bubble_chart Overview

Gastroparesis Syndrome refers to a clinical symptom complex characterized by delayed gastric emptying, with no organic lesions found in the upper digestive tract or upper abdomen upon examination. Based on etiology, it can be divided into primary and secondary types. The primary type, also known as idiopathic gastroparesis, is more common in young women. According to the onset and duration of the disease, gastroparesis can be classified into acute and chronic forms. Chronic gastroparesis is more frequently observed in clinical practice, with symptoms persisting or recurring for months or even over a decade.

bubble_chart Etiology

The cause and mechanism of primary gastroparesis are not yet clear, but the lesion may be located in the gastric muscle layer or the myenteric plexus that innervates the muscle layer. Secondary causes often include: ① diabetes mellitus; ② connective tissue diseases, such as progressive systemic sclerosis (PSS); ③ gastric surgery or vagotomy; ④ infections or metabolic abnormalities; ⑤ central nervous system diseases and certain medications. Additionally, reduced vagal tone and intestinal hormones or peptide substances may also play a role. In gastroparesis, motilin levels and motilin receptor function may be abnormal.

The causes of gastroparesis can be primary gastric motility dysfunction (idiopathic gastroparesis) or secondary to certain systemic diseases and specific gastric surgeries (Table). The mechanism of gastric emptying involves the close interaction of gastric smooth muscle, intrinsic or extrinsic gastrointestinal nervous systems, the central nervous system, and hormones. Any abnormality in these factors can lead to gastroparesis.

Table: Diseases Causing Delayed Gastric Emptying

Gastrointestinal smooth muscle disorders

Amyloidosis

Systemic sclerosis

Dermatomyositis

Myotonic dystrophy

Intestinal or autonomic nervous system disorders

Viral infections (herpes zoster virus, EB virus, cytomegalovirus, etc.)

Diabetes mellitus

Amyloidosis

Idiopathic orthostatic hypotension

Pandysautonomia

Paraneoplastic syndrome

Vagotomy

Partial gastrectomy and Roux-en-Y anastomosis

Central nervous system disorders

Parkinson's disease

Brainstem tumors

Spinal cord injury

Other diseases

Hyperthyroidism

Hypothyroidism

Anorexia nervosa

Gastric ischemia

Idiopathic

bubble_chart Pathogenesis

1. Diabetic Gastroparesis (DGP)

Diabetic patients often exhibit abnormal motility throughout the gastrointestinal tract. Approximately 40% of type I or type II diabetic patients taking oral hypoglycemic agents develop gastroparesis.

In 1937, Ferroir observed weakened gastric motility in diabetic patients during X-ray barium meal examinations. In 1945, Rundles first clearly described the correlation between delayed gastric emptying and diabetes. In 1958, Kassander first introduced the term "diabetic gastroparesis."

The gastrointestinal motility disorder in diabetic gastroparesis patients manifests as the disappearance of phase III of the migrating motor complex (MMC) and postprandial gastric antral hypomotility. Uncoordinated contractions of the antrum, pylorus, and duodenum, along with pyloric spasms, lead to delayed gastric solid emptying. Early-stage DGP patients exhibit impaired proximal gastric receptive relaxation, causing accelerated liquid emptying, but in advanced stages, gastric liquid emptying is also significantly delayed.

The primary cause of delayed gastric emptying in DGP patients is vagus nerve injury (autonomic neuropathy), and hyperglycemia also inhibits gastric emptying. Diabetic patients show reduced gastric acid secretion in response to sham feeding or insulin-induced hypoglycemia, indicating vagus nerve dysfunction. Guy et al. found severe morphological changes in the vagus nerves of diabetic patients, including markedly reduced unmyelinated axon density and thinning of residual axons. However, other studies have not identified morphological abnormalities in the gastric wall or abdominal vagus nerves of diabetic patients. The myenteric plexus in DGP patients also shows no abnormal changes. Carbamylmethylcholine and cisapride can stimulate antral contractions in DGP patients, suggesting intact antral smooth muscle function.

