case study of gerd

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Disclosure statement, clinical presentation of gastroesophageal reflux disease: a prospective study on symptom diversity and modification of questionnaire application.

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Ryan Broderick , Karl-Hermann Fuchs , Wolfram Breithaupt , Gabor Varga , Thomas Schulz , Benjamin Babic , Arielle Lee , Frauke Musial , Santiago Horgan; Clinical Presentation of Gastroesophageal Reflux Disease: A Prospective Study on Symptom Diversity and Modification of Questionnaire Application. Dig Dis 13 May 2020; 38 (3): 188–195. https://doi.org/10.1159/000502796

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Introduction: Symptoms occurring in gastroesophageal reflux disease (GERD) such as heartburn, regurgitation, thoracic pain, epigastric pain, respiratory symptoms, and others can show a broad overlap with symptoms from other foregut disorders. The goal of this study is the accurate assessment of symptom presentation in GERD. Methods: Patients with foregut symptoms were investigated for symptoms as well as endoscopy and gastrointestinal-functional studies for presence of GERD and symptom evaluation by standardized questionnaire. Questionnaire included a graded evaluation of foregut symptoms documenting severity and frequency of each symptom. The three types of questionnaires include study nurse solicitated, self-reported, and free-form self-reported by the patient. Results: For this analysis, 1,031 GERD patients (572 males and 459 females) were enrolled. Heartburn was the most frequently reported chief complaint, seen in 61% of patients. Heartburn and regurgitation are the most common (82.4/58.8%, respectively) in overall symptom prevalence. With regard to modification in questionnaire technique, if patients fill in responses without prompting, there is a trend toward more frequent documentation of respiratory symptoms (up to 54.5% [ p < 0.01]), fullness (up to 93.9%), and gas-related symptoms ( p < 0.001). Self-reported symptoms are more diverse (e.g., throat-burning [12%], mouth-burning [9%], globus [6%], dyspnea [9%], and fatigue [7%]). Conclusions: GERD symptoms are commonly heartburn and regurgitation, but overall symptom profile for patients may change depending on the type of questionnaire.

Since gastroesophageal reflux disease (GERD) has a prevalence of 20% in industrialized countries, symptoms associated with the disease are common in these populations [ 1, 2 ]. In order to define GERD, the authors of the Montreal classification relied heavily on symptoms and their effect on patients: “GERD is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications” [ 1 ]. These symptoms can reduce patient’s well-being and have a negative influence on the quality of life [ 3, 4 ].

In many studies, GERD symptoms are used to define the study populations [ 5‒13 ]. Other studies, however, have some evidence that symptoms are not always reliable as a guide to the diagnosis of GERD [ 14‒17 ]. GERD symptoms such as heartburn, regurgitation, thoracic pain, epigastric pain, respiratory symptoms, globus, and others show a broad overlap with symptoms from other esophageal and gastric disorders such as dyspepsia, esophageal motility disorders, functional heartburn, hypersensitive esophagus, irritable stomach and bowel, and somatoform disorders [ 1 , 14‒17 ]. The wide array of symptoms and potential diagnoses make one consider if there is a specific questioning technique or symptom profile that is more highly suggestive of GERD. Klauser et al. [ 18 ] have stated that heartburn and regurgitation are the most typical symptoms characterizing GERD, but in clinical practice, a large variety of esophageal and extra-esophageal symptoms can be reported.

Over the last 3 decades, our team had documented symptoms of GERD patients in a large data bank. Initially, the evaluations were standardized and leaned heavily on the early DeMeester symptom score and Gastrointestinal Quality of Life Index [ 19‒22 ]. Several years later, these questions were validated within the project of creating a symptom questionnaire featuring 53 items to determine somatoform tendencies [ 17 ]. With the exception of respiratory symptoms, all items in this current questionnaire differentiated significantly between healthy volunteers and patients with foregut symptoms [ 17 ].

The goals of this study are to determine the diversity and most common symptoms of GERD in large patient populations over time. Additionally, we aim to determine if the method of questioning is significant in altering the symptom profile of GERD patients.

Study Design

Over the course of more than 2 decades, our working group had the opportunity to investigate a large population of patients with GERD in a specialized center for benign esophageal and gastric disorders. All patients with foregut symptoms referred for further exploration of esophageal and/or gastric disease underwent a history and physical examination. The symptoms of the patients were evaluated by a standardized questionnaire over the complete time period from 1995 to 2017. Only the method of application for the questionnaires was changed over time, as described in detail below. All patients received an upper gastrointestinal endoscopy and esophageal manometry. In more recent years, a high-resolution manometry was performed [ 23 ]. The presence of pathologic reflux was evaluated by 24-h pH monitoring and later by impedance-pH monitoring.

Varying methods of questionnaire administration were used over the years in different time segments to evaluate the patient’s symptoms, as indicated below:

Group 1: (Study period 1995–1999) The study nurse used the standard questionnaire to ask the patients for the symptoms and marked the answers of the patients regarding presence and severity of the symptoms herself.

Group 2: (Study period 2005–2009) The study nurse handed the questionnaire over to the patients and the patients were left alone to fill in the presence and the severity of the symptoms. The patients could ask for assistance to the nurse, if needed.

Group 3a: (Study period 2015–2017) The study nurse handed the questionnaire over to the patients and the patients were left alone to fill in the presence and the severity of the symptoms in the document.

Group 3b: (Study period 2015–2017) Patients (same patients of Group 3a) were asked to document in a free-text version the 3 most important symptoms that limit or reduce the patient’s quality of life. Patients were instructed by the study nurse to document their most relevant symptoms as precisely as possible. Additionally, the study nurse also handed the standard questionnaire over to the patients and the patients were left alone to fill in the presence and the severity of the symptoms. It is important to notice that the free formulated description of the symptoms by the patients themselves was always conducted before the patients filled in the standardized questionnaire. This order was kept with the aim to avoid influences of the standard questionnaire to the patient formulated free text.

The groups were chosen for different time periods, in which changes of the symptom evaluation was established (solicited, self-reported, and free-form self-reported). The standard symptom questionnaire remained the same over the study duration.

Patient Selection and Inclusion/Exclusion Criteria

The patients were recruited in a tertiary referral center for foregut disorders and its diagnostic functional laboratory and surgery unit. The management of the patients was performed by the same team (same study nurse) over the complete period 1995–2017. The patients were asked to give informed consent to the study evaluation and the diagnostic work-up. The study was approved by our Institutional Review Board.

The data were reviewed in a prospectively maintained databank. Inclusion criteria for this analysis were patients with documented GERD, which required either the presence of esophagitis (esophagitis grading according to Savary-Miller 1–4), pathologic esophageal acid exposure on pH testing, and/or a hiatal hernia with heartburn and/or regurgitation. The hiatal hernia was documented during endoscopy by measuring the vertical extent of the distance between the cardia (beginning of the gastric folds) and the waist of the crurae, best assessed during inspiration (distance >1 cm). Care was taken to measure this length in the beginning of the endoscopy without major air insufflation of the stomach to avoid hernia reduction.

This analysis was not performed in some time periods (2000–2004 and 2010–2014), during which the documentation of symptoms was not rigorously followed due to shortage in personnel for administering the questionnaire. In addition, other exclusion criteria were if patients had other diseases such as cancer, inflammatory bowel disease, esophageal spasm, achalasia, or if they had prior operations for GERD.

The Questionnaire

For symptom evaluation, a standardized questionnaire was established and used over 25 years. The questionnaire included a graded evaluation of foregut symptoms: heartburn, regurgitation, retrosternal/thoracic pain, respiratory symptoms (cough/hoarseness), dysphagia, epigastric pain (pain/cramps/burning), nausea/vomiting, fullness (unpleasant fullness, early satiety), and gas-related symptoms (belching/bloating/flatulence). Patients had to document the severity and frequency of each symptom by grading according to the following system: 0 = no symptoms; 1 = symptom occurring rarely; 2 = symptom occurring occasionally; 3 = symptom occurring monthly and/or with mild intensity; 4 = symptom occurring weekly and/or with moderate intensity; 5 = symptoms occurring daily and/or with severe intensity.

Statistical Methods

Symptom results were analyzed according to their documented overall presence in these patients, independent of their severity, as well as by the most frequently reported significant/chief complaints. The mean intensity of the presented symptoms was analyzed. Statistical comparison with a t test for unpaired samples was used for the comparison of data from the different samples. A chi-square test was used for comparison of group data.

From 1995 to 2017, over 2,000 patients with symptoms indicative of GERD were seen by our team. Patients with other gastrointestinal diseases that could influence foregut symptoms were excluded from this study. In total, 1,031 met all inclusion criteria as GERD patients and were enrolled from 3 different time segments. Group 1 (1995–1999) included 481 patients, Group 2 (2005–2009) had 333 patients, and Group 3a/3b (2015–2017) had 217 patients. There were 572 males and 459 females. Table 1 demonstrates the characteristics of patients in the different groups. Presence of esophagitis, evidence of lower esophageal sphincter incompetence, esophageal acid exposure, and the level of quality of life showed severity of GERD among the patients in different groups over the years.

