December 2019

How to select patients for antireflux surgery? The ICARUS guidelines (international consensus regarding preoperative examinations and clinical characteristics assessment to select adult patients for antireflux surgery).

Gut 2019 11 2;68(11):1928-1941. Epub 2019 Aug 2.

Gastroenteroloy, Tiefenauspital Bern, Bern, Switzerland.

Objective: Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for antireflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for antireflux surgery.

Design: We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous.

Results: Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with oesophagitis Los Angeles (LA) grade B or higher and patients with Barrett's oesophagus are good candidates for antireflux surgery. An endoscopy prior to antireflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short oesophagus. Oesophageal manometry is mandatory to rule out major motility disorders. Finally, oesophageal pH (±impedance) monitoring of PPI is mandatory to select patients for antireflux surgery, if endoscopy is negative for unequivocal reflux oesophagitis.

Conclusion: With the ICARUS guidelines, we generated key recommendations for selection of patients for antireflux surgery.
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http://dx.doi.org/10.1136/gutjnl-2019-318260DOI Listing
November 2019

Validity and reliability of the Quality of Life in Reflux and Dyspepsia (QoLRAD) questionnaire in patients with gastroesophageal reflux disease for the Turkish population.

Turk J Gastroenterol 2019 Jun;30(6):511-516

Division of Gastroenterology, Ege University School of Medicine, İzmir, Turkey.

Background/aims: Gastroesophageal reflux disease negatively affects quality of life. The aim is to improve quality of life because of high recurrence rate. There is a strong need for patient-reported outcome measures. The present study aimed to evaluate the validity and reliability of the Quality of Life in Reflux and Dyspepsia Questionnaire (QoLRAD) to adopt it into Turkish.

Materials And Methods: A total of 142 patients with complaints of heartburn or regurgitation once a week or commonly diagnosed with 24-hour intraesophageal impedance-pH monitoring and/or upper gastrointestinal endoscopy were included in this study. Sociodemographic Data Collection Form, QoLRAD-TR, and Short Form-36 (SF-36) were applied to patients who were off proton pump inhibitors.

Results: The Cronbach's alpha coefficient value of the questionnaire was 0.97, and the intraclass correlation coefficient (ICC) value of the result of test-retest method was between 0.97 (Vitality) and 0.99 (Eating/Drinking Disorders). There was a positive correlation between all subdomains of QoLRAD-TR and SF-36 scales. The lowest correlation (0.10) was between Emotional Distress and Role-emotional Limitations, and the highest (0.34) was between Energy and Vitality.

Conclusion: The QoLRAD test measuring quality of life, except some subdomains in our study that we performed on patients diagnosed with GERD, was found to be valid and reliable.
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http://dx.doi.org/10.5152/tjg.2019.18689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565356PMC
June 2019

A meta-analysis on the cardiac safety profile of domperidone compared to metoclopramide.

United European Gastroenterol J 2018 Nov 10;6(9):1331-1346. Epub 2018 Sep 10.

Ege University Centre for Drug Research & Development Pharmacokinetic Research and Applications (ARGEFAR), Bornova, Izmir, Turkey.

Background: This meta-analysis aimed to assess the cardiac safety profile of domperidone treatment for the risk of cardiovascular (CV) event and QT prolongation.

Methods: Data from nine studies involving 101,155 patients were used for the analysis of CV event risk, while data from eight studies involving 390 patients were used for the analysis of QT prolongation risk.

Results: Meta-analysis findings suggested a significant increase in CV risk under domperidone as compared to no treatment for domperidone doses of >30 mg/day (OR: 3.14, 95% CI, 1.191 to 8.304,  = 0.021), no significant increase in QT prolongation event rates with domperidone (3.54%, 95% CI, 1.73% to 7.10%) and a significantly lower CV risk for domperidone than for metoclopramide (OR: 0.63, 95% CI, 0.58 to 0.70,  < 0.001).

Conclusions: The present meta-analysis indicates that domperidone treatment may not be associated with an overall CV event risk increase at doses ≤30 mg/day and does not result in QT prolongation.
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http://dx.doi.org/10.1177/2050640618799153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206542PMC
November 2018

Proximal Baseline Impedance Analysis Might be a Valuable Clue for Extraesophageal Reflux Diagnosis.

Clin Gastroenterol Hepatol 2018 08;16(8):1362-1363

Department of Gastroenterology and Hepatology, Ege University, Izmir, Turkey.

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http://dx.doi.org/10.1016/j.cgh.2018.04.004DOI Listing
August 2018

Medical treatment of gastroesophageal reflux disease.

