Clinical and economic evaluation of laparoscopic surgery compared with medical management for gastro-oesophageal reflux disease: 5-year follow-up of multicentre randomised trial (the REFLUX trial).

BACKGROUND: Despite promising evidence that laparoscopic fundoplication provides better short-term relief of gastro-oesophageal reflux disease (GORD) than continued medical management, uncertainty remains about whether benefits are sustained and outweigh risks. OBJECTIVE: To evaluate the long-term clinical effectiveness, cost-effectiveness and safety of laparoscopic surgery among people with GORD requiring long-term medication and suitable for both surgical and medical management. DESIGN: Five-year follow-up of a randomised trial (with parallel non-randomised preference groups) comparing a laparoscopic surgery-based policy with a continued medical management policy. Cost-effectiveness was assessed alongside the trial using a NHS perspective for costs and expressing health outcomes in terms of quality-adjusted life-years (QALYs). SETTING: Follow-up was by annual postal questionnaire and selective hospital case notes review; initial recruitment in 21 UK hospitals. PARTICIPANTS: Questionnaire responders among the 810 original participants. At entry, all had documented evidence of GORD and symptoms for > 12 months. Questionnaire response rates (years 1-5) were from 89.5% to 68.9%. INTERVENTIONS: Three hundred and fifty-seven participants were recruited to the randomised comparison (178 randomised to surgical management and 179 randomised to continued medical management) and 453 to the preference groups (261 surgical management and 192 medical management). The surgeon chose the type of fundoplication. MAIN OUTCOME MEASURES: Primary: disease-specific outcome measure (the REFLUX questionnaire); secondary: Short Form questionnaire-36 items (SF-36), European Quality of Life-5 Dimensions (EQ-5D), NHS resource use, reflux medication, complications. RESULTS: The randomised groups were well balanced. By 5 years, 63% in the randomised surgical group and 13% in the randomised medical management group had received a total or partial wrap fundoplication (85% and 3% in the preference groups), with few perioperative complications and no associated deaths. At 1 year (and 5 years) after surgery, 36% (41%) in the randomised surgical group - 15% (26%) of those who had surgery - were taking proton pump inhibitor medication compared with 87% (82%) in the randomised medical group. At each year, differences in the REFLUX score significantly favoured the randomised surgical group (a third of a SD; p< 0.01 at 5 years). SF-36 and EQ-5D scores also favoured surgery, but differences attenuated over time and were generally not statistically significant at 5 years. The worse the symptoms at trial entry, the larger the benefit observed after surgery. Those randomised to medical management who subsequently had surgery had low baseline scores that markedly improved after surgery. Following fundoplication, 3% had surgical treatment for a complication and 4% had subsequent reflux-related operations - most often revision of the wrap. Dysphagia, flatulence and inability to vomit were similar in the two randomised groups. The economic analysis indicated that surgery was the more cost-effective option for this patient group. The incremental cost-effectiveness ratio for surgery in the base case was £7028 per additional QALY; these findings were robust to changes in approaches and assumptions. The probability of surgery being cost-effective at a threshold of £20,000 per additional QALY was > 0.80 for all analyses. CONCLUSIONS: After 5 years, laparoscopic fundoplication continues to provide better relief of GORD symptoms with associated improved health-related quality of life. Complications of surgery were uncommon. Despite being initially more costly, a surgical policy is highly likely to be cost-effective. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15517081. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 22. See the HTA programme website for further project information.

Minimal access surgery compared with medical management for gastro-oesophageal reflux disease: five year follow-up of a randomised controlled trial (REFLUX).

