Gastric Motility Disorders




Gastric Motor Physiology


The stomach is a muscular hollow organ that is functionally divided into proximal and distal regions, each serving a distinct purpose. The fundus and a portion of the gastric body constitute the proximal stomach, which serves as a reservoir for ingesta. This function is accomplished through a combination of receptive and adaptive relaxation. Receptive relaxation is mediated by a vagovagal reflex and allows the fundus to expand upon swallowing and esophageal distension. Adaptive relaxation occurs upon arrival of the ingesta in the stomach, which leads to activation of stretch-sensitive mechanoreceptors in the gastric wall, triggers nitric oxide release from nitrergic neurons, and results in fundic relaxation. Through these two mechanisms the stomach can increase compliance and reduce gastric tone during meals to accommodate food without significantly increasing intragastric pressure. The distal stomach (consisting of the distal gastric body, antrum, and pylorus) then triturates the gastric contents via antral grinding and pyloric contraction, for eventual transfer into the small intestine where further digestion and absorption take place.


Although the proximal stomach demonstrates tonic contractile activity, the smooth musculature in the distal stomach exhibits rhythmic electrical activity. These oscillations in membrane potential are known as “slow waves” and occur at a frequency of approximately three cycles per minute. They originate from the pacemaker region in the stomach, located in the gastric body, and are generated by the interstitial cells of Cajal. If the membrane depolarization reaches a certain threshold, a contraction is triggered. The greater the amplitude of the slow wave, the greater the force of contraction. The strength and duration of these contractions are modulated by “spike potentials,” which are rapid fluctuations in membrane potential superimposed on the crest of the slow wave. Spike potentials do not accompany every slow wave, but instead depend on neurohumoral input related to the digestive state.


In the fasting period, the proximal gastrointestinal tract demonstrates a cyclical motor pattern known as the migrating motor complex (MMC). The MMC consists of three different phases: phase I is characterized by motor quiescence; phase II displays irregular activity consisting of random intermittent contractions of variable amplitude; and phase III consists of rhythmic, repetitive, high-amplitude contractions at the maximal frequency for the location (3 to 4 contractions per minute in the stomach; 10 to 12 per minute in the small intestine). Some authors have assigned the term phase IV to the period during which the contractile activity returns to baseline after phase III.


The phase III myoelectrical activity front ( Figure 28-1 ) can originate from either the antrum or the small intestine, and propagates distally toward the ileum. The interval between phase III can range from every 40 minutes in young infants to 2.5 hours in adults; in children, it occurs approximately every 100 minutes. The role of the MMC is to evacuate indigestible particles from the stomach and small intestine, as well as clear bacteria from the small bowel. It is present in 95% of normal children within a 4-hour window and is an indicator of gastrointestinal neuromuscular integrity. Its absence predicts the need for parenteral nutrition, a poor response to prokinetics, and the development of small intestinal bacterial overgrowth.




Figure 28-1


(A) Phase III of the migrating motor complex (MMC) originating from the antrum during fasting; ( B) transition from phase I fasting activity to a postprandial or “fed” motility pattern.


Approximately 5 to 10 minutes after food is ingested, the MMC is suppressed for at least 2 hours, and the motility of the upper gastrointestinal tract switches to a fed or postprandial pattern ( Figure 28-1 ). This pattern of motor activity consists of intermittent contractions of variable amplitude, some of which are propagating. Circular peristaltic waves originating from the pacemaker region propagate from the mid-body toward the pylorus. During each contraction, larger particles are directed retrograde because of frictional forces against the gastric wall for repeated antral grinding until they are processed to an appropriately reduced size for exit into the duodenum.


Gastric emptying is influenced by multiple factors ( Table 28-1 ), although caloric content is the primary determinant, to allow adequate time for maximal intestinal absorption. The rate of gastric emptying is normally regulated to titrate approximately 2.5 kcal/min into the small intestine. Liquid emptying occurs via first-order kinetics and, as such, occurs more rapidly than solids, as it is not subject to a lag phase.



TABLE 28-1

FACTORS THAT INFLUENCE THE RATE OF GASTRIC EMPTYING
























Slow Gastric Emptying Accelerate Gastric Emptying
Gastric content Solids
Lipids
↑ Osmolar load
↑ Caloric density
↑ Gastric pH
Hot temperature
Hormones GLP-1
Leptin
Cholecystokinin
Peptide YY
Melatonin
Motilin
Ghrelin
Medications µ-Receptor agonists
α2-Adrenergic agonists
Anticholinergics
Proton pump inhibitors
H2 receptor antagonists
Motilin agonists
Ghrelin agonists
5-HT 4 agonists
Dopamine agonists
Acetylcholinesterase inhibitors
Miscellaneous Hyperglycemia
Colorectal distension
Stress
Exercise
Hypoglycemia




Evaluation of Gastric Motor and Sensory Disorders


Gastric Emptying Scintigraphy


Gastric emptying scintigraphy is considered the standard method to assess gastric emptying. Prior to the test, patients fast for a minimum of 6 hours and are instructed to discontinue any medications that may either enhance or impair gastric emptying, such as prokinetics, opioids, and anticholinergic antispasmodics. The standard meal used to assess solid-phase emptying consists of a low-fat egg substitute radiolabeled with technetium-99m, two slices of white bread, jam, and water. Concurrent liquid gastric emptying is not routinely performed, as it has been shown to correlate well with solid emptying but not with symptoms of gastroparesis. Image acquisition occurs immediately after meal ingestion, and then at a minimum of 1, 2, and 4 hours afterward. A diagnosis of delayed gastric emptying is established if there is greater than 60% meal retention at 2 hours, or greater than 10% at 4 hours ( Figure 28-2 ).




Figure 28-2


Normal solid-phase gastric emptying at ( A) 2 hours and ( B) 4 hours; Example of delayed gastric emptying at ( C) 2 hours and ( D) 4 hours.


Ultrasonography


Ultrasonography is a technique free of ionizing radiation that can be used to estimate whole stomach and antropyloric volume, antral area, and transpyloric flow during fasting and fed states. Functional three-dimensional (3-D) ultrasonography allows the simultaneous determination of gastric emptying and gastric accommodation. However, it is technically demanding, and measures only liquid emptying, which has limited its use in clinical practice.


Magnetic Resonance Imaging (MRI)


MRI is a validated, noninvasive method of evaluating gastric emptying without any radiation burden. It can assess gastric emptying of any type of meal and has excellent correlation with scintigraphic techniques. The long procedural times, need for patients to remain stationary in a supine position, and cost of each study have restricted its use in clinical practice.


13 C Breath Testing


Breath testing is an easy to perform, noninvasive technique that assesses gastric emptying of solids or liquids using a meal containing a stable isotope bound to a medium chain fatty acid ( 13 C-octanoic acid). This isotope is retained in the solid phase of the meal; after absorption in the small intestine, it undergoes oxidation in the liver and can be measured as 13 CO 2 in breath samples. Interpretation of the results is based on assumed normal small bowel, pulmonary, pancreatic, and liver function.