Turk J Gastroenterol 2017 12;28(Suppl 1):S48-S52

Clinic of Gastroenterology, Türkiye Yüksek İhtisas Training and Research Hospital, Ankara, Turkey

Proton pump inhibitors (PPIs) are the most effective agents in the first-line and maintenance treatment of gastroesophageal reflux disease. As the grade of esophagitis increases, an increase is also observed in the level of endoscopic response to PPIs. In the first-line therapy of patients with severe esophagitis (Los Angeles (LA) Grade C-D), administration of a standard dose of PPIs bid has been reported to be more beneficial than PPIs qd. While any intermittant and low dose-continuous treatment can be chosen for the maintenance therapy of patients with non-erosive reflux disease or mild esophagitis (LA Grade A-B), continuous use of a standard dose of PPIs is preferred in the maintenance therapy of patients with severe esophagitis (LA Grade C-D). In patients who use PPIs for a long time, the drug must be stopped by gradually decreasing the dose.
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http://dx.doi.org/10.5152/tjg.2017.13DOI Listing
December 2017

How is the gastroesophageal reflux disease prevalence, incidence, and frequency of complications (stricture/esophagitis/Barrett's esophagus/carcinoma) in Turkey compared to other geographical regions globally?

Turk J Gastroenterol 2017 12;28(Suppl 1):S4-S9

Department of Gastroenterology, İzmir Katip Çelebi University School of Medicine, Atatürk Training and Research Hospital, İzmir, Turkey

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http://dx.doi.org/10.5152/tjg.2017.03DOI Listing
December 2017

Consensus Report on Gastroesophageal Reflux Disease in Turkey.

Authors:
Serhat Bor

Turk J Gastroenterol 2017 12;28(Suppl 1):S1-S2

Department of Gastroenterology, Ege University School of Medicine, İzmir, Turkey

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http://dx.doi.org/10.5152/tjg.2017.01DOI Listing
December 2017

The diagnostic value of 24-hour ambulatory intraesophageal pH-impedance in patients with laryngopharyngeal reflux symptoms comparable with typical symptoms.

United European Gastroenterol J 2017 Aug 12;5(5):632-640. Epub 2016 Oct 12.

Department of Gastroenterology, Ege University, Izmir, Turkey.

Background: The diagnosis of laryngopharyngeal reflux is currently based on a combination of the patient history of multichannel intraluminal impedance and ambulatory pH (MII-pH); however, none of these findings alone is specific for the diagnosis of laryngopharyngeal reflux. We aimed to compare the baseline characteristics and esophageal baseline impedance values between patients with and without laryngopharyngeal reflux symptoms.

Methods: We retrospectively analyzed data from two groups of patients with laryngopharyngeal reflux according to their reflux finding score (RFS) as scored by ENTs. Control patients were nonerosive reflux disease patients without laryngopharyngeal reflux. All MII-pH parameters and baseline impedance were analyzed from six levels and the proximal and distal baseline impedance and the ratio of the proximal to distal baseline impedance levels was calculated.

Results: Altogether 123 patients with laryngopharyngeal reflux and 49 control patients were included. A total of 81 of 123 patients had RFS ≥ 7, and 42 of 123 patients had RFS < 7. Baseline impedance analysis showed that patients with laryngopharyngeal reflux symptoms had significantly lower proximal baseline impedance values (1997 ± 51 vs 2245 ± 109,  < 0.05) than the control group. Additionally, patients with laryngopharyngeal reflux symptoms had a significantly lower proximal-to-distal ratio (1.28 ± 0.05 vs 1.53 ± 0.09,  < 0.05). In the subgroup analysis, patients with RFS < 7 were found to have a significantly lower acid exposure time than either the patients with RFS ≥ 7 (3.85 ± 0.65 vs 8.2 ± 1.52,  < 0.05) or the control group (3.85 ± 0.65 vs 6.1 ± 0.81,  < 0.05). Additionally, patients with RFS ≥ 7 had significantly lower proximal baseline impedance levels than the control group (1970 ± 63 vs 2245 ± 109,  < 0.05).

Conclusions: Patients with pathologic laryngopharyngeal reflux symptom scores had lower proximal baseline impedance levels and lower proximal-to-distal ratios, which may reflect the proximal mucosal noxious effect of the refluxate. These results may indicate that laryngopharyngeal reflux symptoms may be due to chronic acid exposure in the proximal segments of the esophagus, and the proximal-to-distal ratio may be used as a new metric for diagnosis.
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http://dx.doi.org/10.1177/2050640616675040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548345PMC
August 2017
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