OBJECTIVES: To determine the long term clinical effectiveness of laparoscopic fundoplication as an alternative to drug treatment for chronic gastro-oesophageal reflux disease (GORD). DESIGN: Five year follow-up of multicentre, pragmatic randomised trial (with parallel non-randomised preference groups). SETTING: Initial recruitment in 21 UK hospitals. PARTICIPANTS: Responders to annual questionnaires among 810 original participants. At entry, all had had GORD for >12 months. INTERVENTION: The surgeon chose the type of fundoplication. Medical therapy was reviewed and optimised by a specialist. Subsequent management was at the discretion of the clinician responsible for care, usually in primary care. MAIN OUTCOME MEASURES: Primary outcome measure was self reported quality of life score on disease-specific REFLUX questionnaire. Other measures were health status (with SF-36 and EuroQol EQ-5D questionnaires), use of antireflux medication, and complications. RESULTS: By five years, 63% (112/178) of patients randomised to surgery and 13% (24/179) of those randomised to medical management had received a fundoplication (plus 85% (222/261) and 3% (6/192) of those who expressed a preference for surgery and for medical management). Among responders at 5 years, 44% (56/127) of those randomised to surgery were taking antireflux medication versus 82% (98/119) of those randomised to medical management. Differences in the REFLUX score significantly favoured the randomised surgery group (mean difference 8.5 (95% CI 3.9 to 13.1), P<0.001, at five years). SF-36 and EQ-5D scores also favoured surgery, but were not statistically significant at five years. After fundoplication, 3% (12/364) had surgical treatment for a complication and 4% (16) had subsequent reflux-related operations-most often revision of the wrap. Long term rates of dysphagia, flatulence, and inability to vomit were similar in the two randomised groups. CONCLUSIONS: After five years, laparoscopic fundoplication continued to provide better relief of GORD symptoms than medical management. Adverse effects of surgery were uncommon and generally observed soon after surgery. A small proportion had re-operations. There was no evidence of long term adverse symptoms caused by surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15517081.

Diagnosis and management of non-erosive reflux disease--the Vevey NERD Consensus Group.

BACKGROUND/AIMS: Although considerable information exists regarding gastroesophageal reflux disease with erosions, much less is known of non-erosive reflux disease (NERD), the dominant form of reflux disease in the developed world. METHODS: An expert international group using the modified Delphi technique examined the quality of evidence and established levels of agreement relating to different aspects of NERD. Discussion focused on clinical presentation, assessment of clinical outcome, pathobiological mechanisms, and clinical strategies for diagnosis and management. RESULTS: Consensus was reached on 85 specific statements. NERD was defined as a condition with reflux symptoms in the absence of mucosal lesions or breaks detected by conventional endoscopy, and without prior effective acid-suppressive therapy. Evidence supporting this diagnosis included: responsiveness to acid suppression therapy, abnormal reflux monitoring or the identification of specific novel endoscopic and histological findings. Functional heartburn was considered a separate entity not related to acid reflux. Proton pump inhibitors are the definitive therapy for NERD, with efficacy best evaluated by validated quality-of-life instruments. Adjunctive antacids or H(2) receptor antagonists are ineffective, surgery seldom indicated. CONCLUSIONS: Little is known of the pathobiology of NERD. Further elucidation of the mechanisms of mucosal and visceral hypersensitivity is required to improve NERD management.

Validation of a brief symptom questionnaire (ReQuest in Practice) for patients with gastro-oesophageal reflux disease.

BACKGROUND: A clinical need exists for a means of assessing symptom control in patients with gastro-oesophageal reflux disease. The ReQuest questionnaire has been extensively validated for symptom assessment in both erosive and non-erosive gastro-oesophageal reflux disease but was designed for research purposes. We derived a shorter version (ReQuest in Practice) that would be more convenient for clinical practice. AIM: To validate ReQuest in Practice in patients suffering from gastro-oesophageal reflux disease. METHODS: Multicentre, non-interventional, crossover comparison. Patients completed ReQuest in Practice followed by ReQuest or vice versa. Before and after a planned endoscopy, patients completed the health-related quality of life questionnaire GERDyzer. Internal consistency and the Intraclass Correlation Coefficient were calculated. Construct validity was evaluated by correlation with ReQuest and GERDyzer. RESULTS: There was high internal consistency of ReQuest in Practice (Cronbach's alpha: 0.9) and a high Intraclass Correlation Coefficient of 0.99. The measurement error of ReQuest in Practice was 4.1. High correlation between ReQuest in Practice and ReQuest (Spearman correlation coefficient: 0.9) and GERDyzer (Spearman correlation coefficient: 0.8) demonstrated construct validity. CONCLUSIONS: ReQuest in Practice was proven to be valid and reliable. Its close correlation with ReQuest makes it a promising tool to guide the clinical management of patients across the full spectrum of both erosive and non-erosive gastro-oesophageal reflux disease.

