Home Treatment of Heartburn

Heartburn and Acid Reflux Cure Program

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Heartburn and Acid Reflux Cure Program Overview

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Clinical Spectrum Natural History And Epidemiology Of Gerd

GERD is a spectrum disease, i.e., a disease composed by many patient subgroups, ranging from symptomatic disease without mucosal lesions (or NERD) to the complications of erosive esophagitis, such as esophageal stricture, ulceration or Barrett's esophagus. Almost all the transitions are possible amongst groups, even if the progression from one stage to the other has been described mainly based upon retrospective data. The natural history of the disease is poorly investigated available data would suggest that symptoms of GERD tend to persist and to worsen with time, independently from the presence and severity of muco-sal lesions or the severity of esophageal acid exposure at presentation. As far as the epidemiological features are concerned, the prevalence of at least monthly GERD symptoms ranges between 26 to 44 in western countries, whereas the prevalence of endoscopic esophagitis at open access endoscopy or in symptomatic patients seem to be very high, up to 20 , with an incidence...

Atypical manifestations of GERD

Many extraesophageal (or supraesophageal) manifestations of GERD are now acknowledged as parts of the disease spectrum 24 we disagree with considering these manifestations as only possible complications of the NERD category, as proposed by Fass and Ofman. If, in fact, it holds true that the majority of such patients do not show esophageal mucosal damage at endoscopy, a definite proportion, between 20 and 30 of such patients do indeed have erosive or ulcerative esophagitis 25 . We too dispute that NERD and atypical'' GERD patients should be regarded as having less severe disease this is however not based on the absence or presence of mucosal damage, but on the pathogenesis of symptom perception in those patients. NERD patients are in fact possibly at least three groups of different patients (true refluxers, patients with esophageal hyperalgesia and patients with psychological disturbances) 9 , and the traditional treatment with antisecretory agents can possibly be more useful in the...

Incidence and prevalence of GERD symptoms

The first and probably more quoted paper concerning the incidence of GERD symptoms is the study by Nebel et al, published in 1976 40 the study was conducted by means of a questionnaire administered to 446 hospitalized and 558 non-hospitalized subjects, as well as in 385 control subjects. In the latter group, daily heartburn occurred in 7 , weekly in 14 and monthly in 15 , giving a total of 36 of subjects having heartburn at least monthly 40 . Data coming from a large national poll 41 about three decade later does confirm the high prevalence of heartburn, with daily heartburn reported by 7 , weekly heartburn by 20 and monthly heartburn by 44 , with an estimated population involved of 13,27 and 61 millions of adult Americans, respectively. A more recent study conducted in two samples of Italian employees, composed by 424 and 344 subjects, respectively, found a lower figure, with a prevalence rate for monthly heartburn of 21 42 . Interestingly enough, symptoms of GERD (as well as reflux...

Mechanisms for heartburn

The mechanisms by which patients with GERD develop symptoms remain incompletely understood. It is postulated that sensitization of esophageal chemo-receptors either directly by exposure to acid reflux or indirectly through release of inflammatory mediators is responsible for symptom generation in GERD 39 . Reducing acid exposure in patients with GERD appears to normalize the sensitivity to acid 40 . However, the emergence of symptoms in patients with a normal esophageal mucosa and thus without obvious inflammation remains perplexing, particularly among patients with functional heartburn where little or no reflux actually occurs. Both animal models and human studies have demonstrated dilation of intercellular spaces during or following esophageal mucosal acid exposure 41 , 42 . These mucosal findings were evident regardless of the presence or absence of esophageal inflammation 42 , 43 . It is assumed that these morphological changes result in an increase in paracellular permeability,...

Frequency of GI symptoms in dyspepsiarelated diseases

The table illustrates the difficulty in establishing a diagnosis in dyspepsia from history alone. Diseases with a significant difference in symptom frequency are shown in bold type. Weight loss and GI haemorrhage are features that increase the likelihood of an underlying gastric cancer. The table emphasizes the importance of careful history, examination and investigations, such as endoscopy, in reaching a precise diagnosis of the cause of indigestion. Table 30.1 Frequency of GI symptoms in dyspepsia-related disease. Table 30.1 Frequency of GI symptoms in dyspepsia-related disease. dyspepsia dyspepsia Heartburn

Medical Therapy Of Gastrooesophageal Reflux Disease

Treatment of gastro-oesophageal reflux disease (GERD) has to take into account that GERD shows a considerable variation in the way of manifestations the spectrum ranges from intermittent heartburn of minor severity to severe daily symptoms additionally, dysphagia and bleeding may be due to complications such as strictures and oesophageal ulcers. Furthermore, gastro-oesophageal reflux has also been linked to a number of symptoms of the respiratory tract (e.g., chronic cough, posterior laryngitis). Thus, the questions arises whether a tailored treatment strategy is necessary for each individual aspect in this broad spectrum. The therapeutic strategy may also be influenced by results from diagnostic procedures, primarily from upper gastrointestinal endoscopy. More than half of the patients undergoing endoscopic evaluation do not reveal any changes of the mucosa (non-erosive reflux disease NERD). These questions will be answered and a practical guideline based upon published literature as...

Erosive Gerd Erd

The above quoted paper by Fass states that patients with erosive esophagitis tend to remain within this group during their lifetime and that Barrett's mucosa does not progress or regress over time, and thus patients continue to harbor this type of lesion as long as they live. In fact this is not true, as transition to Barretts esophagus and to adenocarcinoma has been reported, the latter even in the absence of BE as an intermediate lesion. We have already mentioned the 11 of new developed BE observed in the study by McDougall Lagergren etal 18 have demonstrated that the risk of adenocarcinoma of the esophagus is much more related to the duration and severity of gastroesophageal reflux disease than to the presence of Barrett's esophagus, and therefore the latter could be considered to be a common, but not necessary step, in the evolution of esophageal adenocarcinoma 18 . Similar observations have subsequently been done by Chow et al 19 and by Farrow et al 20 . Conio et al 21 , in a...

Epidemiology of GERD

Before revising the existing literature on this topic, we would like to recall the code numbers for GERD and related disorders according to the ninth International Classification of Diseases (ICD-9) overall, the diseases of the esophagus are coded under the ICD code 530 (Table 1) esophagitis in its various forms, including the one induced by GER, is coded as 530.1, ulcer of the esophagus as 530.2, benign stricture as 530.3. Interestingly enough, in the ICD-9 GERD and hiatal hernia are separated conditions, the latter having the code 553.3 (if not complicated) finally, the symptoms of GERD are listed in the code 787 (GI symptoms), where heartburn is coded as 787.1, dysphagia as 787.2, etc. However, the heterogeneity of this classification does not allow to differentiate, as an example, among esophagitis due to GER or due to other less common causes, such as infection or ingestion of drugs and chemicals. It does also not allow grading of esophagitis severity, as achievable for example...

Dyspepsia

A first-line OTC treatment for heartburn, indigestion and dyspepsia has often been an antacid based on calcium carbonate in combination with magnesium and aluminum salts. Calcium in combination with the other ingredients reduces stomach acid and increases the rate of gastric emptying (Vatier et al 1996). In trials comparing H2 blockers with calcium carbonate tablets, calcium was found to be equipotent, yet delivered a more rapid response and shorter duration of action (Feldman 1996). There have been many papers highlighting the dangers of prolonged use of these traditional antacids however, pure calcium carbonate formulas attract the least concern, with the incidence of 'milk alkali syndrome' resulting from their over use reported to be rare (Ching & Lam 1994, Herzog & Holtermuller 1982).

GERD complications

GERD comprises a spectrum of disease, ranging from non-erosive esophagitis, to complications involving increasingly severe esophageal damage. Complications of reflux disease include erosive esophagitis, esophageal ulceration, peptic stricture, BE, and ade-nocarcinoma of the esophagus. Several studies have shown that complications of GERD tend to occur together. Any GERD complication is 10 times more likely to occur with another GERD complication than without, and this is most often true for strictures Several authors have noted that complications of GERD are more common in the elderly, requiring increased vigilance and a more aggressive approach to diagnosis and treatment by physicians. Brunnen et al estimated the overall incidence of severe esophagitis at 4.5 per 100,000 population, with a dramatic increase after the age of 50 17 . Studies suggest that 50-60 of those with typical reflux symptoms will have erosive eso-phagitis 31 . Collen et al found that complications such as erosive...

Functional heartburn

Among the various manifestations of GERD described so far in this review, functional heartburn may represent the greatest challenge to the clinician. Affected patients present with typical reflux symptoms, yet, as described above, all diagnostic modalities fail to reveal either evidence of pathological acid reflux or an association between symptoms and acid exposure needless to say, there is no macroscopic or microscopic evidence of acid-related mucosal injury. The precise prevalence of this disorder is unknown estimates suggest that approximately 40 of NERD patients (or 20 of all GERD) will fall into this category 3 , 17 - 19 and its pathophysiology remains virtually unexplored 20 . Clinical impressions suggest that there is considerable overlap with other functional disorders such as irritable bowel syndrome and non-cardiac chest pain one can assume, therefore, that such phenomena as visceral hypersensi-tivity and abnormal cerebral perception of visceral events may be involved....