Single Photon Emission Computed Tomography


Single photon emission computed tomography (SPECT) is a scintigraphic technique used to detect changes in postprandial gastric volumes. Intravenously administered 99m Tc pertechnetate is taken up by the gastric mucosa, and a 3-D reconstruction of images taken with a SPECT gamma camera provides a measure of total gastric volume. SPECT has been validated for the measurement of gastric volumes in comparison with the barostat as the gold standard, and has been used in the investigation of adolescents with functional dyspepsia.


Nutrient Drinking Test


The nutrient drinking test was conceived as a surrogate marker of gastric accommodation to differentiate healthy individuals from those with functional dyspepsia. It is based on the assumption that impaired accommodation results in a limited gastric volume capacity, which is reflected in the maximum tolerated ingested volume of a liquid meal of known caloric content after an overnight fast. Normal values for children aged 5 to 15 years have been determined. Comparison with gastric volume measurements by SPECT has shown poor agreement, questioning its utility as a marker of gastric volume.


Wireless Motility Capsule


The wireless motility capsule (WMC) is a nondigestible capsule that is orally ingested and measures intraluminal pH, temperature, and pressure as it travels through the gastrointestinal tract. Changes in pH are the primary method of calculating segmental and whole gut transit times, although the use of additional parameters to improve accuracy has been suggested. Gastric-emptying time measured by WMC correlates with gastric emptying scintigraphy at 4 hours, and the capsule is well tolerated in children as young as 9 years of age.


Antroduodenal Manometry


Antroduodenal manometry (ADM) is used to evaluate motility patterns of the proximal digestive tract by measuring intraluminal pressure. Water-perfused manometry systems are the preferred modality of choice for children. The manometry catheters used are made of silicone or flexible polyvinyl chloride (PVC) with recording ports incorporated along the length of the catheter at customizable intervals. These recording ports consist of an open lumen that is connected to a pneumohydraulic perfusion pump that provides a constant flow of water. Any resistance to flow due to lumen-occluding contractions is recorded as a change in pressure that is detected by external transducers and shown on a computer display. By having several sensors along the length of the catheter, propagating and nonpropagating contractile activity can be measured ( Figure 28-1 ). Among its various clinical uses in functional and motility disorders, ADM has been used to characterize the pathophysiology of gastroparesis and responsiveness to prokinetic therapy. Because of the way the pneumohydraulic system is set up, water-perfused ADM studies are generally nonambulatory and limited to 6 to 8 hours in duration. It is also an invasive procedure, although most patients become accustomed to the indwelling catheter and are able to complete the study. Depending on the perfusion pressure and number of recording ports, the water-load associated with these studies can be significant, and caution must be exercised, particularly in younger patients or those with underlying electrolyte, cardiac, or renal disturbances.


Electrogastrogram


Electrogastrogram (EGG) is a noninvasive method that allows recording of myoelectric activity of the stomach through cutaneous electrodes positioned on the skin in the upper abdomen. Although EGG provides an attractive means of detecting abnormalities in electric rhythm that are associated with disturbed gastric function, the interpretation and clinical utility of this technique remain debatable.


Barostat


Gastric barostat is the gold standard test for the assessment of fundic relaxation in response to a meal. The technique involves the intubation of the esophagus and advancement of a PVC catheter with a deflated plastic or latex balloon into the stomach. The tube is connected to the barostat device, which permits isobaric expansion of the gastric balloon. As the intraballoon pressure is fixed, changes in intraballoon volume reflect changes in tone due to gastric relaxation or contraction. Accommodation is assessed by measuring and comparing intragastric volumes during fasting and postprandial periods, and impairment has been demonstrated in up to 40% of patients with functional dyspepsia. Sensitivity to gastric distension can also be assessed and lower thresholds of discomfort have been identified in adolescents with functional abdominal pain. A major limitation to routine clinical use of the barostat in children is the invasive nature of the study; consequently, it is primarily a research tool in pediatrics.




Rumination Syndrome


Rumination syndrome is a clinical condition characterized by the effortless regurgitation of recently ingested food or liquid that is then either expelled or re-swallowed. It has been described in all age groups, ranging from infancy to adolescence and beyond, with differing etiopathology dependent on the age of presentation. Although originally described mostly in individuals with cognitive developmental delay, it is now more frequently observed in individuals of normal intelligence.


Infancy


The published literature on infantile rumination syndrome demonstrates a male predominance. The age of presentation is typically between 3 and 8 months. Characteristically, rumination syndrome develops in response to a dysfunctional relationship with the primary caregiver. This may occur for several reasons including underlying psychosocial issues that affect the caregiver, relative immaturity of the caregiver or inexperience, or because the situation does not allow for normal caregiver–infant bonding as in the case of critically ill infants admitted to the intensive care unit. As a consequence, there is an absent or underdeveloped emotional connection between the caregiver and infant, which is insufficient in satisfying the infant’s needs. In response, the infant learns to regurgitate gastric contents, which is a self-stimulatory and gratifying behavior. When a significant amount of the ruminated contents are expelled rather than re-swallowed, progressive weight loss, failure to thrive, and even death may occur. Characteristically, symptoms are present when the infant is awake and left on his or her own, but absent during sleep or periods of interaction with engaging objects or persons in the infant’s environment. Typically, there is no improvement with treatment for gastroesophageal reflux (GER) including thickened feeds, upright positioning, formula changes, anticholinergic medications, or nasogastric feeds. The diagnostic criteria for infantile rumination syndrome are outlined in the Rome III guidelines ( Table 28-2 ). Treatment is directed at both the infant and primary caregiver. A temporary caregiver substitute provides the needed care and comfort required to nurture the infant, and engages the infant when rumination behavior is observed in order to abolish the learned behavior. Simultaneously, the infant’s primary caregiver is taught how to recognize and respond to the infant’s physical and emotional needs. The recurrence of symptoms after resolution is uncommon, although it has been described.



TABLE 28-2

DIAGNOSTIC CRITERIA FOR RUMINATION SYNDROME

As adapted from Hyman PE, Milla PJ, Benninga MA, et al. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology 2006; 130 (5):1519–26.










Infant Rumination Syndrome Adolescent Rumination Syndrome
All of the following features for ≥3 months:



  • Repetitive contractions of the abdominal wall, diaphragm, and tongue



  • Regurgitation of gastric contents that are then either expelled, re-chewed, or re-swallowed


AND
At least 3 or more of the following:



  • Onset between 3 and 8 months of age



  • No improvement after treatment for gastroesophageal reflux, anticholinergic medications, dietary modification, enteral feeding, or hand restraints



  • Nondistressing to the infant



  • Does not occur during sleep or when infant is interacting with individuals

All of the following features for ≥2 months:



  • Repetitive painless regurgitation and re-swallowing or expulsion of food that:




    • Occurs shortly after meal ingestion



    • Does not occur during sleep



    • Does not respond to standard therapies for gastroesophageal reflux




  • No retching



  • No alternative inflammatory, anatomic, metabolic, or neoplastic conditions that could explain the patient’s symptoms


Rasquin A, Di Lorenzo C, Forbes D, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2006; 130 (5):1527–37.


