Expert System for Detecting Early Symptoms of Gastroesophageal Reflux Disease (GERD) method Case Based Reasoning (CBR) Using Mobile Android

Persistent Reflux Symptoms in the Proton Pump Inhibitor Era: The Changing Face of Gastroesophageal Reflux Disease

This is the second WGO guideline published to complement World Digestive Health Day themes. WGO guidelines are intended to highlight appropriate, context-sensitive and resource-sensitive management options for all geographical regions, regardless of whether they are considered to be “developing,” “semi-developed,” or “developed.” There is a concern that guidelines from developed countries, by emphasizing high-tech investigations and Barrett esophagus (BE) surveillance, for example, may divert research and clinical resources from more urgent problems in developing and semideveloped countries. However, one could argue that there are similar problems in developed countries and that an overemphasis on complications or “proposed GERD associations” (as in the Montreal Consensus1) is leading to inappropriate investigations and resource utilization even in developed regions. It is also important to emphasize to health care insurers and funding bodies that appropriate, effective therapy is both therapeutic and diagnostic and that conducting mandatory investigations [eg, esophagogastroduodenoscopy (EGD) to permit proton-pump inhibitor (PPI) therapy is not patient-centered and, more importantly, is likely not to be cost-effective. WGO Cascades are thus context-sensitive, and the context is not necessarily defined solely by resource availability. Neither the epidemiology of the condition, nor the availability of resources for the diagnosis and management of gastroesophageal reflux disease (GERD), is sufficiently uniform throughout the world to support the provision of a single, gold-standard approach. WGO Cascades: a hierarchical set of diagnostic, therapeutic, and management options for dealing with risk and disease, ranked by the resources available. GERD is now widely prevalent around the world (Table 1), with clear evidence of increasing prevalence in many developing countries. Prevalence estimates show considerable geographic variation, but it is only in East Asia that they are currently consistently lower than 10%.2 The high prevalence of GERD, and hence of troublesome symptoms, has significant societal consequences, impacting adversely on work productivity3 and many other quality-of-life aspects for individual patients.4,5TABLE 1: GERD Symptoms: Range of IncidencePractice recommendations should be sensitive to context, with the goal of optimizing care in relation to local resources and the availability of health care support systems. The expression of the disease is considered to be similar across regions, with heartburn and regurgitation as the main symptoms. For initial management, the patient may purchase over-the-counter (OTC) medication for heartburn relief or seek further advice from a pharmacist. When patients perceive that their symptoms are more troublesome, they may seek a doctor’s advice; depending on the patient’s circumstances and the structure of the local health care system, patients may seek advice at the primary care level or they may consult a gastroenterology specialist or surgeon, directly or by referral. The WGO Cascade approach aims to optimize the use of available health care resources for individual patients, based on their location and access to various health care providers. CLINICAL FEATURES Predisposing and Risk Factors GERD is a sensorimotor disorder associated with impairment of the normal antireflux mechanisms (eg, lower esophageal sphincter function, phrenicoesophageal ligament), with changes in normal physiology (eg, impaired esophageal peristalsis, increased intragastric pressure, increased abdominothoracic pressure gradient) or, very rarely, excess gastric acid secretion (Zollinger-Ellison syndrome). Eating and Lifestyle An increase in GERD symptoms occurs in individuals who gain weight.6 A high body mass index (BMI) is associated with an increased risk of GERD.7 High dietary fat intake is linked to a higher risk of GERD and erosive esophagitis (EE).8 Carbonated drinks are a risk factor for heartburn during sleep in patients with GERD.9 The role of coffee as a risk factor for GERD is unclear; coffee may increase heartburn in some GERD patients,10 but the mechanism is unknown and it may be due to caffeine, rather than coffee per se. Coffee is not a dominant risk factor. The role of alcohol consumption as a risk factor for GERD is unclear. Excessive, long-term use may be associated with progression to esophageal malignancy, but this may be independent of an effect of alcohol on GERD.11,12 The role of smoking as a risk factor for GERD is unclear, although like alcohol, it is associated with an increased risk of malignancy.13,14 Medication—Certain Medications May Affect GERD See the Patient history and physical examination section. The treatment of comorbidities (eg, with calcium channel blockers, anticholinergics, and nonsteroidal anti-inflammatory drugs (NSAIDs) may negatively affect GERD and its treatment.15 Some medications (eg, potassium supplements, tetracycline, bisphosphonates) may cause upper gastrointestinal (GI) tract injury and exacerbate reflux-like symptoms or reflux-induced injury. Pregnancy Heartburn during pregnancy usually does not differ from the classic presentation in the adult population, but it worsens as pregnancy advances. Regurgitation occurs with approximately the same frequency as heartburn, and GERD in the first trimester is associated with a number of altered physiological responses.16,17 Factors that increase the risk of heartburn18 are: heartburn before pregnancy, parity, and duration of pregnancy. Maternal age is inversely correlated with the occurrence of pregnancy-related heartburn.19 Symptomatology GERD has a wide spectrum of clinical symptom-based and injury-based presentations, which may manifest either separately or in combination. Symptom evaluation is key to the diagnosis of GERD, particularly in the evaluation of the effectiveness of therapy. Heartburn and regurgitation are the most common symptoms, but atypical symptoms of GERD may