3DefinitionThe diagnosis of gastroparesis is based on the combination ofsymptoms of gastroparesis,absence of gastric outlet obstruction or ulceration (documneted on UGIE or Barium swallow),and documentation of delay in gastric emptying.Michael Camilleri et al. Clinical Guideline: Management of Gastroparesis. Am J Gastroenterol 2013
4Gastroparesis in Olmsted County, 1996–2006 IncidenceThe age-adjusted prevalence of definite gastroparesis per 100,000 person was 9.6 (95% CI, 1.8–17.4) for men and 37.8 (95% CI, 23.2–52.4) for women.Incidence & prevalence of gastroparesis in India: ?A. Definite gastroparesis B. Definite+probable gastroparesis C. Definite+probable+possible gastroparesis. Definite gastroparesis: delayed gastric emptying by standard scintigraphy and symptoms of nausea and/or vomiting, postprandial fullness, early satiety, bloating, or epigastric pain for more than 3 months,Probable gastroparesis: symptoms as above plus food retention on endoscopy or an upper GI study, but no scintigraphy had been performed,Possible gastroparesis: typical symptoms alone or delayed gastric emptying by scintigraphy in the absence of GI symptoms.aIncidence per 100,000 person-years, age-adjusted to the population structure of 2000 U.S. whites.bIncidence per 100,000 person-years, age-and gender-adjusted to the population structure of 2000 U.S. whites.Jung HK et al. J Neurogastroenterol Motil. 2010
5Gastroparesis: Etiology Mean age of onset: 34 years. 82%- femalesKendall and McCallum. Gastroenterology 1993.Soykan et al. Dig Dis Sci 1998.
6The motor function of the gut is controlled at three main levels: extrinsic neural control (vagal and sympathetic); intrinsic neural control; and excitability of smooth muscle cells controlled by transmitters. Gastric emptying entails interaction among smooth muscle, enteric and extrinsic autonomic nerves, and the interstitial cells of Cajal (ICC)
7Electrophysiologic basis of gastric peristaltic waves The plateau and action potentials occur during circular muscle contractions. Peristaltic waves originate in the pacemaker area. The frequency (3 cycles per minute [cpm]) and propagation velocity (approximately 14 mm/second) of the gastric peristaltic waves are controlled by the slow wave, which leads the contraction from the proximal corpus to the distal antrum, as shown at electrodes A through D. The solid black linesand arrowsindicate the circumferential and distal propagation of the peristaltic wave, which forms a ring contraction (small arrow), indicating a moving peristaltic contraction. Peristaltic contractions occur three times per minute, the frequency of the gastric slow wave. The increased myoelectrical activity of the plateau potentials and action potentialslinked with the slow wave results in increased amplitude of the EGG signal (thick black lines). The fundus does not participate in the gastric peristalticcontractions.
8Gastric neuromuscular work after ingestion of a solid meal To receive the ingested solid foods and accommodate the volume of food without increasing intragastric pressure, the fundic smooth muscle relaxes (receptive relaxation). The fundus then contracts to empty the ingested food into the corpus and antrum for trituration and emptying. Recurrent corpus-antral peristaltic waves mill the solids into chyme, which is composed of 1- to 2-mm solid particles suspended in gastric juice. Antral peristaltic waves, indicated by the ring-like indentation in the antrum, empty 2 to 4 mL of the chyme through the pylorus and into the duodenal bulb at the slow wave frequency of three peristaltic contractions per minute. Antropyloroduodenal coordination indicates efficient emptying of chyme through the pylorus, which modulates flow of the chyme by varying sphincter resistance. Contractions in the duodenum also provide resistance to emptying.
9Normal gastric emptying The proximal stomach serves as the reservoir of food, and the distal stomach as the grinderSolids are initially retained in the stomach and undergo churning while antral contractions propel particles toward the closed pylorus.Food particles are emptied once they have been broken down to approximately 2 mm in diameter
11Diabetic gastroparesis-pathophysiology Traditionally considered to be Neuropathic.Gastric acid output reduced, Vagus nerve dysfunction reduces pyloric relaxation and thereby prohibits passage of foods.Vagus nerve histology shows myelin degeneration. However, some patients have gastroparesis without evidence of generalized autonomic neuropathy.Non-neuropathicDecreased Interstitial Cells of Cajal (ICCs)HyperglycemiaBlunts antral contraction in healthy humansIn diabetics, hyperglycemia delays gastric emptying that improves with euglycemia.The major functionality of nNOS is control of the muscle tone of the lower esophageal sphincter, the pylorus, the sphincter of Oddi, and the anus. Additionally, it modulates the accommodative reflex of the fundus and the peristaltic reflex of the small intestine.