Childhood and Adolescence


Rumination syndrome in childhood and adolescence is a vastly underappreciated condition. It is often confused with other clinical entities such as gastroesophageal reflux disease (GERD), gastrointestinal dysmotility, or eating disorders. Consequently, patients are usually subjected to extensive unnecessary testing, and it is common to have a delay in diagnosis of more than one year after symptom onset. Similar to adult data, rumination syndrome is more common in females during childhood and adolescence. Estimates have suggested a prevalence of 5.1% to 10.9% across all age groups and levels of cognitive ability.


Various precipitating events may promote the learned behavior of rumination. Stress is the most commonly described trigger: a personal history of a physically or emotionally traumatizing event such as a death in the family or parental divorce; a change in the home or social routine; or acute situational stress. Preceding viral gastroenteritis, coexisting psychiatric disorders, or an eating disorder are other cited precipitants of rumination syndrome.


The mechanism by which rumination occurs has been well described. Episodes of rumination begin with an increase in intraabdominal pressure, which is generated by voluntary but often unintentional abdominal wall contraction. The resultant rise in intragastric pressure may precede the retrograde reflux of gastric contents toward the esophagus when it exceeds the resting pressure of the lower esophageal sphincter (LES), or occurs following a transient LES relaxation. Upward displacement of the larynx and relaxation of the upper esophageal sphincter facilitate the retrograde passage of the gastric contents into the mouth. The regurgitated material is then either masticated and re-swallowed, or expelled from the mouth.


Recently the use of combined high-resolution impedance manometry has helped to further characterize the underlying mechanisms of rumination and provided an explanation for the different phenotypes observed. Primary rumination events are the most common and occur when abdominal pressure increases prior to the onset of retrograde flow into the esophagus. In secondary rumination events, GER precedes the onset of gastric strain and may reflect an involuntary reaction to noxious stimuli in the esophagus. Supragastric belch-associated rumination represents the third pattern of rumination. In this variant, rumination occurs as a result of the antecedent influx of air into the esophageal body and its subsequent expulsion during the supragastric belch sequence. At present, classifying the underlying mechanism of rumination into these subtypes is primarily of academic interest. However, it is possible this information could be used to direct therapy toward the underlying pathophysiology specific to the patient’s rumination phenotype.


Several features can help to differentiate rumination syndrome from similar conditions. One of the hallmarks of rumination is that it is an effortless process in the majority of patients. A report of retching should prompt consideration of an alternative diagnosis. Rumination also typically begins within 10 to 30 minutes after starting a meal, which is in contrast to the time delay between meals and vomiting observed in gastroparetics and GERD. Symptoms of nausea, abdominal pain, bloating, and heartburn may precede or accompany the episode, and the patient may continue to ruminate for up to an hour or beyond. The behavior occurs primarily in association with meals and generally abates at night. Weight loss is common and can be severe, with a median weight loss ranging from 7 to 12 kg reported in pediatric studies. Psychiatric comorbidities such as affective or somatoform disorders are also frequently encountered in this population and can be identified in up to 50% patients.


The most important factor in establishing the diagnosis of rumination syndrome is recognizing the classic presentation ( Table 28-2 ). Adjunctive tests such as antroduodenal manometry and impedance-manometry testing can help to confirm the diagnosis or convince skeptical families or patients. Antroduodenal manometry can demonstrate the characteristic “R-waves” that reflect the simultaneous pressure increases across all sensors as a manifestation of abdominal wall muscle contraction, but may be absent when the patient avoids vomiting during the test. Criteria for the diagnosis of rumination syndrome by combined impedance-manometry has recently been proposed but requires further validation. Other diagnostic modalities such as endoscopy, electrogastrography, and radiographic imaging are either normal, or may identify mild changes that would not completely explain the patient’s presentation. Practitioners must be cautious about interpreting some of the subtle abnormalities that may be encountered during the course of investigations. For example, delayed gastric emptying can be observed on scintigraphy studies. However, the finding may result from ongoing rumination with delayed delivery of the radiolabeled meal to the antrum, thereby prolonging the gastric emptying time in the absence of true gastric motor dysfunction. Furthermore, if a substantial amount of the meal is expelled during rumination, the test results cannot be properly interpreted. Without combined manometry, standard reflux testing is not a high-yield investigation and should be avoided; multiple reflux events will be observed during rumination primarily because of the abdominal wall contraction and not a primary abnormality of the esophagogastric junction. Although reflux testing could reveal a pattern of gastroesophageal reflux occurring almost immediately with the onset of meals and an absence of symptoms overnight, these findings could be obtained more simply and less invasively with a careful patient history.


Behavioral intervention is the cornerstone of treating rumination syndrome. Because abdominal wall contraction initiates the series of events leading to rumination, diaphragmatic breathing is a key component of the behavioral therapy. In this technique, patients are taught to take inspiratory and expiratory breaths using the abdominal wall muscles while keeping the chest motionless. Breathing in this fashion while eating interferes with abdominal wall muscle contraction. This technique has been shown to be effective in patients as young as 6 years of age.


Diaphragmatic breathing is often combined with other behavioral treatment including biofeedback, relaxation or distraction techniques, and/or cognitive behavioral therapy. This multimodal approach has been shown to be highly effective in improving symptoms of patients with rumination syndrome. Gum chewing also seems to reduce the frequency of rumination in children, and this technique can be applied to those with cognitive delays as well. Another potential therapy in the latter population involves tactile stimulation by holding, which appeared to have lasting treatment effects in single-subject experimental studies.


Psychological evaluation should be considered early in the course of management to help identify any mental health or eating disorders that could be barriers to successful treatment. Temporary nutritional support in the form of enteral feeds or parenteral nutrition may be required. Pharmacotherapy generally plays a minor role in the management of rumination syndrome and is usually directed toward the treatment of comorbid symptoms such as sleep disturbances, headaches, and nausea. However, a study that examined the effectiveness of baclofen, a γ-aminobutyric acid (GABA) B receptor agonist that increases lower esophageal sphincter pressure and decreases transient lower esophageal sphincter relaxations, suggested that it could be a useful treatment option.


Fundoplication has been used to treat rumination syndrome and was successful in resolving symptoms in a small study cohort. However, no long-term outcomes were reported and the potential complications of fundoplication including dysphagia, gastric hypersensitivity, gas-bloat, dumping syndrome, gastroparesis, and reoperation must be weighed against the other less invasive therapies that may be equally efficacious.


If untreated, rumination syndrome can have severe consequences including dental erosions, school or work absenteeism, dehydration, weight loss requiring nutritional support, sepsis, and hospitalization. Although there are limited outcome data reported for both adult and pediatric rumination syndrome, most patients respond favorably to behavioral intervention.