Complicated GERD

The important esophageal complications of chronic reflux are strictures, Barrett's esophagus, and adenocarcinoma. Aggressive medical management, preferably with proton pump inhibitors, and close follow-up, using tests to assess symptoms and severity of reflux, are warranted in complicated GERD. Surgical management is contemplated in patients who remain unresponsive to medical therapy. Adenocarcinoma is extremely rare in childhood, but it does occur and should be sought in those with Barrett's esophagus. In an 11 year-old patient, the diagnosis of Barrett's esophagus was reported to progress to adeno-carcinoma 86 . The risk of developing esophageal ade-nocarcinoma increases with hiatal hernia size, Barrett's esophagus length, and acid reflux severity.

NERD and dyspepsia

As overlap between these functional syndromes comes to be accepted as a clinical reality, it has posed a dilemma for those who seek to develop precise clinical definitions for the individual functional disorders. For example, where does NERD end and functional dyspepsia begin 51 This is far more than an issue of semantics the inclusion of patients with predominant heartburn in a dyspepsia study population which examines the response to an acid-suppressing agent will significantly bias the study in a positive direction 52 , 53 as a corollary, the exclusion of heartburn, as advocated by some 54 , will lessen the impact of the same agents. The approach to definition will similarly have a significant impact on studies of the epidemiology, pathophysiology and natural history of the respective disorders. The need to delineate succinct patient categories notwithstanding, the clinical reality is that many NERD patients complain of heartburn and dyspepsia attempts to separate patients on the...

Incidence and prevalence of esophagitis

Studies concerning the incidence rate of reflux esophagitis (RE) and or GERD are very rare historically, the first study on the incidence of (severe) RE was published in 1969 by Brunnen 33 , who gave a figure of 4.5 per 100,000 for ulcerative esophagitis or RE complicated by stricture. The study was conducted among residents older than 12 years from the northwestern region of Scotland, and it comprised a total of 200 patients. The occurrence of esophagitis was confirmed by barium studies in all, and endoscopy in most of the patients. The incidence of severe RE showed an almost exponential rise starting at the age of 40 years. Loof 34 et al publis

Esophageal dysmotility

Gastroesophageal reflux is the result of transient LES relaxation, stress reflux or an abnormally low LES pressure (free reflux or the common cavity phenomenon) (see Fig. 2). Fig. 2. Demonstration of the 3 underlying mechanisms that can lead to gastroesophageal reflux. They include, inappropriate transient lower esophageal sphincter relaxation, reduced lower esophageal sphincter basal pressure leading to free reflux''and stress reflux (with permission from 13 ) Peristaltic dysfunction of the esophageal body in GERD is well documented 16 , 17 . Esophageal peristaltic dysfunction is increasingly observed with more severe grades of erosive esophagitis and particularly in patients with Barrett's esophagus 3 . There has been a long-standing argument as to whether the observed esophageal dysmotility precedes or is caused by GERD 16 . However, studies have demonstrated that elimination of acid reflux and even esophageal mucosal healing do not result in normalization of esophageal body...

Mucosalprotective agents

The main mucosal protective agent is sucralfate, which works by binding damaged mucosa, and forming a protective barrier against the erosive action of pepsin and bile. Sucralfate may have a comparable rate of symptom relief and healing of erosive esophagitis to H2B's 2 . The degree of healing with sucralfate correlates inversely with the degree of injury of the mucosa. However, there are significant drawbacks in using this medication for GERD in the elderly. It requires four time a day dosing, and has a potential for drug-drug interactions with digoxin, phenytoin, quinidine, and warfarin. This medication may reduce the absorption of certain drugs, and other medications must be given 2 hours after sucralfate 35 . Due to the increased medication usage in the elderly, this factor makes sucral-fate difficult to effectively utilize in this population.

Esophageal clearance and mucosal resistance

Of this complex act in infants as early as 35 weeks of gestation. A disruption of the normal swallowing function particularly threatens the airways of fragile and physiologically immature infants with aspiration, apnea, cyanosis, and bradycardia. In older children, as in adults, upright posture confers an advantage in clearing refluxed material by the action of gravity, but this advantage is lacking in infants, who are generally recumbent in supine and semi-seated positions. Esophageal motor responses were nearly normal in response to infusion of saline in piglets with reflux, including those with eso-phagitis, but were impaired in response to acid infusion and influenced by acid volumes as well 38 . Primary esophageal peristalsis, initiated by swallowing, comprises 83 of all esophageal responses to reflux in infants 39 . Secondary peristalsis is induced by reflux and esophageal distention, and plays an important role in clearance during active sleep, thereby being crucial to infants...

Clinical presentations

Esophageal presentations attributed to GERD vary according to the age of the patient, and include regurgitation, irritability, arching, and feeding aversion in infants, and vomiting, chest pain, heartburn, and abdominal pain in older children. Circumstantial evidence strongly suggests a relationship between reflux and a variety of extraesophageal presentations. These extraesophageal manifestations involve the airways or dental erosions. The former are best appreciated in light of the intricate coordination of the intimately related human respiratory and the digestive tracts, especially in fragile infants 46 . The relationship between reflux and respiratory symptoms is bi-directional reflux may precipitate or exacerbate respiratory disease, and vice versa.

Histamine2receptor blockers H2Bs

Disadvantages of H2B therapy include short duration of action, incomplete inhibition of acid in response to a meal, and the development of tolerance 73 . Although the addition of a H2B to twice daily PPI therapy can significantly reduce nocturnal gastric acid reflux, the phenomenon is temporary for most people. Tolerance develops in as short as 1 week, and, after 1 month of continuous therapy, acidity may return to pre-treatment levels 2 , 75 . Although an increase in medication dosage can result in improved healing, cost becomes an issue in this case considering the availability of alternate effective medications.

The clinical context of Barretts esophagus

BE is most commonly recognized as part of the endoscopic evaluation of patients with chronic heartburn and or regurgitation - the most common symptoms of GERD. On a population basis, 5 of adults with chronic GERD have BE 5 . had BE, 0.36 long segment 7 . These patients with presumed asymptomatic BE account for the incidental finding of BE in patients being assessed for upper GI bleeding, ulcers and dyspepsia. The asymptomatic pose a major challenge for screening for BE and cancer prevention and account for a major percent of esophagectomy series for cancer and BE.

The development of neoplasia

Dysplasia is the first step in the neoplastic process. It represents a change in the cytologic characteristics of cells and the glandular architecture detected histologi-cally. The progression of neoplasia can result in cancer - in BE that means EAC. Although the incidence of EAC in BE is controversial, both cohort studies 8 and a funnel analysis of the literature estimate the incidence at 0.5 per year 9 . A more realistic estimate may be the lifetime risk - younger patients do not have a greater risk of developing cancer just because they have a longer life expectancy. An individual patient with BE has an estimated lifetime risk of EAC of 5 or less. This has been documented in a population based study 10 and an accumulation of 10 cohort studies 11 . This is a significantly greater risk than someone with GERD lacking BE or the general population, but less of a risk than perceived by many physicians and patients. What action to take to reduce this risk of EAC will be discussed.

Screening for and surveillance of Barretts esophagus

Risk stratification for screening for BE is not evidence based but is de-facto commonly performed in the US as part of the evaluation of GERD patients. The epidemiology of EAC highlights those at risk and provides indirect evidence for who is likely to have BE. The US annual incidence of EAC is 3.6 100,000 in Caucasian men, 0.8 in African American men and 0.3 in Caucasian women 3 . A population based case control study in Sweden documented the relation of frequency - (> 3 times per week OR 16.7) and longer duration (> 20 years OR 16) of reflux symptoms to the risk of EAC 13 . The longer duration of GERD symptoms have been related to the greater likelihood of finding BE at endoscopy 14 , 15 . The likelihood of finding of BE is age related. Under the age of 45 only 1 of 363 patients with dyspepsia lacking alarm symptoms had BE 16 . Based on an epidemiology study, the median age of onset of BE is estimated to be 40 years of age although the first en-doscopy diagnosing BE is usually...

Treatment of Barretts esophagus medical

The mainstay of medical therapy of BE is proton pump inhibitor (PPI) therapy for the control of underlying GERD symptoms. Patients with BE tend to have more prolonged esophageal acid exposure as a result of a more defective anti-reflux barrier. Many patients require bid dosing to control reflux symptoms. Even bid PPI therapy fails to normalize esophageal pH < 4 exposure in 25 of BE patients in spite of symptom control 30 , 31 . The endpoint of medical therapy is controversial - symptom control versus esophageal pH control. Until more direct data document an effect of esophageal acid control on outcome, this difficult endpoint will unlikely be pursued in practice.

Effect of Helicobacter pylori eradication on GORD symptoms and severity

It is well known that Helicobacter pylori infection leads to a higher intragastric pH during PPI treatment 19 , 20 , 34 , 35 . Patients with Helicobacter pylori infection treated with pantoprazole have better symptom relief and better healing of severe forms of erosive oesophagitis 36 . These results have been confirmed in a study with 483 patients with uninve-stigated heartburn 37 . The definition of Barrett's oesophagus is a subject of controversy over the last years. It is applied to a columnar-lined oesophagus with biopsy specimens that contain specialized intestinal epithelium. This definition applies to patients with long segment and short segment Barrett's oesophagus and those with circumferential disease or tongues. Barrett's oesophagus is the consequence of gastroesophageal reflux.