Patients’ characteristics for each group

Frequency of Chief Complaints and Overall Presence of Symptoms

Heartburn (retrosternal burning rising from the epigastrium to the chest) was the most frequent chief symptom (intensity: 5), independent of exam technique (Table 2 : Group 1: 60%; Group 2: 61%; Group 3a: 61.6%; Group 3b: 48.5%). Table 2 shows the frequency of chief complaints in the different groups. When the questionnaire is filled in by the study nurse (Group 1), the most common symptoms are heartburn and regurgitation (60%, 17%). Additionally in Group 1, other symptoms such as epigastric pain, dysphagia, or gas-related symptoms such as bloating, belching, and flatulence are not often experienced as the primary symptom (frequencies <15%). When comparing between groups, there are significant differences between the reported symptoms (Group 1 vs. Group 2/Group 3a). More often patients self-report respiratory symptoms (1.6% vs. 21.3%/20.2%; p < 0.001), epigastric pain (13.1% vs. 24.7%/12.1%), and gas-related problems (2.6% vs. 27.2%/22.0%; p < 0.01).

Overview on the percentage of documented symptoms with intensity 5 (chief complaint) differentiated for each group

Table 3 provides an overview on the overall presence of symptoms as evaluated in the various time periods. Heartburn and regurgitation are most frequent in Group 1 (82.4 and 58.8%, respectively). If patients fill in the questionnaire themselves, there are significant differences between groups in the presence of documentation of respiratory symptoms (Group 1: 11.8%; Group 2: 24.9%; Group 3a: 54.5%; p < 0.01), fullness (1: 11%; 2: 72.7%; 3: 93.9%; p < 0.001), and gas-related symptoms (1: 34%; 2: 72.7%; 3: 93.9%). These differences are even more pronounced in recent years.

Overview on the percentage of overall presence of documented symptoms differentiated for each group

Administration of Free-Text Form of Symptom Evaluation

When patients report their symptoms in their own words prior to completing the standard questionnaire (Group 3b), the documented variety of symptoms increases compared to the structured questionnaire alone (Table 4 ). In Group 3b, heartburn remains the most frequently reported symptom both as chief complaint (31%) and in the overall presence (48.5%). Reported symptoms are much more diversified: burning in the throat (12%), burning in the mouth (9%), globus (6%), headache (1%), dyspnea (9%), and fatigue (7%; Table 4 ).

Overview on percentage of symptoms in a free-text version self-assessed symptoms versus documentation in a self-assessed structured questionnaire

Intensity of Symptoms and Their Relation to Objective Functional Data

Data on the intensity of symptoms are summarized in Table 5 . The intensity of heartburn is highest in all groups (Group 1: 3.61; Group 2: 3.88; Group 3a: 3.39). The nurse documented the intensity of the symptoms such as regurgitation, retrosternal pain, epigastric pain, and respiratory symptoms higher (Group 1) than the patients themselves (Groups 2 and 3).

Overview on the mean intensity of symptoms differentiated for each group

The relationship between symptom intensity and the esophageal functional status show only for heartburn a significant rise in intensity for patients with and without lower esophageal sphincter-incompetence. These differences were for Group 1: 3.1 vs. 3.9; for Group 2: 3.2 vs. 3.9; for Group 3: 1.8 vs. 3.4 (all p < 0.005). The differences in symptom intensity are also significant for some comparisons with regurgitation; however, all other symptoms have no remarkable differences detected for changes in objective functional status.

We show that despite altering modality of questioning and symptom assessment in GERD patients, heartburn is the most frequently reported symptom. The severity and intensity of heartburn were documented to be the highest among all other symptoms through all years of investigation. The reported intensity of heartburn is significantly increased when the functional status of the antireflux barrier deteriorates. On the other hand, the presence/absence and intensity of other symptoms (e.g., regurgitation, respiratory symptoms, bloating) can depend on the concept and details of questioning. Allowing the patients to report free-form selection of symptoms shows a larger variety of documented chief complaints and other gas-related symptoms that may not be appreciated on standardized questionnaire.

Similar to our study, literature review shows that heartburn is reported to be present in patients with pathologic esophageal acid exposure in 72–99% [ 1 , 3 , 14 , 17 , 18 , 24‒28 ]. Regurgitation is another important symptom in GERD, with a prevalence of 33–86% [ 1, 14, 17, 29, 30 ]. According to some studies, epigastric pain is present in patients with foregut symptoms in 70% and in those with documented pathologic acid reflux in 12–67% [ 1, 3, 14, 17 ]. Our study confirms the importance of heartburn as the classic symptom with the highest intensity and the highest frequency as a chief complaint throughout the study. In Group 3b (free-text format), the symptom of heartburn was further delineated as “burning in the throat” or “burning in the mouth” in up to 14%.

Results of the present study show that the documented presence of symptoms can depend on the method of questioning (e.g., whether the symptoms are asked by a study nurse or if the patients are documenting without solicitation). The more the patient is free in her/his answering the questionnaire, symptom variability increases, especially with increased incidence of gas-related and atypical symptoms. The overall presence of heartburn remains independent of questionnaire administration around 80%. Notably, a statistically significant finding of respiratory symptom presence increases from 11 to 50% and the gas-related symptoms from 30 to 90% depending on questionnaire modality of application. All other symptoms have a much lower incidence in our GERD patients, and therefore, functional investigations are helpful to confirm the disease if esophagitis is absent.

There has been a controversial discussion about symptoms as a diagnostic tool for the presence of GERD, initiated by the Montreal definition [ 1 , 14 , 18‒20 ]. Our study confirms that there is a significant diversity of foregut symptoms present in GERD patients, as well as numerous extra-esophageal complaints such as cough, hoarseness, burning sensation in pharynx, mouth, and tongue in patients [ 1 , 14‒17 ]. Extra-esophageal symptoms can be respiratory symptoms such as chronic cough, hoarseness, and shortness of breath [ 31‒38 ]. There may also be symptoms at the level of the head and neck such as globus or burning in the mouth or throat. Recent studies show limitations of measuring acid reflux in the pharynx with current technology [ 37, 39, 40 ]. It remains difficult to correlate these symptoms with reflux episodes, even with objective testing.

We show that our validated questionnaire provides adequate assessment of patient symptoms. Allowing free-form reporting of symptoms in addition to a structured questionnaire may provide a more robust symptom profile in reflux disease. There is evidence in literature that structured questionnaires are very helpful and effective for symptom evaluation, and this is confirmed by our study [ 41‒46 ]. Several instruments have been published, validated, and successfully used in clinical practice [ 41‒46 ]. Various questionnaires published include the Patient Assessment of Upper Gastrointestinal Symptom Severity Index, the Gastrointestinal Rating Scale, the ­Chinese GERD Questionnaire, the GERD-Health Related Quality of Life Instrument, the Esophageal Symptoms Questionnaire, and the Reflux Disease Questionnaire [ 41‒43 , 47‒50 ]. A systematic review of all the available questionnaires for the assessment of GERD showed that many differ in design, validation, and translation [ 43 ]. One should be aware of the strength and shortcomings of each before selecting one for use [ 43 ]. All instruments have a self-assessment or self-administered mode of application, usually evaluating severity and/or frequency of GERD symptoms with a median of 15 items (6–30 items) [ 41‒43 , 47‒50 ]. The most useful instruments allowed for self-assessment by the patients [ 43 ]. However, none of these surveys allow for a free-text version of symptom documentation such as the one tested in this study.

When using the questionnaire over the years we noticed that many patients added remarks in the margin, indicating a possible lack of options or inadequate description. The unprompted free-form clarification of symptoms stimulated the impetus for providing patients more space to document symptoms in this way. None of the available validated questionnaires leaves room for the patient’s free text. Variations in patient symptoms such as burning in the mouth, tongue, and throat may be important features to document. In the past, one could only speculate that these symptoms were superficially classified as heartburn or odynophagia. Most of the available structured and validated questionnaires focus on heartburn, epigastric pain, fullness, bloating, regurgitation, and dysphagia. Therefore, it may be reasonable to add a free-text section to GERD questionnaires for detection of rare but important symptoms restricting the patient’s quality of life.

While expanding structured questionnaires to integrate all possible symptoms would be able to register all symptom variations, the more items to be answered lengthen and complicate the questionnaire process, potentially reducing applicability. Recently developed technologies allow patients to record symptoms in an electronic diary using a mobile electronic device. These technologies may be able to integrate self-administered and free text from evaluations to receive a more realistic and clinically valuable assessment.

Limitations of this study include the retrospective character of the analysis and the long duration of data sampling. Additionally, there were periods of time during the study period where documentation was not able to be rigorously completed due to shortage of nurses (2000–2004, 2010–2014), so data from these periods were excluded and sample size reduced as a result. Overall, the size of the patient data sampling performed by one team and one study nurse provides a dependable performance of data sampling and robust data for comparison of the changing techniques of administrating the assessment of GERD symptoms.

GERD remains a disease with a wide variety of symptoms experienced by patients. While heartburn and regurgitation remain mainstays of symptom reporting, there may be a range of symptoms and intensities of symptoms that go unreported if not elicited in a free-text format. The variety of symptoms experienced also shows the importance of a full correlating objective workup with esophago-gastro-duodenoscopy, high-resolution manometry, and impedance-pH testing to assist with accurate diagnosis of patients who may need surgical correction of their disease.