Rumination Syndrome


Rumination syndrome is a clinical condition characterized by the effortless regurgitation of recently ingested food or liquid that is then either expelled or re-swallowed. It has been described in all age groups, ranging from infancy to adolescence and beyond, with differing etiopathology dependent on the age of presentation. Although originally described mostly in individuals with cognitive developmental delay, it is now more frequently observed in individuals of normal intelligence.


Infancy


The published literature on infantile rumination syndrome demonstrates a male predominance. The age of presentation is typically between 3 and 8 months. Characteristically, rumination syndrome develops in response to a dysfunctional relationship with the primary caregiver. This may occur for several reasons including underlying psychosocial issues that affect the caregiver, relative immaturity of the caregiver or inexperience, or because the situation does not allow for normal caregiver–infant bonding as in the case of critically ill infants admitted to the intensive care unit. As a consequence, there is an absent or underdeveloped emotional connection between the caregiver and infant, which is insufficient in satisfying the infant’s needs. In response, the infant learns to regurgitate gastric contents, which is a self-stimulatory and gratifying behavior. When a significant amount of the ruminated contents are expelled rather than re-swallowed, progressive weight loss, failure to thrive, and even death may occur. Characteristically, symptoms are present when the infant is awake and left on his or her own, but absent during sleep or periods of interaction with engaging objects or persons in the infant’s environment. Typically, there is no improvement with treatment for gastroesophageal reflux (GER) including thickened feeds, upright positioning, formula changes, anticholinergic medications, or nasogastric feeds. The diagnostic criteria for infantile rumination syndrome are outlined in the Rome III guidelines ( Table 28-2 ). Treatment is directed at both the infant and primary caregiver. A temporary caregiver substitute provides the needed care and comfort required to nurture the infant, and engages the infant when rumination behavior is observed in order to abolish the learned behavior. Simultaneously, the infant’s primary caregiver is taught how to recognize and respond to the infant’s physical and emotional needs. The recurrence of symptoms after resolution is uncommon, although it has been described.



TABLE 28-2

DIAGNOSTIC CRITERIA FOR RUMINATION SYNDROME

As adapted from Hyman PE, Milla PJ, Benninga MA, et al. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology 2006; 130 (5):1519–26.










Infant Rumination Syndrome Adolescent Rumination Syndrome
All of the following features for ≥3 months:



  • Repetitive contractions of the abdominal wall, diaphragm, and tongue



  • Regurgitation of gastric contents that are then either expelled, re-chewed, or re-swallowed


AND
At least 3 or more of the following:



  • Onset between 3 and 8 months of age



  • No improvement after treatment for gastroesophageal reflux, anticholinergic medications, dietary modification, enteral feeding, or hand restraints



  • Nondistressing to the infant



  • Does not occur during sleep or when infant is interacting with individuals

All of the following features for ≥2 months:



  • Repetitive painless regurgitation and re-swallowing or expulsion of food that:




    • Occurs shortly after meal ingestion



    • Does not occur during sleep



    • Does not respond to standard therapies for gastroesophageal reflux




  • No retching



  • No alternative inflammatory, anatomic, metabolic, or neoplastic conditions that could explain the patient’s symptoms


Rasquin A, Di Lorenzo C, Forbes D, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2006; 130 (5):1527–37.


Childhood and Adolescence


Rumination syndrome in childhood and adolescence is a vastly underappreciated condition. It is often confused with other clinical entities such as gastroesophageal reflux disease (GERD), gastrointestinal dysmotility, or eating disorders. Consequently, patients are usually subjected to extensive unnecessary testing, and it is common to have a delay in diagnosis of more than one year after symptom onset. Similar to adult data, rumination syndrome is more common in females during childhood and adolescence. Estimates have suggested a prevalence of 5.1% to 10.9% across all age groups and levels of cognitive ability.


Various precipitating events may promote the learned behavior of rumination. Stress is the most commonly described trigger: a personal history of a physically or emotionally traumatizing event such as a death in the family or parental divorce; a change in the home or social routine; or acute situational stress. Preceding viral gastroenteritis, coexisting psychiatric disorders, or an eating disorder are other cited precipitants of rumination syndrome.


The mechanism by which rumination occurs has been well described. Episodes of rumination begin with an increase in intraabdominal pressure, which is generated by voluntary but often unintentional abdominal wall contraction. The resultant rise in intragastric pressure may precede the retrograde reflux of gastric contents toward the esophagus when it exceeds the resting pressure of the lower esophageal sphincter (LES), or occurs following a transient LES relaxation. Upward displacement of the larynx and relaxation of the upper esophageal sphincter facilitate the retrograde passage of the gastric contents into the mouth. The regurgitated material is then either masticated and re-swallowed, or expelled from the mouth.


Recently the use of combined high-resolution impedance manometry has helped to further characterize the underlying mechanisms of rumination and provided an explanation for the different phenotypes observed. Primary rumination events are the most common and occur when abdominal pressure increases prior to the onset of retrograde flow into the esophagus. In secondary rumination events, GER precedes the onset of gastric strain and may reflect an involuntary reaction to noxious stimuli in the esophagus. Supragastric belch-associated rumination represents the third pattern of rumination. In this variant, rumination occurs as a result of the antecedent influx of air into the esophageal body and its subsequent expulsion during the supragastric belch sequence. At present, classifying the underlying mechanism of rumination into these subtypes is primarily of academic interest. However, it is possible this information could be used to direct therapy toward the underlying pathophysiology specific to the patient’s rumination phenotype.


Several features can help to differentiate rumination syndrome from similar conditions. One of the hallmarks of rumination is that it is an effortless process in the majority of patients. A report of retching should prompt consideration of an alternative diagnosis. Rumination also typically begins within 10 to 30 minutes after starting a meal, which is in contrast to the time delay between meals and vomiting observed in gastroparetics and GERD. Symptoms of nausea, abdominal pain, bloating, and heartburn may precede or accompany the episode, and the patient may continue to ruminate for up to an hour or beyond. The behavior occurs primarily in association with meals and generally abates at night. Weight loss is common and can be severe, with a median weight loss ranging from 7 to 12 kg reported in pediatric studies. Psychiatric comorbidities such as affective or somatoform disorders are also frequently encountered in this population and can be identified in up to 50% patients.