occur, with or without the common symptoms. Atypical symptoms may include epigastric pain20 or chest pain,1,21 which may mimic ischemic cardiac pain, as well as cough and other respiratory symptoms that may mimic asthma or other respiratory or laryngeal disorders. Dysphagia may also occur. A minority of GERD patients have multiple unexplained symptoms, which may be associated with psychological distress22 (Table 2).TABLE 2: GERD Symptoms23,24Natural History Most cases of GERD are mild and are not associated with a significant increase in morbidity or mortality in comparison with the general population. In most GERD patients, the severity of the condition remains stable or improves over a 5-year observation period during current routine clinical care.26 There is a relationship between GERD and obesity: a higher BMI or larger waist circumference and weight gain are associated with the presence of symptoms and complications of GERD, including BE.27 Complicated GERD is characterized by stricture, BE, and esophageal adenocarcinoma. The Montreal consensus includes EE as a complication of GERD (recognizing that the definition of “mucosal breaks” used in the Los Angeles classification includes esophageal ulceration in the range of reflux esophagitis).28 Nonerosive reflux disease (NERD) may progress to EE in approximately 10% of GERD patients,29 and EE may therefore be considered as a manifestation of more severe reflux disease. EE is associated with BE and is a major risk factor for BE. In comparison with patients who were free of GERD at follow-up, those with EE had a 5-fold increased risk of BE after 5 years, in a cohort of the general population in Sweden.30 Globally, BE is rare in patients with GERD. It is more common in western populations. It is not known when BE develops relative to the onset of GERD; however, it appears to be more prevalent in older individuals and is strongly associated with an increased risk of esophageal adenocarcinoma.31 There is a well-documented association between BMI and adenocarcinoma of the esophagus and gastric cardia, although the risk of malignancy in a given individual with GERD is very low.32 Alarm Features Most alarm features are not specific for GERD; many are associated with alternative diagnoses that are unrelated to GERD. In most countries, many of these features relate to gastric cancer, complicated ulcer disease, or other serious illnesses. Dysphagia.33 Odynophagia (painful swallowing). Recurrent bronchial symptoms, aspiration pneumonia. Dysphonia. Recurrent or persistent cough. GI tract bleeding. Frequent nausea and/or vomiting. Persistent pain. Iron-deficiency anemia. Progressive unintentional weight loss. Lymphadenopathy. Epigastric mass. New-onset atypical symptoms at age 45 to 55 years (a lower age threshold may be appropriate, depending on local recommendations). Family history of either esophageal or gastric adenocarcinoma.34 The WGO Global Guideline on common GI symptoms may also be consulted: http://www.worldgastroenterology.org/guidelines/global-guidelines/common-gi-symptoms and http://journals.lww.com/jcge/Fulltext/2014/08000/Coping_With_Common_Gastrointestinal_Symptoms_in.4.aspx. DIAGNOSIS Diagnostic Considerations The presence of heartburn and/or regurgitation symptoms 2 or more times a week is suggestive of GERD.35 Clinical, endoscopic, and pH-metric criteria provide a comprehensive characterization of the disease, although investigations are usually not required to establish a diagnosis of GERD—with the caveat that the pretest probability of GERD varies markedly between geographical regions. The initial evaluation should document the presence, severity, and frequency of heartburn, regurgitation (acid or otherwise), and alarm features; atypical esophageal, pulmonary, otorhinolaryngological, and oral symptoms should also be sought. It may be helpful to evaluate precipitating factors such as eating, diet (fat), activity (stooping), and recumbence; and relieving factors (bicarbonate, antacids, milk, OTC medications). At this point, it is important to rule out other GI diagnoses, particularly upper GI cancer and ulcer disease, especially in areas in which these are more prevalent. It is also important to consider other, non-GI diagnoses, especially ischemic heart disease. Diagnostic questionnaire tools for GERD (reflux disease questionnaires, RDQs) have been developed for epidemiological studies. However, RDQs did not perform particularly well in the Diamond study.36 In fact, diagnosis by a physician such as the family practitioner or GI specialist showed better sensitivity and specificity for the diagnosis of GERD than did the RDQ. Questionnaires are generally difficult to use in clinical practice. A careful history is the basis for symptomatic diagnosis, with EGD being reserved for identifying or excluding significant structural lesions in selected cases. A region-based assessment of the local “pretest probability” may provide some guidance with regard to the choices and sequence of diagnostic tests needed, given the relatively poor predictive value of most symptoms. PPI Treatment as an Aid to Diagnosis “PPI trial.” It is no longer recommended to administer an empirical short-term (1 to 2 week) course of high-dose PPI treatment to determine whether or not the patient’s symptoms are acid related,36 since this is neither sensitive nor specific. Nonetheless, this is commonly done in practice. A formal course of PPI therapy, of adequate duration (usually 8 weeks) is required to assess the treatment response in GERD patients. Weakly acidic reflux episodes may be a substantial proportion of all reflux episodes. If this is the case, such patients may not respond well to PPI therapy (20% to 40% of GERD patients may not respond to PPI treatment).20 In addition, genuinely alkaline reflux may comprise up to 5% of all reflux episodes. In a subset of PPI nonresponders, reflux-like symptoms may be due to functional heartburn, rather than GERD.20 Alternative diagnoses, including peptic ulcer disease, upper GI malignancy, functional dyspepsia, eosinophilic esophagitis, achalasia of the cardia, and cardiovascular disease should also be considered. In patients with cases that are refractory to PPI treatment, ambulatory 24-hour