Evaluation of Gastroparesis


Study evaluating gastric emptying


Strengths


Limitations


Gastric emptying scintigraphy (gold standard)


Well validated, reproducible [4]


Noninvasive [4]


Ability to assess both solid and liquid phases [12]


Radiation exposure [4]


Solid meal might not be tolerated if severe symptoms [13]


Stable isotope breath test


No radiation exposure [4]


Reproducible and correlates with the gold standard [15, 18]


Limited use in patients with malabsorption, liver, or lung diseases [19, 20]


Affected by physical activity [19]


Lack of standardized mathematical analysis of results [19]


Wireless motility capsule


No radiation exposure [19]


Allows the assessment of extragastric motility [24]


Capsule emptying might not match physiologic emptying [29]


Risk of retention or obstruction [19]


Requires further validation in patients with suspected gastroparesis [31]


Antroduodenal manometry


Helps distinguish between myopathic vs. neuropathic etiology of impaired gastric motility [4]


Invasive


Not readily available [34]


Requires expertise [35]


Technically cumbersome


Transabdominal ultrasonography


Can provide data on transpyloric flow and intragastric meal distribution [4, 36]


No radiation exposure


Operator dependent


Performs poorly in obese patients [4]


Magnetic resonance imaging


Can measure gastric emptying, accommodation, and gastric secretions [3]


No radiation exposure


Cost


Lack of standardization


Requires specialized equipment


Requires expertise [4, 7]




Gastric Emptying Scintigraphy


GES was first described in 1966 by Griffith et al. [1] and is currently considered the gold standard for the diagnosis of gastroparesis. In this test, and after an overnight fast, the patient ingests a standardized, radiotracer-bound, low-fat meal (255 kcal) resembling a physiologic meal within 10 minutes. A longer time of ingestion can alter results. Most institutions use 99mTc sulfur colloid-labeled egg sandwich [2] or Egg Beaters egg whites (120 g) with 1–2 slices of bread, strawberry jam (30 g), and water (120 mL). For accurate quantification of gastric emptying, the radiotracer should be tightly bound to the solid phase to prevent it separating from the solid meal and emptying with the liquid phase, generating false-negative results [3, 4]. While earlier studies labeled both solids and liquid phases of a meal, current standardized tests only label the solid phase of a meal, because liquid emptying becomes abnormal only at very advanced stages of gastroparesis. Testing liquid emptying is of value however when evaluating for postsurgical anatomic problems or ruling out dumping syndrome in postsurgical patients [4]. After ingestion, standard imaging of the gastric area is performed with the patient standing after meal consumption (baseline) and then at 1, 2, and 4 hours postprandially with the percentage of radioactivity remaining in the stomach recorded at the different stages using a computerized software and normalized to the baseline value (t = 0). Gastric emptying is considered delayed if there is >60% retention at 2 hours and/or >10% retention at 4 hours [57] (Fig. 3.1). The emptying half-time can also be calculated by extrapolation using the power exponential curve; however, results would only be accurate if the patient does actually empty at least 50% of the ingested meal at the time of imaging [8].

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Fig. 3.1

Abnormal gastric emptying scintigraphy at 4 hours: 1.0 mCi Tc-99 m sulfur colloid was given orally in a meal consisting of 4 oz Egg Beaters, 1 slice of toast, 30 g jelly, and 4 oz water, consumed over 5–10 minutes with 17% of radioactive material retained at 4 hours (normal <10%)


While a 2-hour GES was previously performed to determine gastric emptying, recent studies have proposed a longer duration of 4 hours for a more reliable assessment [911]. A study comparing a 2–4-hour GES found a 29% increase in the number of abnormal studies at 4 hours compared to 2-hour tests [11]. In preparation for the test, patients are asked to discontinue all medications that could alter gastrointestinal motility for 2–7 days prior to the procedure, including prokinetics, narcotics, anticholinergics, and alcohol. On the day of the test, fasting blood glucose should be <275 mg/dL to prevent the slowing of gastric emptying secondary to hyperglycemia [4].


Strengths


GES is a well-validated diagnostic study endorsed by the American Neurogastroenterology and Motility Society of Nuclear Medicine [4]. The study has been shown to be reproducible in healthy subjects. A recent study looked at the reproducibility of GES in symptomatic patients and found relatively reproducible results with a concordance correlation coefficient ranging between 0.54 (0.34–0.7) and 0.83 (0.75–0.9) for GES studies performed the same day [12]. Another strength of GES is the noninvasive nature of the test and its ability to study both solid and liquid phases of gastric emptying if needed [4].


