Psychological Processes, Not Physiological Parameters, Are Most Important Contributors to Symptom Severity in Patients With Refractory Heartburn/Regurgitation Symptoms.

BACKGROUND & AIMS: Physiological and psychological factors have been found to influence esophageal symptom reporting. We aimed to evaluate which of these factors are associated with 3 reflux symptom severity outcomes (ie, Total Reflux, Heartburn, and Sleep Disturbance) through a traditional statistical and a complementary machine-learning approach. METHODS: Consecutive adult patients with refractory heartburn/regurgitation symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing past and current gastrointestinal and psychological health. In the traditional statistical approach, hierarchical general linear models assessed relationships of psychological and physiological variables (eg, total number of reflux episodes) with reflux severity scores. Mediation analyses further assessed pathways between relevant variables. In the machine-learning approach, all psychological and physiological variables were entered into 11 different models and cross-validated model performance was compared among the different models to select the best model. RESULTS: Three hundred ninety-three participants (mean [SD] age, 48.5 [14.1] years; 60% were female) were included. General psychological functioning emerged as an important variable in the traditional statistical approach, as it was significantly associated with all 3 outcomes and mediated the relationship between childhood trauma and both Total Reflux and Heartburn Severity. In the machine-learning analyses, general psychological variables (eg, depressive symptoms) were most important for Total Reflux and Sleep Disturbance outcomes, and symptom-specific variables, like visceral anxiety, were more influential for Heartburn Severity. Physiological variables were not significant contributors to reflux symptom severity outcomes in our sample across reflux classifications and statistical methodology. CONCLUSIONS: Psychological processes, both general and symptom-specific, should be considered as another important factor within the multifactorial processes that impact reflux symptom severity reporting across the reflux spectrum.

Psychological symptoms do not discriminate between reflux phenotypes along the organic-functional refractory GERD spectrum.

OBJECTIVE: Historically, psychological processes are associated with disorders at the functional end of the gastro-oesophageal reflux disease (GERD) spectrum. However, recent research suggests that psychological symptoms are relevant across the entire GERD spectrum. We aim to investigate whether psychological symptoms are associated with reflux phenotype (True GERD, Borderline GERD, reflux hypersensitivity, functional heartburn) along the GERD spectrum in a cohort of refractory reflux patients. DESIGN: Consecutive adult patients with refractory reflux symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing demographic, clinical and psychological information. Bayesian one-way analysis of variance assessed whether psychological variables differed across reflux phenotypes. Next, we applied multinomial and ordinal logistic regressions with clinical, demographic and psychological variables set as independent variables and reflux phenotype as the outcome variable. The complementary machine-learning approach entered all demographic, clinical and psychological variables into models, with reflux phenotype set nominally and ordinally. Cross-validated model performance was used to select the best model. RESULTS: 393 participants (mean (SD) age=48.5 (14.1); 60% female) were included. The Bayesian analyses found no difference in psychological variables across reflux phenotypes. Similarly, age, gender and proton pump inhibitor use were the only significant variables in the multinomial logistic regression and body mass index was significant in both regressions. Machine-learning analyses revealed poorly performing models with high misclassification rates (67-68%) in both models. CONCLUSION: Psychological symptoms do not differ between nor predict reflux phenotype membership in refractory reflux patients. Findings suggest that psychological symptoms are relevant across the spectrum of GERD, rather than specific to functional oesophageal disorders.

Sex and smoking differences in the association between gastroesophageal reflux and risk of esophageal squamous cell carcinoma in a high-incidence area: Golestan Cohort Study.

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.

Higher Body Mass Index Is Associated With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Understanding which eosinophilic esophagitis (EoE) patients will respond to treatment with topical corticosteroids (tCS) remains challenging, and it is unknown whether obesity impacts treatment response. This study aimed to determine whether treatment outcomes to tCS in EoE patients vary by body mass index (BMI). METHODS: This retrospective cohort study of the University of North Carolina EoE Clinicopathologic database assessed subjects age 14 years or older with a new diagnosis of EoE. Their BMI was calculated and histologic, symptom, and endoscopic responses were recorded after tCS treatment. The treatment response of obese (BMI, ≥30 kg/m2) and nonobese EoE status was compared using bivariate and multivariate analyses. RESULTS: We identified 296 EoE patients treated with tCS. Baseline characteristics were similar, although obese EoE patients had more heartburn and hiatal hernias. Histologic response was higher for those who were nonobese compared with obese at fewer than 15 (61% vs 47%; P = .049) and 6 or fewer (54% vs 38%; P = .02) eosinophils per high-power field, respectively. In addition, nonobese patients had significantly greater endoscopic and symptomatic responses. On multivariate analysis, increasing BMI was associated independently with decreased histologic response after accounting for age, heartburn, dilation, and hiatal hernia whether BMI was assessed as a continuous variable (adjusted odds ratio [aOR], 0.93; 95% CI, 0.89-0.98), as nonobese vs obese (aOR, 0.38; 95% CI, 0.21-0.68), or in 4 categories (overweight vs normal [aOR, 0.46; 95% CI, 0.26-0.84] or obese vs normal [aOR, 0.26; 95% CI, 0.13-0.51]). CONCLUSIONS: As BMI increases in EoE patients, the odds of histologic, symptomatic, and endoscopic responses to tCS decreases, with obese patients having an approximately 40% decrease in odds of response.