The most important factor in establishing the diagnosis of rumination syndrome is recognizing the classic presentation ( Table 28-2 ). Adjunctive tests such as antroduodenal manometry and impedance-manometry testing can help to confirm the diagnosis or convince skeptical families or patients. Antroduodenal manometry can demonstrate the characteristic “R-waves” that reflect the simultaneous pressure increases across all sensors as a manifestation of abdominal wall muscle contraction, but may be absent when the patient avoids vomiting during the test. Criteria for the diagnosis of rumination syndrome by combined impedance-manometry has recently been proposed but requires further validation. Other diagnostic modalities such as endoscopy, electrogastrography, and radiographic imaging are either normal, or may identify mild changes that would not completely explain the patient’s presentation. Practitioners must be cautious about interpreting some of the subtle abnormalities that may be encountered during the course of investigations. For example, delayed gastric emptying can be observed on scintigraphy studies. However, the finding may result from ongoing rumination with delayed delivery of the radiolabeled meal to the antrum, thereby prolonging the gastric emptying time in the absence of true gastric motor dysfunction. Furthermore, if a substantial amount of the meal is expelled during rumination, the test results cannot be properly interpreted. Without combined manometry, standard reflux testing is not a high-yield investigation and should be avoided; multiple reflux events will be observed during rumination primarily because of the abdominal wall contraction and not a primary abnormality of the esophagogastric junction. Although reflux testing could reveal a pattern of gastroesophageal reflux occurring almost immediately with the onset of meals and an absence of symptoms overnight, these findings could be obtained more simply and less invasively with a careful patient history.


Behavioral intervention is the cornerstone of treating rumination syndrome. Because abdominal wall contraction initiates the series of events leading to rumination, diaphragmatic breathing is a key component of the behavioral therapy. In this technique, patients are taught to take inspiratory and expiratory breaths using the abdominal wall muscles while keeping the chest motionless. Breathing in this fashion while eating interferes with abdominal wall muscle contraction. This technique has been shown to be effective in patients as young as 6 years of age.


Diaphragmatic breathing is often combined with other behavioral treatment including biofeedback, relaxation or distraction techniques, and/or cognitive behavioral therapy. This multimodal approach has been shown to be highly effective in improving symptoms of patients with rumination syndrome. Gum chewing also seems to reduce the frequency of rumination in children, and this technique can be applied to those with cognitive delays as well. Another potential therapy in the latter population involves tactile stimulation by holding, which appeared to have lasting treatment effects in single-subject experimental studies.


Psychological evaluation should be considered early in the course of management to help identify any mental health or eating disorders that could be barriers to successful treatment. Temporary nutritional support in the form of enteral feeds or parenteral nutrition may be required. Pharmacotherapy generally plays a minor role in the management of rumination syndrome and is usually directed toward the treatment of comorbid symptoms such as sleep disturbances, headaches, and nausea. However, a study that examined the effectiveness of baclofen, a γ-aminobutyric acid (GABA) B receptor agonist that increases lower esophageal sphincter pressure and decreases transient lower esophageal sphincter relaxations, suggested that it could be a useful treatment option.


Fundoplication has been used to treat rumination syndrome and was successful in resolving symptoms in a small study cohort. However, no long-term outcomes were reported and the potential complications of fundoplication including dysphagia, gastric hypersensitivity, gas-bloat, dumping syndrome, gastroparesis, and reoperation must be weighed against the other less invasive therapies that may be equally efficacious.


If untreated, rumination syndrome can have severe consequences including dental erosions, school or work absenteeism, dehydration, weight loss requiring nutritional support, sepsis, and hospitalization. Although there are limited outcome data reported for both adult and pediatric rumination syndrome, most patients respond favorably to behavioral intervention.




Gastroparesis


Gastroparesis is a disorder characterized by delayed gastric emptying without evidence of mechanical obstruction. There are few descriptions of its prevalence in both the adult and pediatric populations, perhaps owing to a lack of recognition of the condition and its presentation by clinicians. Based on published pediatric studies, the mean age of presentation in children ranges from 7.9 to 9 years. There appears to be a similar distribution among males and females in childhood, with a shift toward an increasing female predominance later in adolescence.


Gastric motor function is dependent on the integrity of the digestive tract anatomy, vagus nerve signaling, neurohumoral reflexes, and small intestinal motility. A disruption in any of these pathways can lead to delayed gastric emptying. Several pathologic findings have been observed in full-thickness gastric biopsies from gastroparetic adults in comparison to age- and gender-matched controls. These include morphologically abnormal myocytes, neuronal bodies and pacemaker cells (interstitial cells of Cajal [ICCs]); reduced numbers of neurons and ICCs; basal lamina thickening; fibrosis; and inflammatory infiltrates in the myenteric layer. The clinical significance of these findings has yet to be fully elucidated.


The majority of children with delayed gastric emptying are classified as having idiopathic gastroparesis. Drug-related gastroparesis represents the next most common cause in children. Medications that can inhibit gastric emptying (see Table 28-1 ) include µ-receptor agonists, α2-adrenergic agonists, anticholinergics, proton pump inhibitors, and histamine-2 (H2) receptor antagonists.


Postinfectious gastroparesis is occasionally listed as a subset of idiopathic gastroparesis. Multiple viruses have been associated with postviral gastroparesis, including rotavirus, Epstein-Barr virus, and cytomegalovirus. However, the diagnosis is often established based solely on history without isolating a specific strain.


Diabetic gastroparesis is traditionally considered an adult-onset disease, because autonomic neuropathy is not believed to occur until at least 10 years after disease onset. However, chronically impaired glycemic control and its impact on gastric function may help to explain the pathogenesis underlying the high prevalence of gastric motor disorders observed in children with insulin-dependent diabetes mellitus. The most common motor abnormality described in pediatric gastroparesis is postprandial antral hypomotility. The median age of presentation in this particular population ranges from 11.6 to 15 years old, with the youngest reported patient 5 years of age.


Postsurgical gastroparesis typically occurs due to vagus nerve injury and is a known complication of fundoplication, bariatric surgery, and heart or lung transplantation. Other miscellaneous causes described in the literature include cow’s milk protein allergy, eosinophilic gastroenteropathies, celiac disease, cystic fibrosis, and caustic ingestions.


Children with gastroparesis commonly report one or more of the following, in decreasing order of frequency: vomiting, abdominal pain, nausea, weight loss, early satiety, and bloating. Nausea and abdominal pain occur shortly after meals, but vomiting typically develops several hours later. In a survey of children undergoing gastric emptying scintigraphy, the presence of severe nausea was the symptom most predictive of an abnormal scan. Abdominal pain is rarely the predominant symptom, and other symptoms such as nausea and bloating may be similar in intensity. Severe bloating should prompt the consideration of exacerbating factors such as small intestinal bacterial overgrowth (SIBO). Uncontrolled studies of adults with gastroparesis demonstrated positive breath tests suggestive of SIBO in 39% and 60% of their cohorts. In one study, antibiotic treatment of the SIBO provided symptom relief in 85% of the patients who were available for follow-up.


Gastric emptying scintigraphy is currently the method of choice to evaluate gastric transit. Because there are no validated pediatric protocols or normative values caused by inherent ethical limitations, adult criteria are often applied and greater than 60% meal retention at 2 hours or greater than 10% at 4 hours is considered diagnostic of delayed gastric emptying ( Figure 28-2 ). Traditionally, gastric emptying scintigraphy studies were conducted for up to 2 hours. However, extending the observation window from 2 to 4 hours in pediatric studies improves the diagnostic yield considerably.


