Rationale and efficacy of conservative therapy for gastroesophageal reflux disease.

Major recent advances in the diagnosis and understanding of gastroesophageal reflux disease have afforded the practicing clinician a number of therapeutic options to treat the increasingly recognized affected patient population. With highly effective acid-suppressive therapies available, simple life-style modifications, such as selective food and medicine avoidance, weight loss, smoking cessation, elevation of the head of the bed, and the judicious use of antacids and alginate, have been relegated to a minor, if any, role in the management of these patients. The validity of these recommendations, however, remains consistent with our current understanding of the pathogenesis of gastroesophageal reflux disease. Although few well-designed placebo-controlled trials have been conducted, a review of the medical literature indicates an appreciable efficacy of these interventions, which are founded on well-studied physiologic determinants of gastroesophageal reflux. Most patients with gastroesophageal reflux disease can be managed by reassurance and simple life-style adjustments alone. The therapy for those with chronic or relapsing disease should always include the adjunctive reinforcement of these simple, efficacious, and cost-effective measures.     

Gastroesophageal reflux disease during pregnancy

Approximately two thirds of pregnant patients develop heartburn. The origin is multifactorial, but the predominant factor is a decrease in LES pressure caused by female sex hormones, especially progesterone. Mechanical factors play a small role. Serious reflux complications during pregnancy are rare; therefore EGD and other diagnostic tests are infrequently needed. Symptomatic GERD during pregnancy should be managed with a step-up algorithm beginning with lifestyle modifications and dietary changes. Antacids or sucralfate are considered the first-line medical therapy. If symptoms persist, H2RAs should be used. Ranitidine is probably preferred because of its documented efficacy and safety profile in pregnancy, even in the first trimester. Proton-pump inhibitors are reserved for the woman with intractable symptoms or complicated reflux disease. Lansoprazole may be the preferred PPI because of its safety profile in animals and case reports of safety in human pregnancies.     

Management of reflux disease in clinical praxis in hungary

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a chronic condition that affects a large proportion of the population. The majority of patients are treated in the primary care but effective management of the disease still remains a challenge for specialists as well. A recent survey - based on the case of a typical GERD patient - conducted in Germany indicated that mainly specialists adhered to the guidelines. AIM: The purpose of this study was to conduct a survey among specialists and primary care physician members of the Hungarian Society of Gastroenterology about the practical management of GERD using the same questionnaire as in the German study. METHODS: A questionnaire based on the case of a typical patient with GERD was sent out to a total of 1090 members of the society. The questions concerned general measures for avoiding reflux symptoms (dietary and life-style modifications), diagnosis of GERD and the type of treatment. Answers were compared with those in the German study. RESULTS: A total of 421 questionnaires were evaluated (38 %), which had been returned by 174 general practitioners (GP), 173 gastroenterologists (GE), 41 paediatricians, and 33 surgeons. Only 9 % (38/421) of the responders think that there is no necessity to carry out specific diagnostic approaches before starting any treatment. In 91 % of the cases (25 % always and 66 % only if symptoms persist) doctors carry out specific diagnostic tests (75 % endoscopy, 13 % 24 hours pH-metry, and 12 % X-ray). 47 % of responders start drug treatment at once while 35 % start medications only after getting the results of the requested examinations. 18 % of Hungarian doctors do start with a non-medical therapy. Almost all responders feel that it is important to advise a reduction of weight and a cessation of smoking for GERD patients. Altering specific dietary and life-style habits was considered useful by more than 85 % of our responders. Hungarian physicians were more concerned about different alcoholic drinks and spicy, fatty or bloating meals and less about sweets than their German counterparts. More than 85 % of GPs administer some kind of drug therapy as first choice. Over 65 % of GPs are using the step-down approach with proton pump inhibitors as the initial strategy and 78 %, 76 %, and 81 % of GEs, paediatricians, and surgeons, respectively, do the same. Almost one-third of GPs and paediatricians are willing to continue therapy and almost two-thirds of GPs will reduce the dose of current medical therapy if the GERD patient is responding well to the initial therapy. CONCLUSIONS: Irrespective of the country, specialists are adhering more strictly to the guidelines on the diagnosis and treatment of GERD than general practitioners. The majority of responders, however, ask for endoscopy prior to initiation of any medication and use the step-down approach. Despite the lack of scientific evidence, reduction of weight, cessation of smoking, dietary and life-style modifications are still part of the treatment of GERD in both Germany and Hungary.     

Gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease refers to reflux of gastric contents into the oesophagus leading to oesophagitis, reflux symptoms sufficient to impair quality of life, or long-term complications. Transient relaxation of the lower oesophageal sphincter is believed to be the primary mechanism of the disease although the underlying cause remains uncertain. Obesity and smoking are weakly associated with the disease and genetic factors might be important. A negative association with Helicobacter pylori exists, but eradication of H pylori does not seem to cause reflux disease. Diagnosis is imprecise as there is no gold standard. Reflux symptoms are helpful in diagnosis but they lack sensitivity. Ambulatory oesophageal pH monitoring also seems to be insensitive despite high specificity. Empirical acid suppression with a proton-pump inhibitor (PPI) has reasonable sensitivity but poor specificity. Some evidence suggests that once patients develop the disease, severity is determined early and patients seem to continue with that phenotype long term. Unfortunately, most patients do not respond to life-style advice and require further therapy. H2 receptor antagonists and PPIs are better than placebo in oesophagitis, with a number needed to treat of five and two, respectively. In non-erosive reflux disease, acid suppression is better than placebo but the response rate is lower. Most patients need long-term treatment because the disease usually relapses. The role of endoscopic therapy is uncertain. Anti-reflux surgery is probably as effective as PPI therapy although there is a low operative mortality and morbidity.     

Gastroesophageal reflux disease in pregnancy

Opinion statement Gastroesophageal reflux disease (GERD) in pregnancy presents a special challenge for the clinician, predominantly because of the potential side effects of pharmacologic interventions on the fetus. Lifestyle and dietary modifications, change in sleeping posture, and antacid medications are emphasized, as these options pose little risk to the fetus. When these interventions are not successful, sucralfate, a mucosal protectant with little to no systemic absorption, should be considered next. Therapy with H₂ receptor antagonists or proton pump inhibitors can be considered in patients with refractory symptoms; though not approved for this use, they are likely safe, particularly in third trimester. Prokinetic agents should be used with extreme caution or avoided altogether in the pregnant patient.     

Therapie der stabilen Angina pectoris

Chronic stable angina is a common clinical problem limiting the quality of life. Patients with suspected stable angina require prompt cardiological investigation to ensure that the diagnosis is correct and that the prognosis is evaluated. An initial non-invasive strategy using an exercise test is most appropriate. All patients should be advised regarding life-style modifications to correct risk factors. In the absence of contraindications or intolerance acetylsalicylic acid and statins should be given. ACE-inhibitors are indicated in patients with left ventricular dysfunction, hypertension or diabetes and patients with other high-risk features. Beta blockers are used in all patients after myocardial infarction and those with left ventricular dysfunction. Anti-anginal therapy is based on the use of short-acting nitrates. Beta blockers, calcium antagonists and long-acting nitrates reduce the frequency and intensity of angina. In patients with high-risk features and those whose symptoms cannot be adequately controlled by medications coronary angiography should be considered. Both percutaneous coronary intervention and coronary artery bypass graft operation (CABG) are effective measures to control anginal symptoms. However, only CABG has been shown to improve prognosis in some high-risk patients.     