Review article: diagnosis and clinical investigation of gastro-oesophageal reflux disease: a European view.

In Western populations, many individuals with symptoms of gastro-oesophageal reflux disease (GERD) do not bother to seek medical attention because their symptoms are mild and acceptably controlled by self-medication. Among those who do consult physicians, only a minority present with the classical clinical symptoms of heartburn and regurgitation: more often the pattern is a nonspecific combination of upper gastrointestinal complaints that do not permit confident clinical diagnosis. Oesophagitis is now found in less than 50% of GERD patients and those without oesophagitis are sometimes said to have 'non-erosive reflux disease'. If a patient's clinical history is inadequate for diagnosis and the oesophageal endoscopic appearances are normal, ambulatory pH monitoring may be required if the diagnostic uncertainty is to be resolved. Despite initial enthusiasm, the 'Proton Pump test' for GERD has proved unreliable and has fallen from favour. Intraluminal impedence measurement is currently considered a research tool only. Most European gastroenterologists acknowledge the occurrence of 'atypical' presentations of GERD, including noncardiac chest pain, asthma and hoarseness (laryngitis), though confirmation of GERD as the cause of such symptoms in individual patients is often difficult.

Impact of alcohol related disease and inpatient workload of gastroenterologists in Scotland.

BACKGROUND: Concern among Scots gastroenterologists about alcohol related illness prompted this inpatient prevalence study during the winter of 2000-01. AIMS: To study gastrenterology inpatient workload due to alcohol-related illness, to determine how much was specialty specific, and if there were regional variations. METHODS: 40 Consultant gastrenterologists throughout Scotland collected data on the prevalence of alcohol related conditions among inpatients under their care on each of three specified days during the winter of 2000/2001. All inpatients under the care of participating consultants on the designated study days were included in the study. Overall return rate was 65%. Patients were categorised as follows; (a) general medical inpatients admitted for reasons other than alcohol related illness (b) general medical inpatients with no gastrointestinal or liver disease, but whose admission to hospital was primarily related to alcohol misuse, (c) gastrointestinal (including liver) inpatients admitted for reasons unrelated to alcohol intake, and with no alcohol related disease, and (d) gastrointestinal inpatients whose admission to hospital resulted from alcohol related disease. Additionally the numbers of patients with (e) decompensated liver disease of all causes, (f) decompensated alcoholic liver disease, and (g) the numbers "blocking" acute beds after initial hospitalisation with an alcohol related illness were collected. RESULTS: Overall, 829 general medical and 538 gastroenterology inpatients were entered in the study; total 1367 (705 male, 662 female). Of these, 25% (337/1367) were admitted because of alcohol related illness: 15% (201/1367) had decompensated alcoholic liver disease. Of 538 gastroenterology inpatients, 238 (44%) had problems related to alcohol and 201 of these (37% of all gastoenterology inpatients) had decompensated alcoholic liver disease. Of 246 inpatients with decompensated liver disease, 82% (201) had alcoholic liver disease. Alcohol related illness was significantly more prevalent among male inpatients in the West of Scotland. 10% of specialist gastroentelogy beds were occupied by patients whose discharge was delayed because of alcohol related problems. CONCLUSION: Most Scottish gastroenterlogists contribute to general medical receiving but their specialist inpatient workload is dominated by treatment of patients with alcohol related disease. (44% in gastroenterology v 12% in general medicine). Inpatients with decompensated alcoholic liver disease form 37% of gastroenterology workload. Alcohol related disease contributes to delayed discharge in acute medical units, especially in gastroenterology wards. There are regional differences in prevalence of alcohol related disease, which is greatest in male inpatients in the West of Scotland. Here, alcoholic liver disease accounts for nearly a decompensated liver disease. The findings point to a need to review the current patterns of acute service provision for alcohol related illnesses, so as to assess and improve both the linical effectiveness and cost effectiveness of care, and to ensure that alternatives to acute hospital admission are available when appropriate. This need should not be neglected while efforts are simultaneously being made to improve the early detection of alcohol abuse and prevent irreversible alcohol related disease.

