The natural history of gastro-esophageal reflux disease: a comprehensive review.

Gastroesophageal reflux disease (GERD) is a common disorder of the upper gastrointestinal tract which is typically characterized by heartburn and acid regurgitation. These symptoms are widespread in the community and range from 2.5% to more than 25%. Economic analyses showed an increase in direct and indirect costs related to the diagnosis, treatment and surveillance of GERD and its complications. The aim of this review is to provide current information regarding the natural history of GERD, taking into account the evolution of its definition and the worldwide gradual change of its epidemiology. Present knowledge shows that there are two main forms of GERD, that is erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter comprises the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, which is considered as a pre-cancerous lesion. Although data from medical literature on the natural history of this disease are limited and mainly retrospective, they seem to indicate that both NERD and mild esophagitis tend to remain as such with time and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barrett's esophagus may occur in a small proportion of patients, ranging from 0 to 30%, 10 to 22% and 1 to 13% of cases, respectively. It is necessary to stress that these data are strongly influenced by the use of powerful antisecretory drugs (PPIs). Further studies are needed to better elucidate this matter and overcome the present limitations represented by the lack of large prospective longitudinal investigations, absence of homogeneous definitions of the various forms of GERD, influence of different treatments, clear exclusion of patients with functional disorders of the esophagus.

Voluntary and controlled weight loss can reduce symptoms and proton pump inhibitor use and dosage in patients with gastroesophageal reflux disease: a comparative study.

A wide variety of pieces of evidence has suggested that obesity is associated with a significant increase in the risk for gastroesophageal reflux disease (GERD) symptoms and its complications. The aim of this study was to evaluate the effect of weight loss on reflux symptoms in overweight/obese patients with proven GERD. We enrolled overweight/obese patients with typical GERD symptoms and erosive esophagitis. At baseline, patients underwent detailed reflux symptoms evaluation and anthropometric assessment, and were divided into two treatment groups: group A received proton pump inhibitor (PPI) and a personalized hypocaloric diet and aerobic exercise; and group B received PPI and a 'standard of care diet'. The dietetic treatment was considered effective if at least 10% of weight loss was achieved within 6 months. All patients were evaluated in terms of anthropometric data, GERD symptoms, and PPI use. In group A, mean body mass index (BMI) decreased from 30.3 ± 4.1 to 25.7 ± 3.1 (P < 0.05), and mean weight decreased from 82.1 ± 16.9 kg to 69.9 ± 14.4 kg (P < 0.05). In group B, there was no change in BMI and weight. Symptom perception decreased (P < 0.05) in both groups during PPI therapy, but a higher improvement was recorded in group A. In group A, PPI therapy was completely discontinued in 27/50 of the patients, and halved in 16/50. Only 7/50 continued the same PPI dosage. In group B, 22/51 halved the therapy and 29/51 maintained full dosage of therapy, but none was able to discontinue PPI due to a symptom recurrence. Overall, weight loss of at least 10% is recommended in all patients with GERD in order to boost the effect of PPI on reflux symptom relief and to reduce chronic medication use.

Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure.

Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity.

Epidemiology of thrombocytopenia in patients with chronic hepatitis C: more than meets the eye.

Thrombocytopenia is likely the most common haematological abnormality that can be diagnosed inpatients affected by chronic liver disease. In these patients,the presence of thrombocytopenia may have significant clinical implications. In fact, it can be a limiting factor when considering invasive procedures and may hamper the out come of antiviral therapy with interferon. The prevalence of decreased platelet count in patients with chronic hepatitis Chas been assessed in various studies that evaluated heterogenous patient populations and used various platelet count threshold to identify thrombocytopenia. This review shows that the prevalence of thrombocytopenia in these patients is variable and mainly depends upon the severity of the underlying liver disease and the criterion used to identify this haematological abnormality. Furthermore, the results of this epidemiological review provide an indirect evidence that confirms the multiplicity of aetiological factors underlying the pathophysiology of thrombocytopenia in chronic hepatitis C patients. Lastly, this study shows that up to 25% of patients treated with interferon may develop some degree of thrombocytopenia, and this may be associated with decreased sustained virological response rates.