2. Postoperative Gastroparesis

Gastroparesis often occurs after gastric surgery. The incidence of delayed gastric emptying is 5–10% after vagotomy and 28–40% after vagotomy with pyloroplasty. Truncal vagotomy reduces gastric fundic relaxation, antral contractions, and coordinated pyloric relaxation, leading to accelerated liquid emptying and delayed solid emptying. However, highly selective (parietal cell) vagotomy only prolongs the late stage [third stage] of solid emptying without affecting overall gastric emptying.

About 30% of patients with peptic ulcer and pyloric obstruction develop gastroparesis after subtotal gastrectomy and vagotomy. Proximal gastric barostat measurements in these patients reveal that low residual gastric basal tone is the main cause of gastric stasis. Patients with Roux-en-Y syndrome also exhibit delayed gastric emptying.

Postoperative gastroparesis can involve various types of gastric slow-wave rhythm abnormalities and absence of MMC, which are also associated with delayed gastric emptying.

3. Anorexia Nervosa

Approximately 80% of anorexia nervosa patients exhibit delayed gastric solid emptying, though liquid emptying remains normal. Delayed gastric emptying is accompanied by antral motility rhythm disturbances, low gastric fundic tone, reduced postprandial plasma norepinephrine and neurotensin levels, and autonomic dysfunction. However, patients with similar degrees of weight loss but without anorexia nervosa symptoms show no significant delay in gastric emptying.

4. Diseases Involving Gastric Smooth Muscle

These diseases, in addition to affecting other systemic organs, often involve diffuse gastrointestinal smooth muscle impairment, leading to intestinal motility dysfunction. Although esophageal involvement is more common, gastric smooth muscle can also be affected, resulting in gastroparesis.

Progressive systemic sclerosis frequently causes delayed gastric emptying. The progression of gastrointestinal motility disorders in this condition includes two stages: initial neuropathy and subsequent myopathy due to fibrotic infiltration of the muscle layer.

Dermatomyositis and polymyositis can lead to delayed gastric solid and/or liquid emptying, and the degree of delay correlates with the severity of skeletal muscle weakness.

Most patients with myotonic dystrophy experience delayed gastric emptying of both solid and liquid foods. In these patients, increased tone and enhanced contractile activity in the duodenum and proximal jejunum are thought to result from partial depolarization due to smooth muscle damage, which theoretically could increase resistance to gastric emptying and lead to delayed gastric emptying.

Amyloidosis often involves infiltration of the gastrointestinal muscular layer, leading to motility dysfunction. In 1956, Intriere and Brown reported a case of primary amyloidosis affecting only the stomach. In addition to muscular layer involvement, amyloid neuropathy and intestinal ischemia caused by vascular lesions are also significant factors contributing to gastrointestinal motility dysfunction. Approximately 70% of primary and 55% of secondary amyloidosis cases present with digestive symptoms.

V. Gastroesophageal Reflux Disease

About 60% of patients with gastroesophageal reflux disease exhibit delayed gastric emptying. It remains unclear whether this abnormality is primary or secondary.

VI. Paraneoplastic Syndrome

In some cancer patients, gastroparesis can be part of a paraneoplastic syndrome. Chinn et al. reported seven cases of pulmonary carcinoid, six of which developed gastroparesis. Histological examination revealed degeneration of the myenteric plexus, reduced neurons and axons, infiltration of inflammatory cells such as lymphocytes and plasma cells, glial cell hyperplasia, while the submucosal plexus remained unaffected.

VII. Ischemic Gastroparesis

Liberski et al. recently reported two cases of severe gastroparesis in patients with chronic gastrointestinal ischemia due to mesenteric artery occlusion, accompanied by gastric dysrhythmia and related symptoms. Six months after bypass vascular graft surgery, the patients' gastric solid emptying and electrical rhythm normalized, and symptoms resolved.