Contemporary understanding and management of reflux and constipation in the general population and pregnancy: a consensus meeting.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) and constipation have a major impact on public health; however, the wide variety of treatment options presents difficulties for recommending therapy. Lack of definitive guidelines in pharmacy and general practice medicine further exacerbates the decision dilemma. AIMS: To address these issues, a panel of experts discussed the principles and practice of treating GERD and constipation in the general population and in pregnancy, with the aim of developing respective treatment guidelines. RESULTS: The panel recommended antacids 'on-demand' as the first-line over-the-counter treatment in reflux, and as rescue medication for immediate relief when reflux breaks through with proton pump inhibitors. Calcium/magnesium-based antacids were recommended as the treatment of choice for pregnant women because of their good safety profile. In constipation, current data do not distinguish a hierarchy between polyethylene glycol (PEG)-based laxatives and other first-line treatments, although limitations are associated with stimulant- and bulk-forming laxatives. Where data are available, PEG is superior to lactulose in terms of efficacy. In pregnancy, PEG-based laxatives meet the criteria for the ideal treatment. CONCLUSIONS: The experts developed algorithms that present healthcare professionals with clear treatment options and management strategies for GERD and constipation in pharmacy and general practice medicine.

Clinical perspectives, mechanisms, diagnosis and management of irritable bowel syndrome.

This consensus document reviews the current status of the epidemiology, social impact, patient quality of life, pathophysiology, diagnosis and treatment of irritable bowel syndrome. Current evidence suggests that two major mechanisms may interact in irritable bowel syndrome: altered gastrointestinal motility and increased sensitivity of the intestine. However, other factors, such as psychosocial factors, intake of food and prior infection, may contribute to its development. Management of patients is based on a positive diagnosis of the symptom complex, careful history and physical examination to exclude 'red flags' as risk factors for organic disease, and, if indicated, investigations to exclude other disorders. Therapeutic choices include dietary fibre for constipation, opioid agents for diarrhoea and low-dose antidepressants or infrequent use of antispasmodics for pain, although the evidence basis for efficacy is limited or in some cases absent. Psychotherapy and hypnotherapy are the subject of ongoing study. Treatment should be tailored to patient needs and fears. Novel therapies are emerging, and drugs acting on serotonin receptors have proven efficacy and a scientific rationale and, if approved, should be useful in the overall management of patients with irritable bowel syndrome. Patient and physician education, early identification of psychosocial issues and better therapies are important strategies to reduce the suffering and societal cost of irritable bowel syndrome.

Present medical management of Barrett's oesophagus.

The management of Barrett's oesophagus should aim to treat symptoms, and prevent complications of reflux. Treatment of choice is a proton pump inhibitor, with the option of surgical treatment in younger patients. Uncertainties remain about the significance of short segment Barrett's oesophagus. Doubts also remain about the benefit and cost-effectiveness of conventional surveillance of Barrett's oesophagus; for patients with an annual cancer risk of 0.5% 5-yearly endoscopy and biopsies for patients without dysplasia represent the best strategy Novel modalities such as photodynamic therapy have shown encouraging results for high grade dysplasia or early cancer for patients unsuitable for surgery. Finally, agents such as cyclooxygenase-2 inhibitors hold promise for prevention of malignancy in Barrett's oesophagus.

Pattern of ambulatory pharyngo-oesophageal motility and pH-metry in healthy volunteers.

Oesophago-pharyngeal reflux is widely accepted as an aetiological factor in many laryngeal and lower respiratory tract diseases. This study aims to establish normal reference ranges for pharyngo-oesophageal pH and pressure. Twenty-five asymptomatic healthy volunteers underwent ambulatory pharyngo-oesophageal pressure and pH-metry. Acid exposure times were very low. Only one subject showed any evidence of oesophago-pharyngeal reflux during recumbency. Two distinct upper oesophageal sphincter pressure patterns were observed during recumbency-one with episodic dry swallows and moderate tonic pressures, the other with almost complete manometric quiescence. Negative results, i.e. the exclusion of abnormal cervical reflux, appear to be more achievable than quantifiable positive results, but this is not absolutely clear from our results. Categorisation of an individual as having abnormal upper pH-metry requires use of a synchronous pharyngeal probe. pH-metry is likely to be of value in establishing the role of reflux in relation to laryngeal or respiratory disease.

