STATEMENT 1. GERD reflux disease has a negative impact on the patients’ quality of life. Pathological gastroesophageal reflux can cause esophagitis, Barrett’s esophagitis, and esophageal adenocarcinoma (A / I‑100%).

In developed countries, GERD prevalence is estimated at approximately 20%, based on the occurrence of heartburn and / or regurgitation 1‑2 times a week.^8,9 The prevalence of GERD is estimated at 8.8%–25.9% in Europe, 2.5%–7.8% in Asia, 8.7%–33.1% in the Middle East, 11.6% in Australia, and 23% in South Africa.¹⁰ About 25–40% of American adults report heartburn at least once a month, and about 7%–10% of patients experience heartburn every day.^11,12 In Poland, among 850 people aged 21‑76, GERD symptoms were reported by 36% of the respondents.¹³

GERD has a negative impact on the patients’ quality of life. Reduced productivity and physical activity are especially reported by patients with frequent symptoms.¹⁴ GERD is equally common among men and women but complications are more common in men: erosive esophagitis (about 2 times more often), Barrett’s esophagus (BE) (about 10 times), and esophageal adenocarcinoma (about 8 times).^15-17 Erosive esophagitis was found in 6.4% of patients in China and 15.5% of patients in Sweden in populational studies of patients undergoing endoscopy, regardless of the reported symptoms.^18,19 A prospective study found erosions in the esophagus in 26% of patients with non‑erosive reflux disease (NERD) after 2 years,²⁰ while in another study, erosive esophagitis was found in a follow‑up endoscopy after 5 years in 10% of patients.²¹ GERD is a risk factor for BE, which affects approximately 2% of the population and may progress to esophageal adenocarcinoma.^22-24 GERD increases the risk of esophageal adenocarcinoma (odds ratio [OR], 7.7; 95% CI, 5.3–11.4), especially in patients with long‑term GERD and severe or daily symptoms. The risk, however, is low and accounts for less than 0.001% annually.^25,26 The risk of esophageal adenocarcinoma in patients with BE is clearly greater in those with at least low‑grade epithelial dysplasia.^27-29

Potential pathophysiological factors increasing the risk of GERD include, but are not limited to: lower esophageal sphincter (LES) dysfunction, delayed gastric emptying, impaired esophageal clearance, esophageal motility disorders, obesity, and hiatal hernia.^17,30 Several studies reported an association between increased body mass index (BMI), waist circumference, and weight gain, and the presence of GERD symptoms and complications.^31-36

STATEMENT 2. GERD is a condition that develops when pathological gastric reflux into the esophagus causes troublesome symptoms and / or complications (C / I‑70%, II‑30%)

Acid reflux from the stomach into the esophagus, especially after a meal, is a physiological phenomenon. Therefore, the presence of gastroesophageal reflux or occasional symptoms cannot be defined as a disease. In 2006, a group of 44 experts from 18 countries provided the definition and classification of GERD.⁹ According to the Montreal Consensus, GERD is a condition that develops when gastric reflux into the esophagus causes troublesome symptoms and / or complications. Thus, GERD diagnosis can be made on the basis of the presence of troublesome heartburn and / or regurgitation or GERD complications as a consequence of pathological reflux. Troublesome symptoms are symptoms that have a negative impact on the patient’s quality of life. Most often these are mild symptoms reported at least twice a week or more severe symptoms at least once a week.⁹

The Montreal Consensus distinguishes between esophageal and extraesophageal GERD syndromes (Figure 1). Esophageal syndromes were divided into symptomatic syndromes and syndromes with esophageal injury. Symptomatic esophageal syndromes include a typical reflux syndrome with troublesome heartburn and / or regurgitation. Abdominal pain and sleep disturbances may also be present in this syndrome. In a reflux chest pain syndrome, the pain is the only or predominant symptom of the disease. Esophageal syndromes with injury include: reflux esophagitis, reflux esophageal stricture, BE, and esophageal adenocarcinoma. In the group of extraesophageal syndromes, syndromes with a documented association with reflux were distinguished, including reflux cough syndrome, reflux laryngitis syndrome, reflux asthma syndrome, and reflux dental erosion syndrome, as well as syndromes with a not fully confirmed relationship with GERD, such as pharyngitis, sinusitis, recurrent otitis media, and idiopathic pulmonary fibrosis.⁹ More than a dozen years have passed since the publication of the Montreal definition. Studies published within this time frame confirmed a causal relationship between GERD and reflux cough syndrome and dental erosions. However, there is no clear evidence of a causal relationship between GERD and laryngitis and asthma. The association of GERD with pharyngitis, sinusitis, otitis media, and idiopathic pulmonary fibrosis has not been established. The division of GERD into esophageal and extraesophageal syndromes determines further diagnostic and therapeutic management in GERD and is discussed below.