The diaphragmatic sphincter and hiatus hernia

Endoscopic and radiographic studies suggest that 50-94 of patients with gastroesophageal reflux disease (GERD) have a type-I hiatal hernia while the corresponding prevalence in control subjects ranges from 13-59 37 - 40 . Most patients with severe esophagitis have a hiatal hernia 41 , 42 and 96 of patients with Barretts esophagus have a > 2 cm hiatus hernia 43 . However, the importance of a type-I hiatal hernia is obscured by the misconcep GERD patients with and without hiatus hernia 34 . Of several physiological and anatomical variables tested, the size of hiatus hernia was shown to have the highest correlation with the susceptibility to strain-induced reflux (Fig. 7). The implication of this observation is that patients with hiatus hernia exhibit progressive impairment of the diaphragmatic component of EGJ function proportional to the extent of axial herniation 1 . Fig. 7. Model of the relationship between the lower esophageal sphincter (LES) pressure, size of hernia, and the...

Mechanical properties of the relaxed EGJ

Recent physiologic studies exploring the role of compliance in GERD reported that GERD patients with and without hiatus hernia had increased compliance at the EGJ compared to normal subjects 50 , 51 . These experiments utilized a combination of barostat-controlled distention, manometry, and fluo-roscopy to directly measure the compliance of the relaxed EGJ. Several parameters of EGJ compliance were shown to be increased in hiatus hernia patients with GERD (1) the EGJ opened at lower distention pressure, (2) the relaxed EGJ opened at distention pressures that were at or near resting intra-gastric pressure, and (3) for a given distention pressure the EGJ opened about 0.5 cm wider (Fig. 8). These alterations of EGJ mechanics are likely secondary to a disrupted, distensible crural aperture and may contribute to the physiological aberrations associated with hiatus hernia and GERD. Increased EGJ compliance may help explain why patients with hiatus hernia have a distinct mechanistic reflux...

Proton pump inhibitors

Today, proton pump inhibitors (PPI) are the drug of choice for the vast majority of patients with GERD. This class of drugs consists of substituted benzimid-azoles which are prodrugs activated at low pH in the parietal cell. After entering the acid space of the parietal cell, PPI are transformed to a sulfenamide, a tetracyclic

Clinical efficacy Lifestyle modifications

Several modifications of habits are recommended for patients with GERD. These include rising of the head of the bed, early evening meals with sufficient time to elapse before going to bed, weight reduction, stopping smoking and avoidance of alcoholic beverages etc (for overview, see 22 ). None of these measures have been studied with sufficient quality so far. Therefore, its merits - if there are any - cannot be evaluated based employing the methods of evidence-based medicine. Certainly, some suggestions may have some limited value in an individual patient. It seems, however, questionable to recommend these lifestyle modifications as a prerequisite for starting effective drug therapy. It is completely unknown whether life style modifications have any effect as an adjunct to effective drug therapy.

Treatment of acute reflux symptoms

Treatment which the patient has already found to be unsatisfactory. Second, the next step up the ladder would be the administration of H2-blockers, a class of drugs which have not convincingly shown to be potent enough in patients with GERD consequently, a significant number of patient will remain symptomatic 4 , 16 . Probably after many weeks of inadequate symptomatic responses these patients will finally end up in the therapy they deserve PPI which will effectively suppress the reflux symptoms. Using the alternative strategy with the step-down approach, the goal of resolution of heartburn can be achieved within several days using PPI in 50-80 of patients. During follow-up, the optimal choice of drug and dosing scheme can be established by reducing the dose according to the patient's individual severity and frequency of symptoms. It is not excluded that some of the patients may eventually be treated with (cheap) H2-receptor antagonists if these are capable of controlling symptoms.

Therapy of reflux oesophagitis

Treatment of choice is the administration of PPI. Within 6-8 weeks, oesophagitis has healed in up to 90 , and more than half of the patients are free of heartburn after the first week. Though disappearance of symptoms is a valuable predictor of effective healing 8 , discrepant results can be detected in up to 20 however, in such cases residual lesions are predominantly minor in asymptomatic patients or heartburn of little intensity in healed cases.

Therapy of nonerosive reflux disease

Since PPI are also the most effective therapy in NERD, it is advisable to start treatment with these compounds. However, results from treatment in patients with NERD are much more complex. This has to be ascribed to the heterogenous population solely based upon a careful history of symptoms it is not always possible to exclude patients with predominant non-acid reflux or aerophagia who often also report to suffer from heartburn, but who will eventually not respond to acid inhibitory drug. Thus, the outcome from an effective treatment will also generate valuable diagnostic information. Taken these facts into consideration, prompt response to PPI therapy supports the assumption that pathological reflux is the underlying pathophysiological mechanism though placebo effects cannot be excluded. On the other hand, complete failure of PPI therapy casts doubt on the suspected diagnosis of NERD. responses to PPI therapy are unsatisfactory. The optimal intervals after which the dose escalation...

Endoscopically normal mucosa

The absence of changes in the distal esophagus on conventional endoscopy does not rule out the diagnosis of GERD. It is estimated that upto 70 of patients with typical symptoms of GERD have normal esophageal mucosa on upper endoscopy (NERD) 4 , 6 , 7 . At least, two different approaches have been attempted in these patients biopsies of the normal appearing squamous mucosa and evaluation of the distal esophagus with newer techniques such as high resolution and magnification endoscopy. Although, initial reports in 1970s suggested that histologic features of basal cell hyperplasia and location of the papillae close to the epithelial surface correlated well with the presence of GERD 50 , 51 , other studies directly comparing esophageal 24-hr pH results to histology have attested to the lack of discriminatory value of these histological criteria. In a report of 100 patients, (69 with positive pH studies), Johnson et al 54 found a significant correlation between esophageal acid exposure and...

Utility of endoscopy in addition to confirmation of diagnosis

In patients with atypical symptoms or symptoms over and above those of typical reflux, endoscopy may also have utility in ruling out alternative diseases, such as peptic ulcer disease, eosinophilic esophagitis and complications like adenocarcinoma. Eosinophilic esophagitis, also known as primary eosinophilic esophagitis or idiopathic eosinophilic esophagitis, occurs in adults and in children and represents a subset of eosinophilic gastroenteritis with an isolated severe esophageal eosinophilia. Patients with eosinophilic esophagitis present with symptoms similar to those of gastroesophageal reflux but may be less responsive to antireflux medication. The importance of recognizing this entity, especially in children is underscored by the need for different treatment approaches, e.g., dietary restriction or corticosteroids and in preventing unnecessary fundoplication 62 . Dyspepsia and GERD may overlap and sometimes they may be difficult to distinguish by symptoms alone. Many patients...

Lower esophageal sphincter

Phrenoesophageal Membrane

Obesity take their toll on the supporting structures of the EGJ. The positive peritoneo-pleural pressure gradient acts to push the abdominal contents into the chest and is opposed by the entire surface of the diaphragm. In this respect, only the esophageal hiatus is vulnerable to visceral herniation because it faces directly into the abdominal cavity. Furthermore, since the esophagus does not fill the entire hiatal canal, the integrity of this opening depends upon its intrinsic structures, especially the phrenoesophageal membrane 22 . Add to this susceptibility the repetitive stresses of deep inspiration, Valsalva, vomiting, physiologic herniation with swallowing, and tonic contraction of longitudinal muscle induced by gastroesophageal reflux, and then compound this stress by filling the abdominal cavity with adipose tissue or a gravid uterus and eventually the integrity of the hiatus is gradually compromised. The type-I, or sliding, hiatal hernia described above accounts for the vast...

Transient lower esophageal relaxations

With respect to the role tLESRs play in GERD, it appears that it is not the number but the quality of the refluxate associated with these events. Prolonged manometric recordings have not consistently demonstrated an increased frequency of transient LES relaxations in GERD patients compared to normal controls 32 . However, the frequency of acid reflux (as opposed to gas reflux) during transient LES relaxations has consistently been reported to be greater in GERD patients 32 . The cause for this difference in the frequency of acid reflux during tLESRs is unclear and hypotheses include differences in EGJ morphology and differences in the acid environment of the proximal stomach. While tLESRs typically account for up to 90 of reflux events in normal subjects or in GERD patients without hiatus hernia, patients with hiatus hernia have a more heterogeneous mechanistic profile with reflux episodes frequently occurring in the context of low LES pressure, straining, and swallowing 33 . These...

Lower esophageal sphincter intrinsic sphincter hypotension

Gastroesophageal reflux disease can occur in the context of diminished LES pressure either by strain-induced or free reflux. Strain-induced reflux occurs when a hypotensive LES is overcome and blown open in association with an abrupt increase of intraabdominal pressure 34 . Manometric data suggest that this rarely occurs when the LES pressure is greater than 10 mmHg 34 , 35 . It is also a rare occurrence in patients without hiatus hernia 33 . Free reflux is characterized by a fall in intra-esopha-geal pH without an identifiable change in either intragastric pressure or LES pressure. Episodes of free reflux are observed only when the LES pressure is within 0-4 mmHg of intragastric pressure. A wide open or patulous hiatus will predispose to this free reflux as both the intrinsic and extrinsic sphincter are compromised. A puzzling clinical observation, and one that supports the importance of transient LES relaxations, is that only a minority of patients with gastroesophageal reflux...