Prevalence of upper gastrointestinal symptoms in the general population: a systematic review.

BACKGROUND: A systematic review was undertaken of all studies published as of December 1997, on the population prevalence of upper gastrointestinal (GI) symptoms. METHODS: Studies excluded from consideration were those conducted on subjects attending hospital or primary care clinics, or who were hospitalized or institutionalized; or where studies were conducted in the workplace or on occupational groups. Studies meeting the following criteria were included in the comparative analysis: period studied, sample size and response rate all reported; vague terms such as 'dyspepsia' or 'indigestion' defined if enquired about; abdominal pain or discomfort enquired about; patients with a history, or evidence, of organic disease not excluded from the results. Follow-up studies on groups of patients previously studied were also not included. RESULTS: In the 10 selected studies, the reported prevalence of upper abdominal symptoms (mostly upper abdominal pain or discomfort) ranged from approximately 8% to 54%, while the prevalence of heartburn and/or regurgitation ranged from 10% to 48% for heartburn, from 9% to 45% for regurgitation and 21% to 59% for both/either. CONCLUSIONS: In the case of upper abdominal symptoms, the most likely explanation for the broad range of prevalence reported is variation in the definition of symptoms. In the case of heartburn and regurgitation, different understandings of these terms by different investigators and subjects may have contributed to the range of results. Symptom definitions and what is understood by them should be among the most important considerations when undertaking population prevalence studies on upper GI symptoms, to allow comparisons to be made between studies.

Simultaneous measurement of gastric emptying of a solid meal by ultrasound and by scintigraphy.

OBJECTIVE: Although ultrasonic imaging may represent a valid alternative to scintigraphy for measurement of gastric emptying, most studies comparing the two methods have been carried out with liquid meals. The aim of this study was to compare scintigraphic and ultrasonographic measurements of gastric emptying of a solid meal in healthy subjects and in patients with possible delay in emptying. METHODS: Nineteen subjects were studied: five controls, six patients with gastroesophageal reflux, and eight patients with dysmotility-like dyspepsia. Gastric emptying was measured by both scintigraphy and ultrasonography after ingestion of an 800-calorie solid, realistic meal containing 99mTc-labeled chicken liver. Scintigraphic measurements were made every 15 min for 6 h, and ultrasonic imaging of antral sections was undertaken every 15 min for the first 1 h and every 30 min thereafter. Total emptying times were calculated independently using the two methods, and the emptying patterns recorded by the two methods were compared. RESULTS: Maximal antral dilation occurred 30 min (range 0-90 min) after the end of the meal and persisted until 96 +/- 42 min, by which time gastric radioactivity had decreased from its maximum by 43% +/- 23%. From this time on, the antral cross-sectional area returned toward the basal value, declining faster than the gastric counts recorded by scintigraphy. Total emptying times measured by ultrasound and by scintigraphy were in good agreement in all subjects, with a mean difference of only 4.5 min (limits of agreement, -17.1 to 21.6 min). CONCLUSIONS: Ultrasonographic measurement of antral cross-sectional area provides a valid alternative to scintigraphy for the measurement of total gastric emptying of a solid meal. It is less reliable if other parameters of gastric emptying such as T(1/2) are required.

Functional esophageal disorders.