An emerging diagnostic modality is the wireless motility capsule (WMC), a nondigestible capsule that can measure whole-gut transit based on changes in measured intraluminal pH. Gastric emptying as measured by the WMC correlates well with gastric-emptying scintigraphy at 4 hours, but its use is limited due to the cost of the equipment and size of the capsule.


Other methods used to assess gastric emptying and motor abnormalities in children include ultrasound, magnetic resonance imaging, 13 C breath testing, and antroduodenal manometry. These techniques are described in further detail in an earlier section in this chapter.


Lifestyle modification is an important component in the management of gastroparesis. Multiple, small, low-fat meals are encouraged to minimize discomfort and facilitate gastric emptying. In addition, liquid meal replacements can be useful due to their rapid emptying from the stomach. Dietary fiber intake should be limited to minimize the risk of bezoar formation. Medications that impair gastric motor function should be discontinued.


Prokinetic medications remain the mainstay of treatment for cases that are unresponsive to conservative management. Macrolide antibiotics such as erythromycin and azithromycin have prokinetic activity due to their ability to activate motilin receptors in the stomach. Activation of these receptors induces the myoelectrical activity front known as phase III of the MMC in the antrum, which propagates distally into the small bowel. Erythromycin has been effective at improving gastric emptying and provides symptom relief in adult patients. Clinical prokinetic effects may be observed at doses 10% to 20% of the standard antibiotic dosing. Caution should be exercised with intravenous administration or in combination with a cytochrome P450 (CYP)3A inhibitor, both of which can increase the risk of erythromycin-associated cardiotoxicity. Furthermore, drug holidays are likely required during prolonged use because of downregulation of motilin receptors and tachyphylaxis. Recently azithromycin has been examined as an alternative to erythromycin due to its longer half-life, fewer drug interactions, and less risk of adverse events such as QTc prolongation. Early results have suggested that azithromycin produces an increased frequency of antral activity-front generation in comparison to erythromycin, with a longer duration of effect. A disadvantage of this class of prokinetics is the potential for antibiotic resistance with chronic use.


Metoclopramide and domperidone are dopamine-receptor antagonists that exert their prokinetic effect by preventing endogenous dopamine from inhibiting the motor activity of the stomach. Metoclopramide also has additional antiemetic effects via stimulation of 5-hydroxytryptamine subtypes 4 (5-HT 4 ) and 5 (5-HT 5 ), respectively. However, it has fallen out of favor for many practitioners because of the risk of dystonic reactions, particularly in younger patients, and tardive dyskinesia with chronic use. In contrast, domperidone is effective in accelerating gastric transit and providing symptom relief in gastroparetics, and is associated with fewer central nervous system effects. Pharmacogenetic research has yielded several gene polymorphisms that may help in identifying patients who will exhibit more favorable response profiles to domperidone in the future.


Cisapride, a nonselective 5-HT 4 receptor agonist, is effective in accelerating gastric transit and reducing symptom scores in children with gastroparesis. However, it is now unavailable in many countries because of adverse cardiovascular events reported in adults, and the potential for serious adverse events in low-risk groups including children.


Novel prokinetic agents under investigation include selective motilin receptor agonists (alemcinal, mitemcinal, and KC11458), ghrelin agonists (TZP-101 and TZP-102), 5-HT 4 agonists (prucalopride), D2 dopamine receptor antagonists (levosulpiride and itopride), and acetylcholinesterase inhibitors (acotiamide). To date, adult studies have not demonstrated any convincing efficacy for these compounds and further clinical trials are required.


Gastric electrical stimulation is used to deliver high frequency, short pulse, low-energy stimulation to relieve symptoms of gastroparesis. The technique consists of implanting two electrodes connected to a pacemaker into the seromuscular layer of the stomach. Some centers place an initial testing probe endoscopically ( Figure 28-3 ) that remains in place for a few days to evaluate effectiveness and tolerance before the definitive implantation by laparoscopy. The electrodes are then connected to a pulse generator placed in an anterior abdominal pocket and programmed through a radiofrequency wand. Stimulation protocols vary in amplitude, pulse width, frequency, and interval of cycling. In the largest pediatric case series to date, there was significant improvement in the severity and frequency of vomiting, bloating, and nausea in children with delayed gastric emptying. There was also a reduction in the number of patients who required enteral nutrition support poststimulator, similar to another pediatric cohort. The mechanism of action remains poorly understood, as the stimulation does not entrain gastric rhythm, does not directly cause contraction of the smooth muscle, and symptom improvement does not consistently correlate with accelerated gastric emptying. The stimulator’s effects have been attributed to modulation of vagus nerve activity, but of interest, symptom improvement has been observed postvagotomy. Improved fundic accommodation has also been postulated based on increased barostat volume thresholds before discomfort pre- and poststimulator therapy. A placebo effect has not yet been completely ruled out as the mechanism for the stimulator’s effectiveness. Complications include skin erosion over the site of implantation, pain at the device site, infection of the pocket, and premature drainage of the battery.




Figure 28-3


Gastric electrical stimulator. Temporary placement is performed at select centers in order to evaluate the effectiveness of the stimulator. Two leads are inserted endoscopically (A) into the seromuscular layer of the stomach and that are then secured with an Endoclip (B) . Once stimulation has been deemed effective, a permanent device is placed with the pulse generator surgically inserted into an anterior abdominal pocket (C) .


Intrapyloric botulinum toxin injection has been used to treat pediatric gastroparesis at doses ranging from 100 to 400 units. Although the safety profile of this treatment is encouraging, the durability of the treatment effect is variable and methodologic limitations in published reports cannot rule out the possibility of a placebo effect. Surgical procedures such as pyloroplasty, gastric plication, and gastrectomy are uncommonly performed in pediatric gastroparesis. However, a small study of adult gastroparesis subjects suggested that gastric electrical stimulation with concurrent pyloroplasty may enhance the former’s effectiveness and provide long-lasting symptom improvement in selected patients. Most cases of pediatric gastroparesis have a favorable long-term outcome and eventually experience resolution of their symptoms, with a time to resolution ranging from 6 to 24 weeks after onset of symptoms.




Dumping Syndrome


Dumping syndrome refers to the constellation of signs and symptoms arising from abnormally rapid gastric emptying. This is a well-recognized postsurgical complication after fundoplication, vagotomy, pyloroplasty, gastric bypass or resection, or esophageal atresia repair. Nonoperative causes include duodenal or jejunal bolus feeds, underlying autonomic dysfunction, or congenital microgastria. In pediatrics, the most common cause of dumping syndrome is fundoplication. The true prevalence of dumping syndrome is difficult to determine as symptoms can be nonspecific, may be overlooked, overlap with expected postsurgical complications, and are potentially confounded by the underlying disease processes inherent in the population, which require surgical intervention.


