Updates and new insights into gastroparesis

By Shiyi Liang

Gastroparesis (GP) is a chronic situation when patients suffer from slow and abnormal gastric emptying, which means food could not be passed on to the intestine at normal speed. It is characterised by symptoms of early satiety, bloating, abdominal pain, vomiting, and heartburn.1 Based on a study from Minnesota in 2007, the incidence of GP in males is a quarter of that in females. According to the 222 available case studies of gastroparesis, the incidence per 100,000 person-years in women is 9.8 and 2.4 in men.2 The symptoms of gastroparesis may overlap with other gastrointestinal disorders; therefore, GP is even regarded as an association of other diseases.3 Recently the pathophysiology of gastroparesis has been updated, along with new diagnostic methods and treatments that have been developed – all of which will be discussed in this review.   

Gastroparesis can be idiopathic, diabetic, or postsurgical, and can be caused by other factors with more than 60% of the cases being either idiopathic or diabetic.4 Gastric distention and weaken fundic accommodation reflexes are included in idiopathic gastroparesis pathophysiology.5 Reduced gastric muscle contractility caused by progesterone is thought to be related too.6 Gastroparesis is also found to be associated with diabetic patients. Rok Seon Choung and his team conducted a population-based study on diabetic gastroparesis and identified potential gastroparesis cases that may happen in type I Diabetic Mellitus (DM) and type 2 DM patients using certain indexes and databases. The results showed a 5.2 % cumulative proportion incidence of GP in type 1 DM and 1.0% in type 2 DM, which means GP has a higher risk to type 1 DM patients than to type 2 DM patients.4 There are similarities and differences between idiopathic gastroparesis (IG) and diabetic gastroparesis (DG). They share common symptoms, but some have a higher incidence rate in either IG or DG.7 Diabetic gastroparesis is also considered to happen as a result of vagal nerve dysfunction. A study investigated ghrelin and pancreatic polypeptide responses during sham feeding and meal ingestion in normal subjects and gastroparesis patients show that systemic ghrelin concentration does not increase in either diabetic gastroparesis patients or postsurgical gastroparesis subjects which suggest vagal neuropathy.8

In current studies, neuromuscular abnormalities of gastric motor function are found to be one of the main causes of GP. Gastric peristalsis is controlled by nitrergic neurons, vagal fibres, and intrinsic cholinergic neurons that control gastric antral contraction. Abnormal functioning of these pathways could lead to GP.9 Analysing full-thickness gastric biopsies samples from gastroparetic patients reveals a loss of interstitial cell of Cajal (ICC) and nerve fibres.10

Since GP is often misdiagnosed because of it sharing symptoms with other gastrointestinal diseases, it is more accurate to combine multiple diagnostic test results. Designed questionnaire and a series of physical examinations are used in the initial evaluation stage. Gastroparesis Cardinal Symptom Index is a score rating system collecting the severity of patients. Some physical features can be seen, and it facilitates further diagnosis, for example, dry mucous membranes, eyeball turgor, and resting or orthostatic tachycardia. Blood samples are also taken to analyse specific serological components, e.g., electrolytes and markers.11

Gastric emptying scintigraphy (GES) is a traditional assessment of gastric emptying. Patients are provided with a technetium-99-labelled meal and serial gamma camera scans are taken.9,11 Diagnostic methods have drawback, including the lack of standardization of criteria when performing gastric scintigraphies.11 Choices of meal contents, variability of the image timing, and other parameters are not standardized, which lead to differences in results and difficulties in interpreting them.

Wireless motility capsules are a newly approved diagnostic method for gastric emptying which requires a 2.6 mm diameter ingestible capsule and a receiver. After swallowing the capsule, records of temperature, pH, and pressure will be transmitted to the receiver.9 The information is used to reflect gastric movement and further determinate gastric empty time, small bowel transit time, and colon transit time. The testing period usually lasts for 3-5 days, and abnormal values are when the gastric emptying time is longer than 5 hours.12

Treatment of GP varies according to the severity of the patient with aims to reduce symptom expression. Mild patients might receive diet and nutritional support while severe patients would require assistance from a pharmacological approach or even surgical strategies.