The functional esophageal disorders include globus, rumination syndrome, and symptoms that typify esophageal diseases (chest pain, heartburn, and dysphagia). Factors responsible for symptom production are poorly understood. The criteria for diagnosis rest not only on compatible symptoms but also on exclusion of structural and metabolic disorders that might mimic the functional disorders. Additionally, a functional diagnosis is precluded by the presence of a pathology-based motor disorder or pathological reflux, defined by evidence of reflux esophagitis or abnormal acid exposure time during ambulatory esophageal pH monitoring. Management is largely empirical, although efficacy of psychopharmacological agents and psychological or behavioral approaches has been established for several of the functional esophageal disorders. As gastroesophageal reflux disease overlaps in presentation with most of these disorders and because symptoms are at least partially provoked by acid reflux events in many patients, antireflux therapy also plays an important role both in diagnosis and management. Further understanding of the fundamental mechanisms responsible for symptoms is a priority for future research efforts, as is the consideration of treatment outcome in a broader sense than reduction in esophageal symptoms alone. Likewise, the value of inclusive rather than restrictive diagnostic criteria that encompass other gastrointestinal and non-gastrointestinal symptoms should be examined to improve the accuracy of symptom-based criteria and reduce the dependence on objective testing.

Functional gastroduodenal disorders.

While widely used in research, the 1991 Rome criteria for the gastroduodenal disorders, especially symptom subgroups in dyspepsia, remain contentious. After a comprehensive literature search, a consensus-based approach was applied, supplemented by input from international experts who reviewed the report. Three functional gastroduodenal disorders are defined. Functional dyspepsia is persistent or recurrent pain or discomfort centered in the upper abdomen; evidence of organic disease likely to explain the symptoms is absent, including at upper endoscopy. Discomfort refers to a subjective, negative feeling that may be characterized by or associated with a number of non-painful symptoms including upper abdominal fullness, early satiety, bloating, or nausea. A dyspepsia subgroup classification is proposed for research purposes, based on the predominant (most bothersome) symptom: (a) ulcer-like dyspepsia when pain (from mild to severe) is the predominant symptom, and (b) dysmotility-like dyspepsia when discomfort (not pain) is the predominant symptom. This classification is supported by recent evidence suggesting that predominant symptoms, but not symptom clusters, identify subgroups with distinct underlying pathophysiological disturbances and responses to treatment. Aerophagia is an unusual complaint characterized by air swallowing that is objectively observed and troublesome repetitive belching. Functional vomiting refers to frequent episodes of recurrent vomiting that is not self-induced nor medication induced, and occurs in the absence of eating disorders, major psychiatric diseases, abnormalities in the gut or central nervous system, or metabolic diseases that can explain the symptom. The current classification requires careful validation but the criteria should be of value in future research.

Aims in the management of gastroesophageal reflux disease: a gastroenterologist's viewpoint.

Relieving heartburn and healing esophagitis may appear to be primary aims in the management of gastroesophageal reflux disease, but systematic consideration of the issues demonstrates that there are discrepancies between the fundamental aims of medical management and the aims selected for study in trials of drug efficacy. The initial aims of management are those concerned with diagnosis, patient assessment and the provision of explanation and advice. The therapeutic objectives are alleviating symptoms, preventing complications and, if possible, avoiding recurrence, and should ideally be judged in terms of health gain, including quality of life improvement. Obtaining value for money, by maximizing the health gain in relation to the cost of the overall medical intervention must also be acknowledged as a desirable aim of management, with the proviso that physicians must always treat each patient as an individual and individualize clinical management appropriately.

Quality of life assessment in reflux disease.

The recognition of heartburn and acid regurgitation as manifestations of gastro-oesophageal reflux disease (GORD), and the suppression of these symptoms with therapy, represent an over-simplistic approach to the reflux patient. For GORD, as for other gastrointestinal disorders, it is evident that many patients suffer a greater impairment of well-being than has been appreciated hitherto, and that this impairment can be quantified using modern quality of life measuring techniques. Successful treatment normalizes quality of life in a manner which is substantially, but not wholly, predictable from symptom responses or the healing of oesophagitis. These observations raise the possibility that physicians' therapeutic intentions do not always match the patients' wishes. The appraisal of health status, or quality of life (QOL), is increasingly important in defining the implications of disease and for assessing the outcome of therapy. Hitherto, QOL evaluations have seemed relevant to circumstances of major physical disability and for patients receiving potentially unpleasant treatments, such as cancer chemotherapy, but it is now evident that QOL evaluation has much wider applicability, including relevance to common gastrointestinal disorders such as GORD.