Esophageal mucosal defense mechanisms

Studies have also shown that GERD patients with or without esophagitis have dilated intracellular spaces (DIS), as documented by transmission electron microscopy, which may lead to increase in esophageal permeability to hydrogen ions 37 . Dilated intercellular spaces and reduced mucin production improve after anti-secretory therapy, suggesting that these abnormalities are caused by gastroesophageal reflux 37 , 38 .

Barretts patients

Many studies have shown that the symptom expression in this group of patients is lower than in erosive GERD patients, as a manifestation of a reduced mucosal sensitivity to acid 26 , 27 . On the other hand, the presence of a specialized intestinal metaplasia in the distal esophageal mucosa is associated with a small but not negligible risk of developing adenocarcinoma 28 . In any case, the possibility that patients with Barrett's esophagus may subsequently develop adenocarcinoma is seriously considered by guidelines proposed by gastroenterological associations 29 , 30 , and therefore surveillance is recommended 31 , even if the cost-effectiveness of this recommendation is still debated 32 .

Prevalence

The percentage of patients with reflux symptoms found to have esophagitis at endoscopy varies notably in the published series, from 38 to 75 35 , with an average of 50 or less 36 . Indeed, several recent community-based European studies found even a lower prevalence, of about 30 37 , 38 . In large endo-scopic series, reflecting the percentage of patients in general gastroenterological practice, the prevalence of esophagitis is nowadays higher than that of duodenal and gastric ulcer, and ranks first in the upper GI endo-scopic diagnosis in Europe and USA, with a figure around 20 35 . A recent work from Japan 39 investigating the correlation between symptoms and endoscopic finding in RE was conducted in 8031 subjects undergoing upper GI endoscopy for various reasons (and not randomly selected from the community) and who had not taken medication for GI disease the study found an overall prevalence of 14.9 for RE, with a slight tendency for symptoms to increase in frequency with the...

Morbidity

The morbidity from GERD arises from both esopha-geal and extra-esophageal complications. GERD ac counts for only approximately 6 of massive upper gastrointestinal hemorrhage 48 . More recent data show that this figure is probably increasing, possibly due to the overall increase of GERD prevalence. For example, Newton et al 49 found that in a inpatient population undergoing upper GI endoscopy at a district general hospital, 58 were referred to gastroscopy for investigation of acute upper gastrointestinal bleeding and esophagitis was found in 33 of them. Stricture complicates reflux disease in approximately 10 of patients seeking medical treatment 50 . It is likely that the incidence of these complications is falling since the introduction and the widespread use of potent antisecretory agents, such as the proton pump inhibitors.

Mortality

GERD would appear to be associated with a very low adult mortality rate. According to Brunnen et al 33 , the annual mortality rate from severe esophagitis was 0.1 per 100,000 from 1951 to 1957. When the operative mortality was considered, this figure rose to 0.16 per 100,000. Kieser 51 found that there have been 47 deaths in Switzerland (population in 1963, 5.8 million) from 1963 to 1964 in which hiatal hernia had been a basic, a contributing or an immediate cause of death, leading to a mortality rate of about 0.10 per 100,000 per year 51 . More recently, Rantanen et al 52 have analyzed all death certificated due to GERD in Finland, during the period 1990-95 they found that 52 individuals out of the ca. 5 million inhabitants of Finland died of benign GERD treated conservatively during this period, with a mortality rate of about 0.20 per 100,000 inhabitant per year. This figure is even higher than that reported by Brunnen 33 and by Kieser 51 , and also higher than the figure reported...

Risk factors

On the issue of predictive factors for GERD there is a large bulk of literature, which is however rather confusing and of relatively poor quality. Most of the existing studies are retrospective in nature, very few are case-control and can therefore assess the relative risk (RR) or the odds ratio (OR) for individual factors. Among the latter, we would like to recall the study by Nilsson et al 54 , which shows a dose-response association between increasing body mass index (BMI) and reflux in both sexes, but more significant in women the risk of reflux increased among severely obese (BMI > 35) in comparison with those with BMI < 25, with an OR of 3.3 in men and 6.3 in women. The use of postmenopausal hormone therapy increased in the latter the strength of association 54 . In a cross-sectional survey conducted in 4095 Japanese men, it was found that current smoking was significantly associated with GERD (OR vs non smoking 1.35) as it was alcohol consumption 55 . Obesity, the presence...

The refluxate

Presently, we are unable to measure bile reflux directly. Bilirubin, which can be detected in the refluxate by Bilitec 2000 (a spectrophotometric system that measures bilirubin concentration within the esophagus, independent of pH), has been used as a surrogate marker for bile reflux. However, experts elected to use the term duodenogastroesophageal reflux (DGER) instead of bile reflux to denote that Bilitec measures duodenal contents, which may include bile, pancreatic enzymes and pancreatic juice. However, duodeno-gastroesophageal reflux alone does not appear to cause significant damage to the esophageal mucosa but may act synergistically with acid reflux to produce erosive esophagitis. By using 24-hour esophageal pH monitoring and Bilitec 2000 in patients with GERD, Vaezi et al 33 demonstrated that symptoms or esophageal lesions were relatively uncommon even after partial gastrectomy, where bile reflux is an important component of the refluxate. Furthermore, according to this study,...

Genetic factors

Familial aggregation for GERD, in general, was not demonstrated, but investigators were able to document a significant rate of familial occurrence for both Barrett's esophagus and esophageal adenocarcinoma 64 , 65 . Recently, a large twin study has shown an increased concordance for GERD in monozygotic pairs, compared with dizygotic pairs, suggesting that genetic factors accounted for 31 of the liability to GERD in the U.S. population 11 , 66 . Furthermore, a genetic linkage study in pediatric GERD population mapped a locus in chromosome 13q14. Although the importance of this locus was refuted by a subsequent study, it did not completely exclude the possibility of genetic factors in GERD.

Epidemiology

Gastroesophageal reflux disease is defined as an increased frequency or duration of exposure of the distal esophagus to gastric contents. GERD is a chronic disease, that rarely resolves spontaneously, and it is associated with frequent relapses. Several studies have investigated the prevalence of GERD, though few have specifically targeted the elderly. In the 1970's, Locke et al studied the prevalence of reflux symptoms in the general population using a group of hospital workers in Olmsted County. This study found that 7 of subjects had daily symptoms of heartburn and 14 had weekly symptoms 4 . A 1994 Gallup study reported a similar 19 prevalence of weekly GERD among 1000 randomly selected persons, and 44 of subjects had monthly symptoms 5 . In Finland, a study of 1700 patients found daily, weekly, and monthly heartburn in 5 , 15 , and 21 of subjects, and acid regurgitation in 9 , 15 , and 29 6 . The prevalence of hiatal hernia and esophageal dysfunction increases with age, and since...

Symptoms

The classic symptoms of GERD are heartburn and acid regurgitation, and the presence of these symptoms can be considered diagnostic of the condition, and are sufficient to institute empiric therapy. Elderly patients in a primary care setting commonly Table 1. Prevalence of heartburn in the elderly Table 1. Prevalence of heartburn in the elderly report heartburn, with a prevalence of approximately 15 8 . However, elderly patients often report less severe reflux symptoms, especially in relation to the severity of their disease. Elderly patients also regularly present with various atypical symptoms of reflux disease. Due to the lack of symptoms in many elderly patients, they often present with more severe complications of reflux disease, a consequence of prolonged and untreated GERD 3 . Elderly patients may under-report disease, and physicians may place less emphasis on reflux symptoms when multiple other serious health problems are present, further delaying diagnosis 9 . Heartburn is...

Pathophysiology

Many studies investigated the effect of age on gastrointestinal tract functioning. After multiple conflicting findings, and some drastic paradigm shifts, it is now believed that, in general, many essential aspects of GI function are preserved in old age 1 , 25 . Many of the clinically relevant alterations in esophageal function are more likely due to chronic diseases, medications, and lifestyle exposures, than to purely age-related deficits. Comorbid conditions that may influence gastrointestinal function in older adults include coronary disease, diabetes, chronic obstructive pulmonary disease, and neurological conditions such as stroke and Parkinson's disease 1 , 3 . For example, a hemispheric stroke will affect the components of swallowing under voluntary control, as well as the pharyngeal and esophageal components such as LES relaxation and pharyngeal peristalsis 26 . The elderly also undergo lifestyle changes that exacerbate reflux, including reduced mobility, increased sedentary...