Successful antiviral therapy determines a significant decrease in squamous cell carcinoma antigen-associated (SCCA) variants' serum levels in anti-HCV positive cirrhotic patients.

Aberrant squamous cell carcinoma antigen (SCCA) expression is an early event in hepatocarcinogenesis, and increasing serum levels of SCCA variants IgM immune complexes (SCCA-IgM IC) have been found in cirrhotic patients developing hepatocellular carcinoma (HCC). We longitudinally evaluated a cohort of cirrhotic patients with hepatitis C virus infection (HCV) who underwent pegylated interferon (PEG-IFN) and ribavirin treatment. SCCA-IgM IC levels were assessed in the sera of 33 cirrhotic patients with HCV (21 males, median age 57 years) before, at the end and at 6-month and 1-year follow-up after treatment with PEG-IFN and ribavirin. SCCA-IgM IC serum levels (arbitrary units/mL, AU/mL) were evaluated according to treatment outcome: sustained virological response (SVR) vs nonresponse (NR). Overall, 15 patients obtained a SVR to antiviral therapy (45%). There was no significant difference in baseline SCCA-IgM IC serum levels between SVR and NR patients. When compared to baseline (451.2 AU/mL), SVR patients showed a significant decrease in median SCCA-IgM IC serum levels at the end of treatment (186.8 AU/mL, P = 0.013) and at both 6-month (96.8 AU/mL, P < 0.001) and 1-year follow-up (52.4 AU/mL, P < 0.001), while no significant modification was observed in NR patients. In patients with HCV-related liver cirrhosis, successful antiviral therapy is associated with a dramatic and significant decrease in SCCA-IC serum levels. Because of the pathophysiological correlation between SCCA and liver carcinogenesis, it is hypothesized that in patients with liver cirrhosis, SVR may be accompanied by a decreased proliferative stimulation.

Octatropine methyl bromide and diazepam combination (Valpinax) in patients with irritable bowel syndrome: a multicentre, randomized, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy and tolerability of octatropine methyl bromide plus diazepam (Valpinax) in patients with irritable bowel syndrome (IBS). MATERIALS AND METHODS: We conducted a randomized, double-blind, multicentre study in 186 patients aged 18-65 years with IBS diagnosed according to Rome II criteria. Following a 2-week washout period, patients received octatropine plus diazepam 40 mg/2.5 mg twice daily or placebo for 6 weeks. The primary efficacy endpoint was response to a weekly question: "did you have satisfactory relief of your abdominal pain and discomfort during the last week?" Other endpoints included abdominal swelling, abdominal pain and discomfort, symptom severity, and the number of bowel movements. A prespecified subgroup analysis was conducted in patients with an abdominal pain and discomfort score > or = 3. RESULTS: The primary efficacy endpoint showed a tendency towards a statistically significant benefit for octatropine plus diazepam over placebo among patients with a baseline abdominal pain and discomfort score of > or = 3 (3 vs. 0 patients; p = 0.059). Octatropine plus diazepam demonstrated significant improvements from baseline in all parameters assessed, but not compared with placebo. Adverse events were reported in 15.1% of patients receiving octatropine plus diazepam. CONCLUSIONS: Patients with IBS and an abdominal pain and discomfort score of > or = 3, who may be considered in the active phase of the disease, may derive some benefits from octatropine plus diazepam. This study highlights that Rome II criteria should be considered with particular care in the design of a clinical trial, since it does not consider disease activity level on admission.

Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease.