Reflux in der Schwangerschaft

Gastroesophageal reflux occurs often in pregnancy and is usually interpreted as being intrinsically related to pregnancy and thus not a “real disease.” If the reflux symptoms are inadequately cared for, then gastroesophageal reflux disease (GERD) can have a severe affect on the quality of life of the pregnant woman. The main cause of reflux during pregnancy is a decrease in the lower esophageal sphincter tonus due to hormone level changes brought on by the pregnancy. Symptomatic GERD during pregnancy should be treated according to the step-up algorithm put forth by the European consensus meeting guidelines in 2003, starting with specific lifestyle changes. Antacids are the medication of first choice. Should the symptoms persist, then histamine-2 receptor antagonists can be given. Proton pump inhibitors are not recommended for pregnant women by the consensus meeting guidelines.     

Esophageal manometric changes and gastroesophageal reflux symptoms after distal gastrectomy for gastric cancer

BACKGROUND/AIMS: Gastroesophageal reflux is known to be a common complication after gastrectomy. However, its mechanism is not completely understood. We investigated the effects of distal gastrectomy for gastric cancer on the lower esophageal sphincter (LES) and esophageal motility. METHODOLOGY: In 18 patients who underwent distal gastrectomy reconstructed with Billroth I method for gastric cancer, esophageal motility and LES function were evaluated by means of a low-compliance manometric system. The LES pressure was determined by a rapid pull-through technique. Endoscopy before and after operation determined presence or absence of esophagitis and hiatus hernia. RESULTS: No significant differences were observed in esophageal contractile amplitudes before and after distal gastrectomy. After distal gastrectomy, five patients had reflux symptoms of heartburn and regurgitation; 11 had none. Endoscopy revealed esophagitis after distal gastrectomy in two patients with reflux symptoms and one patient without reflux symptoms. The LES pressure in patients with reflux symptoms decreased significantly after distal gastrectomy (before gastrectomy: 26.1 +/- 1.1 mmHg, after distal gastrectomy: 15.3 +/- 3.5 mmHg, p<0.05). There was no significant change in patients without reflux symptoms. CONCLUSIONS: This study demonstrated that LES pressure after distal gastrectomy in patients with reflux symptoms was significantly lower than that before gastrectomy. This result suggested that LES pressure decrease plays an important role in development of gastroesophageal reflux after distal gastrectomy reconstruction with the Billroth I method.     

Gastroesophageal reflux disease and Barrett��s esophagus

Gastroesophageal reflux disease is the most common gastrointestinal diagnosis recorded during visits to outpatient clinics. The spectrum of injury includes esophagitis, stricture, the development of columnar metaplasia in place of the normal squamous epithelium (Barrett’s esophagus), and adenocarcinoma. Barrett’s esophagus is a premalignant lesion detected in the majority of patients with esophageal and gastroesophageal adenocarcinoma. The incidence of these cancers has been increasing in the United States and they are associated with a low rate of survival (5-year survival rate, 15–20%). When symptoms of gastroesophageal reflux disease are typical and the patient responds to therapy, no diagnostic tests are necessary to verify the diagnosis. Endoscopy is the primary test in patients whose condition is resistant to empirical therapy but its yield in this setting is low because of the poor correlation between symptoms attributed to the condition and endoscopic features of the disease. Clinical experience suggests that lifestyle modifications may be beneficial for gastroesophageal reflux disease although trials of the clinical efficacy of dietary or behavioral changes are lacking. Abundant data from randomized trials show benefits of inhibiting gastric acid secretion and suggest that proton-pump inhibitors are superior to H2-blockers and that both are superior to placebo. In patients with Barrett’s esophagus, antireflux interventions are intended to control symptoms of reflux and promote healing of the esophageal mucosa. If a patient has symptoms refractory to proton-pump inhibitors or cannot tolerate such therapy, antireflux surgery, most commonly Nissen fundoplication, may be an alternative management approach. In patients with high-grade dysplasia, endoscopic therapies or surgical resection must be considered.     

Three year follow up of patients with gastrooesophageal reflux disease.