12NOS – impaired expression Gastric myenteric plexus of spontaneously diabetic biobreeding /Worcester (BB/W) rats was studiedNANC relaxation in gastric muscle preparations in response to transmural stimulation obtained from diabetic BB/W rats was significantly impairedfrequency-dependent NANC relaxation in response to transmural stimulation was markedly antagonized by N(G)-nitro-L-arginine-methyl ester, indicating mediation by the neuronal release of NOTakahashi T et al. Gastroenterology Nov
13NOS – impaired expression The number of NOS-immunoreactive cells in the gastric myenteric plexus and the NOS activity were significantly reduced in diabetic BB/W rats.Northern blot analysis showed that the density of NOS messenger RNA bands at 9.5 kilobases was significantly reduced in the gastric tissues of diabetic BB/W rats.NOS expression in duodenum, ileum, and colon of diabetic animals was not statistically different from controls. Decreased expression of NOS in antrum may contribute to altered gastric emptying observed in diabetics. Similar results were obtained in Streptozocin-diabetic rats.Takahashi T et al. Gastroenterology Nov
14Watkins CC et al. J Clin Invest. 2000 nNOS protein expression in the pyloric myenteric neurons is depleted in diabetic mice: reversal by insulin treatment. (a) Immunohistochemical analysis of nNOS protein expression. nNOS is present in wild-type but not nNOS–/– pyloric myenteric neurons whereas nNOS expression is lost in both NOD diabetic mice. Insulin treatment (1 week) reverses the expression. In situ hybridization analysis of nNOS expression. nNOS mRNA expression is present in wild-type and depleted in nNOS–/– pyloric myenteric neurons whereas nNOS mRNA expression is significantly decreased in diabetic mice.. Loss of fundal relaxation in nNOS–/– or diabetic mice would be expected to accelerate gastric emptying, whereas loss of pyloric or duodenal relaxation may delay gastric emptying. In both nNOS–/– and diabetic mice, the loss of nNOS is associated with delayed gastric emptying consistent with a major physiological effect on pyloric function. This conclusion is supported by our findings of more pronounced depletion of nNOS in the pylorus compared with the fundus and antrum and with the anatomic changes observed in these animals. Insulin restores gastric emptying in this study.Watkins CC et al. J Clin Invest. 2000
15Patterns of Gastric Emptying in Healthy People and in Patients with Diabetic Gastroparesis Non-nutrient liquids empty rapidly; the rate is fastest when there is a large volume. If there are increased calories in the liquid phase of the meal, emptying is relatively constant over time, with a maximum rate of 200 kcal/hour. Thus, solids empty during two phases over 3 to 4 hours: an initial lag period (during which retention occurs), followed by a phase of relatively constant emptying.
16Idiopathic gastroparesis/IG – intact vagal function 13 normal subjects, 9 patients of DG, 10 patients of IG, 5 patients of postsurgical gastroparesisThere were significantly decreased fasting levels of pancreatic polypeptide and ghrelin in the diabetic (79±26pg/ml) and postsurgical gastroparesis groups (51±11 pg/ml) compared to the normal subjects (315±76 pg/ml) and the idiopathic gastroparesis group (161±53 pg/ml).Gaddipati KV et al. Dig Dis Sci. 2006
17IG – intact vagal function Sham feeding was characterized by an increase in pancreatic polypeptide levels in normal controls and patients with idiopathic gastroparesis, with no change in diabetic and postsurgical gastroparesis.Meal ingestion resulted in an increase in pancreatic polypeptide concentration in the normal subjects groups and idiopathic gastroparesis group.Gaddipati KV et al. Dig Dis Sci. 2006
18IG & DG-cellular changes Full-thickness gastric body biopsy specimens were obtained from 40 patients with gastroparesis (20 diabetic) and matched controls.Sections were stained for H&E and trichrome and immunolabeled with antibodies against PGP 9.5, nNOS, VIP, substance P, and tyrosine hydroxylase to quantify nerves, S100β for glia, Kit for ICCs, CD45 and CD68 for immune cells, and smoothelin for smooth muscle cells.Grover M et al. Gastroenterology May