During meals, the proximal stomach can function as a reservoir that allows the gradual release of ingested contents into the small intestine. This ability to increase fundic volume without a rise in intragastric pressure is known as the “accommodation reflex” and involves a reduction in gastric tone with a concomitant increase in compliance in response to food intake. Because this accommodation response is mediated by a vagovagal reflex that activates inhibitory neurons, vagal nerve injury will abolish gastric accommodation in response to distension and allow rapid emptying of ingested food contents into the small intestine, which is considered the key pathophysiologic event of dumping syndrome. Disruption of antropyloric coordination can also accelerate solid-phase gastric emptying. Solids normally remain in the stomach until antral grinding has triturated them into appropriately sized particles for release into the small intestine for further digestion and absorption. Larger particles are retained in the stomach via pyloric contraction and continue to undergo mechanical breakdown. Consequently, any resection or revision of the distal stomach can impair this process and promote premature gastric emptying. Symptoms ( Table 28-3 ) of dumping syndrome are divided into early and late phases, their onset relative to the timing of food ingestion. Early phase symptoms occur within 30 minutes postprandially, whereas the late phase typically manifests 1 to 4 hours after the meal. The arrival of hyperosmolar contents into the duodenum induces fluid shifts from the intravascular to intraluminal space, which is theorized to reduce the effective circulating volume and give rise to the vasomotor symptoms. The gastrointestinal symptoms of dumping syndrome are attributed to increased intestinal peristalsis secondary to luminal distension. However, the exact mechanism remains unclear, as the administration of intravenous fluids does not appear to blunt the manifestations of early dumping syndrome. Rapid absorption of the large dietary carbohydrate load arriving in the small intestine triggers hyperinsulinemia and subsequent reactive hypoglycemia characteristic of late-phase dump­ing syndrome. In infants, young children, or those with cognitive delays, the presentation may consist primarily of nonspecific signs and symptoms such as refusal to feed, retching, tachycardia, paleness and lethargy, diaphoresis, and watery diarrhea. Older patients may be able to better describe the symptoms commonly attributed to dumping syndrome (see Table 28-3 ); early dumping is characterized by both gastrointestinal and vasomotor symptoms, while late dumping consists mostly of vasomotor complaints.



TABLE 28-3

SYMPTOMS OF DUMPING SYNDROME










Early Dumping
(30 minutes postprandially)
Late Dumping
(1-4 hours postprandially)
Gastrointestinal symptoms



  • Early satiety



  • Bloating



  • Nausea



  • Abdominal pain/cramping



  • Diarrhea


Vasomotor symptoms



  • Sweating



  • Flushing



  • Palpitations



  • Dizziness



  • Hypotension



  • Intense desire to lie down




  • Hypoglycemia



  • Hunger



  • Sweating



  • Weakness



  • Confusion



  • Dizziness/syncope



The diagnosis of dumping syndrome relies on clinical acumen, compatible symptoms and history, and supportive diagnostic testing. Symptoms may not manifest until a median of 2.5 months after surgery. In children, a modified glucose tolerance test is typically used to identify the early phase hyperglycemia and late-phase hypoglycemia. This involves an overnight fast followed by the oral or enteral administration of a 1.75 to 2 g/kg bolus of glucose and measurement of blood glucose at approximately 0, 30, 60, 120, and 180 minutes postbolus. Pediatric studies have not demonstrated any correlation between the degree of hypoglycemia and severity of symptoms. Measurement of gastric emptying via scintigraphy may demonstrate accelerated transit, but this technique has yielded inconsistent results. Rapid gastric emptying can be slowed by avoiding large increases in postprandial intragastric pressure through small volume frequent feeds, continuous enteral feeding, and/or restricting fluid intake during meals. Other methods for regulating gastric emptying may include increasing dietary fat content using long-chain triglycerides, or meal viscosity with guar gum, pectin, or carob-bean flour. Adding uncooked cornstarch not only thickens feeds, but also provides a slow and continuous source of glucose, attenuating the development of late-phase symptoms due to its highly branched glucose chains. The dietary intake of easily digestible mono- and disaccharides should be minimized to reduce the risk of reactive hypoglycemia. Pharmacologic agents are second-line therapy in the management of pediatric dumping syndrome. Acarbose is an α-glycosidase hydrolase inhibitor that interferes with carbohydrate absorption in the small intestine by delaying the conversion of oligosaccharides to monosaccharides. Doses of 12.5 to 25 mg before meals with increments up to a maximum of 100 mg per dose have been effective in treating late-phase symptoms in pediatric dumping syndrome. It is well tolerated in children, but can cause flatulence because of bacterial fermentation. Octreotide is an analog of the hormone somatostatin and has similar pharmacologic effects, except for a shorter duration of action. It has been used to treat dumping syndrome because of its inhibitory effects on antral contractions and insulin secretion. It has been extensively studied in adults and can improve symptoms, optimize glycemic control, and delay gastric emptying. Octreotide has demonstrated benefit in pediatric studies. Limiting factors include the need for daily injections, cost, gallstones, and steatorrhea. Diazoxide is a sulfonamide derivative that inhibits insulin release by activating potassium channels in pancreatic β cells. It is used to treat late-phase symptoms. There are surgical options to treat dumping syndrome but because effective and less invasive therapies exist, they are seldom used in children.