STATEMENT 3. The assessment of clinical symptoms is the first step in the diagnostic and therapeutic management of GERD (C / I‑80%, II‑20%).

STATEMENT 4. GERD diagnosis can be made on the basis of the presence of troublesome heartburn and / or regurgitation (typical symptoms) (B / I‑80%, II‑10%, III‑10%).

STATEMENT 5. Sensitivity and specificity of atypical symptoms in GERD diagnosis are lower than of typical symptoms. The etiology of extraesophageal symptoms is multifactorial, and GERD probability is low in the absence of typical symptoms (B / I‑70%, II‑20%, III‑10%).

STATEMENT 6. The presence of alarm symptoms requires imaging studies to be performed in order to exclude an organic disease (B / I‑90%, II‑10%).

According to the Montreal Consensus, the presence of troublesome typical symptoms, that is, heartburn and/or regurgitation is sufficient to diagnose GERD and initiate empirical treatment.^9,17 Unfortunately, as compared with objective diagnostic methods (pH‑metry and endoscopy), the sensitivity and specificity of typical reflux symptoms are suboptimal.^17,37-39 In comparison with typical symptoms, sensitivity and specificity of atypical symptoms in GERD diagnosis are lower.

Heartburn and regurgitation have a sensitivity of about 30%–76%, and a specificity of 62%–96%, with the specificity of acid regurgitation being greater than that of heartburn.^40-42 Other causes of heartburn can be functional disorders (so‑called functional heartburn), eosinophilic esophagitis or esophageal motility disorders. On the other hand, not all GERD patients report heartburn. It was suggested that up to 50% of patients with severe esophagitis remain asymptomatic.⁴³ Similar limitations apply to the usefulness of questionnaires in GERD diagnosis.³⁷ It should also be noted that the typical symptoms are not characteristic of GERD only. They can also occur in other diseases, including gastric and duodenal ulcer disease, gastritis and duodenitis, and gastric cancer. This means that each case suggesting an initial GERD diagnosis requires an individual diagnostic and therapeutic approach.

Chest pain may coexist with other symptoms or be the only symptom of GERD, but it should be remembered that its most common cause is cardiovascular disease.^9,17 GERD may be responsible for approximately 21%–41% of cases of unexplained chronic cough.⁴⁴ The 2016 guidelines for the management of chronic cough listed a set of features suggesting that chronic cough (lasting for more than 8 weeks) may be related to GERD. These include: no exposure to smoking and other environmental pollutants, not taking angiotensin converting enzyme inhibitors, normal chest X‑ray results, and excluded asthma, sinus and bronchial diseases.⁴⁵ Only half of the patients with extraesophageal symptoms simultaneously report typical GERD symptoms. The likelihood of extraesophageal symptoms association with GERD is low in the absence of typical symptoms. Therefore, a multifactorial etiology of extraesophageal symptoms should be kept in mind. GERD may contribute to the pathogenesis of these symptoms only in some patients. It is estimated that only 4%–10% of the symptoms reported by patients who visit laryngologists due to hoarseness, excessive mucus production, sore throat or foreign body sensation are caused by GERD.^9,17,46

GERD patients may report a number of other atypical symptoms, such as nausea, belching, and dyspepsia. These symptoms may also result from the coexistence of other diseases, that is, functional dyspepsia or irritable bowel syndrome.^9,17 In addition, these symptoms can be reported by patients with a number of other conditions including diseases of the stomach, duodenum, gallbladder, pancreas, and intestines. Dysphagia may be reported by patients with esophagitis (approximately 37%) and BE, but it may be a symptom of a post‑inflammatory or neoplastic esophageal stricture, the presence of the Schatzki ring or eosinophilic esophagitis, and may also be a consequence of esophageal motility disorders.^9,17,47

The presence of alarm symptoms requires imaging diagnostic studies before starting the treatment, in order to exclude GERD complications and other possible causes of symptoms, including neoplastic disease. The alarm symptoms include: weight loss, dysphagia, abdominal pain at night (waking the patient up from sleep), persistent vomiting, symptoms of gastrointestinal bleeding, and anemia.^17,37,48

STATEMENT 7. The 14‑day proton pump inhibitor test should not be used routinely for GERD diagnosis (B / I‑50%, II‑50%)

Attempting treatment with a PPI at a standard dose twice a day for 14 days should not be used routinely as a method of GERD diagnosis.^37,49 Symptom relief with the PPI is reported by an average of 69% of patients with reflux esophagitis, 49% of patients with GERD with a normal endoscopy, and 35% of patients with normal endoscopy and pH‑metry.⁵⁰ Among patients reporting heartburn, the PPI test has a sensitivity of about 71%–78% and a specificity of 44%–54%, when compared to a combination of endoscopy and pH‑metry.^37,51-53 In the case of atypical symptoms, as mentioned earlier, the response to PPI treatment is lower, which further reduces the usefulness of this test in GERD diagnosis.^37,53 The limitations of this test include: a significant role of visceral hypersensitivity in symptom modulation, differences in drug doses, and various duration of the test.^37,54-56 The widespread use of the PPI test leads to over‑diagnosis of GERD and PPI abuse.³⁷

STATEMENT 8. It is not necessary to perform upper gastrointestinal endoscopy (EGD), if only typical symptoms are present (B / I‑60%, II‑30%, III‑10%).

