Gastroparesis

Synonyms

Delayed gastric emptying; Gastric stasis

Definition

Gastroparesis is a syndrome characterized by delayed gastric emptying in the absence of mechanical obstruction of the stomach. It is traditionally associated with nausea, vomiting, postprandial fullness, early satiety, bloating, and abdominal pain.

The etiology is multifactorial and the most common causes are diabetes, postsurgical status, and idiopathic. Other causes include medication, Parkinson’s disease, collagen vascular disorders, thyroid dysfunction, liver disease, chronic renal insufficiency, intestinal pseudo-obstruction, and miscellaneous.

Gastroparesis may be due to abnormalities of the fundus (post-vagotomy state, diabetes mellitus, and functional dyspepsia), abnormalities in antroduodenal contraction (low amplitude, frequency, and decreased antral motor function or dysfunction), pyloric dysfunction (idiopathic hypertrophic stenosis and diabetes gastroparesis), or abnormalities in small bowel motility. Diabetic gastroparesis is believed to represent a form of neuropathy involving the vagus nerve. Hyperglycemia itself can also cause antral hypomotility, gastric dysrhythmias, and delayed gastric emptying in some patients. Idiopathic gastroparesis is present in many patients with functional dyspepsia and may in some cases occur after a viral infection.

Symptoms of gastroparesis are often persistent, but some patients experience episodic symptom flares that are separated by asymptomatic periods. There are several complications associated with gastroparesis, namely, deficiencies in vitamins A, B6, C, and K, as well as iron, potassium, and zinc; postprandial hypoglycemic reactions in diabetic patients, and bezoar formation.

The diagnosis is based on the presence of appropriate symptoms/signs, delayed gastric emptying, and the absence of an obstructing structural lesion in the stomach or small intestine. Routine laboratory is useful to identify diseases that are associated with gastroparesis, to rule out other disorders and to assess the nutritional sate of the patient. Patients should undergo an upper endoscopy or barium meal, mainly to exclude mechanical obstruction or mucosa disease as the cause. Gastric emptying scintigraphy of a radiolabeled solid meal is the best accepted method to test for diagnosis, the most useful parameters are gastric retention >10% at 4 h and >70% at 2 h. In patients who have evidence of gastric stasis by a scintigraphy study without an identifiable cause, gastroduodenal manometry can help differentiate myopathic from neuropathic process. Breath testing can also be performed and measure of gastric emptying using the nonradioactive isotope 13C to label octanoate, a medium-chain triglyceride, which can be bound into a solid meal and gastric emptying, can be indirectly determined. This test has been used primarily for clinical research and pharmaceutical studies.

Mild gastroparesis is thought to have a low mortality rate, but patients with decompensated gastroparesis are more likely to develop complications and have related mortality.

Clinical Features

• Incidence

  A study conducted to assess the incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006, revealed that gastroparesis is an uncommon condition in the community, but is associated with a poor outcome.

  The incidence of gastroparesis ranged from 6.3 to 17.2 cases per 100,000 person-years. The true prevalence is unknown, it is estimated to occur in 4% of the adult population, 20–40% of patients with diabetes mellitus, primarily those with long duration of type 1 diabetes mellitus with other complications, and may also be present in 25–40% of patients with functional dyspepsia.

• Age

  About 68% of patients are under 40 years of age at the time of initial presentation, with a mean age of 45 years.

• Sex

  There is a female predominance of gastroparesis, with a female: male ratio of 4:1.

  Several studies showed that female gender was associated with delayed gastric emptying in both functional dyspepsia and in patients with diabetes. There are several theories than can explain this, namely, a possible hormonal cause and female patients seem to seek health care more frequently than males.

• Site

  The stomach is the organ involved.

• Treatment

  Primary treatment of gastroparesis includes dietary manipulation and administration of antiemetic and prokinetic agents. Dietary recommendations include eating frequent smaller-size meals and replacing solid food with liquids, such as soups. Foods should be low in fat and fiber content. Antiemetic agents are administered for nausea and vomiting. The principal classes of antiemetic drugs are antidopaminergics, antihistamines, anticholinergics, and, more recently, serotonin receptor antagonists.