Limitations


Despite GES being the gold standard to investigate gastric emptying, it still has a few disadvantages. Firstly, despite it being noninvasive, patients are exposed to radiation [4], and GES might not be the test of choice in a pregnant woman, for instance. Second, a solid meal might not be tolerated by patients with severe symptoms [13]. Despite it being validated and endorsed by the American Society of Nuclear Medicine, a Western-style test meal might be unfamiliar to patients of other cultures or ethnicities. For example, some Asian centers have modified their test meal to rice-based meals [13].


Stable Isotope Breath Test


The stable isotope breath test comprises the use of the stable isotope 13carbon (13C) in a substrate, like octanoic acid, a medium-chain fatty acid. The 13C-labeled substrate is then bound to a digestible meal such as a muffin, or spirulina platensis, a blue green algae composed of 50–60% protein, 30% starch, and 10% lipids [14]. After an overnight fast, testing starts by collecting pre-meal breath samples, followed by meal ingestion. Upon meal ingestion and following gastric emptying, 13C-octanoate is absorbed in the duodenum and liquefied to chyme. It is then transported through the portal circulation to the liver where it is metabolized to 13carbon dioxide (13CO2) and exhaled during expiration. Since stomach emptying is the rate limiting step of the testing process described, the amount of 13CO2 in an exhaled breath test is representative of gastric emptying [1517]. Post-meal breath samples are collected every 30 minutes and analyzed by isotope-ratio mass spectrometry. Samples are collected every 30 minutes for a total of 4–6 hours. Some studies recommended at least 6 hours of breath sampling because of possible overestimation of T1/2 by 4-hour breath testing [15, 18, 19]. Similarly to GES, agents altering gastric emptying need to be discontinued 2–7 days prior to testing, smoking and alcohol need to be discontinued on the day of testing, done after an overnight fast [19].


Strengths


Stable isotope breath testing is a safe noninvasive indirect test for measuring gastric emptying. It is cheaper than GES and does not involve any radiation which makes it a safe testing option for pregnant or breast-feeding women. It can be performed in outpatient settings and in the community, as breath samples can be shipped to laboratories for analysis [19]. Moreover, breath testing showed reproducible results correlating with GES findings [15, 18].


Limitations


With the test involving duodenal absorption, 13C metabolism in the liver, and pulmonary exhalation of 13CO2, the test would probably be unreliable in patients with small bowel diseases (i.e., celiac disease), pancreatic exocrine insufficiency, liver disease (i.e., cirrhosis), or lung disease [19, 20]. To note, there has been recent attempts to develop a standardized meal with 13C octanoic acid that could be used in patients with celiac disease or lactose intolerance [21]. Another confounder is physical activity which can influence CO2 excretion [19]. Patients are hence asked to minimize physical activity and walking during the test. While the test is widely used in Europe, its use remains mostly for research purposes in the United States (USA) [22], mostly because of lack of standardized mathematical analysis of results, as well as required study duration and frequency of breath sampling [19].


Wireless Motility Capsule


The wireless motility capsule (WMC) (SmartPill Corporation, Buffalo, NY) has been approved by the US Food and Drug Administration (FDA) for the evaluation of gastric emptying and colonic transit time in patients with suspected slow transit constipation [23]. The capsule measures 26.8 mm in length and 11.7 mm in diameter and comprises three sensors for temperature, pH, and pressure [24]. Once ingested, the WMC records measurements of the three variables continuously as it travels through the gastrointestinal tract, and data is transmitted wirelessly and in real time, to a receiver the patient wears on their waste for the study period. Gastric emptying time is considered delayed if it is 5 hours or greater and is defined as the duration it takes for the capsule to reach to duodenum, determined by an increase in pH by >3 units. Small bowel transit time normally takes 2.5–6 hours and is determined from the time the pH increases by >3 units to the time it drops by >1 unit and is sustained for at least 30 minutes. This drop marks the passage of the capsule to the cecum. Colon transit time (normal if 59 hours or less) is determined from the time the WMC enters cecum until it is expelled from the body, marked by sudden drop in temperature or loss of signal [24]. Testing begins in the morning after an overnight fast. Patients are instructed to refrain from taking medications that would alter gastric emptying 2–3 days prior to the test day. Similarly, acid suppressant medications are held to prevent interfering with the pH measurements of the WMC. Proton pump inhibitors are held 7 days prior and histamine receptor blockers 3 days prior to the procedure. On the day of testing, patients ingest a standardized meal consisting of a nutrient bar: Smartbar® followed by 50 cc of water. Patients fast for the 6 hours following meal consumption. They are asked to push the EVENT button and make entry in diary for certain events for the duration of the study after which the receiver is collected and data is downloaded for analysis [24].