esophageal pH/impedance monitoring, with the patient off PPI therapy, may be considered to help characterize symptoms.37 If there has been complete failure to respond to PPI treatment, the PPI should be stopped at least 1 week before 24-hour pH monitoring is performed (rescue antacid may be allowed when necessary), to assess for acid reflux. If the refractory reflux symptoms have responded partially, 24-hour pH monitoring (with or without esophageal impedance monitoring) should be performed with PPI administration being continued, to assess for acid reflux that is persistent despite treatment. Occasionally, 24-hour pH monitoring with esophageal impedance monitoring may be required, with the patient both on and off PPI therapy.38 Helicobacter pylori Infection39 In many countries with a high prevalence of H. pylori infection, peptic ulcer and gastric cancer continue to be more common than GERD and cause much higher morbidity and mortality.40 In this setting, any approach to the diagnosis and management of upper gut symptoms must include an assessment of the risks of infection with H. pylori and an awareness of the overlap among, and difficulty of discriminating between, symptoms of GERD, peptic ulcer disease, and functional symptoms—with a decision regarding the relative merits of a test-and-treat approach in comparison with EGD to test for H. pylori and related diseases before empirical antireflux therapy. Although epidemiological studies show a negative association between the prevalence of H. pylori infection and the presence and severity of GERD, this is not proof of causation. H. pylori infection should be sought and eradication therapy given when indicated in accordance with international, national, or local guidelines.41 Although there may be an inverse correlation between H. pylori infection and GERD prevalence and severity, this may well reflect differing effects of a separate, distinct factor or factors on the 2 conditions, rather than a causal relationship between H. pylori and GERD. Physiological studies using pH monitoring have shown that abnormal esophageal acid exposure, which is the hallmark of esophageal reflux, is not influenced by the presence or absence of H. pylori infection. In most patients, H. pylori status has no effect on symptom severity, symptom recurrence, or treatment efficacy in GERD. H. pylori eradication does not exacerbate preexisting GERD or affect treatment efficacy.42 Indeed, in patients with H. pylori-positive uninvestigated dyspepsia, eradication therapy is associated with a lower prevalence of reflux-like symptoms (36%) than control therapy (49%).43 A subgroup of patients infected with more proinflammatory strains of H. pylori (virulence factors vacA and cagA) may be less likely to have severe esophagitis or BE. This may be because infection in these patients more often causes severe corpus gastritis with atrophy, resulting in reduced acid output. However, these patients are at much greater risk of developing gastric cancer. Eradication therapy in these patients has the potential to reduce the risk of gastric malignancy.41 PPIs and H. pylori PPIs are associated with a worsening of the histologic grade of gastritis in H. pylori-infected patients, accompanied by an increased prevalence of gastric mucosal atrophy and intestinal metaplasia44 that occurs earlier, as well as more frequently, than in H. pylori-infected patients who do not take PPIs. As gastric mucosal atrophy and intestinal metaplasia are known to be the major risk factors for the development of gastric adenocarcinoma, most expert guidelines recommend testing and treating for H. pylori before long-term PPI therapy, particularly in younger patients. Endoscopy EGD is usually performed for new-onset upper GI symptoms, almost irrespective of age, in regions where it is available and affordable and where both the frequency of ulcer disease and the concern about malignancy are high, as in most of Asia.45 The Cascades given below address the limited availability of endoscopy in less well-resourced areas by suggesting the use of empiric H. pylori eradication therapy as a first-line strategy. If EGD is performed in regions where the prevalence of GERD is low, the majority of GERD patients will have NERD; in these circumstances, the sensitivity of EGD for the diagnosis of GERD will be low and the main outcome will therefore be the exclusion of other upper GI diagnoses. Endoscopy is particularly recommended for patients with alarm features suggestive of GERD with complications or of other significant upper GI disease such as dysphagia, bleeding, odynophagia, or weight loss. Patients with dysphagia should undergo investigation for a potential complication or for an underlying motility disorder, achalasia, stricture, ring, eosinophilic esophagitis, or malignancy.25 In several Asian countries, the preference for EGD is driven by the risk of malignancy at an early age and by the availability of “affordable, direct-access” endoscopy—an “endoscopy first” approach. Additional investigations other than EGD are rarely needed; furthermore, they have variable accuracy and are often unavailable. Patient History and Physical Examination The goals of patient evaluation include the assessment of symptoms and risk factors for the diagnosis of GERD and the prediction of long-term sequelae. In this regard, it is important to consider the regional epidemiology of upper GI disease and the pretest probability of GERD relative to other conditions. In Asia, for instance, BE is uncommon and it is not therefore an important risk for esophageal adenocarcinoma, which is itself uncommon. The prevalence of peptic ulcer and gastric cancer are the greater drivers of endoscopy in Asia where, unlike in the west, esophageal adenocarcinoma is less common. Personal and Family History Features The following features may be helpful in making a diagnosis and assessing the severity of GERD: Predisposing factors and risk factors, including family history. Duration of symptoms. Daytime symptoms, including time of day and relationship to meals. Nocturnal symptoms, including impact on sleep and the effects of a recumbent position and large, late evening meals. Treatments and remedies tried, including symptomatic