Diagnosis

There are several factors complicating the diagnosis of GERD in the elderly, and the diagnostic approach in this group should be different than in a younger population. When a healthy young patient presents, with the classic symptoms of heartburn or acid regurgitation, no further testing is needed to diagnose GERD. In this case, the recommendations are to treat first, and reserve diagnostic testing for those with alarming or atypical symptoms, symptoms resistant to medical therapy, those with a sudden onset of symptoms, or patients with chronic relapsing symptoms 3 , 13 , 44 , 50 . Alarm symptoms include GI bleeding, unintentional weight loss, iron deficiency anemia, dysphagia, persistent vomiting, an epigastric mass, or a suspicious barium meal. An improvement in symptoms on acid reduction therapy can be considered diagnostic of GERD 13 . If symptoms show a change in frequency, severity, or periodicity (especially if they become nocturnal), investigation with endoscopy is also...

Treatment

The medical and surgical treatment of GERD in the elderly population generally follows the same principles as for any adult patient with reflux 10 . The basic goals of treatment are relief of symptoms, early detection of lesions, healing of esophagitis, prevention of relapses, and prevention of complications 28 . Evaluation and management of the elderly patient does require attention to more subtle, atypical, or non-specific symptoms, recognition of the importance on maintaining function, and patience in the interaction and in the pace of progress 1 . Education of the patient about the nature of GERD and the factors that may precipitate reflux continues to be the cornerstone of therapy. Characteristics of an ideal agent for the treatment of a chronic condition in an elderly patient include high safety and efficacy, minimal side effects, no need for dose adjustment with age, safety in renal and hepatic insufficiency, a simple dosing regimen, no significant drug interactions, and cost...

Conservative therapy

Medications and GERD Table 5. Medications and GERD 50 . However, this life style modification is being recommended less often given effectiveness of proton pump inhibitors in treating GERD. Other lifestyle changes include weight loss and decreased alcohol intake. Several foods contribute to reflux symptoms, and should be avoided. Foods with an acidic pH can both lower the LES pressure and increase gastric acid secretion, and can precipitate symptoms 30 . Caffeine irritates the esophageal mucosa and increases acid secretion, while fatty foods delay gastric emptying 29 . Additional culprits include chocolate, peppermint, spicy foods, and onions. medications have a direct irritant effect on the esophageal mucosa 9 . An elderly patient's medications should be reviewed, and, especially in the case of the irritant medications, should be taken with plenty of fluids. These conservative measures should be continued throughout all steps of pharmacological therapy, as they help to...

Antacids Alginic acid

GERD therapy in the elderly injurious effects of certain bile acids 71 . They may increase LES pressure, decreasing the amount of gastroesophageal reflux. Alginic acid forms a foamy barrier on top of the refluxate to protect the esophagus from acid-induced damage. These agents have been shown to be more effective than placebo in providing relief of mild to moderate reflux symptoms 20 . Relief of symptoms can be expected in up to 20 of patients. Antacids and alginic acid are not likely to promote healing of the esophageal mucosa, or any other complications of chronic GERD 2 . There are some adverse effects, which may be of particular concern in the elderly, including constipation with aluminum containing preparations and diarrhea with magnesium containing products. Combination products may lessen these effects. Aluminum containing antacids can cause dialysis encephalopathy and osteomalacia, and should be used with caution in those with renal impairment. Antacids may promote...

Maintenance therapy

A high percentage of patients with GERD require long-term, possibly lifelong therapy for symptom control. Maintenance therapy keeps the symptoms under control, and prevents development of complications. After complete healing of esophagitis with omepra-zole, recurrences occur in up to 82 of patients within 3-6 months if no maintenance therapy is given. Early recurrence has been associated with a hypotensive LES, long-standing symptoms, need for long-term treatment for initial symptom relief and healing, high grade esophagitis, hiatal hernia, and continued symptoms despite esophageal mucosal healing 30 . If ranitidine 150 BID was given, 42 recurred in 6 months. With 20 mg omeprazole day, only 17 of patients had recurrences at 6 months, and 33 recurred at 2 years 71 . In a study of 5 maintenance regimens, omeprazole alone (20 mg day) was the most effective regimen, achieving 80 remission 2 . During maintenance therapy with low-dose omeprazole, up to 8 of patients do continue to report...

Surgery

Surgical intervention restores the LES pressure and abolishes acid alkaline reflux into the esophagus 84 . Other indications for surgery, include failed medical treatment, recurrence of symptoms after stopping treatment, and intolerable side effects from medical therapy 3 , 28 , 82 . Surgical therapy should also be considered for patients with respiratory complications such as recurrent aspiration pneumonia, laryngitis, or asthma due to GERD 13 . For asthma, around 70 have had improvement of symptoms, and there are also some reports of improvement in chronic cough 18 . The best surgical candidates are those who receive symptom relief with medication, require large doses of medication to control their symptoms, and have poorly responding aspiration symptoms 72 . Several studies have found no significant differences in intraoperative or post-operative complications between elderly and young groups 13 , 27 , 56 , 82 . The laparoscopic procedure has a morbidity rate of...

Conclusion

Gastroesophageal reflux disease is a common condition in the elderly, and will become more prevalent as the population ages. Elderly patients often do not present with the classic symptoms of heartburn and acid regurgitation, which can delay diagnosis and contribute to the development of complications. Atypical symptoms such as chest pain, pulmonary, and laryngeal symptoms are more common in this group, and reflux should be considered early in the work-up if these symptoms are present. Due to an increase in complications of reflux disease in this population, most elderly patients being evaluated for reflux symptoms should have an upper endoscopy early in the diagnostic process. There are some important age related changes in the esophagus, including decreased secondary peristalsis, decreased salivary secretion, and an increased visceral pain threshold. However, many age-related changes to motility are not thought to be clinically relevant. More aggressive treatment of reflux disease...

Natural history

Infantile GERD is generally regarded to have a favorable natural history, with persistent symptoms in about 5 of infants by one year of age, following a peak at 4 months, and resolving in the large majority between 12 and 24 months of age 7 , 8 . Epidemiological studies of the natural history of GERD and its complications in older children are scarce 9 . Un-selected infants with frequent regurgitation may develop feeding problems in the subsequent year of follow-up 10 . Children with chronic respiratory and neurological diseases commonly exhibit recurrent or chronic GERD symptoms. By nine years of age, children with frequent regurgitation during infancy may be more likely to develop persistent reflux symptoms, a phenomenon exacerbated by maternal smoking and maternal reflux symptoms 8 . Children over one year of age without neurological impairment most commonly have endoscopy-negative GERD, and their esophageal inflammation, even if present, is unlikely to deteriorate during a mean of...

Genetics

GERD and its complications are recognized as clustering within families, suggesting a genetic background for GERD phenotypes. A gene mapped for severe pediatric GERD with prominent respiratory symptoms in five kindreds was localized to chromosome 13q14 15 . Later, a genetic linkage for infantile esophagitis was identified at a separate locus 16 . A candidate gene approach to screen for mutations that might be causally associated with reflux suggests that a GERD1 gene on chromosome 13q14 might be located within 20 kb of SNP160 or SNP168 17 . Due to the heterogeneity in GERD phenotypes, more than one genetic locus may be involved and might influence various of the pathophysiologic factors.

Refluxate

The pathogenicity of the refluxate is determined by the noxiousness of its constituents namely, acid, pepsin, trypsin, and bile salts. Acid in combination with pepsin has been found to be the most injurious to the esopha-geal mucosa. Most patients with reflux have normal gastric pH, and it has been suggested that volume rather than acidity of the refluxate may be more important in the pathogenesis of reflux. Infants, including premature infants of 24 weeks gestation, maintain that basal gastric pH below 4 from day one of life, but acid secretion is modified by neurocrine, endocrine, and par-acrine pathways 32 . Severe reflux, defined by reflux index scores and esophagitis grade, in a small number of children correlated with gastric acid hypersecretion 33 . Pepsin and trypsin, being proteolytic enzymes, are directly damaging to the surface epithelium in their usual milieu, which is pH less than 4 for pepsin, and between 5 and 8 for trypsin. Increased serum pepsin-ogen values in...

Esophageal

Regurgitation and vomiting are the most easily recognizable symptoms of pediatric reflux. Episodes are usually effortless, non-bilious and post-prandial. It is usually the quantity and type of emesis that differentiates physiologic reflux in happy spitters from symptomatic reflux in infantile GERD. Some children have persistent or intermittent symptoms beyond the first year of life. Projectile non-bilious emesis in the first few weeks of life may mimic hypertrophic pyloric stenosis but simply represent reflux, whereas bilious emesis mandates evaluation for intestinal obstruction. Irritability coupled with arching in infants is thought to be a nonverbal equivalent of heartburn and chest pain reported by older children with reflux, and strongly believed to be clinical manifestations of esophagitis. However, these symptoms may correlate poorly with gross and microscopic findings in the esophageal mucosa. Infant crying has been demonstrated in association with reflux episodes during video...

The disease

Intestinal metaplasia (IM) is an epithelium with goblet cells like the small intestine but with a different architecture reflecting the result of an underlying chronic inflammatory condition - GERD. IM is important because it represents the premalignant lesion for esophageal adenocarcinoma (EAC), the most feared complication of BE and the most rapidly rising incidence cancer in the United States and Western Europe since the mid 1970s 2 , 3 .