Strengths


WMC is a safe alternative to gastric emptying testing, free of radiation exposure, and need for gamma camera [19]. Recent studies also showed that pressure measurements can further enhance its utility where pressure can be used to distinguish between diabetic gastroparesis characterized by lower number of contractions and motility indices compared to healthy individuals [25]. Another advantage to using WMC in the diagnosis of gastroparesis is the ability to investigate extragastric motility with a single test. This is useful as extragastric impaired motility occurs in >40% of patients with suspected gastroparesis [26] and because gastrointestinal symptoms correlate poorly with the gastrointestinal segment affected [2628]. Investigating the rest of the gastrointestinal tract along with gastric emptying provides insights about motility in the various segments of the gut which can alter management and improve symptoms [26].


Limitations


The WMC is a big capsule that can be challenging to swallow, and its emptying from the stomach might not occur with the physiologic emptying of food [29]. Another limitation is its risk of retention or obstruction. In all reported cases, however, the capsule was amenable to endoscopic retrieval or passed with a prokinetics [19]. WMC testing is approved in patients with suspected slow transit constipation but still not approved by the FDA to investigate gastric motility in isolation. One study compared gastric emptying time using WMC to GES and found a moderate correlation between both studies done concurrently [30]. Hasler et al. expanded on the previous study by looking at liquid emptying but found device agreement of only 52.8% between WMC and nuclear gastric emptying, which implies that further studies are required for WMC validation in patients with suspected gastroparesis [31].


Antroduodenal Manometry


Antroduodenal manometry provides information about gastric and duodenal contractions and consists of inserting a manometry catheter or transducer with pressure sensors into the pyloric channel endoscopically or under radiographic fluoroscopy [7, 32, 33]. Pressure measurements of the antral, pyloric, and duodenal contraction waves are obtained in fasting and postprandial states. The test can be performed over 5–8 hours in a stationary setting or in a 24-hour ambulatory setting with the latter used to characterize duodenal motor function. In gastroparesis, antroduodenal manometry demonstrates a reduced antral motility index [7, 33].


Strengths


Antroduodenal manometry helps distinguish between a myopathic (i.e., scleroderma, amyloidosis) and a neuropathic (i.e., diabetes mellitus) cause of impaired motility. In patients with a myopathic condition, the test exhibits a decreased frequency and a lower amplitude of migrating motor complexes. In patients with a neuropathic etiology of the disease, the migrating motor complexes have a normal amplitude but are poorly coordinated with loss of propagation [4, 33].


Limitations


This test is not readily available and more validation studies are needed [34]. It is an invasive test and requires expertise to perform the procedure and interpret the results. Moreover, it can be technically cumbersome, and the catheter can migrate from the pylorus when the patient is fed and the stomach dilates [35].


Other Imaging Modalities


Transabdominal ultrasonography and magnetic resonance imaging (MRI) have been proposed as noninvasive diagnostic tools for gastroparesis, but their use remains limited to research purposes for reasons discussed below.


Two-dimensional ultrasonography can provide data about gastric emptying by measuring changes in the antral area, and complete gastric emptying is determined once the antral area returns to its preprandial baseline. Three-dimensional ultrasound can add data on meal distribution and volume inside the stomach [36]. Duplex sonography has also been proposed to look at transpyloric flow and liquid contents [4]. While ultrasound seems to be an appealing noninvasive technique, its use remains limited [3] in the clinical setting because of the significant expertise it requires and given poor performance in obese patients [4].


MRI is another appealing tool that can measure gastric accommodation and emptying every 15 minutes using transaxial abdominal images [3]. It can also differentiate gastric meal from air and hence give information about gastric emptying and gastric secretions [37]. It is expensive however, requires specialized equipment, and is not standardized across centers limiting its use to research only, except for some European centers [4, 7].

Aug 15, 2020 | Posted by in GASTROENTEROLOGY | Comments Off on Evaluation of Gastroparesis

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