STATEMENT 9. EGD is necessary in patients reporting alarm symptoms (B / I‑90%, II‑10%)

EGD is not required when typical symptoms of GERD are present. The indication for EGD is a lack of a response to empirical PPI treatment. The procedure is then used to assess not only possible GERD complications but also to exclude other causes of the symptoms. It should be remembered that treatment should not delay examination of the upper gastrointestinal tract in the presence of alarm symptoms (weight loss, dysphagia, abdominal pain waking the patient up from sleep, persistent vomiting, symptoms of gastrointestinal bleeding, anemia); this diagnostic procedure should be performed immediately.^17,48

EGD confirms the presence of disease complications such as erosions in the esophagus – erosive form of GERD (reflux esophagitis), esophageal postinflammatory stricture, or BE.^48,57 Normal endoscopy results do not exclude GERD. Esophageal erosions are found only in approximately 30%–40% of patients with heartburn not receiving acid suppression therapy, and in less than 10% of patients receiving PPIs.^58,59 The severity of reflux esophagitis is assessed using the Los Angeles (LA) classification (Table 5). It should be kept in mind that low grade esophagitis, that is, grade A according to the LA classification, is not specific for GERD and occurs in 5%–7.5% of asymptomatic individuals.^60-62 In addition, there are difficulties in its endoscopic recognition and some authors suggest that there may also be intraobserver variations in endoscopic assessment of not only grade A but also grade B esophagitis. For this reason, some experts believe that the presence erosive esophagitis of at least grade B indicates GERD.³⁷ The American College of Gastroenterology (ACG) guidelines from 2013 recommend broader GERD diagnostics in the presence of grade A esophagitis.¹⁷

STATEMENT 10. Routine EGD in all patients with symptomatic GERD is not recommended as a screening test for Barrett’s esophagus. However, this examination should be performed in patients with multiple (≥ 3) risk factors: GERD duration above 5 years, age 50 or above, white race, male gender, obesity, BE, and / or grade 1 relative with esophageal adenocarcinoma (B / I‑80%, II‑20%)

BE occurs in approximately 5%–15% of patients with long‑term GERD.^63-65 There is no high‑quality scientific evidence to support screening for BE. However, it seems that BE diagnosis prior to the diagnosis of esophageal adenocarcinoma is associated with better survival.⁶⁶ Most of the published guidelines recommend or allow screening in patients with multiple risk factors, the most important of which seems to be a long duration of GERD.^67-71

STATEMENT 11. Barrett’s esophagus is diagnosed by the presence of glandular epithelium covering at least 1 cm of the distal part of the esophagus, with histopathological evidence of intestinal metaplasia (B / I‑80%, II‑10%, III‑10%).

Due to the adoption of such a definition, neither random biopsy from metaplastic segments more than 1 cm long, nor long‑term surveillance in these cases are recommended.^70,71 However, in such a situation, targeted biopsies should be performed, if macroscopically visible lesions are found. The 1 cm border was adopted due to a low degree of agreement in BE diagnosis in the case of segments more than 1 cm long and a low risk of progression to cancer.^72-74 Most scientific societies do not recognize the presence of gastric metaplasia in the esophagus as a basis for BE diagnosis.

STATEMENT 12. Lesions suggesting Barrett’s esophagus in endoscopy should be assessed according to the Prague C&M Criteria (specifying the length of the circumferential segment and total length of the metaplastic segment). If focal changes are found, their exact location, size, and macroscopic appearance according to the Paris classification should be provided. Additionally, the presence or absence of inflammatory changes should be described (C / I‑90%, II‑10%).

STATEMENT 13. If endoscopy suggests Barrett’s esophagus, specimens should be taken for histopathological examination according to the following scheme:

1. Random sections from 4 quadrants of the metaplastic segment (1 set of sections for every 2 cm of the segment, counting from the upper border of the gastric folds).

2. Targeted sections from the identified macroscopic lesions (B / I‑100%) There is common acceptance for the BE assessment according to the Prague C&M Criteria, and focal changes according to the Paris classification.

   ^75-77

   It is widely recognized that a biopsy in BE is taken according to the Seattle Protocol, and targeted biopsies should be performed for focal lesions.