Definitions 1 NERD

Patients with NERD do not, by definition, have esophagitis and appear to be at low risk to develop esophagitis NERD is best defined, therefore, on the basis of symptoms and or their impact on an individual's health-related quality of life (QOL) 4 . Indeed, it is apparent that NERD patients can, and do, suffer from symptoms as severe as those with ERD, and the impact on quality of life can be at least as disabling in NERD as in other manifestations of GERD 5 , 6 . It is appropriate, therefore, that recent definitions of GERD incorporate the issue of quality of life 4 . In defining NERD, one must be cognizant of prior therapy an esophagus rendered free of esophagitis by acid-suppressive therapy does not constitute NERD. Attempts to define GERD on the basis of histological findings, in those in whom the mucosa is endoscopically normal, have also proven disappointing 7 , 8 . Fig. 1. GERD subgroups Heartburn Fig. 1. GERD subgroups (iii) Those with typical reflux symptoms (i.e., heartburn...

Assessment

Can one predict NERD on the basis of clinical evaluation While the NERD patient is, on average, younger and more likely to be female that the individual with complicated GERD, these demographic features are not sufficiently discriminating to be of diagnostic value. In terms of typical GERD symptoms, neither severity nor duration can discriminate between NERD and GERD, or predict complications or manometric or pH study results. Some atypical or extraesophageal symptoms, in contrast, tend to be associated with NERD and may in of themselves predicate a different therapeutic strategy. It has been suggested, for example, that both laryngitis and asthma related to GERD require more intensive and more prolonged acid-suppressive therapy in order to optimise symptomatic response. It is also abundantly clear that this area continues to suffer from a striking paucity of data derived from randomised controlled clinical trials. Many approaches may be taken to the evaluation of the individual...

Management

Of interest, several studies as well as recent reviews and meta-analyses, while confirming a significant response, in terms of symptom relief, to proton pump inhibitors in NERD, have demonstrated, with some consistency, that these agents are somewhat less effective in NERD 3 , 9 , 59 , 62 - 68 than in ERD 69 . Several factors might explain this somewhat unexpected finding and include the relatively greater importance of abnormal acid exposure in ERD and the significant overlap with functional dyspepsia and other functional disorders 64 , in NERD a disorder where acid suppressing agents have a far smaller impact than in GERD 51 , 52 . This is not to say that NERD patients with dyspepsia do not respond to proton pump inhibitors indeed, functional dyspepsia patients with heartburn are perhaps those most likely to respond to acid suppression 51 - 53 . At the present time there is relatively little information on the use of non-acid suppressing approaches in NERD 62 . In terms of other...

Antacids

Antacids act by neutralising acid thus leading to prompt disappearance of symptoms. Therefore, antacids regularly serve as rescue medication in studies on the effect of acid inhibitory compounds and are also preferred by patients with sporadic heartburn. However, antacid consumption several times a day (which indicates the presence of reflux oesophagitis) should not be encouraged intake of high doses of antacids inherits a lot of problems (diarrhoea due to magnesium, aluminium-induced constipation, interference with other drugs taken etc). Therefore, antacids can only be recommended in patients with infrequent heartburn (which according to the definition of GERD that includes impaired quality of life cannot be regarded as sufferers from reflux disease but from sporadic reflux symptoms).

GABA antagonists

The neurotransmitter y-butyric acid (GABA) has been shown to be involved in the initiation of transient sphincter relaxations of the lower oesophageal sphincter (LES) which are thought to play the major role in the pathophysiology of reflux disease. Attempts have been made to suppress these relaxations not associated with swollowing, e.g. by the prototype of GABAb receptor agonist, baclofen. In fact, GABAergic stimulation increases the pressure in the lower oesophageal sphincter 7 . So far, clinical trials with GABAb agonists in patients with GERD show limited clinical efficacy 9 , 18 , 30 , but it seems too early to make a firm judgement about this interesting and maybe promising pharmacological principle.

Drug therapy

In patients with ERD (Table 1), PPI have been shown to be much more effective than H2-receptor antagonists in terms of healing of erosions, resolution of heartburn, prevention of relapsing heartburn and endoscopic recurrence of erosions 6 , 10 , 14 . The differences are even more pronounced with increasing severity of ERD. According to evidence-based medicine 29 , the superiority can be regarded as proven at the highest possible level I a (confirmed by multiple randomised, double-blind controlled studies and meta-analyses). In a comparative study, omeprazole was even more effective than a combination of the H2-blocker ranitidine at a dose of 150 mg three times daily and the prokinetic agent cisapride 10 mg three times daily 33 . A recent updated Cochrane review also showed that empirical treatment of GERD with PPI was significantly more effective than with H2-blockers 29 . The same applies for a comparison of PPI with prokinetics. Maintenance therapy with PPI was the most effective...

Empirical therapy

In patients with symptoms suggestive of GERD, in many instances it will be impossible to gain access to immediate endoscopy or prompt endoscopy appears not necessary at an early stage but rather an exaggerated diagnostic procedure. This seems, according to recent data of the CADET-PE study 27 , appropriate since reflux disease is by far the dominating endoscopic diagnosis whereas other benign diagnoses (e.g., peptic gastro-duodenal ulcers) were much less frequent and malignancies were rare and occurring only in patients aged over 50 years. Therefore, approaching a given patient with symptoms suggestive of reflux disease but without any alarm symptoms (e.g., dysphagia, weight loss, anaemia etc), the first option will often be empirical therapy a prescription of a PPI is recommended due to its superiority over alternative drugs.

Longterm strategy

Once a patient has been shown to improve with acid suppression therapy, the question of long-term management becomes evident. Since GERD is in most instances a chronic (relapsing) disease, a concept for the further treatment is needed in the vast majority. The speed of recurrence of symptoms after cessation of treatment represents a reliable predictor for the necessity of ongoing therapy those who will become symptomatic within a few days after stopping treatment will probably require (almost) daily doses to achieve prolonged remission whereas those remaining asymptomatic for a considerable period can most likely treated by on demand therapy. Particularly in NERD, cessation of therapy after treatment of an acute episode of reflux symptoms is advisable since about half of the patients will remain in symptomatic remission within a 6-month interval. In symptomatic patients, tailoring of long-term treatment can be well orientated at the presence of symptoms whereas endoscopic guidance is...

Barretts esophagus

The definition of Barrett's esophagus (BE), as discussed at a recent evidence based workshop, is based on a combination of endoscopic and histologic criteria consisting of an abnormal appearing distal esophageal lining (end-oscopic BE) with histologic evidence of intestinal metaplasia (confirmed BE). Barrett's esophagus has been arbitrarily divided into long (> 3 cm) and short segment (< 3 cm), although there is no evidence that a risk gradient for complications (i.e., dysplasia cancer risk) may be demarcated at a particular segment length 26 . The role of gastroesophageal reflux in the development of BE has been consistently shown in animal and human studies. In a rat model, BE could be induced in 80 of the animals following a jejunoesophageal loop. In a recent prospective study of 40 patients who underwent esophagogastrostomy and sub-total esophagectomy (done for adenocarcinoma or squamous cell carcinoma), 10 developed BE above the anastomosis 27 . Longer lengths of BE have been...

Conclusions

Endoscopy is relatively insensitive for making the diagnosis of gastro esophageal reflux disease. However, the presence of erosive esophagitis and or BE is highly suggestive of GERD. The presence of normal mucosa at endoscopy does not rule out the diagnosis of GERD. At present, the role of biopsies in these situations is unsettled and more data are needed. Newer endoscopic techniques such as chromoendoscopy, magnification and high resolution may demonstrate minimal changes in the distal squamous mucosa such as punctate erythema, pinpoint vessels etc. not seen by standard endoscopy. Some of these changes may respond to therapy with proton pump inhibitor. Endoscopy remains the best test to rule out complications of GERD and allows histological confirmation of esophageal pathology such as intestinal metaplasia, dysplasia and adenocarcinoma. Identifying the patient group with severe erosive esophagitis, BE and peptic strictures may help focus aggressive management that may potentially...

Prokinetic agents

This class of agents targets the underlying motility dysfunction that causes GERD. Specifically, they increase lower esophageal sphincter pressure, accelerate gastric clearance, stimulate esophageal peristalsis, and increase the amplitude of esophageal contractions 73 . Each of these agents (bethenechol, metoclopra-mide, domperidone, and cisapride) is effective in improving symptoms and healing erosions. They are especially useful in the presence of dyspeptic symptoms such as nausea, vomiting, and abdominal bloating 10 . Unfortunately, they have a poor adverse event profile, which is of particular concern in an elderly population, and they should therefore be used sparingly in this population. Cisapride was removed from the market in 2000, after 80 deaths due to cardiac arrhythmias were reported. It was the most effective promotility agent for the treatment of GERD, both in relieving symptoms (60 ) and promoting healing 73 . It was as effective as H2B's for mild to moderate disease,...

Antireflux barrier

Transient lower esophageal sphincter relaxation Very low pressure of the LES is a prerequisite for reflux of gastric contents into the esophagus. Most reflux in infants and children, as in adults, occurs primarily in association with transient lower esopha-geal sphincter relaxation (TLESR), defined as an abrupt decrease in LES pressure to the level of the intragastric pressure unrelated to swallowing 18 . Premature infants as young as 26 weeks of gestatio-nal age who were diagnosed with GERD exhibited more acid reflux during TLESRs, compared with healthy controls 19 . TLESRs may be triggered by gastric distention and by increased intra-abdominal pressure 20 , as occurs with straining, obesity, tight clothing, cough, and increased respiratory effort. In infants, extrinsic abdominal compression in semi-seated postures in the post-prandial period is an important factor contributing to the pathogenesis of reflux. Also important are the influences of the meal Delayed gastric emptying has...