INTRODUCTION: Functional dyspepsia and non-erosive reflux disease (NERD) are prevalent gastrointestinal conditions with accumulating evidence regarding an overlap between the two. Still, patients with NERD represent a very heterogeneous group and limited data on dyspeptic symptoms in various subgroups of NERD are available. AIM: To evaluate the prevalence of dyspeptic symptoms in patients with NERD subclassified by using 24 h impedance-pH monitoring (MII-pH). METHODS: Patients with typical reflux symptoms and normal endoscopy underwent impedance-pH monitoring off proton pump inhibitor treatment. Oesophageal acid exposure time (AET), type of acid and non-acid reflux episodes, and symptom association probability (SAP) were calculated. A validated dyspepsia questionnaire was used to quantify dyspeptic symptoms prior to reflux monitoring. RESULTS: Of 200 patients with NERD (105 female; median age, 48 years), 81 (41%) had an abnormal oesophageal AET (NERD pH-POS), 65 (32%) had normal oesophageal AET and positive SAP for acid and/or non-acid reflux (hypersensitive oesophagus), and 54 (27%) had normal oesophageal AET and negative SAP (functional heartburn). Patients with functional heartburn had more frequent (p<0.01) postprandial fullness, bloating, early satiety and nausea compared to patients with NERD pH-POS and hypersensitive oesophagus. CONCLUSION: The increased prevalence of dyspeptic symptoms in patients with functional heartburn reinforces the concept that functional gastrointestinal disorders extend beyond the boundaries suggested by the anatomical location of symptoms. This should be regarded as a further argument to test patients with symptoms of gastro-oesophageal reflux disease in order to separate patients with functional heartburn from patients with NERD in whom symptoms are associated with gastro-oesophageal reflux.

Predictive value of on-treatment response during full-dose antiviral therapy of patients with hepatitis C virus cirrhosis and portal hypertension.

OBJECTIVE: Therapy with full-dose pegylated interferon (PEG-IFN) and weight-based ribavirin has been evaluated in limited series of patients with hepatitis C virus (HCV) and advanced disease. In this study, we evaluated the efficacy and tolerability of full-dose antiviral therapy in patients with compensated, fully developed cirrhosis, and assessed the predictive value of on-treatment virological response. DESIGN AND SUBJECTS: We studied 85 HCV-positive cirrhotic patients (82 Child-Pugh class A; 41 treatment-naïve) who were treated with PEG-IFN alpha-2(a) (1.5 microg kg(-1)week(-1)) or alpha-2(b) (180 microg week(-1)) and weight-based ribavirin for 24 (genotype 2-3) or 48 (genotype 1-4) weeks. Forty-three patients were genotype 1 (51%), and HCV-RNA was >600,000 IU mL(-1) in 53 patients (62%). Prevalence of portal hypertension and diabetes was 81% and 18% respectively. RESULTS: Sustained virological response (SVR) was obtained in 22 patients (26%). Positive serum HCV-RNA at week 4 and week 12 of therapy predicted nonresponse (NR) in 85% (52/61) and 100% (38/38) of patients, respectively. Treatment was discontinued due to adverse events in 14 patients (16%). Genotype 1-4 (P = 0.02) and HCV-RNA >600,000 IU mL(-1) (P = 0.02) were the baseline parameters significantly associated with lack of SVR, whilst positive serum HCV-RNA at week 12 was the only parameter independently associated with NR (100% negative predictive value). CONCLUSION: Full-dose antiviral therapy with PEG-IFN and ribavirin can be safely carried out even in patients with compensated, fully established cirrhosis and portal hypertension. Selecting patients on the basis of HCV genotype and viral load, and application of on-treatment stopping rule may help rationalize treatment in patients who are unlikely to obtain SVR.

A review of the role of soluble fiber in health with specific reference to wheat dextrin.

Dietary fiber is widely recognized to have a beneficial role in overall health, but only at adequate levels (25 - 38 g/day for healthy adults). Wheat dextrin in particular is a soluble fiber that can easily be added to the diet and is widely used in the food industry. There is some debate about whether increased intake of soluble fibers leads to health benefits. This paper reviews the evidence regarding the physiological effects and potential health benefits of the addition of soluble dietary fibers, with specific reference to wheat dextrin, based on a search of PubMed. The evidence suggests that soluble fibers help to regulate the digestive system, may increase micronutrient absorption, stabilize blood glucose and lower serum lipids, may prevent several gastrointestinal disorders, and have an accepted role in the prevention of cardiovascular disease. It is concluded that supplementation with soluble fibers (e.g. wheat dextrin) may be useful in individuals at risk of a lower than recommended dietary fiber intake.