response to therapy; symptom improvement with acid-lowering medications including antacids supports a diagnosis of GERD. Periodic dysphagia or food bolus impaction may suggest reflux-related esophageal injury, stricture or malignancy, as well as eosinophilic esophagitis or esophageal dysmotility.46 Drug History The patient should be asked about any medications that may contribute to upper gut symptoms (not necessarily GERD): Aspirin/NSAIDs, iron, potassium, quinidine, tetracycline, bisphosphonates. Zidovudine, anticholinergic agents, α-adrenergic antagonists, barbiturates. β2-adrenergic agonists, calcium channel blockers, benzodiazepines, dopamine. Estrogens, narcotic analgesics, nitrates, progesterone, prostaglandins, theophylline. Tricyclic antidepressants, chemotherapy. Dietary History In some patients, bloating or constipation may be associated with an increased risk of GERD or gastroesophageal reflux symptoms (GERS).47 Several studies suggest that stopping smoking and some physical measures, as well as modification of meal size and timing, be but there is limited evidence for the of alcohol and dietary including caffeine, and In those who are weight may be associated with improvement in GERD or may increase the for Physical There are usually no physical of GERD. and BMI are to of rarely, be and to other problems such as cardiac disease, and cancer. Diagnostic for GERD A diagnosis of GERD be in the of heartburn and In pregnancy, GERD be on the basis of symptoms If the dominant or most troublesome symptoms are atypical for GERD, other diagnoses should be including H. diseases and disease. In regions with a high prevalence of H. pylori infection, an initial H. pylori test-and-treat or endoscopy should be considered. are pH or monitoring and esophageal be performed but are required to assess structural (eg, in patients with dysphagia symptoms. reflux symptoms or GERD complications be using (Table Diagnostic for Diagnosis ulcer disease. gut and functional heartburn on the basis of a clinical response to therapeutic acid pH monitoring, or impedance pH ring, of the body motility esophageal heart disease, disease. chest Cascades for the Diagnosis of GERD For perform esophageal in regions or for selected patients in regions with features suggest eosinophilic For consider this only there is a high prevalence of BE in the local population and there are For most EGD will not the management, in the absence of alarm features or access to antireflux There is no role for upper GI in the investigation of routine upper GI symptoms (Table Cascades for the Diagnosis of Although the severity and frequency of symptoms between GERD patients, reflux symptoms do not the criteria for a diagnosis of GERD and are with and as or severe symptoms with of and therapy to their of the management of GERD a both with to the and to the health care who or provide therapy. The of GERD management are and of esophageal acid either by local acid or by of gastric acid secretion using or, rarely, antireflux The primary goals of treatment are to symptoms, the patient’s of esophagitis, symptom recurrence, and or complications in the most heartburn less than per week will respond to with an antacid or a week or less medications are very to have any are and are to antacids in this of patients, of or that symptoms and of late at may be in those who are may also reduce the frequency of symptoms. Patients who have more symptoms should be for therapy. A diagnosis of troublesome symptoms 2 or more times per empirical therapy with an acid inhibitor or, may also be used PPIs or are or for symptom relief in patients a If OTC or patients will often to a or primary care The definition of treatment failure to a on the treatment being In treatment may because the patient does not have GERD; in it may be that the treatment is to address the severity of the GERD. In the case, there may be a response to treatment, and management will be by the availability and of more may to care initial management to reflux should on clinical with treatment of the symptoms being the It is to the effective of For patients with mild symptoms, and some patients with PPI therapy is a management in many cases. At the primary care PPIs or a of and therapy be at the for therapy, which may be more than therapy For better symptom patients should be about to use PPI treatment therapy may be defined as the PPI to before and in the of to before the meal of the day as Patients in PPI treatment with or without may from a of therapy to a PPI therapy may not work for a proportion of patients, either because the symptoms are not due to acid an alternative diagnosis should be because the of acid is to control the symptoms. to care should be considered for patients. OTC antacids show in patients with weight in the and is an important of the long-term management of GERD and should not be as a therapeutic as it may reduce the frequency and of symptoms and the grade of of late of precipitating factors, use of a sleep OTC or the most but usually symptom relief and be as Alarm features the Alarm features for patients in the of OTC treatment by the diagnosis, patients with alarm symptoms to and patients on the use of their OTC in some may include the availability of treatment choices varies between countries. for short-term or antacids gastric and these include acid with of for short-term to available than OTC Patients advice for reflux symptoms may from OTC PPI treatment. which have OTC availability in individual the of the OTC PPIs may be available in other Alarm features the Alarm features medication without investigation should be in the presence of the following Heartburn or regurgitation symptoms Duration with severe or after 2 of treatment with an OTC or when a or New-onset heartburn or regurgitation at age 45 to 55 age in several Asian regions. Dysphagia or or of GI and anemia. or of or weight loss. and/or suggestive of chest to or of In or below years of age for or below years for PPIs. The goals of are that the patient should and to an of with the most therapy. If and complete symptom relief is not patients should be recommended to a health care for diagnostic PPI who gastric acid should have an for long-term PPI the long-term for PPIs should be