GERD symptoms are commonly heartburn, regurgitation, fullness, respiratory, and gas/bloat-related. The most important and frequent symptom is heartburn and its intensity parallels objective functional parameters of the esophagus. The overall symptom profile of patients may vary depending on the modality of questioning: practitioner directed, patient questionnaire, or free-form patient reporting of symptoms. Objective studies should be a key component in determining treatment for GERD due to the wide disparity in presenting symptoms.

The authors have no conflicts of interest to declare.

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Chapter 34:  Gastroesophageal Reflux Disease: A Burning Question Level II

Brian A. Hemstreet

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Instructors can request access to the Casebook Instructor's Guide on AccessPharmacy. Email User Services ( [email protected] ) for more information.

After completing this case study, the reader should be able to:

Describe the clinical presentation of gastroesophageal reflux disease (GERD), including typical, atypical, and alarm symptoms.

Discuss appropriate diagnostic approaches for GERD, including when patients should be referred for further diagnostic evaluation.

Recommend appropriate nonpharmacologic and pharmacologic measures for treating GERD.

Develop a treatment plan for a patient with GERD, including both nonpharmacologic and pharmacologic measures and monitoring for efficacy and toxicity of selected drug regimens.

Outline a patient education plan for proper use of drug therapy for GERD.

Chief Complaint

“I’m having a lot of heartburn. These pills I have been using have helped a little but it’s still keeping me up at night.”

Janet Swigel is a 68-year-old woman who presents to the GI clinic with complaints of heartburn four to five times a week over the past 5 months. She also reports some regurgitation after meals that is often accompanied by an acidic taste in her mouth. She states that her symptoms are worse at night, particularly when she goes to bed. She finds that her heartburn worsens and she coughs a lot at night, which keeps her awake. She has had difficulty sleeping over this time period and feels fatigued during the day. She reports no difficulty swallowing food or liquids. She has tried OTC Prevacid 24HR once daily for the past 3 weeks. This has reduced the frequency of her symptoms to 3–4 days per week, but they are still bothering her.

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• Case Study on Gastroesophageal Reflux in Middle-Aged Woman

Patient: Female, 52

Final diagnosis: Gastroesophageal Reflux

Gastroesophageal Reflux signs and Symptoms:  burning pain in the chest that usually occurs after eating and worsens when lying down.

Speciality: Gastroenterology

Causes, symptoms, and treatment of Gastroesophageal Reflux

Gastroesophageal reflux disease (GERD) affects as many middle-aged women as males. It might manifest as heartburn, regurgitation, dysphagia, or chest discomfort. We examined the severity of symptoms in women is significantly more than in men and may contribute to earlier disease recognition and different disease management.

Gastroesophageal Reflux Case Study

A 52-year-old woman was referred to gastroenterology practice for a history of gastroesophageal reflux disease. The patient claims to have had heartburn symptoms for at least five years. Her symptoms responded to over-the-counter medications such as antacid tablets and liquids, but they grew so frequent that she sought medical attention from her primary care physician.

Later, she reported minor acid reflux at least twice a week. She does not have any other chronic medical issues and does not use any other drugs. Her social background includes severe alcohol usage for 20 years, which she discontinued after being diagnosed with liver illness four years ago. There is no family history of gastrointestinal cancer in her family.

Gastroesophageal Reflux Causes

Gastroesophageal reflux disease, often known as GERD, is a digestive illness that affects the muscular ring between your oesophagus and stomach. The lower esophageal sphincter is the term given to this ring (LES). You may have heartburn or acid indigestion if you have it. Doctors believe that some people develop it as a result of a disease known as hiatal hernia. In most situations, GERD symptoms can be alleviated via dietary and lifestyle modifications. However, some people may require taking medication or going under surgery.

Dysphagia, nausea or vomiting, blood in her stool, or accidental weight loss were all symptoms she encountered. Most people can control their GERD symptoms with simple lifestyle modifications and over-the-counter medicines. However, she may require more potent medication or surgery to cure her problems. Because the patient has a history of alcoholism, she is particularly sensitive to this condition.

Gastroesophageal Reflux Age Range

We observed that the usual age group with GERD symptoms is primarily middle-aged women, i.e. (age range 36 to 55).

Gastroesophageal Reflux symptoms

Heartburn is the most common symptom of GERD. (GERD) occurs when stomach acid regularly rushes back into the tube that links your mouth and stomach (oesophagus). Acid reflux (backwash) can irritate the esophageal lining. Many people experience acid reflux on a regular basis.

Common signs and symptoms of GERD include:

• A burning sensation in your chest (heartburn), usually after eating, which could be worse during the night
• Difficulty swallowing
• Regurgitation of food or sour liquid
•  Throat lump sensation

Night-time acid reflux, one might also experience:

• Chronic cough
• New or worsening asthma
• Disrupted sleep

Gastroesophageal reflux risk factors include:

• Bulging the top of the stomach up into the diaphragm
• Connective tissue disorders, such as scleroderma
• Delayed stomach emptying

Gastroesophageal Reflux Symptoms and Treatment

Lying down is one of the home treatments for GERD. According to most researchers, the optimal height of bed head elevation is at least 6-8 inches (15-20 centimetres). This height has been shown in studies to reduce acid reflux when lying down. In reality, the higher the height, the better.

Gastroesophageal reflux management

GERD therapy aims to reduce the quantity of reflux or decrease the damage to the oesophagus lining affected by the refluxed materials.

Over the counter or prescription, medicine recommendations work to address Gastroesophageal reflux causes and symptoms.

• Antacids: These medications can help neutralize the acid in the oesophagus and stomach, therefore alleviating heartburn. Non-prescription antacids give brief or partial relief for many people. Some people benefit from an antacid coupled with a foamy agent. These chemicals, according to researchers, form a foam barrier on top of the stomach, preventing acid reflux.
• H2 blockers: For persistent reflux and heartburn, the doctor may prescribe medicines to decrease stomach acid. H2 blockers, which assist in inhibiting acid production in the stomach, are among these medications. Cimetidine (Tagamet), famotidine (Pepcid), and nizatidine are models of H2 blockers.
• Proton pump inhibitors (PPIs): Often known as acid pumps, medications that reduce stomach acid production by blocking a protein. Dexlansoprazole (Dexilant), esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), omeprazole/sodium bicarbonate (Zegerid), pantoprazole (Protonix), and rabeprazole are all proton pump inhibitors (Aciphex).
• Prokinetics: In rare circumstances, these medicines assist your stomach empty faster, resulting in less acid being left behind. They may also aid in the treatment of symptoms such as bloating, nausea, and vomiting. Domperidone and metoclopramide are two samples of prokinetics (Clopra, Maxolon, Metozolv, Reglan). Many individuals are unable to take them, and those who can only do so for a short time.

In this case, she was initially given an H2 blocker, which proved ineffective, so she was put on proton pump inhibitor treatment for a while. She presently takes 20mg of omeprazole daily, which she finds beneficial, although she does have heartburn if she skips a dosage. The patient can now comfortably swallow meals and liquids and shows no indications of vomiting or nausea. The patient is constantly monitored and encouraged to make certain dietary and lifestyle modifications. She is recommended to abstain totally from alcohol and cigarettes.

Routine check-ups and proper treatments can help patients with Gastroesophageal Reflux cure. Suppose you are experiencing any symptoms mentioned above. In that case, you can follow the Gastroesophageal reflux care plan by getting in touch with the online gastroenterologist doctor . You can talk to the gastroenterologist and consult gastroenterologist online free. Services are available in different cities, consult her as a gastroenterologist, the best doctor in Patna for the stomach , best female gynaecologist in Jhansi , gastro surgeon in Delhi , liver cirrhosis specialist doctor in India, NCR gastro liver clinic Gurgaon, max hospital liver specialist, the gastro & liver clinic Patna Bihar and best physician in Jammu city .

1. Can GERD affect my heart?

GERD and the associated heartburn have nothing to do with heart or heart disease even though the burning chest in pain seems like a pain in the heart.

2. Are there symptoms other than heartburn for GERD?

Other symptoms include regurgitation of acid up in the throat, bitter taste in the mouth, persistent dry cough, and wheezing among others.

3. Why doesn’t the acid harm the stomach?

The stomach has a thick lining that protects it from damage by acid. The oesophagus does not have this lining.

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Nutrition counseling is the assessment of an individual’s dietary intake after which, they are helped set achievable goals and taught various ways of maintaining these goals. The nutrition counselor provides information, educational materials, support and follow-up care to help an individual make and maintain the needed dietary changes for problems like obesity.

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I assist people dealing with weight-related health problems by evaluating the health risks and help in obesity management. I also help patients manage various food allergies.

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Gastroenterology

As a gastroenterologist, my primary focus is the overall health of the digestive system. I treat everything from acid reflux to ulcers, IBS, IBD: Crohns disease and ulcerative colitis, and colon cancer.

Endoscopy is a nonsurgical procedure to examine a person’s digestive tract. It is carried out with an endoscope, a flexible tube with a light and camera attached to it so that the doctor can see pictures of the digestive tract on a color TV monitor.