Cell proliferation of squamous epithelium in gastro-oesophageal reflux disease: correlations with clinical, endoscopic and morphological data.

BACKGROUND: The microscopic assessment of squamous epithelium lesions in gastro-oesophageal reflux disease (GERD) is subjective. The Ki67 nuclear antigen expressed by proliferating cells provides an objective measure of regeneration in the squamous epithelium. AIM: To evaluate Ki67 expression in GERD patients and controls, in comparison with histological lesions, pH-metry and endoscopic data. METHODS: Eighty-seven patients with GERD symptoms and 20 symptom-free controls underwent endoscopy and 24-h pH monitoring. Oesophageal biopsies (4 cm, 2 cm and Z-line) were stained with Ki67/MIB-1 antibodies; the Ki67-positive nuclear area was assessed with an image analysis system and expressed as percentage of the whole epithelial area (Ki67-%). RESULTS: Ki67-% was significantly higher in 32 patients with erosive oesophagitis, 44 endoscopy-negative GERD and 11 patients with functional heartburn than in controls (P = 0.0001). Both controls and patients showed a progressive increase in Ki67-% from 4 cm to the Z-line (P < 0.0001). Ki67-% showed a significant correlation with other conventional histological lesions (P ranged between 0.0151 and <0.0001). CONCLUSIONS: Ki67 evaluation provides quantitative and objective data on squamous epithelium proliferative activity. This marker can be applied in the distinction of endoscopy-negative GERD from healthy controls.

Efficacy in intra-oesophageal acid suppression may decrease after 2-year continuous treatment with proton pump inhibitors.

BACKGROUND: Long-term intra-oesophageal acid suppression with proton pump inhibitors represents a management option for Barrett's oesophagus and severe reflux oesophagitis, but its stability over time has not been adequately assessed. AIM: Our aim was to evaluate prospectively the efficacy of proton pump inhibitors in suppressing intra-oesophageal acidity after 2-year continuous treatment. METHODS: Forty-five patients with Barrett's oesophagus or severe reflux oesophagitis on a proton pump inhibitor regimen (once or twice daily) that normalised the total percentage acid exposure time were re-evaluated by means of 24-h oesophageal pH-monitoring after 2-year of continuous unmodified treatment. RESULTS: A significant rise in the total percentage acid exposure time was observed at 2-year follow-up (P=0.029), owing to an increased value in 27 (60%) cases (9 on a twice daily regimen), higher than normal in 10 of them (22% of the whole group) (3 on a twice daily regimen). In 18 patients (40%) the total percentage acid exposure time was stable or decreased. Heartburn remained efficiently suppressed in all patients. CONCLUSIONS: The efficacy of proton pump inhibitors in suppressing intra-oesophageal acidity during continuous treatment may decrease over time, up to abnormal levels of oesophageal acid exposure in a minority of cases. This may occur without heartburn recurrence and with both once and twice daily regimens.

Potential options to optimize therapy of gastroesophageal reflux disease with proton pump inhibitors.

Proton pump inhibitors (PPIs) are antisecretory agents that are widely used in the short- and long-term management of gastroesophageal reflux disease (GERD) to relieve symptoms, heal esophagitis, and prevent complications, such as strictures and Barrett's esophagus. The total healthcare costs of GERD are high, especially for maintenance treatment. Therefore, the choice of cost-effective therapeutic options is an ineluctable challenge for public health authorities, third-party payers, and patients. In some European Union countries, a recent trend of public health authorities is to promote the choice of less expensive PPIs, regardless of their antisecretory potency--this in spite of the evidence that newer PPIs provide superior symptom relief and esophageal erosion healing compared to earlier drugs. Several large clinical trials have demonstrated the superiority of esomeprazole over other PPIs at standard doses for both initial and continuous maintenance therapy in patients with moderate/severe erosive esophagitis. The non-erosive GERD poses a major challenge as this condition appears more frequently to be less responsive to PPIs. The use of PPIs with the strongest antisecretory properties might reveal to be more adequate and cost-effective, particularly for this indication.