Gastroesophageal Reflux

Gastroesophageal reflux disease (GERD) is a chronic disease usually caused by the reflux of acidic gastric and duodenal contents into the distal esophagus. Major symptoms of GERD are acidity, heartburn, acid regurgitation, and chest pain. It is a digestive disease with the direct medical costs estimated around 9.3 billion dollars annually, and with the symptoms portending a low quality of life. The most common and known phenotype of GERD is Reflux esophagitis (RE). Many countries has a high prevalence of GERD, Especially in USA, about 44% of Americans suffer from GERD symptoms at least once monthly, 17% once weekly, and 7% once daily. Traditionally, GERD is less common in Asians. The overall prevalence of RE in Japanese adults is about 16%. Aging causes various physiologic changes in GIT that may increase the risk of developing complications such as GERD. Age-related changes in the physiology of the esophagus can be divided into two categories: motility and sensory. In general, changes in esophageal motility are mild and tend to be quiet in an older patient. It is possible that both the motility and nerve changes observed in the esophagus of older patients, combined with lower comorbidities and medication use, lead to a higher risk of esophageal mucosa to reflux and cause inflammation and development of GERD-related problems. Previously, it was thought that gastric acid release decreased with age, but further research revealed that the underlying mechanism may have been Helicobacter pylori infection that eventually developed atrophic gastritis. As the prevalence of Helicobacter pylori infection has decreased over the last 3-4 decades, more recent studies have shown that gastric acid secretion is maintained normally in more than 80% of elderly subjects. Comorbidity and commonly used drugs can reduce esophageal sphincter tone, esophageal clearance mechanisms, and saliva production.
 A low-fat diet likely contributes to a more favorable stomach distribution. Male gender, civil servant, smoking, strong tea, alcohol consumption, meat diet and body mass index (BMI) are risk factors associated with GERD. In many countries, dietary fat, cholesterol, saturated fatty acid (SFA), dietary fiber, and other nutrients are associated with GERD. An epidemiological study showed a link between high fat intake and GERD. Also, dietary fiber, particularly cereal fiber, has been found to reduce the risk of adenocarcinoma of the esophagus and stomach, of which GERD is a well-known risk factor. The mechanism may be that dietary fiber reduces the intake of gastric nitrites, which is thought to promote reflux by relaxing the lower esophageal sphincter (LES). A high-fiber diet has played a protective role in GERD. However, dietary fiber reduced the number of gastroesophageal refluxes, but increased their duration, and had no significant effect on gastric emptying and gastric acid secretion. Diet plays an important role in controlling acid reflux symptoms and is the first line of treatment used for people with GERD. Foods high in fiber make you feel full, so you're less likely to overeat, which can contribute to heartburn. So get healthy fiber from these foods, such as whole grains like oatmeal, couscous, and brown rice, root vegetables like sweet potatoes, carrots, and beets, and green vegetables like asparagus, broccoli, and green beans. Lemon juice is generally considered very acidic, but a small amount of lemon juice mixed with warm water and honey has an alkalizing effect, neutralizing stomach acid. In addition, honey has natural antioxidants that protect the health of cells. On the other hand, Ginger is another top digestive aid due to its medicinal properties. It is alkaline in nature and anti-inflammatory, which eases irritation in the digestive tract. Try sipping ginger tea whenever you feel heartburn. The goal is to create a diet based on a healthy variety of foods, including fruits and vegetables, lean protein sources, complex carbohydrates, and healthy fats. If you suspect that food may be triggering or worsening your GERD symptoms, try keeping a daily, weekly diary.

Tu1105 Gastric Acid Output Suppression in Response to Proton Pump Inhibitor Therapy in Symptomatic Versus Asymptomatic GERD Patients: Results of a Prospective Study Measuring Control and Meal-Stimulated Gastric Acid Secretion

Objective By comparing and analyzing the clinical features of non-erosive reflux disease (NERD) and reflux esophagitis (RE), to make clear the difference between them, and provide help for clinical prevention, diagnosis and treatment of gastroesophageal reflux disease. Methods A total of 220 cases of NERD were selected, 220 cases of RE were selected as the control, by completing the general demographic characteristics questionnaire, reflux disease questionnaire, gastroscope and Helicobacter pylori (H.pylori) infection examination, the differences between the two group in the general condition, lifestyle, predisposing factors, disease and recurrence, clinical symptoms, complicated disease were analyzed. Results In general terms: ①NERD was prevalent in women and mainly in the mental labor group. RE occured in men and mainly in manual labor (P 0.05). ③The course of disease and recurrence: Compared with RE group, the course of group NERD was longer, more likely to relapse, and longer recurrence interval (P 0.05). ④Clinical symptom characteristics: in group NERD, the incidences of heartburn, chest pain, belching and acid regurgitation, pharyngeal foreign body sensation and severity were higher than those of group RE (P 0.05). ⑤Overlap irritable bowel syndrome, functional dyspepsia: the incidence of overlap IBS and FD in group NERD was significantly higher than that in group RE (P<0.05). Conclusions There is marked difference between NERD and RE, and both are independent diseases rather than the different stages of the same disease. Key words: Non-erosive reflux disease; Reflux esophagitis; Clinical features; Difference