Functional Dyspepsia


Functional dyspepsia refers to a heterogeneous constellation of recurrent pain or discomfort-predominant symptoms localized to the upper abdomen. The symptom complex is characteristically meal related and may include postprandial fullness, early satiation, bloating, nausea, and/or belching. In contrast to irritable bowel syndrome, there is no symptom relief with defecation, and there is no temporal association with an alteration in stool character or frequency. By definition, there should be no evidence of any alternative causes for the patient’s symptoms, such as inflammatory, anatomic, metabolic, or neoplastic processes. However, there is mounting evidence to suggest that nonerosive changes to the gastroduodenal mucosa may play an important role in the generation of symptoms in this population. The underlying pathophysiology of functional dyspepsia remains poorly understood. Abnormal fasting and postprandial antroduodenal motility parameters, including neuropathic or myopathic patterns similar to patients with chronic intestinal pseudoobstruction, have been identified in patients with dyspepsia. Unfortunately, there are no pathognomonic motor patterns specific to patients with functional dyspepsia. Studies have identified delayed gastric emptying in both adult and pediatric patients. However, the correlation between symptoms and gastrointestinal transit is poor. Conflicting results have been reported not only among different studies, but also within the same study cohorts. This indicates that other mechanisms are involved in functional dyspepsia. Impaired gastric accommodation has been frequently identified in dyspeptic patients using barostat, CT, and nutrient drink challenges. Distension of a poorly compliant fundus may trigger increased afferent signaling from the gut and the perception of abdominal pain. Alternatively, a lack of fundic relaxation may result in the early transfer and abnormal accumulation of gastric contents into the antrum, causing distension and pain. Vagus nerve dysfunction is most likely the underlying cause of these impaired accommodation reflexes, and may be exacerbated by acute and chronic anxiety states. Impaired gastric accommodation has been associated with symptoms of early satiety, abdominal discomfort or pain, belching, and weight loss. Visceral hypersensitivity is another common finding in patients with dyspepsia and may amplify symptoms arising from poor accommodation or dysmotility. In adolescents with functional dyspepsia, patients developed more postprandial symptoms such as nausea and bloating compared to healthy controls during a nutrient drink challenge despite similar volumes ingested. Increased afferent nerve signaling from the gut in response to a normal stimulus or altered processing of normal signals, either peripherally in the spinal cord or centrally in the brain, are suggested mechanisms by which this may occur. Excessive release of cholecystokinin in response to duodenal lipid in dyspeptics is thought to cause exaggerated stimulation of duodenal vagal nerve afferents, and may account for the observed hypersensitivity to duodenal lipid in patients with functional dyspepsia. Chemical hypersensitivity of capsaicin-sensitive gastrointestinal nociceptive pathways, and combined somatic hypersensitivity and abnormal visceral pain modulation secondary to dysfunctional central pain processing have also been identified in functional dyspepsia. Sensitizing events that could contribute to the development of visceral hypersensitivity have been proposed, including: early life events; bacterial infections; allergy; and psychosocial factors such as affective or anxiety disorders, or a history of abuse. Retrospective studies of children who have undergone repair of an umbilical hernia or pyloric stenosis early in life have demonstrated an association with the development of pain-predominant functional gastrointestinal disorders later in childhood. Inflammatory conditions such as allergy or infection have also been described. A case-control study of children aged 4 to 18 years showed that a history of cow’s milk protein allergy during infancy significantly increased the risk of developing dyspeptic symptoms later in life. Acute gastroenteritis has been a frequently identified risk factor for functional dyspepsia. Results from a recent meta-analysis were in support of this view and suggested that approximately 12% of individuals exposed to an infectious gastroenteritis will subsequently develop functional dyspepsia. Enteric pathogens implicated include Salmonella , Campylobacter , Shigella , and Escherichia coli . Histopathologic findings in patients with functional dyspepsia have included low-grade mixed inflammation in the antrum, increased numbers of inflammatory mast cells in gastric biopsies, elevated macrophage and eosinophil counts in duodenal biopsies, and abnormal tight-junction cell-adhesion proteins in the duodenum. These insights may eventually lead to a unifying pathophysiologic mechanism involving an impaired intestinal barrier function, immune dysregulation, and abnormal central pain processing. Helicobacter pylori is the most common chronic bacterial infection worldwide and has a higher prevalence in dyspeptic patients compared to asymptomatic healthy individuals. A meta-analysis evaluating the role of H. pylori eradication in nonulcer dyspepsia concluded that there was a small but statistically significant effect in reducing symptoms. Findings from a recent large, prospective, randomized, double-blind, placebo-controlled trial were in keeping with the meta-analysis; although limited to a single center, a reduction in dyspeptic symptoms of at least 50% using a validated questionnaire was reported by 49% of symptomatic patients in comparison to 36.5% of controls ( p = 0.01). Some of the potential ways in which H. pylori could produce symptoms of epigastric pain or early satiety in the absence of peptic ulceration include visceral hypersensitivity secondary to duodenal acidification and preulcerative microscopic duodenitis, and impaired hunger sensations and gastrointestinal dysmotility secondary to decreased ghrelin production, even in the absence of gastric atrophy. Functional dyspepsia is a clinical diagnosis, and the Rome III Diagnostic Criteria ( Box 28-1 ) for children were most recently updated in 2006. In contrast to the adult guidelines, there is no subdivision into pain or fullness-predominant subtypes, bloating and nausea are not included as part of the symptom complex, and the location of the discomfort is not specific to the epigastrium but more broadly centered in the upper abdomen. The distinction between pain and discomfort can be a difficult concept for children and their parents to understand, and this has limited attempts to apply the adult Rome III Diagnostic criteria to the pediatric population. Eliciting the symptom of bloating is similarly plagued by comprehension difficulties in children. There have been no studies examining the age at which the adult criteria could be applied to older children and adolescents. However, whether doing so would alter management is debatable, as there is ongoing controversy about the utility of the current adult criteria. Nausea is also notably absent from the pediatric criteria, despite a high prevalence in children with functional dyspepsia. In a study of children with chronic abdominal pain, 29% with functional dyspepsia had coexistent nausea. However, because nausea is a predictive symptom of gastroparesis, this finding may represent the subset of patients who also have delayed gastric emptying. Gastroparesis has been identified in up to 20% of children diagnosed with functional dyspepsia, and because of the similarities between the symptom complexes, it can be very difficult to distinguish between the two conditions. Although the guidelines perform well in terms of identifying patients who are ultimately found to have abnormalities on endoscopy, the inter-rater reliability of the Rome III Diagnostic Criteria for pain-predominant functional gastrointestinal disorders in children is only slight to fair. Patients with a history of persistent right upper or lower abdominal pain, persistent vomiting, gastrointestinal blood loss, anemia, weight loss, nocturnal pain, or dysphagia should undergo further evaluation. H. pylori infection should be ruled out, particularly in patients with risk factors, if there is a positive diagnosis, eradication therapy is indicated. In the absence of H. pylori infection, initial empirical pharmacotherapy may consist of acid suppression with a proton pump inhibitor. If the child or adolescent is able to describe early satiety or postprandial fullness as the primary symptom, alternative empiric therapies could be considered such as prokinetics, or a fundic relaxant such as buspirone; if there is concurrent delayed gastric emptying, prokinetic therapy would likely offer more benefit than the latter. In patients who have concurrent functional constipation, improving stool output may have a beneficial effect on dyspeptic symptoms. Assessing for the presence of psychiatric comorbidities is recommended due to the impact on abnormal pain modulation and gastric accommodation. Unless used to treat an underlying affective or anxiety disorder, the empiric use of selective serotonin reuptake inhibitors is not recommended, as it is no more effective than placebo and has a high incidence of adverse effects. However, there is some suggestion that mirtazapine, a noradrenergic-serotonergic antidepressant with multiple receptor affinities, can be effective in improving quality of life and weight gain in dyspeptic patients with early satiety independent of its antidepressant effects. There may also be a role for adjunctive treatment with tricyclic antidepressants. In a nonplacebo controlled trial, approximately 75% of children with functional dyspepsia responded well to treatment with either amitriptyline or imipramine with minimal adverse effects. Tricyclic antidepressants do not appear to reduce overall symptoms by improving drinking capacity and may exert their effect instead by altering central afferent signal processing. Despite advances in our understanding, functional dyspepsia remains a condition confounded by marked clinical heterogeneity that likely explains the unsatisfactory therapies available at present. Future refinements of the diagnostic criteria and further evaluation of current and novel therapies are warranted.


Jul 24, 2019 | Posted by in GASTROENTEROLOGY | Comments Off on Gastric Motility Disorders
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