Gastroparesis (gastric stasis) is derived from Greek words gastro/gaster or stomach, and paresis or partial paralysis. It is a clinical condition resulting from delayed gastric emptying in the absence of mechanical obstruction and is associated with upper gastrointestinal symptoms. Most common symptoms include nausea, vomiting, early satiety, postprandial fullness, upper abdominal pain, bloating, and weight loss. These symptoms can be severely disabling and can adversely impact the quality of life in patients suffering from this disorder. Several etiologies can lead to this clinical entity; the most common of these are idiopathic, diabetic and postsurgical. Pathophysiology of gastroparesis is poorly understood, but important mechanisms associated are the loss of interstitial cells of Cajal and inability to express neuronal nitric oxide synthase. Gastric emptying scintigraphy (gold standard), 13C-octanoate breath testing, and a wireless motility capsule are the diagnostic tests used to diagnose this condition. Management of gastroparesis includes initial restoration of the nutritional state, optimizing glycemic control, symptom relief and improvement in gastric emptying. Medical management includes the use of prokinetic agents such as metoclopramide, erythromycin, and anti-emetic agents. Endoscopic and surgical methods are used for refractory cases. Intrapyloric botulinum injection, gastric electrical stimulation, venting gastrostomy, feeding jejunostomy, pyloroplasty, partial gastrectomy and most recently endoscopic techniques such gastric peroral endoscopic myotomy (G-POEM) are being utilized for relieving symptoms.
The most common etiologies for gastroparesis are Idiopathic in 64%, diabetes in 31%, and post-surgical in the remaining patients. Other less frequent etiologies include association with functional bowel disorders, dysmotility syndromes, Chagas disease, post-viral, neurological disorders, endocrine conditions, connective tissue disorders, radiation, gastric ischemia, and medications (opioids, anticholinergics, anti-diabetic medications).
Estimating the prevalence of gastroparesis is a great challenge as symptoms usually are not comparable to a gastric emptying study. According to an epidemiologic study from Olmsted County, the prevalence of gastroparesis was found to be 24.2 per 100,000 persons and incidence of 6.3 per 100,000 persons per year.
The pathophysiology of gastroparesis is poorly understood and is not well defined, but important mechanisms associated are the loss of interstitial cells of Cajal and inability to express neuronal nitric oxide synthase. For gastric emptying to occur there needs interaction between smooth muscles, extrinsic nerves, intrinsic or enteric nerves and interstitial cells of Cajal (ICC). It has been hypothesized that there might be a poor interplay between local enteric system along with decreased local secretion of nitric oxide(NO). Nitric oxide is required for smooth muscle relaxation, as a result causing accommodation of fundus and impairment in pyloric muscle relaxation. ICC generate slow wave and transmit to the smooth muscle thus enabling contraction, which is impaired with loss of ICC. Thus both contributing to delayed gastric emptying. There are several ongoing studies to determine pathophysiology, expect to improve our understanding soon.
Histopathologic studies from tissues of diabetic and idiopathic gastroparesis patients showed several changes like loss of ICC, decreased nerve fibers, increased smooth muscle fibrosis, and abnormal macrophage-containing immune infiltrates. On electron microscopy, there is abnormal connective tissue stroma, thick basal lamina around ICCs and myocytes, and large empty nerve endings suggest more profound conduction defects, which supports the above discussion.
Patients present commonly with cardinal symptoms like nausea, vomiting, early satiety, postprandial fullness, upper abdominal pain, bloating and weight loss. The gastroparesis cardinal symptom index (GCSI) is a validated clinical instrument that be can be used to assess symptoms in patients suffering from gastroparesis. This instrument has three subscales: (fullness/early satiety, nausea/vomiting, and bloating) and rates of symptom intensities from zero (none) to five (very severe) and the total is used for severity of the disease. The GCSI is used to assess response to therapy and not primarily as a diagnostic tool. In addition to gastric symptoms, the slow and unpredictable gastric emptying can cause wide fluctuations in blood sugar levels especially so in diabetic patients. In addition, this may cause weight loss, fatigue, calorie deficit, gastric bezoar formation.