19IG vs DG-cellular changes Histologic abnormalities were found in 83% of patients.The most common defects were loss of ICC with remaining ICC showing injury, an abnormal immune infiltrate containing macrophages, and decreased nerve fibers.On light microscopy, no significant differences were found between DG and IG with the exception of nNOS expression, which was decreased in more patients with IG (40%) compared with DG patients (20%) by visual grading.ICC were greatly reduced in the distal stomach in diabetic mice manifesting delayed gastric emptying, impaired electrical pacemaking, and reduced motor neurotransmission.Grover M et al. Gastroenterology May
20IG vs DG- Ultrastructural differences Tissue was collected from anterior aspect of stomach, midway between GC and LC where the gastroepiploic vessels meet, at ~ 9 cm proximal to pylorus, from 20 DG, 20 IG and 20 patients undergoing gastric bypass for obesity4 tissue strips for each patient 1 mm × 10 mm long and containing the muscularis propria plus a small portion of the tunica submucosa, were immediately cut after the full thickness biopsy was obtained and processed for electron microscopyThe NIDDK GpCRC J Cell Mol Med July
21IG vs DG- Ultrastructural differences ICC were affected in both diabetic and idiopathic gastroparesis.19/20 DG patients had a thickened basal lamina around smooth muscle cells and nerves.In contrast, tissues from 18/20 patients with IG did not have the thickened basal lamina around smooth muscle cells and nerves but had more intense fibrosis than those from DGNerve damage was much more prominent in IG with both nerve cell bodies and nerve fibers affected to a greater degree.Unlike in DG, glial cells were also abnormal in IGneuronal cell body, nerve fibers and glial cells were markedly altered in idiopathic gastroparesis, while only nerve ending abnormalities wereseen in the diabetic patients. Smooth muscle cell abnormalities were not commonly seen in diabetic and idiopathic gastroparesis and gap junctions were maintained in all patients studied. However, contractile activity of the muscle coat may still be compromised because the smooth muscle cells wereencased in a less elastic stroma. residual ICC were rarely in contact with each other and smooth muscle cells and never to nerve endings. This is in sharpcontrast to what is seen in control tissues.The NIDDK GpCRC J Cell Mol Med July
22Clinical Manifestations Nausea %Vomiting %Bloating 75%Early Satiety %Abdominal pain %Rule out rumination syndromePain- burning, vague or crampy, localised, nocturnal and exacerbated by meals. Rumination syndrome - daily, early postprandial, effortless regurgitation of food, which typically occurs with each meal for months. Nausea, vomiting, early satiety, and postprandial fullness correlate better with delayed gastric emptying than upper abdominal pain and bloating.Differentiation: CVS, cannabinoid use.Soykan et al. Dig Dis Sci Nov; 43(11):
23Dyspepsia & gastric emptying In a meta analysis of 17 studies involving 868 dyspeptic patients and 397 controls, significant delay of solid gastric emptying was present in 40% of patients of FD1Severity of delay does not correlate with symptomsRapid gastric emptying, rather than delayed gastric emptying, might provoke functional dyspepsia.2Other GI motor abnormalities, altered visceral sensation and psychosocial factors should be considered in evaluating patients of dyspepsia.1. Perri F et al. Am J Gastroenterol 1993.2. Kusano M et al. J Gastroenterol Hepatol Apr
24Gastroparesis: a proposed classification Grade 1: Mild gastroparesisSymptoms relatively easily controlledAble to maintain weight and nutrition on a regular dietor minor dietary modiﬁcationsGrade 2: Compensated gastroparesisModerate symptoms with partial control withpharmacological agentsAble to maintain nutrition with dietary and lifestyleadjustmentsRare hospital admissionsGrade 3: Gastroparesis with gastric failureRefractory symptoms despite medical therapyInability to maintain nutrition via oral routeFrequent emergency room visits or hospitalizationsAbell et al. Neurogastroenterol Motil (2006) 18, 263–283
25Diabetic Gastroparesis (DG) Prevalence of delayed emptying in longstanding Type-1 and 2 Diabetics: 27-58% and 30% respectivelyDiabetic gastroparesis typically develops after DM has been established for ≥10 years, and patients with type 1 diabetes might have triopathythe community prevalence was estimated to be ~ 5 % among type 1 diabetics, 1 % among type 2 diabetics, and 0.2 % of controls in Olmsted County, Minnesota.