Data on the natural course of gastrooesophageal reflux disease are sparse. One hundred and sixty six patients with typical reflux symptoms (heartburn and/or acid regurgitation) and pathologic pH monitoring (reflux time > 8.2% upright and/or > 3.0% supine) were studied. The patients were followed up by questionnaire and interview for a mean of 41 (seven to 86) months after diagnosis of reflux disease. Ten patients had died of diseases not reflux related. In 117 (75%) of the remaining 156 patients data on the course of gastrooesophageal reflux disease could be obtained. In 12 patients anti reflux surgery had been performed. Forty one (39%) of the remaining 105 patients have stopped taking medical therapy, in 13 of these patients symptoms had completely disappeared. Sixty four patients continued on medication (40 on demand, 24 regularly). When asked how their symptoms would be if they completely stopped medication, 71 patients considered their symptoms to be equal or worse and 21 patients to be improved as compared with the initial investigation. Patients with persisting symptoms at follow up had significantly more supine reflux (p < 0.05) at the initial pH monitoring as compared with patients with improved symptoms. The presence and grade of oesophageal erosions at initial endoscopy, duration of symptoms, age, sex, and smoking habits had no influence on the course of gastrooesophageal reflux disease. In conclusion, reflux symptoms disappear only in a minority of patients with proven gastrooesophageal reflux disease. More than half of all patients continue medication, either on demand or regularly. Severe supine reflux is an unfavourable prognostic factor.     

Diagnosis and treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease(GERD) is a common disease with a prevalence as high as 10%-20% in the western world. The disease can manifest in various symptoms which can be grouped into typical,atypi-cal and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of alarm symptoms,these symptoms can allow one to make a presumptive diagnosis and initiate empiric therapy. In certain situations,further diagnostic testing is needed to confirm the diagnosis as well as to assess for complications or alternate causes for the symptoms. GERD complications include erosive esophagitis,peptic stricture,Barrett's esophagus,esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modification,medical therapy and surgical therapy. Life-style modifications including weight loss and/or head of bed elevation have been shown to improve esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression which can be achieved with antacids,histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy,others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The purpose of this review is to discuss the current approach to the diagnosis and treatment of gas-troesophageal reflux disease.     

Gastroesophageal reflux disease

Opinion statement Lifestyle modifications should be discussed with every patient with symptoms of chronic gastroesophageal reflux disease (GERD). Proton pump inhibitors are the most efficacious medical therapy for GERD. H₂ receptor antagonists are likely to be effective in patients with mild to moderate GERD and for occasional symptoms. Promotility drugs have limited efficacy and produce frequent side effects. Surgery is a reasonable option for chronic management. Endoscopic therapy remains experimental until more long-term results are available.     

Proton Pump Inhibitors Improve Acid-Related Dyspepsia in Gastroesophageal Reflux Disease Patients

It has been reported that proton pump inhibitors are more effective than H2 receptor antagonists in patients with functional dyspepsia. Dyspeptic symptoms that respond to proton pump inhibitors are classified as acid-related dyspepsia. A new questionnaire for assessing gastroesophageal reflux disease (GERD), the Frequency Scale for Symptoms of GERD, covers the 12 most common symptoms of GERD patients. A quantitative assessment of the changes of reflux symptoms and acid-related dyspepsia was made in GERD patients receiving proton pump inhibitor therapy. Sixty-eight GERD patients receiving proton pump inhibitor therapy completed the questionnaire before and after treatment for 8 weeks. There is a significant positive correlation between reflux symptoms and acid-related dyspepsia before and after therapy (r = 0.569 and r = 0.569; both P's < 0.001) and acid-related dyspepsia in patients with both nonerosive and erosive GERD. We conclude that GERD patients suffer not only from reflux symptoms, but also from acid-related dyspepsia, and proton pump inhibitors improve both types of symptoms.     

