**5. Empirical treatment**

Therapeutic trial may be employed as a means of diagnosis. This has proved successful in the management of GERD but the story in FD is entirely different because its pathogenesis is poorly understood and there is no effective treatment. Also, there is often a substantial placebo effect. The new drug, Acotiamide, an acetylcholinesterase inhibitor is promising and has been shown to be efficacious and safe in the elimination of meal-related FD symptoms [86]. Though not yet approved for treatment of FD, it holds high promise as no adverse events were recorded.

#### **5.1. Duodenal eosinophilia**

Delayed gastric emptying occurs in 23-59% of patients with FD [72]. Research has shown that delayed gastric emptying may be related to postprandial fullness and vomiting with symp‐ toms being more frequently found in female patients than in males [73-75]. Other studies have failed to confirm any difference in the occurrence of FD symptoms between patients with

Assessment of gastric emptying is commonly performed for such indications as nausea, vomiting and dyspepsia. However, there is a poor correlation of symptoms to observed

Techniques of gastric emptying include scintigraphy, which is the standard method in clinical practice, but is associated with radiation exposure. Newer non-invasive methods include wireless motility capsule and gastric emptying breath testing. Ultrasound, single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) are pre‐

The duodenum is implicated in the pathophysiology of FD. Duodenal hypersensitivity and

**Duodenal hypersensitivity to lipid:** Duodenal infusion of lipid in subjects with FD increased gastric distension and symptoms in a dose-dependent fashion [78]. Symptom relief is achieved with administration of Loxiglumide, a cholecystokinin A receptor antagonist and this suggests that cholecystokinin release following a lipid stimulus is the mediator of gastric hypersensi‐ tivity in FD [79] Using cholecystokinin infusion as a challenge test is appealing [80] but is not

Buspirone challenge test [81] is another chemical hypersensitivity test. This chemical is a serotonin 1A agonist that acts at the hypothalamic level to stimulate prolactin release. The extent of prolactin release following Buspirone challenge is a reliable measure of central 5HT

**Duodenal sensitivity to acid infusion:** Studies on the presence of duodenal hypersensitivity to acid in FD patients and its role in the pathophysiology of FD remain controversial. Samson et al [84] reported that duodenal acid infusion induced nausea in a subset of FD patients, but not in healthy controls, suggesting the presence of duodenal hypersensitivity to acid in FD patients. However, other studies found that dyspeptic symptoms such as nausea could be

Therapeutic trial may be employed as a means of diagnosis. This has proved successful in the management of GERD but the story in FD is entirely different because its pathogenesis is poorly understood and there is no effective treatment. Also, there is often a substantial placebo effect.

abnormal responses to various substances have been observed in FD.

sensitivity which can be impaired in patients with FD [82, 83].

induced by duodenal acidification in healthy volunteers [85].

normal or delayed gastric emptying [76, 77]

18 Dyspepsia - Advances in Understanding and Management

abnormalities.

dominantly research tools.

yet available for clinical use.

**5. Empirical treatment**

**4.7. Chemical hypersensitivity test**

Eosinophils and mast cells may be specifically recruited to the duodenum, altering sensation and motility [87]. The duodenum, which is often ignored in the search for pathophysiologic explanations for FD may be key to the symptom experience in FD. Mast cells induce eosinophil migration and eosinophils activate mast cells [88]. Degranulation from mast cells and eosino‐ phils leads to neural stimulation and smooth muscle contraction, which in turn results in gastrointestinal symptoms, such as abdominal pain and bloating [89]. While a significant increase in mast cells has not been observed in the duodenum of patients with FD, duodenal eosinophilia in FD has been described [90, 91]. This finding is exciting, because, in patients undergoing endoscopy, duodenal biopsy is safe and easy to perform. This finding also has a potential therapeutic implication which further research would unravel.


**Table 2.** Summary of structural and functional abnormalities of the gastrointestinal tract in functional dyspepsia

In conclusion, dyspepsia is a very common clinical problem globally. Majority of patients with this problem have FD, defined traditionally as dyspepsia in which investigations, including upper gastrointestinal endoscopy fail to reveal a structural, biochemical or other pathophy‐ siologic reason for the symptom. The pathophysiology of FD remains poorly understood.

Recent information from research shows that there are structural and physiological changes in FD that may hold the key to further understanding of the pathogenesis of this disease. These include Helicobacter pylori infection, abnormalities of gastric accommodation, abnormalities of gastric emptying, duodenal eosinophilia duodenal hypersensitivity to acid and lipids. These changes have prospects of being deployed in future for the diagnostic evaluation of FD. The implication of this is that FD may not be idiopathic after all. Research is likely to shed more light on this in future.

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