26DG-natural history20 patients (6 men and 14 women) of diabetes mellitus (16 with type-1 DM, 4 with Type-2 DM)No differences in mean gastric emptying of the solid component (retention at 100 minutes at baseline: 56% +/- 19% vs. follow-up: 51% +/- 21%, P = 0.23) or the liquid component (time for 50% to empty at baseline: 33 +/- 11 minutes vs. follow-up: 31 +/- 12 minutes, P = 0.71) during follow-upJones KL et al. Am J Med 2002
27DG-natural historyMean blood glucose (17.0 +/- 5.6 mmol/L vs /- 4.9 mmol/L, P = 0.007) and HbA(1c) (8.4% +/- 2.3% vs. 7.6% +/- 1.3%, P = 0.03) levels were lower at follow-up.There was no difference in symptom score (baseline: 3.9 +/- 2.7 vs. follow-up: 4.2 +/- 4.0, P = 0.78).There was evidence of autonomic neuropathy in 7 patients (35%) at baseline and 16 (80%) at follow-up.In patients with diabetes mellitus, any marked changes in either gastric emptying or upper gastrointestinal symptoms were not observed during a 12-year period. Diabetic gastroparesis is not a rapidly progressive disorder. Parasympathetic function was evaluated by the variation (R-R interval) in the heart rate during deep breathing and the immediate heart rate response to standing (“30:15”). Sympathetic function was assessed by the fall in systolic blood pressurein response to standing. The result of each test was scored as 0 (normal), 1 (borderline), or 2 (abnormal).Jones KL et al. Am J Med 2002
28DG-natural historyBetween , 86 patients of DM underwent assessmentSolid gastric emptying percentage of retention at 100 min) was delayed in 48 (56%) patients and liquid emptying (50% emptying time) was delayed in 24 (28%) patients.At follow-up in 1998, 62 patients were known to be alive, 21 had died, and 3 were lost to follow-up.Kong MF et al. Diabetes Care 1999
29DG-natural historyIn the group who had died, duration of diabetes (P = 0.048), score for autonomic neuropathy (P = 0.046), and esophageal transit (P = 0.032) were greater than in those patients who were alive, but there were no differences in gastric emptying between the two groups.Of the 83 patients who could be followed up, 32 of the 45 patients (71%) with delayed solid emptying and 18 of the 24 patients (75%) with delay in liquid emptying were aliveGastroparesis was not associated with a poor prognosisIn IG, Symptoms may resolve over several years. Normal pH response after sham feedingsKong MF et al. Diabetes Care 1999
30IG vs DG - DifferencesOut of 416 patients, 254 patients of IG, 137 with DG and 25 with other causesMore likely to be female (89% vs 71%-T1 vs 76%-T2), Caucasians (90% vs 77% vs 76%)Mean Age at enrollment: T2DM (53 ± 11) > IG (41 ± 14) > T1 DM (39 ± 11 years)Obesity in: T2 DM (71%) vs 28% (T1DM) vs IG (26%)The NIDDK GpCRC. Clin Gastroenterol Hepatol. 2011
31IG vs DG - DifferencesNausea and vomitings are the most common symptoms prompting evaluation for DGAbdominal pain was more often a symptom prompting evaluation for IG (76% IG, 60% T1DM, 70% T2DM; p=0.01).Patients with IG have more early satiety and abdominal pain compared with patients with DG who have more severe retching.The NIDDK GpCRC. Clin Gastroenterol Hepatol. 2011
32IG vs DG - Differences20% having chronic but stable symptoms, 33% having chronic but worsening symptoms, 33% having chronic symptoms with periodic exacerbation, and 10% having a cyclic pattern.Patients with T1DM were more likely to have grade 3 gastroparesis severity (29% IG, 49% T1DM, 39% T2DM) and had greater frequency of hospitalisations due to dehydrationThe NIDDK GpCRC. Clin Gastroenterol Hepatol. 2011
33IG vs DG - DifferencesThe symptoms with highest severity at enrollment were stomach fullness and postprandial fullness for IG, nausea for T1DM, and stomach fullness for T2DM.DG had more severe retching and T1DM had more severe vomiting than IGSeverity of postprandial fullness and upper abdominal pain in: IG > DGSeverity of stomach fullness in: IG > DG.The NIDDK GpCRC. Clin Gastroenterol Hepatol. 2011
34IG vs DG - DifferencesGastric retention in: T1 DM (47 ± 27% at 4 hours) > T2 DM (33 ± 24) > IG (28 ± 19)IG had an increase in endometriosis and migraine headaches, whereas T2DM had an increase in coronary artery disease.An acute onset of symptoms was reported in approximately half of the patients in each of the IG, T1DM, and T2DM.An initial prodrome was present at the start of symptoms in a minority, approximately 15% of cases, without significant differences among the three groups.Patients with T1DM were more likely than IG to be treated with gastric electric stimulation. There was a slight increase in feelings of hopelessness as assessed by BDIand a slight increase in the trait anxiety score in T1DM patients compared to IG.The NIDDK GpCRC. Clin Gastroenterol Hepatol. 2011
35Evaluation Clinical Evaluation Evaluate Volume Status Abdominal distention, Succussion splashClues to other etiologiesMalar rash, sclerodactylyCachexia, lymphadenopathyLabElectrolytesProtein/albuminGlucoseThyroid/parathyroidIf suspected, autoantibodies for scleroderma, SLE, polymyositis
36Gastric emptying scintigraphy Medications that affect gastric emptying should be stopped at least 48 h before diagnostic testing; test started aft er blood glucose is < mg / dl.