VIII. Idiopathic Gastroparesis

This refers to gastroparesis of unknown cause, accounting for about 50% of patients with delayed gastric emptying. These patients can be broadly divided into two groups: one diagnosed with functional dyspepsia, and the other with diffuse gastrointestinal smooth muscle involvement. The latter group exhibits motility disorders throughout the gastrointestinal tract, often presenting with diagnoses such as irritable bowel syndrome or chronic intestinal pseudo-obstruction in addition to gastroparesis.

bubble_chart Clinical Manifestations

The motility disorders of gastroparesis often manifest as:

1. Hypomotility of the gastric antrum, leading to delayed gastric emptying.

2. Reduced compliance of the proximal stomach, resulting in weakened gastric accommodation.

3. Decreased pressure in the proximal stomach, causing delayed liquid gastric emptying.

4. Discoordinated movement between the stomach, pylorus, and duodenum. Therefore, the primary manifestation of this condition is delayed gastric emptying. Common symptoms include early satiety, postprandial upper abdominal fullness, and discomfort after eating.

bubble_chart Auxiliary Examination

1. Gastric Emptying Function Measurement There are many methods for examining gastric emptying function, and currently, the radionuclide gastric emptying test is considered the preferred choice. For any patient with unexplained dyspepsia, if conditions permit, routine radionuclide-labeled solid and liquid gastric emptying tests should be performed. This test is of significant value for diagnosis and also serves as an important objective evaluation tool for observing the efficacy of prokinetic drugs. The intubation method and X-ray barium meal or radiopaque marker tests are less commonly used due to their numerous shortcomings. Impedance technology can measure gastric liquid emptying and may be widely adopted in the future. Ultrasonic measurement of gastric emptying, due to its high technical requirements, is currently only used as a research tool.

2. Intragastric Manometry This examination is only performed when gastric emptying tests show abnormalities. Intragastric manometry in patients with gastroparesis can reveal gastric motility disorders, with postprandial antral hypomotility being the most common. In patients with gastroparesis after subtotal gastrectomy, proximal gastric static pressure measurements may show low basal tension.

3. Electrogastrography (EGG) Surface electrogastrography is a non-invasive examination method. The basic gastric electrical rhythm is a slow-wave potential of 3 cycles per minute, which determines the frequency and conduction direction of gastric muscle contractions. Once the slow-wave potential disappears, gastric action potentials and contractions cannot occur. It has been found that various types of gastroparesis can exhibit abnormal gastric electrical rhythms, such as gastric tachycardia, gastric bradycardia, and gastric dysrhythmias. These abnormalities can lead to delayed gastric emptying, and some prokinetic drugs can restore them to normal.

bubble_chart Diagnosis

If symptoms of gastroparesis are present, especially vomiting large amounts of food several hours after a meal, a preliminary diagnosis of gastroparesis can generally be made after normal findings on X-ray barium meal and gastroscopy or after excluding mechanical (organic) obstruction. A definitive diagnosis requires gastric emptying tests, intragastric manometry, or electrogastrography.

bubble_chart Treatment Measures

1. General Treatment

Patients with gastroparesis should be given a low-fat, low-fiber diet, with frequent small meals and mainly liquid foods to facilitate gastric emptying. Since smoking can slow gastric emptying, smoking cessation is recommended. The use of drugs that delay gastric emptying should be avoided as much as possible (Table).

Table Drugs That Delay Gastric Emptying

Drug Name	Therapeutic Use	Mechanism of Action
Potassium Salts	Electrolyte Balance	Unknown
Dopamine	Vasoconstrictor for Shock	Via Dopamine Receptors
L-Dopa	Parkinson's Disease	Via Dopamine Receptors
Nifedipine	Antihypertensive for Colicky Pain	Calcium Channel Blocker
Isoproterenol	Antiasthmatic	β-Adrenergic
Sucralfate	Peptic Ulcer, etc.	Mucosal Protectant
Aluminum Hydroxide Gel	Peptic Ulcer, etc.	Antacid
Opioid Preparations	Diarrhea	Increases Smooth Muscle Tone
Tricyclic Compounds	Antidepressant	Anticholinergic
Phenothiazines	Psychiatric Disorders	Anticholinergic
Synthetic Estrogens	Hormone Therapy	Gastric Hormone Receptors

2. Treatment of Primary Diseases

For diabetic gastroparesis, hyperglycemia should be controlled as much as possible, as some patients may experience symptom improvement with better glycemic control. Patients with anorexia nervosa should be supplemented with adequate calories to improve gastric emptying, and correcting psychological disorders is also necessary for complete symptom recovery. Malageleda et al. reported a case where gastroparesis symptoms disappeared and gastric motility returned to normal after the removal of a lung tumor. As mentioned earlier, ischemic gastroparesis caused by chronic mesenteric artery occlusion can fully recover after vascular reconstruction.