Initial assessment of upper gastrointestinal tract by esophagogastroduodenoscopy or barium radiography is done to rule out a mechanical obstruction. The most common test used in clinical practice is the gastric scintigraphic emptying of solids. A study result of retention of solids at 4 hours is considered to be diagnostic of gastroparesis. Other alternative methods to assess gastric emptying include motility testing by a wireless capsule and 13 C breath testing using octanoate or spirulina integrated into a solid meal. Drugs that affect the gastric emptying should be held at least 48 hours prior to the study. Furthermore, patients with diabetes should have plasma blood glucose less than 275 mg/dl to eliminate acute impairment of gastric emptying from hyperglycemia.
Diet and Lifestyle Changes
The initial goal of management of gastroparesis is the restoration of fluid and electrolyte balance. Also, nutritional status and blood sugar levels should be optimized. Dietary modifications include switching to small frequent meals, low-fat diet. Drinks such as carbonated and alcoholic beverages and foods rich in insoluble fiber should be avoided entirely. In addition, quitting smoking has also been reported to be helpful. Oral intake is encouraged, and if the patient does not tolerate solid foods, then liquid diet could be attempted. In case of intolerance to oral diet, enteral feeding by post-pyloric feeding tube can be used. Parenteral nutrition is not encouraged and remains the last alternative if everything else fails.
Pharmacological and Surgical Methods
Use of prokinetics like metoclopramide, erythromycin and anti-emetics can help relieve symptoms. Metoclopramide is the first-line agent; it is a dopamine D2 receptor antagonist that increases contractility, resting tone of GI tract and thereby promotes gastric emptying. It is recommended to use the lowest possible dose for the shortest duration of time given its extrapyramidal side effects unless benefits outweigh risks. Domperidone is similar to metoclopramide but with fewer central side effects and can be used when there are adverse effects with the use of metoclopramide. It is not FDA approved for use in the USA. Domperidone can be prescribed by obtaining expanded access investigational new drug from FDA. Erythromycin can be used for a short course to promote gastric emptying, but prolonged use is associated with tachyphylaxis and should be used sparingly. Other antiemetics used are prochlorperazine, promethazine, ondansetron, and tricyclic agents such as nortriptyline in the case of refractory emesis.
Intrapyloric botulinum injections have been demonstrated to improve symptoms in patients that are refractory to above medical therapies. The effects of the botulinum injections last for about 3 to 6 months. Lack of randomized controlled trials to support the use of botulinum is the main limitation. A gastric electrical stimulator (GES) used in refractory patients as an alternative modality, it delivers high frequency and low energy stimulation to the stomach, thus enhancing gastric motility. Studies have also shown improvement in symptoms and gastric emptying from the use of GES. Surgical approaches include venting gastrostomy, feeding jejunostomy, pyloroplasty and partial gastrectomy are performed when medical therapy fails for symptom relief. A new emerging, less invasive endoscopic technique gastric peroral endoscopic myotomy (G-POEM) is being evaluated to the relieve the symptoms of gastroparesis. The initial studies are encouraging, will need further studies to evaluate efficacy and safety.
Gastroparesis mimics several other conditions such as like anorexia nervosa, bulimia, and rumination syndrome. Therefore, these conditions need to be excluded prior to making a diagnosis of gastroparesis. Other conditions such as cyclical vomiting syndrome and chronic cannabinoid use may also have a similar clinical pattern as gastroparesis.
Gastroparesis is a clinical condition associated with obstructive gastric symptoms in the absence of mechanical obstruction that is observed in a variety of clinical conditions. There is no definitive treatment for this condition currently. Unfortunately, management options are limited and mostly focused on symptom relief. Several new treatment alternatives are emerging to manage this condition but need further studies to evaluate clinical benefit.
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