Refractory Heartburn: A Challenging Problem in Clinical Practice

Gastroesophageal reflux disease (GERD) is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Heartburn and regurgitation are the typical symptoms of GERD. The treatment of GERD encompasses lifestyle modifications, pharmacological, endoscopic, and surgical therapy. The majority of the patients respond to 4–8 weeks of proton-pump inhibitors therapy, but 20–42% will demonstrate partial or complete lack of response to treatment. While these patients have been considered as having refractory heartburn, a subset of them does not have GERD or have not been adequately treated. The main causes of refractory heartburn include: poor compliance; inadequate proton-pump inhibitors dosage; incorrect diagnosis; comorbidities; genotypic differences; residual gastroesophageal reflux; eosinophilic esophagitis and others. Treatment is commonly directed toward the underlying cause of patients’ refractory heartburn.     

High prevalence of reflux symptoms in duodenal ulcer patients who develop gastro-oesophageal reflux disease after curing Helicobacter pylori infection

BACKGROUND: Gastro-oesophageal reflux disease may develop following eradication of Helicobacter pylori. However gastro-oesophageal reflux disease could be preexistent and misdiagnosed since patients often misinterpret gastro-oesophageal reflux disease symptoms or focus their attention on abdominal symptoms. A questionnaire for analysis of gastro-oesophageal reflux disease symptoms has not been used until now. METHODS: A total of 70 patients with duodenal ulcer and Helicobacter pylori gastritis, without oesophagitis and/or typical gastro-oesophageal reflux disease symptoms were studied. All patients received a questionnaire with 5 items focused on abdominal symptoms and 5 on gastro-oesophageal reflux disease symptoms. The two symptom scores were calculated separately. After Helicobacter pylori treatment, follow-up consisted of clinical controls every 3 months for 1 year. Patients were asked to describe their complaints and to answer the questionnaire. If gastro-oesophageal reflux disease symptoms recurred endoscopy was performed. RESULTS: At interview, all patients reported a significant improvement in their abdominal symptoms after eradication; however 23 patients (32.8%: group A) reported the occurrence of gastro-oesophageal reflux disease symptoms, and 5 of them developed oesophagitis; gastrooesophageal reflux disease symptoms did not appear in the remaining 47 patients (group B). Basal gastro-oesophageal reflux disease score was significantly higher in group A than in group B (1.9+/-1.5 vs 0.9+/-0.9, p<0.005), while the abdominal symptoms score was not different. Following eradication, the score for abdominal symptoms decreased significantly (4.2+/-1.5 vs 1+/-0.8, p<0.0001) in the two groups; conversely, the total gastro-oesophageal reflux disease score remained unchanged, improving in 2 patients in group A and 11 in B, and worsening in 5 in group A and in 1 in B. Presence of hiatus hernia and male sex significantly correlated with the development of reflux symptoms. CONCLUSIONS: Patients who present with gastro-oesophageal reflux disease after Helicobacter pylori eradication are likely to already be affected by gastro-oesophageal reflux disease.     

19例胃食管反流病患者根除幽门螺杆菌后食管酸反流的变化

目的：在胃食管反流病(GRED)患者根除幽门螺杆菌(Hp)是否会加重胃食管反流目前存在很大争议。本研究将采用食管内24h pH监测及食管测压检查的方法，定量观察GERD患者根除Hp治疗前后食管酸暴露及食管动力的变化。方法：连续选取我院门诊就诊的Hp阳性GERD患者。Hp感染诊断依据RUT和UBT或UBT和血清学检查。所有入选对象均在内镜检查后1～3d内行食管内24h pH监测和食管测压检查，同时评估反流症状。给予1周三联根除Hp治疗(奥美拉唑20mg，克拉霉素0．25g，阿莫仙1．0g，均bid)。疗程结束3个月后^14C—UBT检查，证实Hp根除者复查食管内24h pH监测和食管测压，同时重新评估反流症状。随访期间不用抑酸剂及促动力剂。结果：共23例Hp阳性GERD患者入选了本研究，其中19例患者完成了根除Hp前后的对比研究。在入选时有6例患者内镜下表现符合反流性食管炎，24h食管内pH监测提示病理性反流者10例。在确定根除Hp3个月后反酸、腹痛症状明显改善，食管24h pH监测各项参数与根除前相比均无显著性差异。LESP根除前10mm Hg(7．7—15．9)，根除后15mm Hg(10—20．6)，前后相比有显著性差异。食管体蠕动无明显改变。结论：本研究在GERD患者根除Hp3个月后反流症状有改善，食管酸暴露情况无明显变化，LESP较根除前增高，提示在GERD患者根除Hp有可能改善胃食管反流症状。     