What is the significance of the Hill classification?

This study aimed to investigate the significance of Hill classification to predict esophagitis, Barrett's esophagus, gastroesophageal reflux disease (GERD) symptomatology, and future prescriptions of proton pump inhibitors in clinical practice. A total of 922 patients (546 women and 376 men; mean age 54.3 [SD 18.4] years) who underwent gastroscopy between 2012 and 2015 were analyzed. Patient questionnaire regarding symptoms were compared with endoscopy findings. A medical chart review was done that focused on the prescription of PPIs, additional gastroscopies, and GERD surgery in a 3-year period before the index gastroscopy and in a 6-year period afterward. In patients naïve to PPI prescriptions (n = 466), Hill grade III was significantly associated with esophagitis (AOR 2.20; 95% CI 1.00-4.84) and > 2 PPI prescriptions 6 year after the index gastroscopy (AOR 1.95; 95% CI 1.01-3.75), whereas Hill grade IV was significantly associated with esophagitis (AOR 4.41; 95% CI 1.92-10.1), with Barrett's esophagus (AOR 12.7; 95% CI 1.45-112), with reported heartburn (AOR 2.28; 95% CI 1.10-4.74), and with >2 PPI prescriptions (AOR 2.16; 95% CI 1.02-4.55). In patients 'non-naïve' to PPI prescription (n = 556), only Hill grade IV was significantly associated with esophagitis, reported heartburn, and with >2 PPI prescriptions. The gastroscopic classification in Hill grades III and IV is important in clinical practice because they are associated with esophagitis, Barrett's esophagus, symptoms of GERD, and prescriptions of PPIs, whereas a differentiation between Hill grades I and II is not.

Efficacy of laparoscopic fundoplication in patients with chronic cough and gastro-oesophageal reflux.

BACKGROUND: The outcome of anti-reflux surgery in patients with suspected gastro-oesophageal reflux-induced cough is frequently uncertain. The aims of this study were to assess the efficacy of laparoscopic fundoplication for controlling cough in patients with chronic cough without asthma, who have pathologic gastro-oesophageal reflux, and to identify predictors of response. METHODS: From a prospective database of 1598 patients who have undergone laparoscopic fundoplication, 66 (4%) with proven gastro-oesophageal reflux disease (GORD) and chronic cough without asthma were studied. All patients underwent gastroscopy and 24-h pH monitoring before operation. Heartburn and regurgitation were assessed using a modified DeMeester score. Severity of cough before and after surgery was self-assessed by the patient using a visual analog scale at a minimum of 12 months post-operatively (median 43 mo; range: 14-104 mo). Patients were considered to have responded to fundoplication if they had no cough or the cough had improved by 50% or more after operation. RESULTS: Cough and heartburn/regurgitation were relieved in 61% (40/66) and 90% (44/49) of the patients, respectively. The presence of typical GORD symptoms or oesophagitis, and pH study variables did not predict the response of the cough to fundoplication. CONCLUSION: Refinement in the aetiological diagnosis of chronic cough due to GORD is necessary for improved outcome. Patients diagnosed with GORD-related chronic cough need to be counseled regarding their expectations from anti-reflux surgery.

Efficacy and safety of laparoscopic Roux-en-Y gastric bypass in symptomatic patients following fundoplication failure: a meta-analysis.