37Patient Preparation NPO at least 3 hours prior to the procedure No smoking for 3 hours prior to the procedureEnsure that diabetics receive orange juice 4-12 hrs before examinationBriefly explain to the patient:The oral administration of the radiotracerPositioning and immobilization during the imagingTobacco smoking delays gastric emptying
38Procedure Time 1.5 hrs liquid, up to 3-4 hrs solid Baseline solid Study:Prepare one or two eggs/chicken liver/idli (in AIIMS) and mixed in radiotracerStir and scrambleOr prepare choice of gastronomic vehicle with radiotracerAdminister to patient PO with ml of water. Encourage patient to eat quicklyThe Technetium (Tc)-99m sulfur colloid radiolabeled meal consisted of the equivalent of two large eggs, two slices of bread and jam with water. Emptying of fats is slow as compared to emptying of proteins or carbohydrates. Incomplete meal ingestion can lead to values suggesting more rapid emptying. Vomiting a portion of the ingested meal after the initial baseline image may lead to lower subsequent estimated gastric retention values, so that GE appears faster than it was. extending measurements out to 4 h increases the detection rate of delayed emptying.
39Procedure (cont) Patient Supine Place patient in supine position. Acquisition should be started as quickly as possible after ingestion of foodPosition camera anterior or LAOInstruct patient to remain motionless during imagingObtain Patient images every 5 minutes up to 30 minutes, then every 15 minutes thereafter, allowing the patient to ambulate between imagesOr preset dynamic images for minutes. Patient remain motionless under cameraSupine is good for checking esophageal reflux
40Procedure (cont) Patient standing Position patient standing or sitting, one image facing camera. Optional :one image with back to cameraObtain immediate images, then every 10 minutesStanding, sitting, then standing uses normal movement and gravity to aid realism in study
41Procedure Liquid Study Baseline Liquid StudyAdd 500 uci of 99mTc-DPA TO 120 ml, of water or orange juiceAdminister to patient PO, encourage patient to drink quickly.Images same as solid study, although only imaged for 1.5 hoursLiquid GE tests are generally not clinically useful, because normal emptying of liquids is frequently maintained despite very severe gastroparesis for solids (41). Meals currently used for measuring GE consist of a variety of foods, including chicken liver, eggs, egg whites, oatmeal, or pancakes.
42Normal ResultsLiquid (e.g., radiolabeled water or orange juice ) t1/2 (50%) at minutes ) or 80% in 1 hourSolid (Type and size of meals and population varies): t1/2 (50%) movement out the stomach within a lower limit of 32 minutes to an upper limit of 120 min with and adult mean of 90 min.Delayed GE (gastric retention) was determined to be >90% at 1 h, >60% at 2 h and>10% gastric retention at 4 h.Terminate study before 60 min if gastric emptying becomes > 95%<30% retention at 1 h (50) is indicative of rapid GE. For rapid GE, currently, the 1-h GE value is recommended.
43Wireless motility capsule Medications that alter gastric pH and gastric emptying should be discontinued ≥ 3-7 days before the WMC test. WMC has been FDA approved for evaluation of suspected gastroparesis and of colonic transit in the setting of chronic constipation.