Randomised clinical trial: mucosal protection combined with acid suppression in the treatment of non-erosive reflux disease - efficacy of Esoxx, a hyaluronic acid-chondroitin sulphate based bioadhesive formulation.

BACKGROUND: Several studies have shown that patients with non-erosive reflux disease (NERD) are less responsive to proton pump inhibitors (PPIs) than those with erosive disease as they belong to different subgroups, in whom factors other than acid can trigger symptoms. AIM: To evaluate whether combined therapy (mucosal protection plus acid suppression) would improve symptom relief compared to PPI treatment alone. METHODS: In a multicenter, randomised, double-blind trial, 154 patients with NERD were randomised to receive Esoxx (Alfa Wassermann, Bologna, Italy), a hyaluronic acid-chondroitin sulphate based bioadhesive formulation, or placebo, in addition to acid suppression with standard dose PPIs for 2 weeks. Symptoms (heartburn, acid regurgitation, retrosternal pain and acid taste in the mouth) and health-related quality of life (HRQL) were evaluated before and after treatment. The primary endpoint was the proportion of patients with at least a 3-point reduction in the total symptom score. RESULTS: At the end of treatment, the primary endpoint was reached by 52.6% of patients taking Esoxx compared to 32.1% of those given placebo (P < 0.01). The same was true also for HRQL, evaluated by means of the Short Form-36 questionnaire, which improved with both treatments, but some items were significantly better after Esoxx plus PPI therapy. CONCLUSION: The synergistic effect of Essox with PPI treatment suggests that mucosal protection added to acid suppression could improve symptoms and HRQL in NERD patients.

Postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance can link PPI-responsive heartburn to reflux better than acid exposure time.

BACKGROUND: Acid exposure time (AET) is considered the most useful parameter to predict response of reflux-related heartburn to medical or surgical treatment. However, recent studies showed high rates of heartburn response to proton pump inhibitor (PPI) therapy in patients with normal AET. We aimed to compare the efficacy of postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) with AET in linking PPI-responsive heartburn to reflux. METHODS: Off-therapy impedance-pH tracings from 425 patients, 317 with PPI-responsive and 108 with PPI-refractory heartburn were blindly re-analyzed. Demographic and endoscopic characteristics, conventional impedance-pH variables, PSPW index, and MNBI were assessed with multivariate logistic regression to identify factors independently associated with PPI responsiveness. Prediction models were developed to assess the strength of reflux linkage with factors independently associated with PPI responsiveness by calculating the area under the curve (AUC) at receiver-operating-characteristic (ROC) analysis. KEY RESULTS: At multivariate logistic regression analysis, AET, MNBI, and PSPW index were the only factors independently associated with PPI responsiveness, abnormal values found in 60%, 76%, and 92% of PPI-responsive cases (P<.017). At ROC analysis, PSPW index (AUC:.794, P=.002) and MNBI (AUC: 0.742, P=.003), both separately and combined (AUC: 0.811, P<.001) linked reflux with PPI-responsiveness better than AET (AUC: 0.687). CONCLUSIONS & INFERENCES: AET, PSPW index, and MNBI are independently associated with PPI-responsive heartburn. PSPW index and MNBI can link PPI-responsive heartburn to reflux better than AET and should become part of the standard analysis of impedance-pH tracings.

The added diagnostic value of postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance in refractory reflux disease studied with on-therapy impedance-pH monitoring.