Revisional surgery may be required in a subset of patients who remain symptomatic despite undergoing laparoscopic fundoplication (LF) for gastroesophageal reflux disease (GERD). While revisional LF (RLF) is feasible in these patients, laparoscopic Roux-en-Y gastric bypass (LRYGB) may serve as an alternative, although its efficacy and safety remains unknown. This study aimed to determine the outcomes of LRYGB in symptomatic patients following failed LF for GERD. MEDLINE, EMBASE, and PubMed databases were systematically searched for studies reporting LRYGB outcomes in symptomatic adults despite undergoing LF for GERD. Postoperative symptom resolution, recurrence of heartburn and dysphagia, proton pump inhibitor (PPI) use, and body mass index (BMI) reduction were assessed to determine LRYGB efficacy. Postoperative morbidity and mortality were used to evaluate LRYGB safety. Twenty-two studies with 1523 patients were included. Pooled rates of symptom resolution, recurrence of heartburn and dysphagia, PPI use, morbidity, and mortality were 71.6% (95% CI 59.4-86.4), 15.6% (8.9-27.3), 20.7% (12.5-34.3), 29.6% (18.8-46.5), 39.5% (29.9-52.3), and 2.2% (1.2-4.0), respectively, following LRYGB. Similar rates were observed after RLF. However, BMI reduction was significantly greater after LRYGB compared with RLF (mean difference 6.1 kg/m2, 4.8-7.4; p < 0.0001). LRYGB resulted in symptom relief in a majority of patients, and proved comparable to RLF regarding symptom recurrence and PPI use. Morbidity and mortality following LRYGB also did not differ from RLF. However, LRYGB was associated with considerably greater weight loss relative to RLF. Therefore, LRYGB is efficacious and an acceptable revisional procedure in symptomatic GERD patients who have previously undergone LF.

Limitations of Heartburn and Other Societies' Criteria in Barrett's Screening for Detecting De Novo Esophageal Adenocarcinoma.

BACKGROUND & AIMS: Despite extensive Barrett's esophagus (BE) screening efforts, most patients with esophageal adenocarcinoma (EAC) present de novo. It is unclear how much of this problem is the result of insensitivity or poor applications of current screening guidelines. We aimed to evaluate the sensitivity of guidelines by determining the proportion of prevalent EAC cases that meet the American College of Gastroenterology (ACG) or the British Society of Gastroenterology (BSG) guidelines for BE screening and determine whether changes to criteria would enhance detection. METHODS: A retrospective single-center cohort from the United States (n = 663) and a prospective multicenter cohort from the United Kingdom (n = 645) were collected and analyzed independently. Screening eligibility was determined as patients with chronic reflux and at least 2 or more risk factors as defined by the guidelines. We calculated the proportion of screening-eligible patients and then compared BE/EAC risk factors between screening-eligible and screening-ineligible patients using the chi-squared or Student t test as appropriate. RESULTS: In the Mayo clinic cohort there were 54.9% EAC cases and in the UK cohort there were 38.9% EAC cases that were not identified by ACG or BSG screening criteria, respectively. Among patients who did not meet the screening criteria, lack of heartburn was observed in 86.5% in the Mayo clinic cohort and in 61.4% in the UK cohort. Other risk factors that were lacking included obesity (defined as a body mass index of ≥30 kg/m2) and family history of EAC. Eliminating chronic reflux from the ACG/BSG criteria improved eligibility for screening from 45.1% to 81.3% (P < .001) in the Mayo Clinic cohort and from 61.1% (n = 394) to 81.5% (n = 526; P < .001) in the UK cohort. However, reflux may be difficult to ascertain from the history, and by including proton pump inhibitor use status in addition to the BSG criteria, screening eligibility improved by 10.0% in the UK cohort (n = 459; P < .001). CONCLUSIONS: ACG/BSG BE screening guidelines have limited our ability to detect prevalent EAC. An optimized approach to identifying the individuals most suitable for EAC screening needs to be implemented, particularly one that does not rely on chronic reflux symptoms.

Hiatal hernias associated with acid reflux: size larger than 2 cm matters.

Hiatal hernia (HH) is associated with gastroesophageal reflux disease (GERD); the effect of HH size on GERD is not well defined. To evaluate the relationship between HH size as measured by high-resolution esophageal manometry (HREM) and reflux parameters on esophageal pH-impedance testing (multichannel intraluminal impedance-pH [MII-pH]) to define HH sizes associated with GERD. HREM and MII-pH studies were reviewed. The relationship of HH size to other parameters was analyzed with multivariable logistic regression. Correlation coefficients were determined using Spearman and Pearson's tests. A total of 897 patients underwent both HREM and MII-pH. There were 529 (58.9%) patients with HH size <1 cm, 203 (22.6%) with HH 1.0-1.9 cm, and 165 (18.4%) with HH ≥2 cm. Larger HH size was associated with lower esophageal sphincter (LES) basal and residual pressures (r = -0.43 and r = -0.48, p < 0.01), higher acid exposure time (AET) (r = 0.17, p < 0.01), number of acidic refluxes (r = 0.16, p < 0.05), and number of reflux episodes detected by impedance (total r = 0.22, p < 0.01). HH ≥ 2 cm compared with smaller size HH was associated with higher proximal AET%, acidic refluxes, and reflux episodes detected by impedance (p < 0.05). Increasing HH size was associated with older age, higher AET, and number of reflux episodes. HH ≥2 cm was associated with multiple worsened GERD parameters. Low LES pressure was weakly associated with an increase in the number of reflux episodes. Larger HHs, particularly >2 cm, are associated with more severe GERD parameters.