44A schematic representation of the patient procedure for performing a wireless motility capsule study. The WMC should not be administered to patients with a history of gastric bezoar, swallowing disorders, dysphagia to food or pills for any reason, suspected strictures or fistulae along the gastrointestinal tract, physiologic gastrointestinal obstruction, gastrointestinal surgery within the previous 3 months, Crohn's disease, diverticulitis, or an implanted or portal electromechanical medical device (eg, a cardiac pacemaker or infusion pump). The WMC is ingested immediately following ingestion of a standardized 260-kcal nutrient bar (SmartBar, which consists of 17% protein, 66% carbohydrate, 2% fat, and 3% fiber) and 50 mL of water. In order to avoid the potential effects of exercise on transit measurement, the patient is instructed to avoid strenuous or vigorous exercise during the testing period.Farmer A D et al. United European Gastroenterology Journal 2013;
45The external appearance of the wireless motility capsule (a), which records pH, temperature, and pressure in real time as it traverses the GI tract in comparison to a wireless endoscopy capsule (b). A small (6" × 4" × 1.5") lightweight external data recorder containing a rechargeable battery is attached to a specially designed belt worn around the patient’s waist, and the patient is instructed to keep the data receiver within 5 feet of his or her body during the testing period (3–5 days). The patient is instructed regarding how to manually record activities such as meals, sleep, and bowel movements by pushing an event button on the data receiver. the WMC is not dissimilar to the WCE in that it is constructed of polyurethane and contains a battery that provides power to the capsule for at least 5 days.10 The WMC contains a high-frequency transmitter that broadcasts data in real time to an external receiver. The WMC has dimensions of 26.8 mm × 11.7 mm (vis-à-vis the wireless capsule endoscopy (WCE; PillCam; Given Imaging, Israel) measuring 26 × 11 mm). In contrast to the WMC, the WCE encompasses a miniature, encapsulated video camera designed to image the entire small bowel, taking approximately 50,000–60,000 digital images per study.Farmer A D et al. United European Gastroenterology Journal 2013;
46A sample motility graph showing data from a wireless motility capsule A sample motility graph showing data from a wireless motility capsule. Temperature, pH, and pressure measurements can be used to calculate gastric emptying, small bowel transit, colonic transit, and whole gut transit times, as well as other motility information. Immediately following ingestion of the WMC, there is an abrupt rise in recorded temperature from ambient temperature to normal body temperature (approximately 36°C). The WMC’s exit from the stomach is defined by an abrupt rise in pH (≥2 pH units), which corresponds to the capsule’s passage from the acidic environment of the stomach to the more alkaline environment of the proximal duodenum. the WMC, representing a nondigestible solid, has been shown to empty with return of phase 3 of the migrating motor complex, which occurs upon complete emptying of solid food from the stomach. Passage into the cecum is defined by a sustained (>10 minutes in duration) pH drop of at least 1 pH unit, which occurs as the WMC leaves the alkaline environment of the terminal ileum and enters the more acidic environment of the cecum. If the pH drop in the ileocecal junction is not evident, abrupt changes in pressure wave frequency or amplitudemay provide supportive evidence of the transition from the small bowel to the colon. 75% of patients with a GET over 12 hours had a numberof gastric contractions below the fifth percentile of normal, compared to 8% of patients with a GET less than 12 hours. When adding together WMC contractile activity by measuring areas under pressure curves, constipated patients with normal colonic transit (<59 hours) or mildly to moderately delayed transit (59–100 hours) exhibited contractility that was 33–50% higher than in healthy controls. This increase was most prominent in patients with constipation-predominant irritable bowel syndrome. In contrast, a preliminary evaluation of a cohort enriched with severely constipated patients found that profound delays in colonic transit (>100 hours) were associated with significantly reduced contractile activity. the WMC’s manufacturer defined rapid transit as a CTT less than 5 hours and delayed colonic transit as a CTT greater than 59 hours. In a postmarketing analysis of nearly 6,000 shippedcapsules, there have been 20 reports of prolonged capsule retention (5 in the stomach, 2 in the small intestine, and 13 in the colon), which corresponds to a retention rate of 0.33%. An upper endoscopy was required for extraction of the 5 capsules that were retained in the stomach. Of the remaining 15 cases, only 1 capsule required drug intervention; the other 14 capsules passed spontaneously. There were no obstructions requiring surgical intervention.
47Comparison of the various techniques, currently utilized, indicating their relative advantageous and disadvantageous features.Comparison of the various techniques, currently utilized, indicating their relative advantageous and disadvantageous features. Validation studies are extensive for scintigraphy. Results of breath test are unreliable in the presence of malabsorption, liver failure, pancreatic or pulmonary disorders.Farmer A D et al. United European Gastroenterology Journal 2013;
48Clinical impactThe association of delayed emptying with specific symptoms is relatively weakGastric emptying tests do not yield a high diagnostic specificityWith few exceptions, most studies have failed to demonstrate a correlation between the severity of delayed emptying and response to prokineticsAn initial treatment approach should be required before performing gastric emptying testIn refractory patients or in those with symptoms that impair nutritional status or the ability to function normally, assessment of gastric emptying may play a pivotal roleTack J et al. Best Pract Res Clin Gastroenterol. 2009
49GERD-Gastric emptying study Gastroparesis can be associated with and may aggravate GERD.Evaluation for the presence of gastroparesis should be considered in patients with GERD that is refractory to acid-suppressive treatment.Michael Camilleri et al. Clinical Guideline: Management of Gastroparesis. Am J Gastroenterol 2013
50Treatment algorithmPramlintide and GLP-1 analogs may delay gastric emptying in diabetics. Cessation of these treatments and use of alternative approaches should be considered before initiation of therapy for gastroparesis.