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Gastroenterology is a specialty that evaluates the entire alimentary tract from the mouth to anus and involves studying the diseases of the pancreas.

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A liver transplant is a surgical procedure that removes a patient’s non-functioning liver and replaces it with a healthy liver from a deceased donor or a portion of healthy liver from a living donor. It is reserved as a treatment option for people who have significant complications due to end-stage chronic liver disease or in case of sudden failure of a previously healthy liver.

The association between night eating syndrome and GERD symptoms among university students at An-Najah National University in Palestine: a cross-sectional study

Affiliations.

• 1 Department of Medicine, College of Medicine and Health Sciences, An-Najah National University, Nablus, 44839, Palestine.
• 2 Department of Internal Medicine, GI and Endoscopy Unit, An-Najah National University Hospital, Nablus, 44839, Palestine.
• 3 Department of Nutrition and Food Technology, College of Medicine and Health Sciences, An- Najah National University, Nablus, 44839, Palestine. [email protected].
• PMID: 38760691
• PMCID: PMC11100070
• DOI: 10.1186/s12876-024-03259-y

Background: Night eating syndrome (NES) is a kind of eating disorder. NES association with gastroesophageal reflux disease (GERD) symptoms among university students is still not fully understood. We aimed to determine the relationship between NES and the presence of GERD symptoms among university students at An-Najah National University in Palestine.

Methods: This study involved undergraduate students from An-Najah National University. The data were collected through online surveys from November to December 2023. The sampling frame involved voluntary sampling, as the data were collected using a structured questionnaire to collect data on sociodemographic variables, medical history, lifestyle habits, nutritional status, GERD risk, and NES. The GERD questionnaire (GerdQ) was used to assess symptoms, while the Arabic version of the validated Night Eating Questionnaire (NEQ) was used to assess night eating. Physical activity was assessed using the short form of the International Physical Activity Questionnaire (SF-IPAQ), and adherence to a Mediterranean diet was assessed using the validated Arabic version of the MEDAS. Both univariate and multivariate analyses were also conducted to assess the study hypotheses.

Results: The study involved 554 participants, 59.9% female. A total of 33.4% reported GERD symptoms, with 10.3% having NES. A strong association was observed between GERD and NES and between GERD and physical activity. Night eating syndrome (AOR = 2.84, CI = 1.07-3.19), high physical activity (AOR = 0.473, CI = 1.05-3.19), and non-smoking (AOR = 0.586, CI = 1.27-7.89) were identified as independent predictors of GERD symptoms.

Conclusion: This study revealed that 33.4% of undergraduate students were at risk of GERD, with night eaters having a greater risk. GERD risk was negatively associated with physical activity level and smoking status. No associations were found between GERD risk and weight status, Mediterranean diet adherence, sociodemographic factors, or sleep disturbances.

Keywords: Gastroesophageal reflux disease (GERD); Lifestyle; Mediterranean diet; Night eating syndrome (NES); University students.

© 2024. The Author(s).

• Cross-Sectional Studies
• Diet, Mediterranean / statistics & numerical data
• Gastroesophageal Reflux* / epidemiology
• Middle East / epidemiology
• Night Eating Syndrome* / epidemiology
• Risk Factors
• Students* / statistics & numerical data
• Surveys and Questionnaires
• Universities
• Young Adult

• Case Report
• Open access
• Published: 20 May 2024

An acute gastric volvulus in a child with congenital left diaphragmatic hernia: a case report

• Zesheng Yang 1 , 2   na1 ,
• Xiaoying Xie 1 , 2   na1 ,
• Shicheng Wang 1 , 2 ,
• Guanghua Pei 1 , 2 &
• Jianghua Zhan 1 , 3  

BMC Pediatrics volume  24 , Article number:  348 ( 2024 ) Cite this article

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Acute complete gastric volvulus is a rare and life-threatening disease, which is prone to gastric wall ischemia, perforation, and necrosis. If it is not treated by surgery in time, the mortality rate can range from 30 to 50%. Clinical presentations of acute gastric volvulus are atypical and often mimic other abdominal conditions such as gastritis, gastroesophageal reflux, gastric dilation, and pancreatitis. Imaging studies are crucial for diagnosis, with barium meal fluoroscopy being the primary modality for diagnosing gastric volvulus. Cases of acute gastric volvulus diagnosed by ultrasound are rarely reported.

Case presentation

We reported a rare case of acute gastric volvulus in a 4-year-old Chinese girl who presented with vomiting and abdominal pain. Ultrasound examination revealed the “whirlpool sign” in the cardia region, raising suspicion of gastric volvulus. Diagnosis was confirmed by X-ray barium meal fluoroscopy, which indicated left-sided diaphragmatic hernia and obstruction at the cardia region. Surgical intervention confirmed our suspicion of acute complete gastric volvulus combined with diaphragmatic hernia.

In this case, we reported an instance of acute complete gastric volvulus. Ultrasound revealed a “whirlpool sign” in the cardia, which is likely to be a key sign for the diagnosis of complete gastric volvulus.

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Introduction

Acute complete gastric volvulus is a rare and life-threatening disease in which the stomach rotates more than 180 degrees around its axis [ 1 , 2 ]. It can lead gastric wall ischemia, perforation, and necrosis. If it is not treated by surgery in time, the mortality rate can range from 30–50% [ 3 ]. Clinical presentations of acute gastric volvulus are atypical and often mimic other abdominal conditions such as gastritis, gastroesophageal reflux, gastric dilation, and pancreatitis. Imaging studies are crucial for diagnosis, with barium meal fluoroscopy being the primary modality for diagnosing gastric volvulus. There are limited cases reported of acute gastric volvulus diagnosed by ultrasound. We reported a rare case of acute gastric volvulus in a 4-year-old Chinese girl who presented with vomiting and abdominal pain. Ultrasound examination revealed the “whirlpool sign” at the cardia region, raising suspicion of gastric volvulus. Diagnosis was confirmed by X-ray barium meal fluoroscopy, which indicated left-sided diaphragmatic hernia and obstruction at the cardia region. Surgical intervention confirmed our suspicion. Notably, the patient was unaware of her underlying congenital left diaphragmatic hernia prior to the acute presentation of gastric volvulus. The case highlights the challenge posed by the asymptomatic nature of certain congenital conditions in clinical practice.

Case description

A 4-year-old girl was admitted to the hospital due to vomiting and abdominal pain that had persisted for two days. Upon admission, clinical examination revealed reduced subcutaneous fat, a soft non-distended abdomen, tenderness around the umbilical region. No other positive findings were observed on physical examination. Routine laboratory tests were all within the normal range.

The abdominal plain film showed consistently increased density in the left lung field, absence of a gastric bubble, and an air-fluid level in the lower right abdomen, indicating intestinal obstruction. Abdominal ultrasound examination revealed a “whirlpool sign” approximately 18 × 17 mm 2 in size at the gastric cardia (Fig.  1 ) with a counterclockwise rotation. The gastric cavity was dilated, and a portion of the stomach was located within the thoracic cavity (Fig.  2 ). The pylorus was not clearly visualized. Ultrasound diagnosed: gastric volvulus combined with diaphragmatic hernia. Barium meal fluoroscopy showed a fluid-filled cystic shadow in the left upper to middle lung field that did not significantly change with position. The left diaphragmatic margin was indistinct, the right diaphragmatic margin was smooth, the mediastinum was markedly shifted to the right, and the distal end of the gastric decompression tube was positioned at the level of the right diaphragmatic margin. Following oral administration of a compound barium solution, it was obserevd that the contrast agent filled the esophagus but was obstructed as it descended toward the distal end of the esophagus, resulting in a “bird’s beak” appearance (Fig.  3 ). The proximal esophagus was dilated, and there was frequent reflux of the contrast agent. Regardless of trying to remove the gastrointestinal decompression tube, the descending of the contrast agent was still blocked. By repeated observations in various positions, the distal digestive tract cannot be visualized. X-ray diagnosed left diaphragmatic hernia and obstruction of the cardia.

Emergency Surgery and Postoperative Progress: The acute gastric volvulus posed a life-threatening risk to the patient, necessitating emergency surgery. The surgical procedure was as follows: under laparoscopy, a significant defect in the left diaphragm was observed. This diaphragmatic defect existed independently and was not connected to the esophageal hiatus. The stomach, small intestine, spleen, pancreas, and a portion of the colon had all herniated into the left thoracic cavity. The stomach was markedly distended (Fig.  4 ), exhibiting high tension and local signs of ischemic necrosis. As laparoscopy failed to relocate the abdominal organs to the abdominal cavity, an open surgical approach was adopted. An approximately 8 cm oblique incision below the left costal margin was made to access the abdominal cavity. The stomach, small intestine, spleen, pancreas, and part of the colon were carefully relocated back into the abdominal cavity. During the procedure, it was noted that the stomach had undergone a counterclockwise rotation of 360° (Fig.  5 ). Following the reduction, areas of ischemic necrosis in the serosal layer of the gastric wall were identified, and repaired by interrupted suturing. The left diaphragm was adequately mobilized, and surrounding adhesions were released. And interrupted sutures with 2 − 0 Micro-bridge sutures were used to repair the diaphragm. Further release of adhesions at the root of the mesentery enhenced reduction. After this, the small intestine and colon were arranged within the abdominal cavity. Gastric fixation was not performed during the surgery. The operation lasted for 3 h and 2 min, with a blood loss of around 52 ml.