[State of the Art Diagnostics of the Esophagus]. / State of the Art Diagnostik des Ösophagus.

State of the Art Diagnostics of the Esophagus Abstract. Modern diagnostics of the esophagus is highly technical. It mainly includes endoscopic, radiological, nuclear medicine, functional and electrochemical examinations. Diagnostic tools for esophageal disorders involve esophagogastroduodenoscopies with chromoendoscopy, manometric and pH-impedance catheters as well as radiological techniques, such as CT, MRI or PET-CTs. The patient's history including the main clinical symptoms such as heartburn or dysphagia, and the physical examination will determine the choice and order of subsequent examinations. The esophagogastroduodenoscopy is one of the most important diagnostic tools and has a very low complication rate. During esophagogastroduodenoscopy biopsies, chromoendoscopy or therapeutic interventions can be performed. Endosonography is essential for the staging of esophageal cancer and accuracy can be improved by endosonographically guided biopsies. A CT scan completes the tumor staging and is essential to search for metastases. For motility disorders high resolution manometry is the gold standard which can be supplemented with esophagus barium swallow exams. pH-impedance catheters can be used for diagnosis of reflux. MRI swallow exams are predominantly applied in clinical studies but may be more frequently used in the future.

Ineffective esophageal motility in Chicago Classification version 4.0 better predicts abnormal acid exposure.

BACKGROUND: The updated Chicago Classification version 4.0 (CCv4.0) establishes a more stringent criteria to diagnose ineffective esophageal motility (IEM). This study aims to investigate the clinical significance of IEM in CCv4.0 in the context of gastroesophageal reflux disease (GERD). METHODS: A retrospective study was conducted among suspected GERD patients who had heartburn and/or regurgitation as their chief complaints and completed esophageal function tests in our center from 2017 to 2019. Patients were further grouped as "CCv3.0 IEM" and normal motility according to Chicago Classification version 3.0 (CCv3.0), and as "CCv4.0 IEM" and normal motility according to CCv4.0. The clinical characteristics, high-resolution manometry, esophageal reflux monitoring, and proton pump inhibitor (PPI) efficacy were compared between different groups. Multivariate analyses were performed to identify esophageal motility parameters associated with reflux burden and symptom outcome. RESULTS: Of 172 subjects included, 93 patients were identified as CCv3.0 IEM, 69 as CCv4.0 IEM. IEM in either version was concomitant with elevated acid burden and impaired esophageal clearance as compared to normal motility in corresponding diagnostic criteria, while the only presence of IEM in CCv4.0 was predictive to abnormal acid exposure (AET > 6%: OR = 2.66, 95% CI [1.27-5.56], p < 0.01). The presence of "CCv3.0 IEM" and low EGJ-CI (EGJ-CI < 39.1 mmHg·cm) had no added value in predicting increased reflux burden. No interaction effect was found between the presence of IEM and a weakened EGJ. None of the manometric variables was capable of predicting PPI response. CONCLUSIONS: Stringent criteria of IEM in CCv4.0 can better predict abnormal acid exposure as compared to CCv3.0.

Effects of coexisting upper gastrointestinal symptoms on daily life and quality of life in patients with gastroesophageal reflux disease symptoms.