BACKGROUND: On-therapy impedance-pH monitoring in proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) yielded conflicting results. We aimed to assess the diagnostic value of postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) in PPI-refractory heartburn. METHODS: On-therapy impedance-pH tracings from 189 consecutive patients with PPI-refractory heartburn were blindly reviewed. Patients were subdivided into refractory reflux esophagitis (RRE), healed reflux esophagitis (HRE), non-erosive reflux disease (NERD), and functional heartburn (FH) according to endoscopic and conventional impedance-pH findings. The diagnostic accuracy of PSPW index and MNBI in separating NERD from FH was assessed with receiver-operating-characteristic (ROC) analysis. Objectively documented persistent reflux remission at 3-year follow-up in 53 patients who underwent laparoscopic fundoplication served to evaluate PSPW index and MNBI as independent predictors of PPI-refractory GERD confirmed by positive surgical outcome. KEY RESULTS: Median PSPW index and MNBI values were significantly lower in 39 RRE (16%; 1145 Ω) than in 41 HRE (25%; 1741 Ω) and in 68 NERD (29%; 2374 Ω) patients, and in all three GERD subgroups compared to 41 FH cases (67%; 3488 Ω) (P<.008). At ROC analysis, comparing NERD to FH the area under the curve was 0.886 with PSPW index and 0.677 with MNBI (P=.005). PSPW index was an independent predictor of PPI-refractory GERD (odds ratio 0.6983, P=.012). CONCLUSIONS & INFERENCES: At on-therapy impedance-pH monitoring, PSPW index and MNBI efficiently distinguish PPI-refractory NERD from FH. The PSPW index represents an independent predictor of PPI-refractory GERD.

A study of 4- and 7-day triple therapy with rabeprazole, high-dose levofloxacin and tinidazole rescue treatment for Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori treatment failure is becoming an emergent problem in clinical practice. Shorter treatment duration should improve compliance to therapy and keep an acceptable H. pylori eradication rate. AIMS: To evaluate the efficacy of two rabeprazole, high-dose levofloxacin and tinidazole-based regimens as 'rescue' treatment for H. pylori eradication in an open-label, randomized, pilot study carried out in a clinical practice setting. METHODS: Eighty-five consecutive patients who have previously failed at least one H. pylori eradication attempt were randomized to receive rabeprazole (20 mg, b.d.), levofloxacin (500 mg, b.d.) and tinidazole (500 mg, b.d.) either for 4 (4-day RLT, n = 42) or 7 days (7-day RLT, n = 43). Cure of H. pylori infection was assessed by means of 13C-urea breath test. RESULTS: The 7-day RLT achieved 84% (95% CI: 69-93%) and 86% (95% CI: 72-95%) eradication rates in intention-to-treat and per-protocol analyses respectively. The shorter treatment obtained an 83% (95% CI: 69-93%) eradication rate in both intention-to-treat and per-protocol analysis. Both regimens were well tolerated, although patients who received the 4-day RLT reported fewer side-effects. CONCLUSIONS: In patients who have previously failed at least one H. pylori eradication attempt, both 4- and 7-day rabeprazole, high-dose levofloxacin, tinidazole-based regimens are effective in curing the infection in more than 80% of patients.

Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux disease: esomeprazole versus lansoprazole.

BACKGROUND: Acid suppression is the mainstay of therapy in gastro-oesophageal reflux disease. Esomeprazole 40 mg is more effective than lansoprazole 30 mg in healing mucosal lesions in severe erosive reflux oesophagitis. However, data comparing esomeprazole with lansoprazole in patients with complications of gastro-oesophageal reflux disease, such as ulcerative reflux oesophagitis and Barrett's oesophagus, are lacking. AIM: To compare the efficacy of esomeprazole and lansoprazole at their standard dosages in suppressing oesophageal acid exposure in complicated gastro-oesophageal reflux disease. METHODS: Thirty patients with complicated gastro-oesophageal reflux disease (7 with ulcerative reflux oesophagitis and 23 with Barrett's oesophagus), randomly assigned to receive 40 mg esomeprazole (n=16) or 30 mg lansoprazole (n=14) once daily, underwent oesophageal 24-h pH monitoring while on therapy. Total, upright diurnal and supine nocturnal percentage acid reflux time were assessed. RESULTS: Esomeprazole was significantly more effective than lansoprazole in decreasing oesophageal acid exposure. Normalisation of both total and supine nocturnal percentage acid reflux time was obtained in 12 of 16 (75%) patients treated with esomeprazole but only in 4 of 14 (28%) cases treated with lansoprazole (p=0.026). CONCLUSIONS: Normalisation of oesophageal acid exposure can be achieved in the majority of complicated gastro-oesophageal reflux disease cases with esomeprazole 40 mg once daily.