3. Prokinetic Drugs

The use of prokinetic drugs is currently the most effective treatment for most patients with gastroparesis. Prokinetic drugs are a class of medications that restore, enhance, and coordinate the contractile activity of gastrointestinal smooth muscles, accelerating the movement of luminal contents.

Carbamylmethylcholine can increase the frequency and amplitude of gastric contractions, but radionuclide gastric emptying tests have shown that it does not accelerate gastric emptying. Therefore, some argue that this drug does not belong to the category of prokinetic drugs.

Currently commonly used prokinetic drugs include metoclopramide, domperidone, and cisapride. These drugs can increase the frequency and amplitude of antral contractions, enhance the coordination of antroduodenal contractions, and are used to treat various types of gastroparesis. They can accelerate gastric emptying and improve clinical symptoms. However, the long-term therapeutic effects of metoclopramide and domperidone are not ideal, whereas cisapride still demonstrates good efficacy with prolonged use.

In recent years, the prokinetic effect of erythromycin has attracted considerable attention. As a motilin receptor agonist, erythromycin stimulates gastrointestinal motility, inducing postprandial gastric activity similar to phase III of the migrating motor complex (MMC). This results in strong antral contractions, reduced pyloric pressure, improved coordination between antral and duodenal contractions, and accelerated emptying of solid food (including larger undigested particles).

In 1990, Janssens et al. first used erythromycin to treat diabetic gastroparesis with favorable short-term outcomes. In 1993, Richards et al. reported its efficacy in idiopathic gastroparesis, demonstrating that erythromycin—whether administered intravenously, orally for short-term (4 weeks), or as long-term maintenance therapy (1–11 months)—enhanced gastric solid emptying, improved clinical symptoms, and showed no significant side effects. Erythromycin also proved effective for gastroparesis caused by nervous anorexia, post-vagotomy, progressive systemic sclerosis, and chemotherapy-induced gastroparesis.

Regarding dosage, Camilleri recommends starting with 3 mg/kg intravenously every 8 hours, switching to oral administration (250 mg three times daily) once the patient tolerates food intake, generally for no more than 10 days. For patients who tolerate erythromycin well, prolonged use for several months may be considered as long as symptom improvement persists without side effects.

Side effects of erythromycin include nausea, vomiting, and diarrhea. High doses have been associated with reports of ventricular tachycardia. Erythromycin may also induce subclinical presynaptic neuromuscular junction inhibition, exacerbating symptoms in myasthenia gravis patients. Long-term use raises concerns about inducing antibiotic-resistant strains. Derivatives like EM-523 and EM-574, which retain prokinetic activity without antibacterial effects, could resolve this issue.

Motilin—Peeters et al. administered intravenous motilin to six patients with severe diabetic gastroparesis, significantly accelerating both liquid and solid gastric emptying. Thus, motilin may offer a novel therapeutic approach for gastroparesis in the future.

Prokinetic drugs with different mechanisms may be combined or alternated when necessary to avoid side effects and tachyphylaxis associated with high-dose or prolonged monotherapy.

IV. Surgical Treatment

For a minority of refractory gastroparesis patients, surgical intervention may be considered. Some reports indicate significant symptom relief after subtotal gastrectomy and gastrojejunostomy in idiopathic gastroparesis. Postoperative gastroparesis patients have also shown improvement following extensive gastrectomy and Roux-en-Y drainage. Yeung et al. reported a diabetic patient with refractory gastroparesis and intractable nausea/vomiting after vagotomy and pyloroplasty for duodenal ulcer, who achieved long-term remission via fluoroscopy-guided percutaneous gastrostomy tube placement after failed prokinetic therapy.

V. Other Therapies

Gastric pacing can normalize disordered gastric slow-wave rhythms, restoring proper motility. Preliminary trials in postoperative gastroparesis patients with dysrhythmias show some efficacy, though further research is needed to clarify its technical challenges and therapeutic role in gastroparesis.