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) is a common disease encountered in daily medical care and clinical problem which hampers daily life and reduces quality of life (QOL). The coexistence of GERD-related symptoms with the typical GERD symptoms, such as heartburn or acid regurgitation, and various upper abdominal symptoms is frequently observed in patients with GERD. However, the effect of these coexisting symptoms on the daily life and QOL of patients with GERD has not been clarified. Therefore, the effects of the various upper abdominal symptoms coexisting with GERD on the daily life and QOL of such patients were compared. METHODS: A total of 113 newly diagnosed patients who visited our hospital with typical GERD symptoms were assessed using the modified frequency scale for the symptoms of GERD (MFSSG), gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test (GERD-TEST), and short-form 8-item health survey (SF-8) questionnaires. The "gastroesophageal reflux symptom" (7 items) and "dyspepsia symptom" (7 items) groups were divided into two "typical symptoms" and two "atypical symptoms" for a total of four categories. The Pearson's correlation coefficient and multiple regression analysis were used to evaluate the correlations between each symptom category and dissatisfaction for daily life [eating, sleeping, daily activities, mood, as well as dissatisfaction for daily life-symptom subscale (SS), which is the average of the four items in the GERD-TEST, the physical component summary [PCS] and mental component summary [MCS] of the SF-8, and the influence of each symptom category on the daily life and QOL. RESULTS: The incidences of each symptom category in patients with GERD were high: typical GERD (100%), atypical GERD symptoms (67.3%), typical functional dyspepsia (FD) (71.7%), and atypical FD (75.2%). Pearson's correlation analysis demonstrated significant correlations between each symptom category and living status (dissatisfactions of eating, sleeping, daily activities, daily life-SS) and almost all items in SF-8 (PCS, MCS) (P < 0.05). Multiple regression analysis indicated the largest influences of each symptom category on living status and QOL in descending order: dissatisfaction for eating (atypical FD, typical FD), daily activities (atypical FD, typical FD, typical GERD), mood (atypical FD), daily life-SS (atypical FD, typical FD), PCS (typical FD), and MCS (atypical FD) (P < 0.05). CONCLUSION: Coexisting FD symptoms, particularly atypical FD symptoms, had a large influence on the impairments of daily life and decreases in QOL. Daily medical care of GERD requires attention to coexisting symptoms and their treatment instead of just focusing on the chief complaints by patients.

The evaluation of recumbent reflux by multichannel intraluminal impedance pH testing for patients with gastroesophageal reflux disease and sleep disturbance.

BACKGROUND AND AIM: The relationship between gastroesophageal reflux disease (GERD) and sleep disturbance has recently been pointed out and is garnering substantial attention. Although there are reports that point out the effectiveness of medical treatment for sleep disturbance associated with GERD, examinations of the pathological condition, including reflux during sleep, are inadequate. In the present study, we evaluated the recumbent reflux in patients with GERD and sleep disturbance using multichannel intraluminal impedance pH (MII-pH), and attempted to suppress recumbent reflux by surgical treatment to examine the pathophysiology of patients with GERD and sleep disturbance. MATERIALS AND METHODS: Of the 47 patients with GERD-related diseases in whom laparoscopic fundoplication was performed at The Jikei University Hospital from January 2016 to June 2017, 31 patients (average age: 55.9 ± 13.8 years, male in 25), excluding 9 with surgical indications only for esophageal hiatal hernia and 7 without postoperative evaluation, were the subjects of this study. All surgical procedures were performed by the Toupet method. We used the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep disturbance, setting 5.5 as the cut-off value, based on the report by Doi et al., with any conditions beyond this value deemed sleep disturbance. The evaluation of gastroesophageal reflux was carried based on the MII-pH using the Sleuth, manufactured by Sandhill Corporation, with an automatic analysis carried out by computer. Furthermore, recumbent abnormal reflux was defined as recumbent all reflux (times) > 7. All evaluations were performed preoperatively and at 3 months after the operation. The data were expressed in medians and interquartile ranges, with p < 0.05 defined as statistically significant by the Mann-Whitney, Wilcoxon, or Chi-squared test. RESULTS: Although sleep disturbance was found in 19 cases (61%), 8 (42%) of which were actually confirmed as nighttime abnormal reflux, of whom 5 cases (63%) showed significant improvement in their sleep disturbance following the operation, with a PSQI score of lower than 5.5. Among these 5 cases, postoperative recumbent abnormal reflux was also significantly reduced as compared with the preoperative condition (17 vs. 2 times/day, p = 0.042). Furthermore, sleep disturbance improved and recumbent abnormal reflux also decreased in two cases, with sleep disturbance improved by controlling the nighttime reflux via surgery in a total of 7 cases (87.5%). Although the PSQI score was as high as 14 points before and after the operation in one case, the rate of recumbent abnormal reflux was remarkably reduced, with sleep disturbance and recumbent reflux considered irrelevant. Furthermore, regarding the frequency of recumbent acid/non-acid reflux, while non-acid reflux was significantly more frequent in the patients with recumbent reflux complications (9 vs. 1 time/day, p < 0.001), there was no marked difference in the frequency of acid reflux. CONCLUSIONS: Among cases with GERD and sleep disturbance, approximately one-third of them showed findings suggestive of the involvement of recumbent reflux in sleep disturbance, with reflux characterized by non-acid reflux.