Nocturnal Gastroesophageal Reflux: Assessment and Clinical Implications

Objective To investigate the application and clinical significance of 24-hour multichannel intraaluminal impedance-pH (MII-pH) monitoring in gastroesophageal reflux disease (GERD).Methods Fiftythree patients with GERD were enrolled in this study according to the Montreal consensus (consulting for twice reflux a week or above) from July 2011 to June 2012.Patients were divided into erosive esophagitis (EE,n =25)group and non-erosive reflux disease (NERD,n =28) group after endoscopy and MII-pH monitoring.Fifteen healthy volunteers were recruited as the normal controls.The change of pH and MII-pH parameters were compared among the three groups and the significance of the change was investigated.Results Twenty-four-hour pH monitoring showed that all the acid reflux events in the EE and the NERD groups were significantly higher than those in the control group (P ＜ 0.05).MII-pH monitoring showed that the frequencies of total reflux,acid reflux,weakly acidic reflux and percentage of acid reflux in the GERD group were higher than in the control group (total reflux:83 (54,118) vs.62 (44,111) vs.42 (20,70),P =0.003 ; acid reflux:45 (25,79) vs.22 (11,45) vs.3(1,10),P =0.000 ;weakly acidic reflux:36(18,47) vs.43(21,82) vs.23(11,43),P =0.001 ;percentage of acid reflux:53％ (37％,81％) vs.32％ (13％,48％) vs.11％ (1％,23％),P =0.002).The frequency and percentage of acid reflux in the EE group were higher than those in the NERD group (P =0.000)The percentage of weakly acidic reflux in the NERD group was higher than in the EE group (66％ (43％,79％) vs.46％ (21％,57％),P ＜0.01).The frequencies of liquid reflux and mixed reflux in the GERD groups were higher than those in the control group (22 (12,40) vs.18 (12,26) vs.9 (4,18) ; 54 (39,79) vs.42 (25,77) vs.29(14,48) ;P ＜0.01).The frequency of gas reflux in the control group was higher than in the GERD group (86(56,207) vs.31 (14,62) vs.34 (15,119),P ＜ 0.01).The frequency and percentage of proximal reflux in the GERD group were significantly higher than in the control group (28(18,41) vs.16(12,34) vs.3 (2,9) ; 33％ (22％,49％) vs.29％ (22％,35％) vs.11％ (6％,22％),P ＜ 0.001).The percentage of symptom positive index in patients with acid reflux,non-acidic reflux and total reflux in the EE group were 36.0％ (9/25),20.0％ (5/25) and 56.0％ (14/25) respectively which were higher than in the NERD group (21.4％ (6/28),14.3％ (4/28) and 35.7％ (10/28)).Conclusion MII-pH monitoring can detect more reflux events.Acid reflux plays an important role in GERD.The detective rate of GERD will be elevated when combined with MII-pH monitoring in the diagnosis.MII-pH monitoring has a distinct advantage in diagnosing GERD. Key words: Gastroesophageal reflux disease; Erosive esophagitis; Non-erosive reflux disease; Multichannel intraluminal impedance-pH monitoring

Laparoscopic sleeve gastrectomy (LSG) may exacerbate preexisting gastroesophageal reflux disease (GERD) or induce de novo GERD. Previous studies have identified preoperative GERD as a risk factor for postoperative GERD, but the predictive value of diverse GERD assessment methods remains unclear. This study aimed to evaluate the impact of preoperative GERD-Q scores and endoscopic Los Angeles (LA) classification on early postoperative GERD symptoms after LSG, as well as their individual and combined predictive value for postoperative GERD. This study retrospectively analyzed the prospectively collected data of patients with obesity who underwent LSG at a medical institution during a one-year period. GERD symptoms were assessed pre- and postoperatively using the GERD-Q score, with a score ≥ 8 indicating GERD symptoms. Preoperative esophagitis was evaluated via endoscopy using the LA classification. A total of 371 individuals were included in the study, 91 (24.53%) developed GERD symptoms during follow-up. Kaplan-Meier analysis revealed an increasing cumulative incidence of GERD over time: 6.45% [95% confidence interval (CI): 3.81-9.02%] at 3 months, 21.41% (16.93-25.64%) at 6 months, and 26.69% (21.84-31.24%) at 1 year. Log-Rank Tests demonstrated significant associations between the cumulative incidence of GERD and preoperative GERD symptoms and LA classification. After performing multivariable Cox regression analysis and adjusting for age, sex, body mass index (BMI), and other confounding factors, it was found that preoperative GERD symptoms (hazard ratio [HR] = 1.88, 95% CI: 1.09-3.24, P = 0.024), preoperative RE (HR = 2.85, 95% CI: 1.81-4.50, P < 0.001) and higher LA grades (LA-A: HR = 2.83, 95% CI: 1.77-4.53, P < 0.001; LA-B/C: HR = 3.05, 95% CI: 1.07-8.72, P = 0.038) were both independent risk factors for postoperative GERD. In the symptom-endoscopy combined assessment model, risk remained significant in the only endoscopy positive group (HR = 3.22, 95% CI: 1.96-5.29, P < 0.001), the only GERD-Q positive group (HR = 2.41, 95% CI: 1.16-4.98, P = 0.018) and the double-positive group (HR = 2.65, 95% CI: 1.17-6.00, P = 0.020). After LSG, the cumulative incidence of postoperative GERD showed a continuous upward trend with prolonged follow-up. Preoperative LA-A grades, LA-B/C grades and GERD-Q positivity were independent risk factors for postoperative GERD.