Intraoperative Diagnosis: (1) Left diaphragmatic hernia with cardia obstruction, (2) Gastric volvulus. Postoperatively, the patient received mechanical ventilation assistance for 14 h. On the 6th postoperative day, the child’s abdominal drainage fluid increased and turned yellow-green. Bedside ultrasound indicated localized fluid accumulation in the upper left abdomen, suggesting a possible leakage of digestive fluids. An urgent abdominal exploration was performed, which revealed a roughly 3 mm perforation in the gastric wall (at the original suture line). Intermittent full-layer suture were applied to the perforation, and the seromuscular layer was reinforced with suture. The patient managed without respiratory assistance throughout the second surgery. On the 9th postoperative day, the child was gradually allowed to drink water. And the diet was slowly advanced. The patient fully recovered and was discharged 17 days after the surgery. Following discharge from the hospital, we conducted rigorous follow-up procedures. The initial follow-up took place one week post-discharge, followed by monthly check-ins for 8 months. Throughout this period, our focus was primarily on monitoring the patient’s weight and growth. We are pleased to report a weight gain of 2.5 kg and confirm that her growth and development align with normal parameters for her age group during the follow-up period. Despite undergoing two surgeries, the patient’s recovery process was smooth, and she is currently in good health. Long-term follow-up will be continued to ensure her ongoing well-being.

Ultrasound displayed the “whirlpool sign” at the cardia (indicated by the arrow)

Ultrasound revealed extreme gastric dilation, with a significant portion located within the thoracic cavity

X-ray contrast imaging demonstrated a “bird’s beak” appearance in the distal esophagus

Laparoscopy revealed significant gastric distention

The base of the torsion (indicated by the arrow)

Gastric volvulus refers to an abnormal rotation of the stomach along its long or short axis, leading to gastric obstruction. Gastric volvulus can be categorized as primary or secondary based on its etiology. Primary gastric volvulus occurs when only the gastric ligaments (hepatogastric, gastrohepatic, gastrosplenic, and gastrocolic ligaments) are excessively long, lax, or absent, without the presence of other congenital malformations that might cause the gastric torsion. Secondary gastric volvulus, on the other hand, is caused by abnormalities in adjacent organs such as the diaphragm and/or spleen.

Based on the rotation axis of gastric volvulus, gastric volvulus can be divided into organoaxial, mesenteroaxial, and mixed types [ 4 , 5 , 6 ]. The organaxis is the most common type of gastric volvulus, referring to the torsion of the stomach along its long axis (the line between the cardia and the pylorus), and often coexists with a diaphragmatic defect. The mesenteroaxial type refers to the torsion of the stomach along the axis of the midpoint of the great curvature of the stomach and the lesser curvature of the stomach; the mixed type is extremely rare and has both the above two torsion manifestations.

In the presented case, the occurrence of gastric volvulus is related to the congenital diaphragm defect. The position of the stomach is displaced due to the hernia of the stomach through the diaphragm defect into the thoracic cavity or other organs due to ligament pull. The stomach is rotated counterclockwise along the axis of the line between the cardia and the pylorus. Rotation greater than 180° is considered to be complete torsion, which can easily lead to gastric outlet obstruction and strangulation [ 7 , 8 , 9 ]. Complete torsion is common in the organoaxial type and is characterized on X-ray fluoroscopy by a sudden narrowing of the lower esophagus and a “bird’s beak” appearance. The case described in our study represents a complete secondary organoaxial gastric volvulus.

Clinically, gastric volvulus can be divided into chronic and acute. Chronic gastric volvulus often presents with intermittent upper abdominal pain, nausea, postprandial vomiting, and abdominal distension. It is typically managed conservatively. Acute gastric volvulus, on the other hand, is not only rarer but has a sudden onset, with severe abdominal pain and non-bilious vomiting as the main symptoms, requiring immediate surgical reduction. The reported case is an instance of acute gastric volvulus, with clinical manifestations of vomiting and abdominal pain. It can be challenging to differentiate acute gastric volvulus from other causes of upper gastrointestinal obstruction. In this particular case, an abdominal X-ray was performed when symptoms appeared, leading to a misdiagnosis of intestinal obstruction.

Acute gastric volvulus is considered a surgical emergency, and if not promptly treated with surgery, it can lead to gastric wall ischemia, perforation, necrosis, and even a life-threatening situation in children. Hence, early diagnosis is of paramount importance. Borchardt described three symptoms to help with the diagnosis: upper abdominal pain, repeated retching, and inability to insert a nasogastric tube [ 10 ]. In our case, Borchardt’s triad was prominently exhibited. However, clinical presentations of gastric volvulus in most children are atypical, and some may not exhibit any of the aforementioned clinical symptoms [ 11 , 12 ]. X-ray fluoroscopy is considered a key diagnostic modality for gastric volvulus [ 13 , 14 , 15 ]. However, in cases of complete gastric volvulus, the contrast agent may not pass into the stomach, and the diagnosis may be limited to cardia obstruction. Moreover, there are literatures suggest that barium meal radiography in patients with delayed diagnoses of acute gastric volvulus, especially those with a longer history, may carry a higher risk of gastric perforation [ 6 , 8 ].

Ultrasound is a non-invasive and convenient method for detecting relevant abdorminal abnormalities such as diaphragmatic hernias, splenic anomalies, and gastric volvulus. It was reported that abdominal ultrasound in an adult patient with chronic intermittent gastric volvulus revealed gastric midportion constriction, referred to as the “peanut sign”, which can be indicative of gastric volvulus [ 16 ]. In another study of a 6-year-old patient with acute mesenteroaxial gastric volvulus, ultrasonography highlighted a distended and fluid-filled stomach, which was displaced in a cephalic position compared to esophagus and a pylorus pointing downward in a cranial caudal orientation. The case was ultimately confirmed as gastric volvulus through barium meal fluoroscopy [ 17 ].

In this study, we conducted an abdominal ultrasound examination on a patient with acute complete organoaxial gastric volvulus and observed a distinctive feature known as the “whirlpool sign” at the cardia. This sign is a specific sign of torsion-type diseases, and the degree of the whirlpool is closely related to the extent of torsion. In this case, the patient had an exceedingly rare complete gastric volvulus with a 360° rotation, making the “whirlpool sign” highly pronounced. Ultrasound, being a real-time imaging modality that can be performed in any direction, enabled us to clearly visualize the “whirlpool sign” at the cardia. Therefore, this sign proves to be valuable in diagnosing complete gastric volvulus, especially in younger children who may not cooperate with instructions, making ultrasound challenging to X-ray barium studies. Moreover, ultrasound, being non-invasive, painless, and radiation-free, can be repeated as necessary.

In ultrasound examination, the whirlpool sign, as a widely documented finding, can be observed in various intestinal torsions, including small bowel torsion, cecal torsion, sigmoid colon torsion, closed-loop intestinal obstruction, and others [ 18 , 19 ]. Its significance as a diagnostic indicator is particularly prominent, especially in pediatric patients presenting with acute abdominal pain, where early diagnosis and intervention are crucial. Although gastric torsion is relatively rare, the observation of this feature in ultrasound examinations holds important diagnostic value. In this case report, gastric torsion was successfully diagnosed through ultrasound examination, with the “whirlpool sign” playing a key role in the diagnostic process. Therefore, in similar challenging cases, the use of ultrasound examination should be considered, with a specific focus on the presence of the “whirlpool sign” to enhance opportunities for early diagnosis and treatment.

For acute complete gastric volvulus, immediate surgical intervention is strongly recommended. The choice between laparoscopic and open surgery via the abdominal approach can be based on the surgeon’s preference [ 20 , 21 ]. The surgical procedure typically involves the following steps: reduction of the gastric volvulus, evaluation of gastric wall, exploration of secondary factors, gastric fixation, and evaluation of the need for anti-reflux operation [ 17 , 22 ]. In this case, the child underwent laparoscopic surgery to reduce the gastric volvulus and repair the diaphragmatic hernia, but due to the failure of laparoscopy to reduce the abdominal organs back into the abdominal cavity, an open surgical approach was adopted. Gastric fixation was not performed during the surgery.

Acute complete gastric volvulus is an extremely rare condition in children. Early diagnosis and immediate surgical intervention are key factors for a successful outcome. Our study showed that ultrasound examination plays a valuable role in the diagnosis of acute complete gastric volvulus. In addition to detecting the “whirlpool sign” at the gastroesophageal junction, it can also identify associated anomalies such as hiatal hernia. The “whirlpool sign” on ultrasound is a distinct feature visible in various rotations of the gastrointestinal tract, including gastric volvulus. While acute gastric volvulus itself is uncommon, the presentation of the whirlpool sign is rare. This case further validates the effectiveness of the “whirlpool sign” in another gastrointestinal misalignment—gastric volvulus. The “whirlpool sign” on ultrasound has pathological features, high sensitivity to volvulus, and is a useful indicator. Familiarity with and emphasis on the whirlpool sign during ultrasound examination are crucial for pediatricians and sonographers to ensure timely intervention, thereby improving the prognosis of pediatric patients and reducing the incidence of complications.