Barrett's esophagus patients are becoming younger: analysis of a large United States dataset.

BACKGROUND: Barrett's esophagus (BE), a complication of long-term gastroesophageal reflux disease (GERD), has been reported to affect 6-8% of those with heartburn. Most patients are males, Caucasians and middle aged. However, there are no recent demographic studies that evaluated the proportion trends of BE. We aimed to assess proportion trends of BE over an 11-year period, using a very large national dataset. METHODS: This was a population-based analysis of the national Explorys dataset. Explorys is an aggregate of electronic medical record database representing over 54 million patients. Proportions of BE's variables such as age, gender, race, BMI, and treatment with PPI were recorded during an 11-year period. BE patients were classified into seven age groups (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, ≥ 70 years old). Secular trends of the proportion of BE were assessed over time for each age group. RESULTS: The majority of patients diagnosed with BE were ≥ 70 years old across all calendar years. However, the proportion of BE patients who were ≥ 70 years old has significantly decreased between 2006 and 2016 (- 19.9%, p < 0.001). The proportion of patients with BE increased in all age groups but most prominently in the age groups, 30-39: 2.07%, 40-49: 3.64%, 50-59: 6.89%, 60-69: 6.18%, p < 0.001. BE was significantly more common in those who were Caucasian and male. PPI usage fell significantly in those who were ≥ 70 years old (- 20.8%, p < 0.001), but increased in the other remaining age groups. CONCLUSIONS: The proportion of BE patients who are 70 years and older has significantly dropped. Younger patients' groups have demonstrated the highest increase in the proportion of BE patients, especially those in the age group of 30-39 years old.

Model to Select On-Therapy vs Off-Therapy Tests for Patients With Refractory Esophageal or Extraesophageal Symptoms.

BACKGROUND & AIMS: It is not clear whether we should test for reflux in patients with refractory heartburn or extraesophageal reflux (EER) symptoms, such as cough, hoarseness, or asthma. Guidelines recommend testing patients by pH monitoring when they are on or off acid-suppressive therapies based on pretest probability of reflux, determined by expert consensus. However, it is not clear what constitutes a low or high pretest probability of reflux in these patients. We aimed to develop a model that clinicians can use at bedside to estimate pretest probability of abnormal reflux. METHODS: We performed a prospective study of 471 adult patients with refractory heartburn (n = 214) or suspected EER symptoms (n = 257) who underwent endoscopy with wireless pH monitoring while they were off acid-suppressive treatment and assigned them to groups based on symptoms at presentation (discovery cohort). Using data from the discovery cohort, we performed proportional odds ordinal logistic regression to select factors (easy to obtain demographic criteria and clinical symptoms such as heartburn, regurgitation, asthma, cough, and hoarseness) associated with esophageal exposure to acid. We validated our findings in a cohort of 118 patients with the same features from 2 separate tertiary care centers (62% women; median age 59 years; 62% with cough as presenting symptom). RESULTS: Abnormal pH (>5.5% of time spent at pH <4) was found in 56% of patients with heartburn and 63% of patients with EER (P = .15). Within EER groups, abnormal pH was detected in a significantly larger proportion (80%) of patients with asthma compared with patients with cough (60%) or hoarseness (51%; P < .01). Factors significantly associated with abnormal pH in patients with heartburn were presence of hiatal hernia and body mass index >25 kg/m2. In patients with EER, the risk of reflux was independently associated with the presence of concomitant heartburn (odds ratio [OR] 2.0; 95% confidence interval [CI] 1.3-3.1), body mass index >25 kg/m2 (OR 2.1; 95% CI 1.5-3.1), asthma (OR 2.0; 95% CI 1.2-3.5), and presence of hiatal hernia (OR 1.9; 95% CI 1.2-3.1). When we used these factors to create a scoring system, we found that a score of ≤2 excluded patients with moderate to severe reflux, with a negative predictive value of 80% in the discovery cohort and a negative predictive value of 85% in the validation cohort. CONCLUSION: We developed a clinical model to estimate pretest probability of abnormal pH in patients who were failed by proton pump inhibitor therapy. This system can help guide clinicians at bedside in determining the most appropriate diagnostic test in this challenging group of patients.

Prevalence of acidic and non-acidic refluxes in patients with functional dyspepsia and its risk factors investigated by means of multichannel intraluminal pH-monitoring.