52Dietary/Non-medical Poor evidence - Multiple small meals Liquid instead of solid mealsLow fat, Reduce indigestible fiberDiscontinue medications that slow emptying if possible
53NutritionIf oral intake is insuffi cient, then enteral alimentation by jejunostomy tube feeding should be pursued (after a trial of nasoenteric tube feeding).Indications for enteral nutrition include :unintentional loss of 10 % or more of the usual body weight during a period of 3 – 6 monthsrepeated hospitalizations for refractory symptoms.Michael Camilleri et al. Clinical Guideline: Management of Gastroparesis. Am J Gastroenterol 2013
54Antiemetics No evidence from controlled trials Phenothiazines Prochlorperazine (Stemetil)Promethazine (Phenergan)Serotonin 5-HT3 antagonistsOndansetron (Zofran)Muscarinic antagonisitsButylscopolamine (Buscopan)
55Prokinetics-algorithm Metoclopramide (Maxalon)Only FDA approved drug for gastroparesisErythromycinDomperidone (Motilium/Vomidon)Not FDA approved in USCisapride (Prepulsid)Removed from market 2000Cardiac toxicity
56Pasricha et al. J Neurogastroenterol Motil, Vol.19
57Endoscopic Therapy Venting PEG Botox injection – Pylorus Pyloric Balloon Dilation (No published evidence)Temporary placement of stimulation leads in stomach to predict response to more permanent stimulator
58Intrapyloric injection of Botox 23 patients (5 males, 19 idiopathic) underwent 2 UGIEs with 4 week intervalInjection of saline (in 11 as first injection) or botox 4×25 U (in 12 patients) in a cross-over RCTBefore the start of the study and 4 weeks after each treatment, they underwent a solid and liquid gastric emptying breath test with measurement of meal-related symptom scores, and filled out the GCSIGCSI is based on three subscales: post-prandial fullness/early satiety (4 items- stomach fullness, not able to finish a normal size meal, feeling excessively full after meals, loss of appetite); nausea/vomiting (3 items- nausea , rectching, vomitings), and bloating (2 items- bloating, stomach or belly visibly larger).Arts J et al. Aliment Pharmacol Ther. 2007
59Intrapyloric injection of Botox Significant improvement in emptying and GCSI was seen after initial injection of saline or botox.No further improvement occurred after the second injectionNo significant difference in improvements of solid t(1/2) and liquid t(1/2), meal-related symptom scores or GCSIIn a cohort of predominantly idiopathic gastroparesis patients, botox is not superior to placebo in improving either symptoms or the rate of gastric emptying. although there is a need for further study in patients with documented “ pylorospasm. ”Arts J et al. Aliment Pharmacol Ther. 2007
60Surgical Gastrostomy for venting and jejunostomy for feeding Completion gastrectomy in markedly symptomatic PSGPyloroplasty (± jejunal feeding tube placement)Subtotal gastrectomy + Roux-Y reconstruction for gastric atony due to PSG)Gastric Electrical StimulationCost prohibitive especially for TPN
61Gastric Electric Stimulation Gastric Neurostimulation (Enterra) High Frequency (~ 4 x Slow Wave Freq)Low Energy with short pulse12 bpmFrequencyGastric Pacing:Pacing is an application of an electrical stimulus that activates contraction of gastric smooth muscle, entraining at that rate of intrinsic slow wave by a low frequency high energy long pulse stimulation. Pacing needs implantation of too large and heavy batteries. Neurostimulation activates a nausea and vomiting control mechanism utilising a high frequency low energy short pulse stimulation to achieve symptomatic relief. Miniaturisation and implantation is possible with neurostimulation.3 bpm Low Frequency (~ Slow Wave Freq)High Energy with long pulseEnergy
62Mechanisms of action of gastric electrical stimulation UnknownGastric emptying not consistently improvedGastric dysrhythmias not normalisedIncreased gastric accommodationIncreased vagal afferent activityIncreased thalamic activityMcCallum RW et al. Neurogastroenterol Motil 2013
63Enterra therapy: Humanitarian device exemption Enterra therapy was granted approval as a Humanitarian Use Device (HUD) to be used in patients with refractory diabetic or idiopathic gastroparesis, restricted to institutions where Institutional review board approval has been obtainedFDA 2000
64Enterra therapy CE mark Indication Enterra therapy is indicated for the treatment of patients with chronic intractable (drug refractory) nausea and vomitings secondary to gastroparesisGES improves nausea and vomitings more than abdominal pain.
66GES improves nausea an vomitings more than abdominal pain.