Erosive esophagitis

Multiple studies have shown that only 30-40 of patients with typical reflux symptoms (i.e., heartburn, regurgitation) have evidence of erosive esophagitis (Fig. 1) on upper endoscopy whereas the other 60-70 of patients even with troublesome reflux symptoms have no clear-cut esophageal mucosal abnormalities 2 - 7 . Thus, overall endoscopy is an insensitive test for diagnosing reflux disease. However, if detected, erosive esophagitis has a good positive predictive value for the diagnosis of GERD as discussed below. The presence of erosive esophagitis has a good correlation with results of 24 h pH monitoring showing increased esophageal acid exposure. In a study by DeMeester etal 13 , the combination of typical reflux symptoms (i.e., grade-II or -III heartburn and or regurgitation, scale of severity 0-3) and the presence of erosive esophagitis or Barrett's esophagus on en-doscopy had a 64 sensitivity and 97 specificity for accurately diagnosing GERD as defined by a positive 24-hr...

Extraesophageal

Apnea is a frequently cited extraesophageal manifestation of reflux in infants, but the causal relationship is controversial, despite being examined by multiple investigators. Most episodes of apnea of prematurity occur in the post-prandial period, and likely follow bouts of regurgitation, and yet studies using impedance and monitoring cardiorespiratory events have been contradictory 52 , 53 . In 21 infants with a history of intermittent reflux and apnea, 81 of apneic events did not follow episodes of reflux 52 . However, using pH and impedance testing in 22 infants with a history of irregular breathing and reflux, 29.7 (49 of 165) apneic episodes were associated with reflux, though only 22.4 of these were related to acid reflux 53 , (Fig. 1) 54 . Apnea related to reflux has been explained on the basis of a Gastroesophageal reflux has been associated with several important otolaryngologic manifestations, includ- Fig. 1. Intraluminal impedance and simultaneous pH probe and pneumogram...

Pathological Considerations

The normal esophagus is lined by squamous epithelium, but it is readily damaged by the chronic injury of duodeno-gastroesophageal reflux disease. Repair is affected in this abnormal environment by columnar intestinal and gastric cells, an example of phenotypic plasticity. The mucosa has adapted to hostile environmental conditions by a metaplastic response. Three distinct

Answers To Patients Frequently Asked Questions

Aloe gel is traditionally used for burns, wounds and inflammatory skin disorders. There is good scientific evidence that aloe may be of benefit in these conditions however, the chemical composition of Aloe vera products will vary depending on geographical and processing factors. Traditionally, aloe is also used internally for dyspepsia, gastrointestinal ulcers and IBS. 2007 Elsevier Australia

Nutrition And Esophageal Adenocarcinoma

Increased risk of esophageal adenocarcinoma with both GERD and obesity may be attributed to the independent association of these two etiological factors with each other. This failed to be confirmed in one large case-controlled study from Sweden (79), thereby raising the possibility that hormonal effects may underlie the association of obesity and esophageal cancer.

Clinical Presentation

Patients with oesophageal disease may be asymptomatic, but usually experience one or more of the following chest pain, heartburn (a retrosternal burning sensation), reflux of food and dysphagia (difficulty swallowing). Dysphagia can be painful (odynophagia) or progressive due to benign or malignant strictures, i.e., initially for solid foods, e.g., meat, then soft foods and ultimately liquids. Patient localisation of the site of obstruction can be poor. Occult bleeding can lead to iron-deficiency anaemia while haemorrhage (haematemesis) can be potentially life threatening (varices) or self-limiting due to linear tears of the OG junction mucous membrane after prolonged vomiting (Mallory-Weiss syndrome).

Colonization And Succession Of Human Intestinal Microbiota With

The habitats of the intestinal microbiota vary in different parts of the human GI tract (8). In healthy persons, acid stomach contents usually contain few microbes. Immediately after a meal, counts of around 105 bacteria per milliliter of gastric juice can be recorded bacteria including streptococci, enterobacteriaceae, Bacteroides and bifidobacteria derived from the oral cavity and the meal. The microbiota of the small intestine is relatively simple and no large numbers of organisms are found. Total counts are generally 104 or less per milliliter, except for the distal ileum, where the total counts are usually about 106 ml. In the duodenum and jejunum, streptococci, lactobacilli and Veillonellae are mainly found. Towards the ileum, E. coli and anaerobic bacteria increase in number. In the caecum, the composition suddenly changes and is similar to that found in feces, and the concentration may reach 1011 per gram of content.

Gastrointestinal side effects

Gastrointestinal side effects are the most common side effects of almost all antiret-roviral drugs - nucleoside analogs, NNRTIs and particularly protease inhibitors -and occur especially during the early stages of therapy. Typical symptoms include abdominal discomfort, loss of appetite, diarrhea, nausea and vomiting. Heartburn, abdominal pain, meteorism and constipation may also occur. Nausea is a common symptom with zidovudine-containing regimens diarrhea occurs frequently with zidovudine, didanosine and all PIs, particularly nelfinavir, as well as with saquinavir and lopinavir r, atazanavir and ritonavir. Treatment with zidovudine rarely leads

Clinical Features Of Patients With Megaloblastic Anemia

Megaloblastic anemia is usually a disease of middle-aged to older age with a high predilection for women. Severe anemia, in which the hemoglobin drops to 7 to 8 g dL, is accompanied by symptoms of anemias such as shortness of breath, light-headedness, extreme weakness, and pallor. Patients may experience glossitis (sore or enlarged tongue), dyspepsia, or diarrhea. Evidence of neurological involvement may be seen with patients experiencing numbness, vibratory loss (paresthesias), difficulties in balance and walking, and personality changes. Vitamin B12 deficiency causes a demyeliniza-tion of the peripheral nerves, the spinal column, and the brain, which can cause many of the more severe neurological symptoms such as spasticity or paranoia. Jaundice may be seen, because the average red cell life span in megaloblastic anemia is 75 days, a little more than one half of the average red cell life span of 120 days. The bilirubin level is elevated, and the lactate dehydrogenase (LDH) level is...

Differential Diagnosis

Epigastrium Gastritis, peptic ulcer, gastroesophageal reflux disease, esophagitis, gastroenteritis, pancreatitis, perforated viscus, intestinal obstruction, ileus, myocar-dial infarction, aortic aneurysm. Left Upper Quadrant Peptic ulcer, gastritis, esophagitis, gastroesophageal reflux, pancreatitis, myocardial ischemia, pneumonia, splenic infarction, pulmonary embolus.

Physical Examination

Differential Diagnosis Calculus cholecystitis, cholangitis, peptic ulcer, pancreatitis, appendicitis, gastroesophageal reflux disease, hepatitis, nephrolithiasis, pyelonephritis, hepatic metastases, gonococcal perihepatitis (Fitz-Hugh-Curtis syndrome), pleurisy, pneumonia, angina, herpes zoster.

Bisphosphonates alendronate Fosamax

Patients should take the pill in the morning with 2-3 glasses of water, at least 30 minutes before any food or beverages. No other medication should be taken at the same time, particularly calcium preparations. Patients should not lie down after taking alendronate to avoid gastroesophageal reflux. Contraindicates include severe renal insufficiency and hypocalcemia.

What Does the Term Dyspareunia Mean

In 1874, Barnes (1) coined the term dyspareunia. He felt that it would be a convenient way of summarizing the different conditions underlying painful intercourse just as 'dyspepsia' is used to signify difficult or painful digestion, we want a word to express the condition of difficult or painful performance of the sexual function (p. 68). Although the usefulness of the term dyspepsia is a matter of some controversy (2), the diagnosis of dyspareunia has not been seriously challenged and is still used by all major classificatory systems, such as the DSM-IV-TR (3) and the ICD-10 (4). The lack of specificity of the word dyspareunia is evidenced by the growing number of overlapping terms (e.g., vul-vodynia, vulvar vestibulitis syndrome, dysesthetic vulvodynia, vestibulodynia) denoting presumed disease entities. The majority of these terms originate from a recent renewed interest in painful vulvar conditions. Even prior to this increased interest, the term dyspareunia was often used...

Ishaan S Kalha and Frank A Sinicrope

Barrett's esophagus is an acquired condition in which specialized metaplastic intestinal epithelium with goblet cells replaces the normal stratified squamous epithelium anywhere in the esophagus. The relationship between long-standing gastroesophageal reflux disease (GERD), the development of specialized intestinal metaplasia in the distal esophagus, and subsequent progression to adenocarcinoma has been clearly established. Once Barrett's esophagus is diagnosed, it is critical to extensively biopsy the segment of Barrett's epithelium to exclude dysplasia and cancer. Management of Barrett's esophagus should focus on relieving symptoms of GERD and performing endoscopic surveillance at appropriate intervals. The timing of surveillance endoscopy is governed by the presence of mucosal dsyplasia and its pathologic grade. Recommendations about endoscopic surveillance intervals will undoubtedly be modified as the natural history of Barrett's esophagus becomes better understood. Studies to...