OBJECTIVE: Introduction: Previous studies performed by conventional pH-monitors showed that a significant proportion of patients with functional dyspepsia have abnormal acidic gastroesophageal reflux. The investigation, using advantages of multichannel intraluminal pH-monitoring, were not conducted. The aim to reveal the prevalence of all types of refluxes in patients with functional dyspepsia and to estimate risk provoking factors for abnormal reflux. PATIENTS AND METHODS: Methods and materials: Patients were divided into 6 groups. The 1st, 2nd and 3rd groups covered 127 adult patients with epigastric pain syndrome, postprandial distress syndrome and mixed variant respectively. The 4th included 69 NERD patients suffered from frequent (more than one episode per week) heartburn. The 5th group also consisted of 22 NERD patients without heartburn or with rare heartburn-regurgitation. The reference group included 30 subjects without dyspeptic complaint and established diagnoses of gastro-esophageal diseases. For all persons the 200-min MII-pH-monitoring was performed with standardized stimulating breakfast (507kcal, 100 mg caffeine, 300ml) recording basal and postprandial phases. RESULTS: Results: It was found that the difference in comparison to the reference group in the number of refluxes is determined by the number of acid refluxes and not by weakly-acidic and weakly-alkaline refluxes. Patients with functional dyspepsia from all subgroups had an excessive amount of acidic refluxes in comparison with the reference group - 3.7±0.7, 4.7±0.8 and 2.8±0.7 vs 1.8±0.3 episodes (p<0.05). Using the previously obtained threshold values for abnormal acidic reflux (> 6 episodes per 200 min.) and total refluxes (>17 episodes per 200 min.) it was revealed that 22.8% patients with FD had abnormal GER. In addition, 16.5% had an isolated excess of non-acidic reflux. All three dyspeptic groups didn't have a significant difference in the distribution of patients among subtypes of abnormal presence or absence of acidic/non-acidic refluxes. CONCLUSION: Conclusion: In functional dyspepsia abnormal acidic reflux are common and affect 22.8% of patients. It is independently associated with hiatal hernia (OR=4.17), previously healed a peptic ulcer (OR=3.90), occasional heartburn (OR=1.25), body mass index (OR=1.11), younger age (OR=0.97).

From Heartburn to Barrett's Esophagus, and Beyond.

BACKGROUND: Gastroesophageal reflux disease (GERD) affects an estimated 20% of the population in the USA, and its prevalence is increasing worldwide. About 10-15% of patients with GERD will develop Barrett's esophagus (BE). AIMS: The aims of this study were to review the available evidence of the pathophysiology of BE and the role of anti-reflux surgery in the treatment of this disease. RESULTS: The transformation of the squamous epithelium into columnar epithelium with goblet cells is due to the chronic injury produced by repeated reflux episodes. It involves genetic mutations that in some patients may lead to high-grade dysplasia and cancer. There is no strong evidence that anti-reflux surgery is associated with resolution or improvement in BE, and its indications should be the same as for other GERD patients without BE. CONCLUSIONS: Patients with BE without dysplasia require endoscopic surveillance, while those with low- or high-grade dysplasia should have consideration of endoscopic eradication therapy followed by surveillance. New endoscopic treatment modalities are being developed, which hold the promise to improve the management of patients with BE.

Ineffective esophageal motility: clinical, manometric, and outcome characteristics in patients with and without abnormal esophageal acid exposure.

The etiology and clinical impact of ineffective esophageal motility (IEM) remain poorly understood. Unless gastroesophageal acid reflux (GERD) is identified, symptomatic patients with IEM are challenging to treat. We sought to determine whether any clinical or functional characteristics could distinguish those patients with IEM and either normal or abnormal esophageal acid exposure.In this retrospective cohort study, we identified 46 consecutive patients presenting with heartburn, and other GER symptoms who underwent clinical, endoscopic, and functional evaluation that included high-resolution manometry (HRM) and ambulatory pH monitoring. IEM was defined using the Chicago Classification criteria (v.3) as ≥50% ineffective swallows (DCI ≤ 450 mmHg.s.cm). Esophageal acid exposure by ambulatory pH monitoring was considered abnormal when total time with esophageal pH < 4 exceeded 4.2%.Of the 46 IEM patients identified, 19 (mean age: 42 years, 37% female), had normal esophageal acid exposure and 27 patients, mean age 54 years, 33% female, evidence of pathologic acid reflux. There was a 12 years age difference between the groups, with those with normal acid exposure being significantly younger (P < 0.01); the mean body mass index (BMI) was 22.6 ± 0.6 in the normal group and 25.4 ± 0.7 in the abnormal group (P < 0.001); otherwise the groups were endoscopically and histologically similar. Symptoms were not discriminatory and heartburn and regurgitation were the most prevalent in both groups. HRM did not discriminate symptomatic patients with IEM and either normal or abnormal esophageal acid exposure. Proton pump inhibition (PPI) therapy was significantly more effective (74% vs. 10%) in patients with pathologic acid reflux (P < 0.001). As pH exposure becomes abnormal in the context of IEM, there is dominance for supine reflux.IEM appears to be an early, primary event, eventually associated with pathologic acid exposure, particularly supine. Higher BMI is also associated with abnormal esophageal acid exposure in such patients. GER symptoms are not discriminatory in patients with IEM with and without underlying pathologic acid reflux. Clinical response to PPI in such patients depends on the presence of esophageal pathologic acid exposure. Those with IEM and normal acid exposure remain symptomatic and mostly resistant to therapy.