  Patients refractory to the initial treatment can be difficult to manage, treatment may involve switching prokinetic and antiemetic agents, combining prokinetic agents, injecting botulinum toxin into the pylorus, using gastrostomy/jejunostomy tubes, or implanting a gastric electric stimulator.

• Outcome

  The natural history of gastroparesis is largely unknown.

  The study performed by Soykan et al., including 146 patients with gastroparesis seen over 6 years, revealed that 74% required continuous prokinetic therapy, 22% were able to stop prokinetics, 5% had undergone gastrectomy, 6.2% went onto gastric electrical stimulation (pacing), and 7% died. At some point, 21% had required nutrition support with a feeding jejunostomy tube or periods of parenteral nutrition. A good response to pharmacological agents can be expected in the viral and dyspeptic subgroups, Parkinson’s disease, and the majority of diabetics, whereas a poorer outcome to prokinetics can be expected in postgastrectomy patients, those with connective tissue disease, a subgroup of diabetics, and the subset of idiopathic gastroparesis dominated by abdominal pain and history of physical and sexual abuse. Appreciation of the different etiologies and psychological status of the patients may help predict response to prokinetic therapy.

  Community studies of the outcome of gastroparesis are lacking, and studies conducted in tertiary referral centers may not reflect findings encountered in the general population.

Macroscopy

Normally there are no macroscopic abnormalities described in association with gastroparesis.

Microscopy

Pathologic assessment of gastric tissue in patients with gastroparesis is limited.

Gastroparesis Clinical Research Consortium (GpCRC) recently described the cellular changes associated with diabetic (DG) and idiopathic (IG) gastroparesis. Full-thickness gastric body biopsies were obtained from 40 gastroparetics (20 diabetic) and matched controls. In this study, the majority of patients with gastroparesis (83%) had defined gastric wall cellular abnormalities. Hematoxylin and eosin staining was graded as normal in all 20 patients with diabetic gastroparesis and in 19 patients with idiopathic gastroparesis. Smoothelin immunolabeling was decreased in three patients with diabetic gastroparesis and in six with idiopathic gastroparesis. Presence of fibrosis as determined by trichrome staining was present in one patient with diabetic and two patients with idiopathic gastroparesis. All other patients had normal trichrome staining, including eight of the nine patients with abnormal smoothelin immunolabeling.

Histologic examination of gastric tissues from patients with severe gastroparesis reveals heterogeneous and inconsistent defects in the morphology of enteric neurons, smooth muscle and interstitial cells of Cajal, and increased levels of inflammatory cells.

Vagus nerves from patients with diabetes exhibit variable levels of myelin degeneration.

Immunophenotype

Gastroparesis Clinical Research Consortium (GpCRC) also showed that the most commonly observed findings were loss of interstitial cells of Cajal (ICC) and an immune infiltrate containing macrophages, characterized by an increase in CD45 and CD68 immunoreactivity in both DG and IG. A 14–17% decrease in the number of enteric nerve fibers as defined by Protein Gene Product 9.5 (PGP9.5) immunoreactivity was also seen. Less common were changes in nNOS, vasoactive intestinal peptide (VIP), substance P (SP), and tyrosine hydroxylase (TH).

Differential Diagnosis

• 1. Gastroparesis should be differentiated from delayed gastric emptying due to mechanical obstruction of the stomach. An upper endoscopy should be performed to exclude obstruction.

• 2. Mucosal inflammation due to infection or acid-peptic disease can exacerbate gastroparesis symptoms.

• 3. Idiopathic gastroparesis may be difficult to distinguish from functional dyspepsia in some cases. Presentation with predominant pain and less nausea is considered to be more typical of functional dyspepsia, whereas dominant nausea with minimal pain is more consistent with idiopathic gastroparesis.

So, other conditions potentially causative of symptoms, such as gastric outlet obstruction, peptic ulcer disease, neoplasm, small bowel obstruction, or IBD, should be excluded by endoscopy or contrast radiology prior to conferring a diagnosis of gastroparesis.