Surveillance of Barretts Esophagus

Barrett's esophagus is usually discovered during endoscopic evaluation of patients who have symptoms caused by GERD or esophageal cancer. Studies suggest that in the general population, however, more than 90 of cases of Barrett's esophagus are not recognized, and many patients with the condition have few or no symptoms of GERD (Spechler, 1994). It is important to risk-stratify patients with GERD symptoms to determine who should undergo diagnostic upper endoscopy to effectively screen for Barrett's esophagus. Guidelines recommend that patients with longstanding GERD symptoms, especially but not exclusively white men over 50 years of age, undergo endoscopy at least once to screen for Barrett's

Suggested Readings

Cameron AJ, Lagergren J, Henriksson C, et al. Gastroesophageal reflux disease in monozygotic and dizygotic twins. Gastroenterology 2002a 122 55-59. Champion G, Richter JE, Vaezi MF, Singh S, Alexander R. Duodenogastro-esophageal reflux relationship to pH and importance in Barrett's esophagus. Gastroenterology 1994 107 747-754. Falk GW. Gastroesophageal reflux disease and Barrett's esophagus. Endoscopy 2001 33 109-118. Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999 340 825-831. Romero Y, Cameron AJ, Locke GR 3rd, et al. Familial aggregation of gastro-esophageal reflux in patients with Barrett's esophagus and esophageal adeno-carcinoma. Gastroenterology 1997 113 1449-1456. Spechler SJ. Screening and surveillance for complications related to gastroesophageal reflux disease. Am J Med 2001 111 Suppl 8A 130S-136S.

Diseases of the Esophagus

Esophageal Varices Abnormalities Xray

Has the patient had heartburn for extended periods Esophagitis Inflammatory changes of the esophageal mucosa may be due to gastroesophageal reflux, caustic injury, candidiasis, or viral infection in immunocompromised patients. Sometimes Crohn disease can affect the esophagus in the child and adolescent (Fig. 9.19).

Irritable Bowel Syndrome

More recently, a study of 208 adults with IBS observed before and after a 2-month Intervention period of changes in symptoms (Budy et al 2004). A significant reduction in the incidence of IBS by 26.4 and a significant shift in self-reported usual bowel pattern toward 'normal' were also reported after treatment. The Nepean Dyspepsia Index (NDI) total symptom score significantly decreased by 41 after treatment and a significant 20 improvement in the NDI total QOL score.

Scleroderma

Sensorineural hearing loss has been reported to occur, but has not been found to correlate with other disease manifestations (20,21). Virtually the entire gastrointestinal tract can be affected in scleroderma. Swallowing dysfunction due to oropharyngeal involvement can occur (22) and increase the risk of aspiration. Esophageal dysmotility and nonobstructive dysphagia are seen in the majority of patients, making symptoms of gastroesophageal reflux very common.

Clinical Summary

S was 45 years old at the time of his death. He had smoked cigarettes for 25 years, had hypertension, and was a known non-insulin dependent diabetic (type II) controlled with oral hypoglycemic drugs. He was moderately obese, weighing 105 kg and 175 cm length (BMI 34 kg m2). He also had a history of illicit intravenous drug use with scarred veins in the antecubital fossa. He had clinical evidence of diabetic neuropathy, and peripheral vascular disease (intermittent claudication and sexual dysfunction). He was admitted to the hospital because of complaints of indigestion and progressive discomfort radiating to both arms. The presumptive diagnosis was acute inferior wall myocardial infarction, and he was treated with tissue plasminogen activator (TPA). The patient slowly became clinically stable after his creatine kinase (CK) peaked at 1555 U L. On medication, and 3 days later, he had a low level stress exercise ECG, which was negative for ischemia. He was discharged home with a plan...

Ajowan

Therapeutic Uses and Folklore ajowan is highly valued in India as a gastrointestinal medicine and an antiseptic. It is combined with salt and hot water and taken after meals to relieve pain in bowel or colic pain, and to improve indigestion. Ajowan was also a traditional remedy for cholera and fainting spells. Westerners generally use it against coughs and throat issues. Ajowan is an ingredient in mouthwashes and toothpastes because of its antiseptic properties.

Omeprazole Prilosec

Indications gastric acid hypersecretion conditions gastritis gastroesophageal reflux (GERD) erosive gastritis peptic ulcer disease prevention of acid aspiration pneumonitis during surgery. Dose (adult) Duodenal ulcer 20 mg day PO for 4-8 weeks. GERD or severe erosive esophagitis 20 mg day for 4-8 weeks maintenance therapy for erosive esophagitis 20 mg day. Gastric ulcer 40 mg day PO for 4-8 weeks. Pathological hypersecretory conditions 60 mg PO once daily to start doses up to 120 mg 3 times day have been administered administer daily doses > 80 mg in divided doses. Dose (ped) 0.6-0.7 mg kg dose PO once daily increase to 0.6-0.7 mg kg dose PO every 12 hrs if needed (effective range 0.3-3.3 mg kg day). Clearance extensive hepatic metabolism 80 renal elimination.

Ranitidine Zantac

Actions competitive inhibition of histamine at H2 receptors of the gastric parietal cells inhibits gastric acid secretion, gastric volume, hydrogen ion. Indications duodenal and gastric ulcers esophageal reflux reduction of gastric volume increasing gastric pH prevention of acid aspiration pneumonitis during surgery prevention of stress ulcers.

Adverse Effects

Bleeding is the major adverse effect of bivalirudin and occurs more commonly in patients with renal impairment. Injection site pain has been reported in individuals given sc bivalirudin (Fox et al., 1993). Mild headache, diarrhea, nausea, and abdominal cramps have also been reported (Fox et al., 1993). In the Hirulog Angioplasty Study (HAS) (now known as the Bivalirudin Angioplasty Trial BAT ), the most frequent adverse effects included back pain, nausea, hypotension, pain, and headache. Approximately 5-10 of patients reported insomnia, hypertension, vomiting, anxiety, dyspepsia, bradycardia, abdominal pain, fever, nervousness, pelvic pain, and pain at the injection site (Bittl et al., 1995 Sciulli and Mauro, 2002) (Table 3).

Gist290

The symptoms at presentation often reflect the site of origin of the tumor. Patients with esophageal GISTs most often present with dysphagia, odynophagia, weight loss, dyspepsia, retrosternal chest pain, or hemat-emesis. Modified barium swallow or endoscopic evaluation is often diagnostic.

Lemon Balm

Therapeutic Uses and Folklore since ancient times, lemon balm was used to heal wounds, sores, and bee and wasp stings. Called the elixir of life in Europe, it was mixed into a drink to ensure longevity and to treat asthma, stomach ailments, indigestion, menstrual cramps, and fevers.

Valerian

Historical note The sedative effects of valerian have been recognised for over 2000 years, having been used by Hippocrates and Dioscorides in ancient Greece Over the past 500 years, it was widely used in Europe as a calmative for nervousness or hysteria and also to treat dyspepsia and flatulence. Legend has it that the Pied Piper put valerian in his pockets to attract the rats out of Hannover Valerian was widely used by the Eclectic physicians and listed in the United States Formulary until 1 946.

RHuSCF

The adverse event profile associated with r-metHuSCF was first defined in two small phase 1 clinical trials investigating its utility in patients with cancer receiving chemotherapy (29,30). When administered to 17 patients with nonsmall-cell lung cancer in incremental doses of 10, 25, and 50 g kg d before the administration of chemotherapy, a specific pattern of adverse events emerged. At the lowest dose level, adverse events were limited to the injection site. At dose levels > 10 g kg d, adverse events occurred as multisystem systemic reactions. Dose-related mild-to-moderate reactions occurred in all patients at all dose levels and included edema, urticaria, erythema, and pruritus. These reactions, mild to severe, as well as angioedema and der-matographia, occurred at distant cutaneous sites. Cough, throat tightness, sore throat, dyspepsia, and hypotension were transient and did not result in patient withdrawal from the study (29). In another phase 1 trial of identical design,...

Gastric Carcinoid

Gastric carcinoid tumors can be separated into three distinct groups on the basis of clinical and histopathological findings, and these groupings will determine subsequent management. These groupings are those associated with CAG-A those linked with the Zollinger-Ellison (ZE) syndrome and those arising as solitary, usually large, sporadic tumors (3). It is likely that up to 75 of gastric carcinoid tumors are associated with CAG-A, usually linked to pernicious anaemia (80-87). This condition, because of the link to pernicious anaemia, is more frequently found in women, with a peak incidence in the sixth and seventh decades (80,84,85). These CAG-A-related carcinoids are frequently an incidental finding during gastroscopic investigation of indigestion, frequently < 1 cm in size and multiple, and nearly always located in the gastric body and fundus (80,84,85). CAG-A is associated with hypochlorhydria which results in hyper-gastrinemia (86), and this resulting oversecretion of gastrin...

Reasons, Remedies And Treatments For Heartburns

Reasons, Remedies And Treatments For Heartburns

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