   ^78-80

STATEMENT 14. In patients with (LA) grade C and D reflux esophagitis, and in doubtful B grade, follow‑up EGD should be performed after 8 weeks of PPI therapy to exclude Barrett’s esophagus (B / I‑60%, II‑40%).

STATEMENT 15. Biopsy specimens should not be taken for histopathological examination to diagnose Barrett’s esophagus and during surveillance EGD in the presence of active inflammatory lesions (reflux esophagitis) (B / I‑100%)

BE often coexists with reflux esophagitis. This brings about two important implications. First, inflammatory changes may mask the presence of the metaplastic segment, especially with high intensity inflammatory changes (LA grades C and D and, in doubtful cases, grade B), and a short lingual segment of BE.^81,82 Secondly, due to difficulties in distinguishing between dysplasia and regenerative changes, biopsy specimens should not be taken for histopathological examination in the presence of inflammatory changes, in order to avoid a false positive diagnosis of dysplasia.^70,83-85

STATEMENT 16. The diagnosis of any degree of dysplasia (including indeterminate dysplasia) requires confirmation by a second pathologist, preferably an expert in the field of gastrointestinal pathology (B / I‑90%, II‑10%)

The diagnosis of dysplasia in BE is difficult, and the degree of agreement among pathologists is low.^86-88 Low‑grade dysplasia seems to be overly diagnosed mainly because it is difficult to distinguish from regenerative changes.⁸³ More than 4 out of 5 diagnoses of low‑grade dysplasia may not be confirmed by experts in the pathology of BE. On the other hand, if the diagnosis is confirmed (the presence or absence of dysplasia) by a second pathologist, its diagnostic effectiveness increases significantly.^69,84,89,90

STATEMENT 17. Long‑term endoscopic surveillance is recommended in patients with Barrett’s esophagus (B / I‑70%, II‑30%).

STATEMENT 18. Patients diagnosed with dysplasia and a very long metaplastic segment (≥ 10 cm) should be monitored or treated in a center specialized in the management of Barrett’s esophagus (C / I‑60%, II‑40%).

STATEMENT 19. Surveillance may be discontinued in patients without dysplasia who were over 75‑80 years of age at the time of the last surveillance EGD (C / I‑70%, II‑30%)

Long‑term endoscopic surveillance in BE leads to the diagnosis of esophageal adenocarcinoma at earlier stages and, consequently, to improved survival of patients with adenocarcinoma.^66,91,92 In order to ensure the highest level of quality of management in BE, the American Gastroenterological Association and the European Society of Gastrointestinal Endoscopy (ESGE) proposed that diagnostics and supervision in the case of dysplasia as well as BE treatment should be carried out in expert centers with sufficient clinical experience and appropriate training, personnel, and equipment.^71,85 For metaplastic segments 10 or more centimeters long, the risk of progression to cancer may be comparable to BE with dysplasia. Therefore, such a cut‑off point was arbitrarily established for referral to an expert center.⁷¹ The proposed time to discontinue surveillance was also determined arbitrarily, based on life expectancy.⁹³

STATEMENT 20. Time intervals of EGD surveillance in Barrett’s esophagus without dysplasia should depend on the overall length of the metaplastic segment:• from 1 to below 3 cm (short segment) ‑ every 5 years • from 3 to below 10 cm (long segment) ‑ every 3 years (C / I‑60%, II‑40%)

The risk of progression to adenocarcinoma increases with the length of the metaplastic segment.⁷³ These time intervals were arbitrarily proposed by the ESGE for the European population.⁷¹ The prerequisite for such intervals is high‑quality EGD surveillance, that is, examination by an appropriately trained physician, high‑resolution equipment, and biopsy collection in accordance with the Seattle protocol.

STATEMENT 21. In patients diagnosed with dysplasia not specified in a random biopsy, a follow‑up EGD should be performed after 6 months. If this examination does not reveal dysplasia, then surveillance should be continued as in Barrett’s esophagus without dysplasia (B / I‑70%, II‑30%).

STATEMENT 22. In patients diagnosed with la ow‑grade dysplasia in a random biopsy, a follow‑up EGD should be performed after 6 months. If this examination does not confirm dysplasia, another examination should be performed after 12 months. If no dysplasia is found in this examination, then surveillance should be continued as in Barrett’s esophagus without dysplasia (B / I‑70%, II‑30%)

Even if the diagnosis of dysplasia is confirmed by an another histopathologist, about 30% of patients experience regression of dysplastic changes. On the other hand, confirmation of the diagnosis of dysplasia at the next time point significantly increases the risk of progression to cancer.^84,90,94

STATEMENT 23. Routine distal esophageal biopsy for GERD diagnosis is not recommended (B / I‑70%, II‑30%)

Comments in Supplementary material, Part 2.1. See appropriate references.^{17,37,59,95-102}

STATEMENT 24. Ambulatory 24‑hour intraesophageal monitoring of pH and impedance or pH only should be considered in patients reporting atypical GERD symptoms, in patients with refractory GERD, and in patients qualified for antireflux surgery (C / I‑80%, II‑20%).