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Zesheng Yang and Xiaoying Xie contributed equally to this work and share first authorship.

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Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, China

Zesheng Yang, Xiaoying Xie, Shicheng Wang, Guanghua Pei & Jianghua Zhan

Department of Ultrasound, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), No.238 Longyan Road, Beichen District, Tianjin, 300134, China

Zesheng Yang, Xiaoying Xie, Shicheng Wang & Guanghua Pei

Department of General Surgery, Tianjin Children’s Hospital(Children’s Hospital of Tianjin University), Tianjin, China

Jianghua Zhan

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Z.S.Y. : Data curation, Writing – original draft. X.Y.X. and S.C.W. : Writing – review & editing. G.H.P. and J.H.Z. : Supervision, Validation, Writing – review & editing.

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Correspondence to Zesheng Yang or Guanghua Pei .

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This study was approved by the Medical Ethics Committee of Tianjin Children’s Hospital, and all participants were informed and consented.

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Z.S.Y. was responsible for data curation and drafting the initial manuscript. X.Y.X. and S.C.W. contributed to writing – review & editing. G.H.P. and J.H.Z. supervised, validated, and contributed to writing – review & editing. All authors have read and approved the final manuscript.

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Yang, Z., Xie, X., Wang, S. et al. An acute gastric volvulus in a child with congenital left diaphragmatic hernia: a case report. BMC Pediatr 24 , 348 (2024). https://doi.org/10.1186/s12887-024-04834-8

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DOI : https://doi.org/10.1186/s12887-024-04834-8

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Presentation and Epidemiology of Gastroesophageal Reflux Disease

Joel e. richter.

1 Joy McCann Culverhouse Center for Swallowing Disorders, Division of Digestive Diseases & Nutrition, University of South Florida College of Medicine, Tampa FL

Joel H. Rubenstein

2 Veterans Affairs Center for Clinical Management Research, Ann Arbor, MI

3 Barrett’s Esophagus Program, Division of Gastroenterology & Hepatology, University of Michigan Medical School, Ann Arbor, MI

Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder in the United States, and leads to substantial morbidity, though associated mortality is rare. The prevalence of GERD symptoms appeared to increase until 1999. Risk factors for complications of GERD include advanced age, male sex, white race, abdominal obesity, and tobacco use. Most patients with GERD presents with heartburn and effortless regurgitation. Coexistent dysphagia is considered an alarm symptom, prompting evaluation. There is substantial overlap between symptoms of GERD and those of eosinophilic esophagitis, functional dyspepsia, and gastroparesis, posing a challenge for patient management.

By consensus, gastroesophageal reflux disease (GERD) has been defined as the effortless movement of stomach contents into the esophagus or mouth causing troublesome symptoms or complications ( 1 ). We review the clinical presentation and epidemiology of GERD. The cardinal symptoms of GERD are heartburn and regurgitation. GERD is exceedingly common, ranking as the most frequent gastrointestinal diagnosis associated with outpatient clinic visits in the United States (US), with nearly 9 million visits in 2009.( 2 ) Although complications such as bleeding erosive esophagitis or peptic stricture are becoming less common, individuals with GERD symptoms have a decrement in their quality of life that is similar to patients with inflammatory bowel disease.( 2 ) To accurately diagnose and manage GERD, it is important to recognize the epidemiologic risk factors for GERD, the variety of presenting symptoms and their relative likelihood of representing pathological reflux, and the potential for overlap with other gastrointestinal disorders.

Clinical Presentation

Heartburn and acid regurgitation are the classic symptoms of GERD. Patients generally report a burning feeling in the retrosternal area, raising into the chest and radiating toward the neck, throat and occasionally the back.( 1 ) It occurs post-prandially—particularly after large fatty meals or the ingestion of spicy foods, citrus products, fats, chocolates, or alcohol. The supine position and bending over may exacerbate heartburn. Nighttime heartburn may cause sleeping difficulties and impair next-day function ( 3 ). Sleep deprivation as well as psychological or auditory stress may lower the threshold for symptom perception ( 4 ). GERD can be diagnosed based on symptoms, such as the occurrence of heartburn 2 or more days a week, although symptoms can be less frequent if they are troublesome and have adverse effects on well-being ( 1 ). The frequency and severity of heartburn do not associate with degree of esophageal damage.

Regurgitation has been more inconsistently described in clinical trials and epidemiological studies on GERD. Per the Montreal consensus statement, regurgitation is defined as the “perception of flow of refluxed gastric contents into the mouth or hypopharynx.”( 1 ) Among patients with daily regurgitation, lower esophageal sphincter pressure is often low; many patients have associated gastroparesis, and esophagitis is common, making this symptom more difficult to treat medically than classic heartburn ( 5 ).

The lack of a standard for the diagnosis of GERD has made it difficult to define the accuracy of the typical reflux syndrome of troubling heartburn and/or regurgitation. The Diamond Study from the United Kingdom attempted to address this question in patients presenting to family practitioners with complaints of upper gastrointestinal symptoms ( 6 ). GERD was present in 203/308 patients (66%), based on endoscopic esophagitis and/or abnormal acid exposure or a positive symptom association probability from 24-hr pH tests. Only 49% of patients with GERD selected either heartburn or regurgitation as their most troublesome symptom, followed by dyspepsia, bloating, regurgitation, and abdominal pain or discomfort that was not characterized as dyspepsia. Sensitivity and specificity values for symptom-based diagnosis of GERD were 63% and 63% by family practitioners and 67% and 70% by gastroenterologists, respectively. Questionnaires about reflux symptoms did not perform any better—they identified patients with GERD with only 62% sensitivity and 67% specificity. Nor could response of symptoms to treatment with the proton pump inhibitor (PPI) esomeprazole (40 mg for 2 weeks) increase diagnostic precision—a positive response to the PPI test was observed in 69% of patients with GERD and 51% of patients without GERD ( 7 ). Similarly, a well-performed meta-analysis cast doubt on the diagnostic accuracy of the PPI trial, finding that it identified patients with GERD with 78% sensitivity and 54% specificity ( 8 ).

Less-common symptoms of GERD include dysphagia, chest pain, water brash, odynophagia, burping, hiccups, nausea, and vomiting. Dysphagia is considered an alarm symptom in patients with GERD that warrants upper endoscopy ( 9 ). Dysphagia usually occurs in patients with long-standing heartburn with slowly progressive dysphagia for solids. Weight loss is uncommon because patients have good appetites. The most common causes are peptic stricture and severe inflammation, but dysphagia can be the first symptom of Barrett’s esophagus with esophageal cancer. The chest pain associated with GERD can be indistinguishable from that of ischemic cardiac pain. GERD is a more frequent cause of non-cardiac chest pain than esophageal motor disorders.( 1 ) The most problematic and controversial symptoms associated with GERD are chronic cough, chronic laryngitis (including hoarseness, globus sensation, and throat clearing), and asthma. Although potential mechanisms of pathogenesis have been identified, trials of medical and surgical anti-reflux treatments have produced uncertain and inconsistent results ( 1 ). Some patients with GERD are asymptomatic. This is particularly true in older patients—perhaps because of decreased acidity of the reflux material or decreased pain perception. Many older patients present first with complications of GERD because of long-standing disease with minimal symptoms. This is a particular problem for patients with Barrett’s esophagus; European population studies found that 44%–46% of patients did not report symptoms of GERD ( 10 , 11 ).

Overlap With Other Disorders

GERD symptoms overlap with those of other syndromes. This poses a challenge to diagnosis and can alter medical and surgical treatments.

Eosinophilic esophagitis (EoE)

The issue of how to differentiate EoE from GERD has confounded clinicians and researchers since the recognition of the disease. This diagnostic dilemma began with a pathology study of pediatric patients in 1982, which found that eosinophils in the esophageal squamous epithelium could be a manifestation of GERD, documented by 24-hr pH tests ( 12 ). Pathologists rapidly accepted the concept, and it became common clinical practice to attribute esophageal eosinophilia to GERD. The first report describing EoE as a unique syndrome, characterized by solid food dysphagia and distinct from GERD by esophageal tests, was published in 1993 ( 13 ). Subsequently, EoE was considered a chronic immune- or antigen-mediated esophageal disease. However, many cases still overlapped with GERD, so the PPI trial became the most logical and convenient means to differentiate GERD from EoE. This practice was based on the assumption that the only major effect of PPIs is to inhibit gastric acid production. Accordingly, in 2007, the American Gastroenterological Association’s consensus report defined EoE as a primary disorder characterized by esophageal symptoms, esophageal biopsies with more than 15 eosinophils per high-powered field, and the “absence” of pathologic GERD—evidenced either by normal results from pH tests or lack of response to PPIs ( 14 ).