Water load test before and after PPI therapy in patients with gastro-oesophageal reflux disease

BACKGROUND: Patients with gastro-oesophageal reflux disease may complain of epigastric pain, bloating, early satiety, epigastric fullness, epigastric burning, nausea and vomiting. AIMS: To evaluate the symptoms in response to gastric distension and its relationship to a therapeutic course in patients with gastro-oesophageal reflux disease using the water load test, compared to healthy controls. METHODS: Thirty gastro-oesophageal reflux disease patients with grade A oesophagitis (studied before and after 4 weeks of therapy with esomeprazole, 40 mg per day) and 15 patients with reflux-related symptoms demonstrated at wireless pH monitoring (non-erosive reflux disease) were compared to 30 healthy volunteers. RESULTS: Patients with grade A oesophagitis and with reflux-related symptoms ingested significantly lower water volumes than did controls, before onset of fullness, without statistically significant difference between erosive or non-erosive gastro-oesophageal reflux disease; this variable improved in patients after treatment. Nausea scores were higher basally in patients, pre- and post-therapy, and improved after therapy. Thirty-minute fullness and bloating scores improved after therapy in all gastro-oesophageal reflux disease patients compared to controls and pre-therapy. In all pre-treatment patients, a significant correlation was found only with epigastric fullness; after treatment, there was no significant relationship between the water load and the symptom scores. CONCLUSIONS: In patients with reflux-related symptoms, with or without grade A oesophagitis, the water load test is frequently abnormal, suggesting an altered gastric function. This could explain the incomplete resolution of symptoms after treatment in some patients, and should lead to additional studies aimed at exploring gastric function in gastro-oesophageal reflux disease patients.     

Simultaneous intraesophageal impedance and pH measurement of acid and nonacid gastroesophageal reflux: effect of omeprazole

BACKGROUND & AIMS: Nonacid reflux may explain symptoms in acid-suppressed patients. Simultaneous intraesophageal impedance and pH measurement was used to evaluate the frequencies of postprandial acid and nonacid reflux before and after omeprazole administration. METHODS: Twelve heartburn patients underwent two 2-hour studies of intraesophageal impedance and pH in the right lateral decubitus position after a refluxogenic meal; session 1 without medication, session 2 after 7 days of omeprazole twice daily. Acid and nonacid reflux were quantified. RESULTS: Two hundred seventeen reflux episodes were detected before and 261 after omeprazole treatment (P > 0.05). Percentage of acid reflux decreased (from 45% to 3%, P = 0.02) and nonacid reflux increased (from 55% to 97%, P = 0.03) after omeprazole. Heartburn and acid taste were more commonly linked to acid reflux but were also produced by nonacid reflux. Regurgitation was reported equally in acid and nonacid reflux. Delta(pH) > 1 did not help predict the presence of symptoms during nonacid reflux. CONCLUSIONS: During treatment with omeprazole, postprandial reflux becomes predominantly nonacid. Symptoms are more common with acid reflux but are also produced by nonacid reflux. Simultaneous intraesophageal impedance and pH may be useful in evaluating the role of nonacid reflux in symptoms that persist despite adequate acid suppression.     