Pathophysiological characteristics of the various forms of gastro-oesophageal reflux disease. Spectrum disease or distinct phenotypic presentations?

BACKGROUND: The traditional approach to gastro-oesophageal reflux disease as a spectrum disease has recently been criticised and the distinct phenotypic presentations model has been proposed. AIM: To evaluate the main pathophysiological characteristics of various gastro-oesophageal reflux disease presentations. METHODS: Oesophageal manometry and 24-h pH-monitoring were performed in a gastro-oesophageal reflux disease series collected in a 7-year period. RESULTS: Four hundred and twenty-one subjects were studied. Mean total percentage acid reflux time was significantly higher in long-segment Barrett's oesophagus and in ulcerative oesophagitis than in all the other gastro-oesophageal reflux disease groups, whilst in short-segment Barrett's oesophagus results were quite similar to those found in non-erosive reflux disease and in erosive reflux disease. Patients with ulcerative oesophagitis and long-segment Barrett's oesophagus were older than all the other gastro-oesophageal reflux disease groups. The mean lower oesophageal sphincter pressure was significantly reduced in non-erosive reflux disease, erosive reflux disease, ulcerative oesophagitis, short-segment Barrett's oesophagus and long-segment Barrett's oesophagus as compared with functional heartburn and hypersensitive oesophagus and with controls. CONCLUSIONS: In keeping with the spectrum model of gastro-oesophageal reflux disease, severity of acid reflux increases from non-erosive reflux disease through erosive reflux disease up to ulcerative oesophagitis and long-segment Barrett's oesophagus. Ulcerative oesophagitis and long-segment Barrett's oesophagus could represent an advanced step in the natural history of gastro-oesophageal reflux disease. Our results do not confirm the distinct phenotypic presentations hypothesis.

Normal values of 24-h ambulatory intraluminal impedance combined with pH-metry in subjects eating a Mediterranean diet.

BACKGROUND AND AIMS: Multichannel intraluminal impedance combined with pH-metry is a novel technique for studying gastro-oesophageal reflux. As refluxes are particularly frequent after meals, we carried out this study in order to assess the impact of a Mediterranean diet on normal values of impedancemetry. METHODS: Twenty-five Italian healthy subjects (13 men, median age 29 years, range 22-67 years) without reflux symptoms were recruited for this study. They underwent oesophageal 24-h impedance + pH-metry. A Mediterranean diet was given to all subjects on the day of examination and its total energy intake was 9668.5 kJ (2300 kcal). RESULTS: A total of 1518 refluxes were recorded during 24 h with more upright than recumbent episodes (median 15 versus 0; p<0.01). The median total acid exposure time was 0.5% (range 0-4.2%). Acid and weakly acidic refluxes were equally reported (49% versus 51%). Weakly acidic episodes were more frequent than acid ones during 1-h postprandial periods (68% versus 32%; p<0.0001). Liquid-only and mixed refluxes reached the proximal oesophagus (15 cm above lower oesophageal sphincter) in 42.6% of cases. Median acid clearing time was longer than median bolus clearing time (28 s versus 12 s; p<0.01). CONCLUSIONS: This study provides normal values of pH-impedancemetry in Italian people eating a Mediterranean diet and are suitable for comparative pathophysiological investigations on reflux patients who have dietary habits similar to those of our country.