To assess the impact of laparoscopic sleeve gastrectomy (LSG) on gastroesophageal reflux disease (GERD) symptoms and to determine factors associated with the occurrence of post-LSG GERD symptoms. This is a retrospective study that included all obese patients who underwent LSG in Aseer Central Hospital, during the period from August 2017 to August 2019. GERD-Health-Related Quality of Life questionnaire was used to assess the patients' pre- and postoperative GERD symptoms and their satisfaction toward their general health. The study included 326 patients (195 males and 131 females) with a mean age of 39.43 ± 11.17 years. Postoperatively, GERD symptoms newly developed in 105 patients (32.2%), while 25 patients out of 127 with preoperative GERD symptoms (19.69%) showed resolution of symptoms. There were significant associations (p < 0.001) between the old age, smoking and existence of comorbidities, and the occurrence of postoperative heartburn and regurgitation symptoms. Postoperatively, excess weight loss (EWL) was significantly associated with postoperative regurgitation (p = 0.045) and patients showed significant improvement in their satisfaction toward their health condition even those who developed GERD symptoms. After LSG, GERD symptoms developed in about one-third of the patients while symptoms improved in only one-fifth of patients. Older patients, smokers, patients with comorbidities, and patients with more EWL had significantly worse GERD symptoms postoperatively. Weight loss rather than GERD symptoms significantly influenced patients' satisfaction toward their general health. Further prospective studies are needed to determine the relationship between weight loss and other factors associated with post-LSG reflux and overall quality of life.

COMPARED TO OTHER GASTROINTESTINAL (GI) SYMPTOM COMPLEXES, the medical management of gastroesophageal reflux disease (GERD) appears fairly straightforward. Whereas there are few pharmacotherapeutic options for many other GI symptoms for which patients may seek medical advice, the majority of patients with troublesome GERD symptoms can be rendered asymptomatic with a once-daily dose of a proton pump inhibitor (PPI) within 4 to 8 weeks of starting therapy. Thus, many may consider GERD an easily treated problem that can be vanquished with the mere stroke of a pen. Yet as a gastroenterologist, I find my patients with GERD to be some of the most difficult to treat. The patients I see are the relatively small group who do not obtain relief with that PPI prescription. Unfortunately, there are currently few therapeutic options that are effective in alleviating GERD symptoms that persist despite PPI use. While I often recommend that patients take their PPI twice daily instead of once, or switch to another PPI, this decision is based on limited data from uncontrolled open-label trials with significant methodologic flaws.1,2 Stepping down PPI therapy from double-dose to standard doses is successful for most patients.3 There are no other proven therapies, and I am left with limited therapeutic options for patients with refractory GERD. These patients are the proverbial high-hanging fruit that are the most difficult to reach. However, these fruit can grow the largest, rewarding those who develop tools to snare them. It is important to gain a better understanding of GERD pathophysiology to devise better strategies for helping these patients to obtain relief. GERD has been traditionally thought of as the reflux of acidic gastric contents into the esophagus, resulting in symptoms and/or esophageal injury. The gold standard diagnostic criteria for GERD involves 24-hour esophageal pH monitoring, requiring an intra esophageal pH of less than 4 for more than 4% of the time over a 24-hour period. It is generally believed that if there is no gastric acid production, there can be no reflux symptoms. However, reflux symptoms often persist. Studies confirm that the majority of patients with GERD-like symptoms, despite high-intensity (double-dose or greater) PPI therapy, have a very low prevalence of reflux by the gold standard definition.4 So what are the mechanisms responsible for ongoing symptoms? Because PPIs have been so effective in relieving GERD symptoms, the basic mechanism that enables gastroesophageal reflux has been mostly ignored. I am referring here to the presence of both anatomic factors, such as the presence of a hiatus hernia, and physiologic factors, specifically the function of the lower esophageal sphincter (LES). It is possible that non-acid gastric contents that access the esophagus through a faulty LES may cause symptoms. Another possibility may be that GERD-like symptoms are independent of gastroesophageal reflux, and are merely interpreted as GERD. A new clinical tool may help both investigation and management. With multichannel impedance manometry (MIM), an impedance catheter is passed transnasally into the esophagus. It detects the presence of gas and fluid in the esophagus, and the direction of travel (i.e., towards the stomach with a swallow, towards the mouth with gastroesophageal reflux). With MIM and pH monitoring, reflux episodes can be counted and separated into acidic and non-acidic events. If further combined with a patient symptoms diary, a clinician can determine the relationship of GERD-like symptoms to reflux events. Using MIM, researchers have shown that patients with GERD who are treated with PPIs do not have fewer reflux events, but the refluxate composition changes from primarily acidic to primarily non-acidic.5 Baclofen, which decreases LES relaxation frequency, decreases reflux events and symptom burden.6 Unfortunately, due to its side-effect profile, baclofen will likely not be widely used for refractory GERD symptoms. However, there may be other medications that improve LES function and have similar effects. It is also possible that surgical interventions may be useful for patients with refractory GERD symptoms who have ongoing non-acidic reflux.7 Hopefully, the development of MIM will foster further research into the pathophysiology of refractory GERD, allowing pharmaceutical developers to better identify potential therapeutic targets, and giving clinicians the tools necessary to pluck the juiciest fruit right from the highest reaches of the trees. Meanwhile, pharmacists should strive to identify patients with symptoms refractory to PPI therapy, who may be candidates for a PPI reduction or discontinuation. ■