67GES for the Treatment of Gastroparesis: A Meta-Analysis 13 papersTotal Symptom Severity ScoreRequirement for Enteral orParenteral Nutritional SupportVomiting Symptom Severity ScoreChange in Weight (kg)Nausea Symptom Severity ScoreOf 13 included studies, 12 lacked controls and only one was blinded and randomized. Following GES, patients reported improvements in total symptom severity score (3/13 studies, mean difference 6.52 ; P = 0.01), vomiting severity score, nausea severity score (4/13), SF-36 physical composite score (4/13), SF-36 mental composite score (4/13), requirement for enteral or parenteral nutrition (8/13), and 4-h gastric emptying (5/13, 12.7%). Weight gain did not reach significance (3/13, 3.68 kg [CI: -0.23, 7.58]; P = 0.07). The device removal or reimplantation rate was 8.3%.O’Grady G, et al. World J Surg 2009; 33:
68GES for the Treatment of Gastroparesis: A Meta-Analysis Complications8.3 %(22/265 patients, 10/13 studies)Infection 8Skin erosion 6Pain at site 4Gastric perforation 2Device migration 1Volvulus 1O’Grady G, et al. World J Surg 2009; 33:
69GES for the Treatment of Gastroparesis: A Meta-Analysis A meta-analysis of 10 studies (n = 601) using high-frequency GES to treat patients with gastroparesis from January 1995 to January 2011GES significantly improved both TSS (P < ) and gastric retention at 2 h (P = 0.003) and 4 h (P < ) in patients with diabetic gastroparesis (DG), while gastric retention at 2 h (P = 0.18) in idiopathic gastroparesis (IG) patients, and gastric retention at 4 h (P = 0.23) in postsurgical gastroparesis (PSG) patients, did not reach significance.High-frequency GES is an effective and safe method for treating refractory gastroparesis. DG patients seem the most responsive to GES, both subjectively and objectively, while the IG and PSG subgroups are less responsive and need further research.Chu H et al. J Gastroenterol Hepatol. 2012
70Glucose Control in Diabetic gastroparesis Patients HbA1c Reductionat 6 and 12 months vs. BaselineBaseline 8.6%Baseline 9.4%Baseline 9.8%At 6 mthsAt 12 mths8.5%8.4%6.5%Forster et al: Further experience with gastric stimulation to treat drug refractory gastroparesis. Am J Surgery 2003; 186(6):Lin et al: Treatment of Diabetic Gastroparesis by High-Frequency Gastric Electrical Stimulation. Diabetes Care 2004; 27(5),Van Der Voort et al: Gastric Electrical Stimulation Results in Improved Metabolic Control in Diabetic Patients Suffering From Gastroparesis. Exp Clin Endocrinol Diabetes 2005; 113:38-42
71Nutritional SupportLin et al: Treatment of Diabetic Gastroparesis by High-Frequency Gastric Electrical Stimulation. Diabetes Care 2004; 27(5),
72Conclusion More studies on gastroparesis are warranted in India WMC is as good and has advantages compared to gastric emptying scintigraphy, the gold standardGES is a good choice for refractory gastroparesisTreatment options are likely to improve after the pathophysiology of gastroparesis is better understood.
74WAVESS*: Study Design Multicenter double blind crossover March 14-15, 1997WAVESS*: Study Design Multicenter double blind crossoverONRandomBaseline1/2Implant1/2OFFPhase IPhase II12612MonthsN= Patients17 diabetic16 idiopathic* Worldwide Anti-Vomiting Electrical Stimulation StudyStudy Initiation Meeting USA, Washington13
75Gastric Electrical Stimulation Enterra System (Medtronic)
76The History of Gastric Stimulation 1972: Kelly and Laforce at Mayo Clinic induced antegrade and retrograde conduction of slow waves in canines with gastric stimulation.1988: McCallum et al at University of Virginia showed increased gastric emptying in canines with vagotomy1997: Familoni et al reported improved peristalsis in canines with GES1998: The WAVESS study group demonstrated the feasibility of GES, leading to Enterra therapy.
77The History of Gastric Stimulation 1963 – Bilgutay et al.: Gastric stimulation was practiced for the treatment of postoperative ileus.
78Surgery Laparoscopy - 3 Ports Left upper quadrant port becomes stimulator pocketLength of stay: 2-3 daysEvaluate neurostimulator parameters before discharge
79Lead Location Greater curvature Leads placed 10cm from pylorus Utilize measuring tape or 10cm suture lengthLeads 1cm apart
80One centimeter electrode length in stomach wall Lead PlacementProximal anchoringpoint utilizingwinged/trumpet anchorOne centimeter electrode length in stomach wall
81Lead Fixation Disc sutured to stomach wall 1-2 sutures Lead suture wire clipped to disc1-2 clips
82Switch on and interrogation Device is initiated remotelyA system check is performed and impedance is checkedPower setting is programmed and rechecked on discharge
83Comparison of methods used to assess gastric emptying Parkman et al. Neurogastroenterol Motil Feb