A randomized,double-blind,placebo-controlled clinical study of the histamine H<Subscript>2</Subscript>-receptor antagonist famotidine in Japanese patients with nonerosive reflux disease

BACKGROUND: To investigate whether histamine H2-receptor antagonists are sufficient to treat heartburn in nonerosive reflux disease in Japanese, who produce less gastric acid than Westerners, the efficacy of famotidine in Japanese nonerosive reflux disease patients was studied in a double-blind, placebo-controlled, parallel group-comparative, multicenter study. METHODS: The Los Angeles classification system with Japanese modifications was used to assess the severity of nonerosive reflux disease. Famotidine (10-or 20-mg doses) or placebo was administered to patients twice daily for 8 weeks. Heartburn symptoms were recorded daily by patients. RESULTS: A total of 528 patients participated in the study. The percentage of days without heartburn, the primary end point of the efficacy evaluation, was 62% for 40 mg and 59% for 20 mg of famotidine, and 55% for placebo, with a statistically significant difference between the 40-mg dose and placebo (P = 0.001; significance level, 0.025 one-sided). Famotidine at both doses provided immediate relief from heartburn, and relief persisted throughout the 8-week study with the 40-mg dose. CONCLUSIONS: The results indicate that famotidine relieves heartburn symptoms in Japanese nonerosive reflux disease patients.     

Natural history of gastro-oesophageal reflux disease without oesophagitis (NERD) – a reappraisal 10 years on

BACKGROUND AND AIM: Ten years ago we published a study describing the 6-month outcome of 33 outpatients with typical gastro-oesophageal reflux disease symptoms and pH-metry proven excess gastro-oesophageal reflux but without endoscopical evidence of oesophagitis, currently referred to as patients with gastro-oesophageal reflux disease without oesophagitis. We now present an update of that report concerning morbidity, drug consumption and quality of life of the original patients 10 years after the initial diagnosis. METHODS: The study consisted of the retrieval and revision of all clinical and instrumental records concerning the cohort of 33 above-mentioned patients. Data are available regarding annual intervals within the first 5 years from original diagnosis and, subsequently, with a follow-up ranging from 7 to 14 years (median 10 years). The records of these 33 patients were reviewed, including the results of clinical visits at the outpatients department, of oesophagogastroduodenoscopies and pH- metries. Finally, a telephonic interview was conducted by means of a structured questionnaire, aiming at evaluating present symptoms, actual therapy if any, health-related quality of life and other information regarding any gastro-oesophageal reflux disease symptoms. RESULTS: Of the original 33 patients, 31 are still alive and 2 were lost to follow-up. Of the 29 remaining, only 1 is definitively not complaining of any gastro-oesophageal reflux disease-related symptoms. Within 5 years of the first diagnosis, oesophagitis was found in all but one of the 18 subjects who underwent repeated endoscopy. At the latest follow-up check, after a median of 10 years, out of the 28 still complaining of gastro-oesophageal reflux disease symptoms, 21 (75%) were presently taking antisecretory drugs (proton pump inhibitors and H-2 receptor antagonists) because of gastro-oesophageal reflux disease symptoms/lesions, 12 of whom intermittently or on demand and the remaining 9 continuously. Two patients (2/28) underwent antireflux surgery, but despite this were still taking antisecretory drugs (in one case H2-RA; in the other proton pump inhibitor). The health-related quality of life, self-evaluated by the patient by means of a VAS scoring from 0 (worst possible) to 10 (best possible) increased significantly from 3.2 to 6.5 from baseline (before therapy) to present time, possibly due to the positive effect of present therapy. CONCLUSIONS: Our study conducted on a cohort of endoscopy-negative patients with pH-metry-confirmed reflux disease has shown that after a median time of 10 years following the original diagnosis, the majority of patients have, in fact, developed reflux oesophagitis and are on prolonged antisecretory therapy because of recurrent gastro-oesophageal reflux disease symptoms/lesions. The study confirms that gastro-oesophageal reflux disease without oesophagitis, as well as gastro-oesophageal reflux disease at large, is a chronic disease characterised by increasing severity with time, which requires protracted medical therapy in a vast proportion of patients. Absence of endoscopic oesophagitis at presentation does not represent a positive prognostic factor.