The nutrition approach usually provides patients with well-designed small meals with limited contents that delay gastric emptying, such as fat and fibre, and supplied with vitamins and advised to avoid alcohol and smoking.13 

Pharmacological therapies include prescribing prokinetics drugs and antiemetic agents. Antidopaminergic agents, such as metoclopramide and domperidone, are dopamine receptor antagonists, which decrease delayed emptying. However, serious side effects range from extrapyramidal effects to delayed ventricular repolarisation (QT prolongation), so patients must strictly follow their prescription. Erythromycin and cisapride are examples of motilin agonists used, alongside 5-hydroxytrptamine receptor 4 (5HT4) agonists which can also be used. These two examples both increase antral contraction and increase gastric emptying. However, erythromycin is replaced by tegaserod and velusetrag, two other 5HT4 receptor agonists, due to cardiac arrhythmias as one of the side effects.9 

Currently, not much is known about GP and patients often have impaired life qualities. There are still lots of limitations in the recent understanding of the pathophysiology and treatments, alongside treatments and diagnostic methods not discussed in this review. Further investigation should be focused on updated treatments and improvements. 

References:

  1. NHS. Gastroparesis. Available from: https://www.nhs.uk/conditions/gastroparesis/ [Accessed 25th October 2021]
  2. Jung H, Choung R, Locke G, Schleck C, Zinsmeister A, Szarka L et al. The Incidence, Prevalence, and Outcomes of Patients With Gastroparesis in Olmsted County, Minnesota, From 1996 to 2006. Gastroenterology. 2009;136(4):1225-1233. Available from: doi:10.1053/j.gastro.2008.12.047
  • Stanghellini V, Tack J. Gastroparesis: separate entity or just a part of dyspepsia? Gut. 2014;63(12):1972-1978. Available from: doi:10.1136/gutjnl-2013-306084
  • Choung R, Locke R, Schleck C, Zinsmeister A, Melton J, Talley N. Risk of Gastroparesis in Subjects With Type 1 and 2 Diabetes in the General Population. Am J Gastroenterol. 2012;107(1):82-88. Available from: doi:10.1038/ajg.2011.310
  • Hasler W. Gastroparesis. Curr Opin Gastroenterol. 2012;28(6):621-628. Available from: doi: 10.1097/MOG.0b013e328358d619
  • Ali T, Hasan M, Hamadani M, Harty R. Gastroparesis. South Med J. 2007;100(3):281-286. Available from: doi: 10.1097/SMJ.0b013e31802f3795
  • Parkman H, Yates K, Hasler W, Nguyen L, Pasricha P, Snape W et al. Similarities and Differences Between Diabetic and Idiopathic Gastroparesis. Clin Gastroenterol Hepatol. 2011;9(12):1056-1064. Available from: doi:10.1016/j.cgh.2011.08.013
  • Gaddipati K, Simonian H, Kresge K, Boden G, Parkman H. Abnormal Ghrelin and Pancreatic Polypeptide Responses in Gastroparesis. Dig Dis Sci. 2006;51(8):1339-1346. Available from: doi:10.1007/s10620-005-9022-z
  • Usai-Satta P, Bellini M, Morelli O, Geri F, Lai M, Bassotti G. Gastroparesis: New insights into an old disease. World J Gastroenterol. 2020;26(19):2333-2348. Available from: doi:10.3748/wjg.v26.i19.2333
  1. Grover M, Farrugia G, Lurken M, Bernard C, Faussone–Pellegrini M, Smyrk T et al. Cellular Changes in Diabetic and Idiopathic Gastroparesis. Gastroenterology. 2011;140(5):1575-1585.e8. Available from: doi:10.1053/j.gastro.2011.01.046
  1. Hasler W. Gastroparesis: Symptoms, Evaluation, and Treatment. Gastroenterol Clin North Am. 2007;36(3):619-647. Available from: doi:10.1016/j.gtc.2007.07.004
  1. Saad R. The Wireless Motility Capsule: a One-Stop Shop for the Evaluation of GI Motility Disorders. Curr Gastroenterol Rep. 2016;18(3):14. Available from: doi:10.1007/s11894-016-0489-x
  1. Camilleri M. Novel Diet, Drugs, and Gastric Interventions for Gastroparesis. Clin Gastroenterol Hepatol. 2016;14(8):1072-1080. Available from: doi:10.1016/j.cgh.2015.12.033

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