STATEMENT 25. In patients with a high probability of GERD as the cause of symptoms (abnormal endoscopy or pathological reflux in pH or pH and impedance monitoring test), reflux monitoring (preferably pH and impedance) should be performed on PPI therapy (B / I‑80%, II‑20%).

STATEMENT 26. In patients with a low probability of GERD (normal endoscopy, atypical / extraesophageal symptoms), monitoring of pH and impedance, or possibly only pH, is best performed off PPI therapy in order to confirm or rule out GERD (B / I‑90%, II‑10%).

STATEMENT 27. The parameters of reflux monitoring that best support GERD include: abnormal acid exposure in the esophagus (AET >6), abnormal reflux number (>80), and a positive correlation of symptoms with reflux (symptom association probability [SAP] and symptom index [SI]) (C / I‑70%, II‑30%).

Ambulatory reflux monitoring is possible through the use of 24 h pH measurement (pH‑metry) or multichannel intraesophageal pH and impedance monitoring. There is no need for ambulatory reflux monitoring in patients responding to PPI treatment and not qualified for antireflux surgery.¹⁰³ Currently, monitoring is performed mainly to exclude or confirm GERD in patients with normal upper GI endoscopy, reporting atypical symptoms, in patients with persistent symptoms despite PPI therapy (refractory GERD), and in patients who are considering antireflux surgery.^{17,37-39,49,54,95}

Monitoring of pH or pH and impedance determines the pathophysiological basis of GERD, that is, excessive esophageal acid exposure and reflux episodes, and assesses the relationship between the reported symptoms and reflux. As compared with pH‑metry alone, pH and impedance monitoring detects not only acid reflux but also nonacid reflux and assesses its correlation with the symptoms reported by the patient. Monitoring of pH and impedance is therefore advantageous in the assessment of patients receiving PPI treatment, and is considered a gold standard in GERD diagnosis. However, one should take into account the still limited availability of this test in Poland, as compared with classic pH‑metry. The assessment of esophageal acid exposure time (AET) remains the most reproducible parameter and a predictor of response to antireflux therapy, both pharmacological and surgical.^37,104,105 Currently, it is proposed to consider AET below 4% as normal (physiological) and AET above 6% as abnormal. For AET in the 4‑6 range (considered inconclusive), a detailed evaluation of other parameters, including the number of refluxes, is required. A total number of reflux episodes below 40 per day is considered physiological, more than 80 episodes – completely abnormal, and values in between are viewed as intermediate (inconclusive).^37,57 The clinical relevance of the number of reflux episodes remains unknown. An important advantage of reflux monitoring is the assessment of a correlation between the patient’s symptoms and reflux by the use of indexes, most often SI, and the index determining the probability of a symptom‑reflux correlation, SAP. SI index, assessing the percentage of symptoms preceded by reflux, is considered positive when it exceeds 50%. SAP index is more mathematically complicated and it takes into account the number of reflux episodes, symptom events, and reflux–related symptoms. SAP result above 95% is positive, which means that the probability of a random symptom‑reflux correlation is lower than 5%.^{37-39,57,93,106-108} Although SAP index appears to be more reproducible than SI, clinical practice shows that the best assessment of reflux‑symptom correlation is obtained by analyzing both indexes, which are predictors of response to PPI or surgical treatment regardless of AET value.^{37,38,95,109,110} It should be mentioned that the assessment of the symptom‑reflux correlation is difficult, especially with a small number of symptoms (more reliable with at least 3 episodes of symptoms) and low acid exposure, and it depends on the correctness of the patient’s reporting of symptoms. Moreover, in the cases of some atypical symptoms, the assessment of indexes may be significantly difficult (eg, the accuracy and reliability of cough analysis may require acoustic detection) or impossible (eg, chronic laryngitis).^37-39,57,95 Symptoms are more likely to occur without PPI treatment, so pH and impedance monitoring off PPI therapy increases the likelihood of a positive symptom‑reflux correlation.¹¹¹ Monitoring of pH and impedance allows for the assessment of nonacid (weakly acidic) reflux and the correlation of these reflux episodes with symptoms. However, the importance of such a correlation is not fully understood. Automatic analysis requires manual verification, as it overestimates the number of nonacid reflux events and may misjudge their association with symptoms.¹¹²

In the diagnosis of GERD, the importance of additional parameters including: bolus exposure, baseline impedance, mean nocturnal baseline impedance (MNBI) and postreflux swallow‑induced peristaltic wave (PSPW) are not well understood due to a small number of studies. It was shown that MNBI and PSPW can be particularly helpful in the differential diagnosis of GERD and functional heartburn.^37,57