This mutually exclusive paradigm began to fall apart as editorials raised the possibilities of a complex interaction between GERD and EoE. These raised questions such as: does EoE cause GERD? Does GERD cause EoE? Or do these merely co-exist, because GERD is such a common disease? ( 15 ) Subsequently, Ngo et al ( 16 ) described 3 patients with EoE and significant mucosal eosinophilia who improved, based on clinical and histological features, after 2 months of PPI therapy. Several years later, Molina-Infante et al ( 17 ) published findings from 35 patients with mucosal eosinophilia (more than 15 eosinophils per high-powered field); 75% responded to rabeprazole (20 mg, twice daily) for 2 months. All 17 of the patients with GERD profile and objective acid reflux, based on endoscopy or pH tests, responded to this treatment. However, 50% of the patients with an EoE-like profile and normal pH test results also responded to the rabeprazole.

The recognition of this condition, which was termed PPI-responsive esophageal eosinophilia (PPI-REE), caused further confusion. Studies documented that 23% to 61% of patients with symptomatic esophageal eosinophilia respond to PPI treatment ( 18 ). Furthermore, the clinical, endoscopic, histologic and even esophageal gene-expression features of PPI-REE and EoE are virtually identical ( 19 ). PPI-REE therefore resembles EoE far more than it resembles GERD.

An exciting discovery around this controversy has been the recognition that EoE and GERD could each arise via cytokine-mediated esophageal injury. In contrast to the model in which refluxed acid causes a chemical injury that destroys esophageal cells, studies from patients and animal models indicated that the esophageal damage found in patients with GERD was caused by inflammatory cells, which are attracted to the esophagus by cytokines produced by esophageal epithelial cells following exposure to refluxed acid and bile ( 20 , 21 ). Studies of cultured esophageal epithelial cells revealed anti-cytokine effects of PPIs that were entirely independent of effects on gastric acid production—these could heal GERD and EoE. Omeprazole was found to block eotaxin-3 secretion stimulated by T-helper 2 cytokines produced by esophageal cells from patients with EoE or GERD ( 22 ) and block secretion of interleukin 8, a mediator of eosinophilic inflammation after exposure to acid and bile salts in esophageal epithelial cells from patients with GERD ( 23 ).

The current focus on how to distinguish EoE from GERD may therefore be counterproductive, since the 2 diseases often co-exist with complex interactions. Patients with GERD with the typical reflux syndrome associated with erosive esophagitis and hiatal hernia can have mucosal eosinophilia, which often is confined to the distal esophagus. It is not clear what proportion of patients with GERD present with these features, but it is likely to be less than 10% ( 24 ). The etiology of their mucosal eosinophilia may be secondary to direct acid injury or secondary to the effects of GERD on esophageal barrier function, which renders the epithelium permeable to food antigens and causes antigen-induced esophageal eosinophilia ( 25 ). Regardless, PPIs can reduce both mechanisms of pathogenesis; careful separation by esophageal manometry and pH – impedance testing is necessary for only patients who require surgical anti-reflux treatment.

Functional dyspepsia

Population-based studies have identified GERD and dyspepsia, defined as pain or discomfort centered in the upper abdomen, as some of the most common upper gastrointestinal tract symptoms—estimated prevalence values are approximately 20% for each ( 26 ). Therefore, it should not be surprising that the distinction between GERD and functional dyspepsia may not be clear cut. More than 33% of patients with functional dyspepsia also report heartburn and acid regurgitation and vice versa. This was well illustrated in the Diamond study, in which 42% of the patients without GERD reported dyspepsia as their first- or second-most troubling symptom, whereas this value was 37% in patients subsequently found to have GERD ( 6 ).

Furthermore, endoscopy and pH tests do not separate these groups with a high level of confidence. A large systematic review of more than 5000 patients with a primary complaint of dyspepsia found endoscopic evidence of esophagitis in 13.4% of patients, followed by peptic ulcers in 8.0% ( 27 ). Several studies identified patients with functional dyspepsia using Rome II or III criteria and performed 24-hr pH tests. Tack et al ( 28 ) reported that 23% of patients with functional dyspepsia had abnormal acid exposure times, and their symptom profile was mainly epigastric pain. A similar study of an Asian population, performed by Xiao et al ( 29 ), found that 31.7% of patients had abnormal acid exposure times, with the highest percentage (48.9%) in patients who claimed epigastric burning was their predominate symptom. In this study, the proportion of patients with a response to PPI therapy at 1 month was highest (85%) in those with epigastric burning; the proportions were lower in patients with epigastric pain (51.5%), postprandial distress with fullness (66.7%), or early satiation (41.1%). A study of 626 patients with erosive GERD treated with pantoprazole to esophagitis healing observed a 62% overlap between GERD and dyspepsia symptoms ( 30 ). Remarkably, the dyspepsia symptoms improved by 50% during PPI treatment and unlike the reflux symptoms, which usually relapsed with treatment cessation, the dyspepsia symptoms showed a trend to further decrease.

Gastroparesis

The importance of delayed gastric emptying in the pathogenesis of GERD is controversial. Early studies indicated that up to 50% of patients with reflux had delayed emptying of solids ( 31 ). However, more recent studies, using a standardized 4-hr gastric emptying test, found an overlap in 8%–20% of patients ( 32 ). Conceptually, impaired gastric emptying results in a greater volume of material in the stomach, which could be available to directly reflux into the esophagus or generate distension of the proximal stomach triggering transient lower esophageal sphincter (LES) relaxations. Recent studies with impedance-pH testing found that acid reflux values were not increased, but consistent with the reflux of meal contents, the increase was in post-prandial liquid or mixed reflux events and non/weakly acid reflux ( 33 ). Women and diabetics are more likely to have gastroparesis with secondary GERD. Complaints of abdominal bloating, pain, nausea, vomiting or constipation should be helpful clues and manometry often shows a normal LES pressure. Treating the gastroparesis with diet and prokinetics can alleviate the need for PPIs or anti-reflux surgery.

Prevalence and Trends

The pooled prevalence of at least weekly GERD symptoms reported from population-based studies worldwide is approximately 13%, but there is considerable geographic variation.( 34 ) Accurate estimates are difficult due to heterogeneity in study designs, but the prevalence of GERD appears to be highest in South Asia and Southeast Europe (more than 25%), and lowest in Southeast Asia, Canada, and France (below 10%) ( Figure 1 ).( 34 ) There are no data on the prevalence of GERD in Africa. In the US, estimates of the prevalence of GERD symptoms have ranged from 6% to 30%, with heterogeneity related to the particular questionnaire used, including the threshold frequency and duration of symptoms required to be classified as GERD.( 34 ) The prevalence of at least weekly GERD symptoms in the US is approximately 20%.( 35 ) There are approximately 110,000 hospital admissions annually in the US for GERD.( 36 ) Importantly, the prevalence of GERD symptoms in North America, Europe, and Southeast Asia has increased approximately 50% relative to the baseline prevalence in the early to middle 1990s, but has plateaued since then.( 35 ) In a population-based longitudinal study of a Norwegian county from 1995 through 2009, the annual incidence of any new GERD symptoms was 3.1%, and of severe GERD symptoms was 0.2%.( 37 ) Among individuals with any GERD at baseline and excluding those who were using anti-reflux medications, symptoms resolved spontaneously in 2.3% per year; among those with severe GERD, 1.2% spontaneously resolved per year.

(Adapted from Eusebi, et al. Gut . 2017. doi: 10.1136/gutjnl-2016-313589)( 34 )

Complications

The predominant complications of GERD include dysphagia (including from peptic strictures, Schatzki’s rings), bleeding from erosive esophagitis, and esophageal adenocarcinoma (discussed in other sections of this issue). In 3 population-based studies of patients agreeing to undergo endoscopy regardless of symptoms, the prevalence of erosive esophagitis ranged from 6.4% in China to 15.5% in Sweden.( 38 – 40 ) Among individuals without symptoms of GERD, the prevalence of erosive esophagitis ranged from 6.1% in China to 9.5% in Sweden. Erosive esophagitis may frequently be a transient phenomenon. In a prospective, longitudinal study, 26% of individuals with non-erosive reflux disease at baseline were found to have erosive esophagitis on repeat endoscopy 2 years later, and in another similar study, erosive esophagitis was found in 10% of individuals 5 years later.( 41 42 ) And among those with Los Angeles Grade A erosive esophagitis at baseline, 21% had more severe findings at 5 years.

Though death from erosive esophagitis is rare, mortality increased in the US from 1.0 per million individuals per year in 1968 through 1972 to 2.1 per million in 1988 through 1992.( 43 ) But recurrent strictures requiring repeat endoscopic dilation in individuals with a prior dilation decreased from 16% in 1992 to 8% in 2000, possibly related to the increase in use of proton pump inhibitors.( 44 ) From 2003 to 2006, there were approximately 10,570 hospital admissions annually for erosive esophagitis, and 14,000 admissions for esophageal stricture.( 36 ) Esophageal adenocarcinoma is the most feared complication of GERD, and its precursor lesion, Barrett’s esophagus, is also a sequella of GERD. Barrett’s esophagus and esophageal adenocarcinoma are discussed in detail in other articles in this issue of Gastroenterology .