Background &Objective:Gastro esophageal reflux disease (GERD) broadly includes the whole spectrum of reflux disease symptoms like heartburn or acid regurgitation to endoscopic, reflux esophagitis or Barrett’s esophagus. Our aim therefore was to study the association between Gastroesophageal reflux disease symptoms and various lifestyle factors.Methods:A descriptive cross-sectional study was carried out in the outpatient department of Darul Sehat Hospital, Zubaida Medical Center and Liaquat National Hospital & Medical College, Karachi, Pakistan from January 2018 to October 2018. The selected candidates were asked to fill a validated GERD questionnaire and they were also asked about their lifestyle factors. Odds ratio and their 95% confidence interval were estimated using binary logistic regression with GERD symptoms as the study outcome.Results:A total of 2000 respondents completed the questionnaire. 69.3% gastroesophageal reflux disease cases were found in participants above 35 years of age while 56.9% subjects were male. The most common lifestyle factors associated with GERD were less exercise time (90.9%) (OR, 6.47; 95% CI, 4.91-8.53), 78.3% participants had habit of eating midnight snacks (OR, 5.08; 95% CI, 4.03-6.40), 87.3% participants reported less interval between dinner and sleep (OR, 6.98; 95% CI, 5.36-9.08). The most important factor relieving GERD symptoms was raising the head of bed during sleep (79.4%) while 43.3% subjects with the habit of post dinner walk reported fewer symptoms of GERD.Conclusion:Lifestyle factors particularly less physical activity, late evening meals, inadequate sleep, smoking and post dinner lying were found to be associated with GERD symptoms.

Epidemiological studies have shown that 10-48% of people in developed countries have gastroesophageal reflux disease (GERD) symptoms such as heartburn and acid regurgitation. The present study aimed to examine the prevalence of GERD symptoms and GERD in Japanese subjects. A cross-sectional study of Japanese subjects who visited a clinic for a routine health check up was carried out. Subjects were asked to fill out a self-report questionnaire. GERD was defined as the presence of heartburn and/or acid regurgitation at least twice per week. Of the 6035 eligible subjects, 2662 (44.1%) reported having had heartburn and/or acid regurgitation during the past year: 124 (2.1%) daily, 275 (4.6%) twice per week, 773 (12.8%) twice per month and 1490 (24.7%) less than twice per month. Three hundred and ninety-nine (6.6%) subjects were diagnosed as having GERD and there was no relationship between the prevalence of GERD and either sex or age. The prevalence of bothersome GERD symptoms was significantly higher in subjects with GERD than in those without GERD. Approximately 6.6% of Japanese have GERD and most persons with GERD described heartburn or acid regurgitation as bothersome.

Occasional acid reflux occurs frequently in the general population but gastroesophageal reflux disease (GERD), a chronic disease that affects millions of adults and children, is diagnosed if persistent reflux occurs more than twice a week. The development of proton pump inhibitors (PPIs) dramatically improved the treatment of GERD; however, the treatment of patients with refractory GERD remains a challenge. Dexlansoprazole (TAK-390MR, Kapidex), a pure enantiomer of lansoprazole, is a PPI that, with a novel dual delayed release formulation, provides prolonged inhibition of gastric acid secretion resulting in marked improvements in symptoms of GERD with high maintenance rates and good tolerability. Dexlansoprazole recently received Food and Drug Administration approval for the once-daily oral treatment of heartburn associated with symptomatic nonerosive GERD, the healing of erosive esophagitis (EE) and the maintenance of healed EE.

Introduction: To evaluate the correlation of gastroesophageal reflux disease (GERD) symptoms with normal BMI in presence of abdominal obesity, in multiethnic South Asian population. Methods: Prospective, cross sectional analytical, multicenter study was conducted from February 2009 to March 2010. Patients’ relative sitting in outpatient clinics with no comorbids, non-smoker and non-alcoholic with normal BMI (18.5-22.9 for Asians) were included. They were asked for consent and to fill a validated GERD questionnaire for the presence of GERD symptoms. Abdominal obesity was defined as waist circumference (WC) ≥90cm (for Asians) and waist hip ration (WHP) >0.90 (for Asians). Study subjects were measured for WC and WHR. WC were categorized into group A= (WC ≤79cm), B= (WC 80-89cm) and C= (WC ≥90cm), whereas WHP was grouped into A= (≤0.90) and B= (≥0.91). Descriptive analyses were done to measure percentages (%) and mean ± standard deviation. Odds Ratios (OR) and their 95% Confidence Intervals (CI) were estimated using Logistic Regression, with gastroesophageal reflux (GER) symptoms as an outcome. P value of 0.05 was considered as significant. Results: Subjects analyzed were 1260. Mean age was 36.33 ± 14.36 years. Overall, GERD symptoms were present in 42.2% (532/1260). Male were predominant by 56.2% (708/1260). Numbers of participants in WC groups were A=477 (mean WC=72.94±4.6), B=349 (mean WC=83.8±2.67) and C=434 (mean WC=94.61±4.45). GERD symptoms were progressively increased as waist circumference increased, i.e. 30.19% (A=144/477), 37.25% (B=130/349), 59.45% (C=258/434), respectively. Odds ratio and p values for group WC=B and WC=C were p=0.034, OR=1.37 (1.03-1.84) and p=0.001, OR 3.39 (2.56-4.45), respectively, when compared with group WC=A. Numbers of participants in WHR groups were A=571 (mean WHR=0.86±0.05), B=689 (mean WHR=0.94±0.39). GERD symptoms were 32.92% (188/571) and 49.93% (344/689) in group WHR=A and WHR=B, respectively. Odds ratio and p value for group WHR=B were p=0.001, OR=2.03 (1.61-2.56) when compared with group WHR=A. Conclusion: Regardless of normal BMI, GERD symptoms can occur in presence of abdominal obesity.