Currently, it is recommended that monitoring of pH and impedance or pH only is performed off PPI therapy to determine baseline AET in patients with no prior GERD confirmation or low probability thereof, for example, patients with normal EGD, who did not have a previous pH‑metry and report atypical symptoms. This differentiates patients with GERD from those with hypersensitive esophagus or functional heartburn. In the impedance and pH monitoring, a hypersensitive esophagus is diagnosed when there is a normal number of reflux and AET events but symptoms are correlated with reflux. In a patient complaining of heartburn with a normal test result and lack of symptom‑reflux correlation, the diagnosis is a functional heartburn. It is also recommended to monitoring the PPI therapy in the patients qualified for antireflux surgery.^{17,37-39,57,95,113} It was demonstrated that an abnormal 24 h pH‑metry is a predictor of symptom improvement after antireflux surgery.¹¹⁴ On the other hand, patients with typical symptoms and a normal endoscopy are less likely to respond to the surgery.¹¹⁴ The Lyon consensus recommends that pH or pH and impedance monitoring are performed prior to the antireflux surgery, especially in patients with normal EGD or LA grade A and B esophagitis.³⁷ When measuring pH and intraesophageal impedance, or pH alone in patients with low probability of GERD, one should also remember to discontinue drugs blocking histamine H2 receptor.

Monitoring of pH and impedance during PPI therapy (at a standard dose, twice a day) is recommended in patients with documented GERD, that is, positive pH or pH and impedance monitoring, or GERD complications in EGD (reflux esophagitis, especially LA grade C or D, esophageal stricture, BE), to assess the correlation of persistent symptoms with reflux episodes despite therapy and / or determine their cause, for example insufficient acid suppression, poor compliance / adherence.³⁷

Recent guidelines of the British Society of Gastroenterology (BSG, 2019) favor the use of pH and impedance monitoring for primary evaluation of patients with refractory PPI, chest pain, or laryngological / pulmonary symptoms. In patients qualified for anti‑reflux surgery, but responding to PPI treatment, BSG recommends pH‑metry. On the other hand, pH and impedance monitoring enables a more accurate assessment of patients with GERD refractory to PPI therapy and qualified for surgery. Moreover, BSG prefers to perform pH and impedance monitoring over pH‑metry in patients with recurrent or persistent symptoms after surgery.¹⁰³ BSG guidelines also recommend pH and impedance monitoring in patients with idiopathic pulmonary fibrosis, cystic fibrosis or other lung diseases qualified for lung transplantation in whom GERD is suspected.¹⁰³

In comparison with other diagnostic methods, ambulatory monitoring of pH or pH and impedance is more accurate in the assessment of reflux, however, it does not always allow for the exclusion or confirmation of GERD. The sensitivity and specificity of pH monitoring is high (80‑100%) in patients with reflux esophagitis, while in patients with normal endoscopy it is lower.¹⁷ Factors that may affect the procedure, its results, and interpretation of the test include: discomfort resulting from the presence of a transnasal probe, limitation of physical activity and altered meals, and daily variability in the occurrence of symptoms and reflux episodes. Tables 3 and 4 list a number of other limitations of the testing methods discussed above that should be considered during data interpretation.

STATEMENT 28. Pharyngeal pH monitoring is not recommended in GERD diagnostics (C / I‑90%, II‑10%).

STATEMENT 29. Routine evaluation of duodeno‑gastro‑esophageal reflux is not recommended in GERD diagnostics (C / I‑90%, II‑10%)

Comments in Supplementary material, Part 2.2. See appropriate references.^{17,35,37,39,95,115-117}

STATEMENT 30. Esophageal manometry is not recommended for GERD diagnostics (C / I‑90%, II‑10%).

STATEMENT 31. Esophageal manometry should be performed in GERD patients qualified for anti‑reflux surgery (C / I‑90%, II‑10%)

Comments in Supplementary material, Part 2.3. See appropriate references.^{17,37,103,118-121}

STATEMENT 32. Contrast‑enhanced radiography of the esophagus should not be performed in GERD diagnostics (B / I‑80%, II‑20%)

Comments in Supplementary material, Part 2.4. See appropriate references.^{17,39,95,122,123}

STATEMENT 33. Diagnosis of reflux laryngitis syndrome as extraesophageal GERD should not be based on the results of laryngoscopy (B / I‑100%)

Comments in Supplementary material, Part 2.5. See appropriate references.^{17,37,95,124-129}

STATEMENT 34. In the treatment of GERD, lifestyle modifications are recommended, including: weight reduction in overweight and obese patients, head of bed elevation during sleep and avoiding meals at least 3 hours before bedtime (B / I‑60%, II‑40%).