Demographic Risk Factors

There are a number of well-recognized risk factors for GERD and its complications ( Table 1 ). In North America and in Europe, there is no association between sex and symptoms of GERD, but in South America and in the Middle East, women are approximately 40% more likely to report GERD symptoms than men.( 34 ) There is no clear association between sex and esophageal stricture.( 36 44 ) However, men are at greater risk than women for erosive esophagitis (summary odds ratio, 1.57; 95% CI, 1.40–1.76).( 45 ) Also men are at greater risk for Barrett’s esophagus and much greater risk for esophageal adenocarcinoma than women.

Risk Factors for GERD and Complications

Advancing age has been inconsistently associated with an increased risk for GERD symptoms. In a meta-analysis, the summary odds ratio for 50 years or more vs less than 50 years of age was 1.32, but with an I 2 value of 91.5%, indicating substantial heterogeneity among study results.( 34 ) However, advancing age is more strongly associated with complications of GERD ( Figure 2 ).( 36 ) Age is clearly associated with hospitalizations for esophageal strictures.( 36 46 ) Most recently, advancing age was strongly associated with hospitalizations for erosive esophagitis.( 36 ) However, in the late 1980s, advanced age was inversely associated with hospitalization for erosive esophagitis (odds ratio for more than 85 years vs 65–69 years of age, 0.66; 95% CI, 0.65–0.67).( 46 ) This reversal in association of age with erosive esophagitis suggests a cohort effect, whereby individuals born in an earlier generation may have been less likely to develop erosive esophagitis than later generations when they reached the same age. Such a cohort effect would most likely be explained by changes in environmental exposures (described in sections below). Esophageal adenocarcinoma is also associated with increased age, but there too, a cohort effect appears to be responsible for the increasing incidence.( 47 )

Upper graphs: age fractions expressed as percent of all patients with a given diagnosis. Lower left graph: age-specific rates of first-listed adenocarcinoma per 100 000, reflux esophagitis per 100 000, esophageal reflux per 10 000, Barrett’s esophagus per 100 000, hiatal hernia per 10 000, and esophageal stricture per 10 000 US population. Lower right graph: age-specific rates of all-listed adenocarcinoma per 100 000, reflux esophagitis per 10 000, esophageal reflux per 10 000, Barrett’s esophagus 10 000, hiatal hernia per 1000, and esophageal stricture per 10 000 US population. (From Thukkani N. & Sonnenberg A., Alimentary Pharmacology and Therapeutics . 2010;31( 8 ):852–61).( 36 )

In the US, there appears to be similar prevalence of GERD symptoms among different races.( 44 48 ) However, whites are at greater risk for erosive esophagitis, strictures, Barrett’s esophagus, and esophageal adenocarcinoma.( 36 48 49 )

Estimates of the proportion of phenotypic variance in GERD symptoms explained by genetic factors has ranged from 0 to 22%.( 50 – 52 ) In a twin study, 13% of the variance in GERD symptoms was estimated to be due to genetic effects, but even that proportion appeared to be mediated by anxiety and depression.( 52 ) The genetic risk for GERD is polygenic with no individual mutation found to be significantly associated with GERD in genome wide association studies, though larger studies might yet still be able to identify statistically significant individual mutations.( 50 51 ) Given the recent increase in prevalence of GERD symptoms relative to the broad sweep of evolutionary history, the etiology of GERD seems to be largely related to environmental exposures.

Environmental Risk Factors

Two major factors that may explain the trends are the obesity epidemic and the decreasing prevalence of Helicobacter pylori -associated gastritis. Obesity is a major risk factor for GERD symptoms, with odds ratio of 1.73.( 34 ) Obesity is also associated with erosive esophagitis (odds ratio, 1.59), Barrett’s esophagus (odds ratio, 1.24), and esophageal adenocarcinoma (odds ratio, 2.45).( 53 ) In particular, a body distribution of abdominal obesity has been associated with complications of GERD (erosive esophagitis odds ratio, 1.87; Barrett’s esophagus odds ratio, 1.98; and esophageal adenocarcinoma odds ratio, 2.51).( 53 ) Observational studies have demonstrated that reducing the body mass index by at least 3.5 kg/m 2 increases odds for disappearance of GERD symptoms by 1.5- to 2.4-fold.( 54 ) Randomized trials have confirmed that weight loss, and in particular a decrease in waist circumference, result in improved GERD symptoms and decrease in esophageal acid exposure.( 54 )

Obesity is largely related to caloric excess and/or lack of physical activity, so the association of obesity with GERD and its complications could be confounded by diet or physical activity. Certain foods can induce symptoms of GERD (e.g., fatty foods, chocolate, soda pop), and obese individuals may consume those foods more regularly than non-obese individuals. However, from a cross-sectional epidemiologic study, it would be difficult to find significant associations with specific components of the diet, since many patients with GERD symptoms would naturally try to avoid those foods. There are few data from epidemiologic studies to demonstrate an association between GERD symptoms and specific foods that cause them ( 54 55 ) There have been weak associations between diets low in fruits and fiber, and high in sweets and fat with GERD symptoms.( 56 – 60 ) Furthermore, a small prospective study demonstrated that even before losing substantial weight, obese patients experienced improvement in their GERD within only 6 days of initiating a low-carbohydrate diet, demonstrating that diet is an important risk factor for GERD.( 61 )

Likewise, the relationship between physical activity and GERD is complex. On 1 hand, certain forms of physical activity are associated with an increased risk of GERD. For instance, activities in a stooped posture, bicycle riding, weight lifting, swimming, and even surfing have been associated with increased risk of GERD, particularly during or shortly after the activity. ( 62 – 64 ) On the other hand, moderate, regular aerobic exercise has been inversely associated with GERD symptoms.( 58 60 ) Physical activity at work has a positive association with GERD symptoms, and yet leisure physical activity has had a negative association with GERD symptoms.( 56 )

In addition to the increasing prevalence of obesity, the falling prevalence of H pylori gastritis might explain the trends in GERD and its complications.( 43 ) A proportion of patients with H pylori infection develop atrophy in the gastric body and decreased gastric acid secretion. It has been proposed, therefore, that H pylori infection might prevent GERD in patients who are otherwise susceptible to it. Barrett’s esophagus and esophageal adenocarcinoma have been inversely associated with H pylori infection—particularly the cytotoxin-associated gene A (cagA+) strain.( 65 66 ) A meta-analysis has likewise found an inverse association between H pylori and erosive esophagitis.( 67 ) However, there is a much stronger inverse association in East Asia than in North America, and equivocal evidence for an association in Europe. Although H pylori gastritis tends to be predominantly in the gastric body in Asia, it is predominantly in the antrum in western countries.( 68 ) Antral gastritis would be more prone to having excessive rather than diminished gastric acid secretion due to positive feedback causing corpus acid secretion. There were some early reports describing an increase in GERD symptoms following eradication of H pylori ,( 69 70 ) but a subsequent meta-analysis found no such effect.( 71 ) There is little evidence that H pylori prevents symptoms of GERD in Western populations, and the inverse association between H pylori with erosive esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma may be independent of an effect on reflux.( 72 )

There are additional environmental exposures that are associated with GERD but they may not explain the trend in prevalence of GERD. For instance, tobacco use is weakly associated with GERD symptoms in cross-sectional studies (summary odds ratio, 1.26).( 34 ) This relationship is supported by an 18-year longitudinal study, in which individuals who decreased tobacco smoking were 3-fold more likely to have reductions in symptoms of acid regurgitation and heartburn than individuals who continued to smoke tobacco.( 73 ) Tobacco is also an important risk factor for erosive esophagitis,( 74 – 78 ) and esophageal adenocarcinoma.( 79 80 ) Though there are few data on peptic strictures, tobacco is associated with esophageal strictures in patients with endoscopic mucosal resection or with radiation therapy.( 81 82 )

Similarly, in observational studies, alcohol use was not strongly associated with GERD symptoms (summary odds ratio, 1.11), but there is substantial heterogeneity in results among studies.( 34 ) Patients with GERD symptoms often report that symptoms are made worse by drinking alcohol, and randomized studies have demonstrated that ingestion of alcohol induces acid reflux more so than water.( 83 84 ) Though patients often report worse symptoms with red wine than white (perhaps related to the tannins in red wine), a randomized trial found that red wine has less effect on lower esophageal sphincter relaxation and acid reflux than white wine.( 85 ) A well-designed study did not find a positive association of current alcohol use with erosive esophagitis,( 86 ) and there is no positive association between alcohol use and Barrett’s esophagus.( 87 )

Future Directions

GERD is an extremely prevalent condition, and became more common up until the turn of the last century. There are several important demographic factors associated with the risk of complications from GERD, but none are strongly associated with GERD symptoms. Environmental factors are strongly related to both GERD symptoms and complications, including obesity, tobacco use, and inversely with infection with H pylori . Classic symptoms of heartburn and effortless regurgitation are only modestly sensitive and specific for GERD. There is considerable overlap among GERD and gastroparesis, functional dyspepsia, and eosinophilic esophagitis, which can pose significant management dilemmas.

Acknowledgments

JHR was funded by the US Department of Veterans Affairs (I01-CX000899) and the National Institutes of Health (U01CA199336). JHR was received research funding from Shire.

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