Nutcracker esophagus: demographic, clinical features, and esophageal tests in 115 patients.

Nutcracker esophagus (NE) is a common esophageal motility disorder chacterized by high amplitude peristaltic contractions in the distal esophagus. While previous studies have examined selected aspects of this condition (e.g. pathogenesis and treatment), there is a paucity of data regarding demographic and clinical features in large cohorts of patients. The aim of this study was to describe demographics, clinical features, comorbidities, time to diagnosis, source of patient referral by specialty, and medication use in a large cohort of patients with NE. We retrospectively analyzed consecutive cases of NE diagnosed from 2008-2010. The electronic medical records of these patients were reviewed, and relevant information was extracted. We identified 115 patients with NE. The median age was 62 years (range 25-87 years), and 63% were female. The median time patients experienced symptoms prior to diagnosis was 24 months (0-480 months). Most patients presented to an internal medicine consultant (42%) or to a gastroenterologist (35%). Presenting symptoms were chest pain (31%) and dysphagia (21%). Gastroesophageal reflux disease (GERD) symptoms were common: heartburn occurred in 51% of patients, 77% had a prior history of GERD, and 78% were receiving acid suppressive medications. GERD was confirmed by testing in at least 35%. Psychiatric comorbidity occurred in 24% with half the patients receiving psychotropic medications. Irritable bowel syndrome (IBS) and fibromyalgia co-existed in 15% and 12% of patients, respectively. Surprisingly, opioids were prescribed to 26% of patients. No statistically significant correlation was found between esophageal motility parameters and symptoms. In this study, NE patients were more commonly middle-aged females experiencing a considerable amount of time between symptom onset and diagnosis. Many were initially evaluated by internists for dysphagia or chest pain and had a history of GERD. Medication prescribed prior to diagnoses frequently involved acid suppression, but narcotic and psychotropic prescriptions were also commonly used. Central sensitization syndromes (fibromyalgia and IBS), psychiatric comorbidity, and reflux commonly coexisted. Our study suggests that future investigations should address the role and interaction of GERD and psychiatric disorders in NE.

pH-Impedance Findings and proton pump inhibitors-responsiveness in patients with typical gastroesophageal reflux disease symptoms in a large single-center Italian series.

INTRODUCTION: A multicenter study with a limited sample size found that absence of esophagitis, presence of functional digestive disorders, and overweight were associated with proton pump inhibitors (PPI) failure. AIM: To assess clinical and reflux patterns associated with PPI-responsiveness. MATERIALS AND METHODS: Patients with typical gastroesophageal reflux disease (GORD) symptoms had 24 hours pH-impedance monitoring off therapy. Responders had <2 days of symptoms per week while on standard-dose/double-dose PPI. Clinical and reflux parameters were considered for analysis. RESULTS: A total of 514 patients were included (267 women), 185 patients were considered PPI responders, and 329 were considered nonresponders. In the whole population, the only significant factor in the prediction of responsiveness to PPI at the multivariate analysis was the presence of esophagitis (P=0.028). The factors identified as significant in patients with a pathologic acid exposure (142 patients) in the prediction of responsiveness to PPI were overweight (body mass index >25 kg/m(2)) and the presence of esophagitis (P=0.019 and 0.043, respectively). CONCLUSIONS: We confirm that no reflux pattern demonstrated by 24 hours pH-impedance monitoring is associated to PPI response in GORD patients. Presence of esophagitis in the whole population and overweight in patients with pathologic GORD, but not dyspepsia, are strongly associated with PPI-responsiveness.