STATEMENT 35. PPIs are currently the most effective class of drugs in relieving GERD symptoms and healing inflammatory lesions of the esophagus (A / I‑80%, II‑20%).

STATEMENT 36. PPIs are a safe group of drugs, the use of which is associated with a small percentage of side effects (A / I‑90%, II‑10%).

STATEMENT 37. Histamine 2 receptor antagonists can be used to control symptoms in patients with GERD and normal endoscopy, as an add‑on therapy (especially at night) in the case of insufficient PPI effectiveness, and as a treatment in gradually reduced doses (“step‑down”) after obtaining symptom remission with PPI (B / I‑90%, II‑10%).

STATEMENT 38. Antacids and / or topical mucosal preparations can be used on demand to relieve intermittent GERD symptoms, or as add‑on therapy to acid suppression therapy (PPI or PPI and histamine 2 receptor antagonists) for better symptom control (B / I‑100%).

STATEMENT 39. The routine use of prokinetic drugs is not recommended (B / I‑60%, II‑30%, III‑10%).

STATEMENT 40. Surgical treatment can be an effective method of GERD treatment in a carefully selected group of patients. Fundoplication can be performed in patients with pathological reflux confirmed by pH or pH and impedance monitoring (off PPI therapy), who responded to PPI therapy but do not want to take PPIs chronically; or when there are side effects of PPI therapy; or when symptoms (regurgitation) persist despite PPI therapy in a patient with a known mechanical defect of the antireflux barrier (eg, hiatal hernia) (B / I‑60%, II‑40%).

STATEMENT 41. Surgical treatment is not recommended in patients with extraesophageal GERD symptoms, especially isolated and unresponsive to PPI therapy. It can only be considered in patients with objectively confirmed GERD that is refractory to pharmacological treatment (B / I‑100%).

STATEMENT 42. The presence of a typical reflux syndrome is an indication for empirical PPI therapy (A / I‑90%, II‑10%).

STATEMENT 43. Empirical PPI therapy for 8 weeks is recommended for symptom relief (A / I‑90%, II‑10%).

STATEMENT 44. Empirical PPI therapy should be started at the standard dose, applied once a day (A / I‑90%, II‑10%).

STATEMENT 45. For optimal inhibition of hydrochloric acid secretion, classic PPIs are administered 30‑60 minutes before meals (A / I‑90%, II‑10%).

STATEMENT 46. Maintenance treatment with PPIs is recommended in patients with recurrence of symptoms after PPI discontinuation. This treatment should be carried out at the lowest effective dose, daily, on‑demand, or intermittently (B / I‑80%, II‑20%).

STATEMENT 47. On‑demand or intermittent PPI therapy may be considered in patients with nonerosive and uncomplicated GERD and in patients with LA grade A esophagitis at an early age in whom other potential factors contributing to acid reflux were eliminated (B / I‑60%, II‑40%).

STATEMENT 48. Histamine H2 antagonists may be used as maintenance therapy in patients with normal endoscopy to control symptoms. Antacids and / or topical mucosal preparations may also be considered (B / I‑90%, II‑10%).

STATEMENT 49. In the absence or partial response to once daily PPIs, apply PPIs at the standard dose twice daily for 8 weeks. Alternatively, a different PPI can be used and / or a drug from a different group can be added (add‑on therapy): histamine H2 receptor antagonists, antacids and / or topical mucosal preparations (B / I‑60%, II‑30%, III‑10%).

Management algorithm is shown in Figure 2. Comments in Supplementary material, Part 2.6. See appropriate references.^{37,51,213-215}

STATEMENT 50. Refractory GERD should be considered in the absence of symptom improvement after 8 weeks of treatment with the standard dose of PPIs used twice daily (B / I‑90%, II‑10%).

STATEMENT 51. The first step in managing a patient suspected of refractory GERD is to reassess the symptoms and ensure that the patient is taking the medication correctly (A / I‑90%, III‑10%).

STATEMENT 52. Diagnosis of refractory GERD includes EGD, ambulatory pH and impedance monitoring, and esophageal manometry (B / I‑100%).

STATEMENT 53. Functional heartburn and hypersensitive esophagus are significant causes of PPI therapy failure (B / I‑60%, II‑40%)

Management algorithm is shown in Figure 2. Comments in Supplementary material, Part 2.7. See appropriate references.^{17,49,51,53,93,95,96,118-121,131,136,144,215-225}

STATEMENT 54. Due to the multifactorial etiology of extraesophageal symptoms, in these cases a laryngological and pulmonological / allergological evaluation is necessary. Ideally, diagnosis of the causes of extraesophageal symptoms should be performed prior to gastroenterological evaluation (C / I‑80%, II‑20%).

