Functional Dyspepsia (FD) is a frequent disorder in Western Countries (1). In last years many definitions of Dyspepsia have been attempted and, actually, the last iteration of Rome III criteria defined FD as the presence of one or more of the following symptoms (epigastric pain, epigastric burning, postprandial fullness, early satiation) thought to originate in the gastro-duodenal region, in the absence of any organic, systemic, or metabolic disease that is likely to explain the symptoms (2). The pathophysiology of FD is unclear, but it is likely to be multifactorial (1). Putative mechanisms include overlapping disorders of upper gastrointestinal motor and sensory function. Among them, delayed gastric emptying, impaired fundic accommodation to a meal, altered visceral sensation (eg, increased gastric hypersensitivity to mechanical distention, and duodenal hypersensitivity), H pylori–induced gastritis and increased sensitivity to acid infusion have been encountered in many patients with FD. Therefore, the main therapeutic approaches to its management are represented by acid inhibition, prokinetic drugs and H. pylori eradication (Figure 1). However, the role of acid suppression is controversial, and randomized controlled trials evaluating the efficacy of anti-secretory therapy have given conflicting results (1,3). A meta-analysis of controlled, randomized trials with Proton Pump Iinhibitors (PPIs) in functional dyspepsia reported that this class of agents was superior to placebo with a number needed to treat of 7. In particular, four trials compared PPI therapy with placebo and antacids in 2164 patients with uninvestigated dyspepsia. PPI therapy was more effective (RR, 0.65; 95% CI, 0.55– 0.78), with a number needed to treat (NNT) of 5 (95% CI, 4–7). Eight trials compared PPI therapy with placebo in 3293 patients with non-ulcer dyspepsia. PPI therapy was significantly superior to placebo with a number needed to treat of 9. The lower rate of response compared with that obtained in patients with uninvestigated dyspepsia was due to the exclusion of patients with organic dyspepsia by endoscopy, because these latter ones respond satisfactorily to PPIs. Anyway, there was significant heterogeneity between results and the major problem with these trials remains potential misclassification bias in terms of GERD. In a more recent meta-analysis Wang et al. (4) evaluated a total of 7 studies consisting of 3725 patients analyzed. There was a modest but statistically significant difference in symptom relief in FD patients receiving PPIs (40.3%) compared with those given placebo (32.7%) (RRR, 10.3%; 95% CI, 2.7%–17.3%). The estimated number needed to treat was 14.6 patients (95% CI, 8.7–57.1). This finding was consistent across different doses of PPIs and the patients’ status of Helicobacter pylori infection. It is relevant to note that a large placebo effect has been documented in many trials aimed at treating FD and it can range from 5% to 85% of patients with an average value of about 40% (1,3,4). It has been speculated that this may be due to variance in trial duration, patient selection, recruitment issues, number of subjects included in the study and other study design factors. Finally, we have recently published a large prospective study(5), where patients with Functional Heartburn (FH) identified by means of impedance-pH monitoring had a high association with dyspeptic symptoms and they resulted to be less responsive to PPI treatment than patients with pH-POS NERD and Hypersensitive Esophagus (Figure 2). This finding seems to confirm the poor response of Functional Dyspepsia to PPIs. In conclusion, no therapy has been shown to be highly effective in patients with FD. PPIs seem to be more effective than placebo in several meta-analyses, but this occurs mainly in dyspeptic patients complaining of epigastric pain and burning, even if the degree of treatment response appears to be from mild to moderate. Patients with an overlap of FH and dyspeptic symptoms respond less than patients with NERD and Hypersensitive Esophagus to anti-secretory therapy and this seems to sustain the fact that patients with functional GI disorders are less likely to respond to antisecretory drugs and other treatments have to be adopted.

Barrett's esophagus: proton pump inhibitors and chemoprevention II.

SAVARINO, EDOARDO VINCENZO;
2011

Abstract

Functional Dyspepsia (FD) is a frequent disorder in Western Countries (1). In last years many definitions of Dyspepsia have been attempted and, actually, the last iteration of Rome III criteria defined FD as the presence of one or more of the following symptoms (epigastric pain, epigastric burning, postprandial fullness, early satiation) thought to originate in the gastro-duodenal region, in the absence of any organic, systemic, or metabolic disease that is likely to explain the symptoms (2). The pathophysiology of FD is unclear, but it is likely to be multifactorial (1). Putative mechanisms include overlapping disorders of upper gastrointestinal motor and sensory function. Among them, delayed gastric emptying, impaired fundic accommodation to a meal, altered visceral sensation (eg, increased gastric hypersensitivity to mechanical distention, and duodenal hypersensitivity), H pylori–induced gastritis and increased sensitivity to acid infusion have been encountered in many patients with FD. Therefore, the main therapeutic approaches to its management are represented by acid inhibition, prokinetic drugs and H. pylori eradication (Figure 1). However, the role of acid suppression is controversial, and randomized controlled trials evaluating the efficacy of anti-secretory therapy have given conflicting results (1,3). A meta-analysis of controlled, randomized trials with Proton Pump Iinhibitors (PPIs) in functional dyspepsia reported that this class of agents was superior to placebo with a number needed to treat of 7. In particular, four trials compared PPI therapy with placebo and antacids in 2164 patients with uninvestigated dyspepsia. PPI therapy was more effective (RR, 0.65; 95% CI, 0.55– 0.78), with a number needed to treat (NNT) of 5 (95% CI, 4–7). Eight trials compared PPI therapy with placebo in 3293 patients with non-ulcer dyspepsia. PPI therapy was significantly superior to placebo with a number needed to treat of 9. The lower rate of response compared with that obtained in patients with uninvestigated dyspepsia was due to the exclusion of patients with organic dyspepsia by endoscopy, because these latter ones respond satisfactorily to PPIs. Anyway, there was significant heterogeneity between results and the major problem with these trials remains potential misclassification bias in terms of GERD. In a more recent meta-analysis Wang et al. (4) evaluated a total of 7 studies consisting of 3725 patients analyzed. There was a modest but statistically significant difference in symptom relief in FD patients receiving PPIs (40.3%) compared with those given placebo (32.7%) (RRR, 10.3%; 95% CI, 2.7%–17.3%). The estimated number needed to treat was 14.6 patients (95% CI, 8.7–57.1). This finding was consistent across different doses of PPIs and the patients’ status of Helicobacter pylori infection. It is relevant to note that a large placebo effect has been documented in many trials aimed at treating FD and it can range from 5% to 85% of patients with an average value of about 40% (1,3,4). It has been speculated that this may be due to variance in trial duration, patient selection, recruitment issues, number of subjects included in the study and other study design factors. Finally, we have recently published a large prospective study(5), where patients with Functional Heartburn (FH) identified by means of impedance-pH monitoring had a high association with dyspeptic symptoms and they resulted to be less responsive to PPI treatment than patients with pH-POS NERD and Hypersensitive Esophagus (Figure 2). This finding seems to confirm the poor response of Functional Dyspepsia to PPIs. In conclusion, no therapy has been shown to be highly effective in patients with FD. PPIs seem to be more effective than placebo in several meta-analyses, but this occurs mainly in dyspeptic patients complaining of epigastric pain and burning, even if the degree of treatment response appears to be from mild to moderate. Patients with an overlap of FH and dyspeptic symptoms respond less than patients with NERD and Hypersensitive Esophagus to anti-secretory therapy and this seems to sustain the fact that patients with functional GI disorders are less likely to respond to antisecretory drugs and other treatments have to be adopted.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2482579
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