STATEMENT 55. Empirical PPI therapy (standard dose twice a day) can be started in patients with extraesophageal symptoms with concomitant typical GERD symptoms. This treatment should be continued for 8‑12 weeks (C / I‑90%, II‑10%).

STATEMENT 56. In patients with improvement of symptoms after PPI therapy, treatment should be continued with the lowest effective dose. Lack of improvement after PPI requires further diagnostics (C / I‑90%, II‑10%).

STATEMENT 57. Empirical PPI therapy should not be initiated in patients reporting only extraesophageal symptoms. In these cases, a comprehensive laryngological, pulmonological / allergological assessment (if not performed previously) and pH and impedance or pH monitoring (before PPIs are instituted) are necessary to confirm or rule out GERD (C / I‑80%, II‑20%)

Comments in Supplementary material, Part 2.8. Management algorithm is shown in Figure 3. See appropriate references.^{17,45,46,95,226,227}

STATEMENT 58. In the case of chest pain, possible cardiological causes should be ruled out first. Before starting PPI therapy, the following diagnostics should be performed: EGD, pH or pH and impedance monitoring, and esophageal manometry (C / I‑70%, II‑20%, III‑10%).

STATEMENT 59. PPI therapy should be started in patients with chest pain and confirmed GERD (C / I‑90%, II‑10%).

STATEMENT 60. In patients with chest pain that do not respond or partially respond to PPI therapy, the addition of pain modulators may be considered (C / I‑50%, II‑50%)

Comments in Supplementary material, Part 2.9. See appropriate references.^17,228

STATEMENT 61. The presence of dysphagia is an indication for an urgent endoscopy with biopsy to exclude cancer, GERD complications, and eosinophilic esophagitis (A / I‑100%)

Comments in Supplementary material, Part 2.10. See appropriate references.^{17,38,39,47,103,229}

STATEMENT 62. Belching can be a symptom of GERD, but it can also result from functional and behavioral disorders (C / I‑70%, II‑30%)

Comments in Supplementary material, Part 2.11. See appropriate references.^95,96,230

STATEMENT 63. In pregnant women with GERD, it is recommended to modify the lifestyle and diet. Pharmacological treatment should be carried out at the lowest effective dose and for the shortest duration possible. Preferred drugs are alginates and sucralfate. PPIs can be used in case of severe symptoms (B / I‑100%)

Management algorithm is shown in Figure 4. Comments in Supplementary material, Part 2.12. See appropriate references.^49,231-238

STATEMENT 64. PPIs at a standard dose taken once a day for 8 weeks are used in the treatment of reflux esophagitis. Patients with LA grade C and D reflux esophagitis and esophageal stricture require maintenance therapy (A / I‑80%, II‑10%, III‑10%).

STATEMENT 65. Chronic PPIs therapy in asymptomatic patients with Barrett’s esophagus, although under discussion, is recommended by most experts (B / I‑80%, II‑20%).

STATEMENT 66. In patients with Barrett’s esophagus and GERD symptoms and / or esophagitis, it is recommended to use PPIs at doses sufficient to control GERD symptoms and heal inflammatory lesions (B / I‑80%, II‑20%).

STATEMENT 67. In patients with Barrett’s esophagus without GERD symptoms, PPI therapy at a standard dose once a day is recommended (C / I‑80%, II‑20%).

STATEMENT 68. Endoscopic treatment of Barrett’s esophagus should be carried out in an expert center specializing in this field (C / I‑90%, II‑10%).

STATEMENT 69. Endoscopic resection and / or ablative therapy should not be used in Barrett’s esophagus without dysplasia (B / I‑90%, II‑10%).

STATEMENT 70. All visible focal lesions, regardless of the degree of neoplasia, should be removed endoscopically (preferably by endoscopic mucosal resection) to obtain an appropriate histopathological assessment (A / I‑100%).

STATEMENT 71. Endoscopic treatment of esophageal adenocarcinoma T1a meeting the criteria for oncological completeness is considered the treatment of choice (A / I‑100%).

STATEMENT 72. Endoscopic treatment of esophageal adenocarcinoma in T1b (sm1) stage, meeting the criteria for oncological completeness, may be considered as an alternative to surgical treatment (C / I‑90%, II‑10%).

STATEMENT 73. Barrett’s esophagus with persistent (in two consecutive studies) macroscopically invisible (low or high grade) dysplasia (diagnosed by random biopsy) should undergo ablative treatment (B / I‑100%).

STATEMENT 74. After endoscopic removal of visible focal lesions containing dysplasia / neoplasia (regardless of its degree), the remaining metaplastic epithelium should be destroyed, preferably by RFA technique (A / I‑80%, II‑20%)

Comments in Supplementary material, Part 2.13. See appropriate references.^{17,67,70,71,85,94,136,138,141,239-253}