- Email: [email protected]
W2059 Small Intestinal Bacterial Overgrowth (SIBO) in Patients with Gastroparesis
AGA Abstracts
(p=0.60) between both groups, 270±38 ml and 278±46 ml for HS and FD resp. The lower range of normal (mean-2SD) for accommodation volume was 194 ml in HS. None of the patients with functional dyspepsia had an accommodation volume lower than 194 ml. Accommodation ratio did not differ significantly (p=0.072) between both groups, 11±7 en 8±2 for HS and FD resp. After meal intake (0-15 min) an increase in intragastric contents, apart from the meal, was observed in both groups, 18±33 ml and 11±44 ml for HS and FD resp., only significant in HS (p<0.05). Hereafter (15-30 min) a significant decrease in intragastric contents was observed in both groups, -31±32 ml and -23±24 ml for HS and FD resp. (p<0.05). Conclusions: Using Magnetic Resonance Imaging we did not observe a difference in volume response to a liquid meal between healthy subjects and patients with functional dyspepsia, nor did we observe a difference in accommodation response. These results are in contrast to various barostat studies. After meal intake intragastric contents increased most likely due to gastric secretion. Only in healthy subjects this increase was significant, that might reflect impairment in gastric secretion in patients with functional dyspepsia.
W2057 Growth Hormone Secretagogue Receptor Ligand (GHRL) Gene and G-Protein β3 Subunit (GNB3) Gene Polymorphisms Are Associated with Functional Dyspepsia Kwang Jae Lee, Marie Yeo, Sung Won Cho Background/Aims: Studies on the genetic variation associated with functional gastrointestinal disorders have shown inconsistent results, which is probably attributed to complex multifactorial pathophysiology and ethnic differences. The genotype of GNB3 C825T polymorphism associated with an increased risk of functional dyspepsia (FD) is not consistent in previous studies. Various candidate genes may be relevant to FD. There may be a ethnic difference of genetic susceptibility of FD. Thus, we aimed to examine genetic variations of candidate genes, including ADRA2A, ADRA2C, GNB3, GHRL, and SLC6A4, in FD patients and in healthy subjects. Methods: 140 patients with FD, diagnosed by the Rome II criteria and 139 healthy controls who had no chronic or recurrent GI symptoms participated in the study. FD was subcategorized into dysmotility-like dyspepsia (FD-Dy), ulcer-like dyspepsia (FD-Ul) and unclassified (FD-Un). Thirty-two validated single nucleotide polymorphisms (SNPs) were selected from a public SNP database, based on the previous reports and the functional location within the gene. Genotyping was performed using multiplex PCR and the complementary oligonucleotides arrayed on the microplates (SNPware Tag array). Genetic association analysis by presuming the four genetic models and performing logistic regression was carried out. Results: Twenty-five SNPs were polymorphic, defined by a minor allele frequency > 0.05, in healthy controls, which were not significantly deviated from the HardyWeinberg equilibrium. GA and AA genotypes of GHRL IVS3-1069G/A (rs42451), relative to GG genotype, and CC genotype of GNβ3 1569A/C (rs5439), relative to AA and AC genotypes, were associated with a decreased risk of FD. There was no genotype of candidate genes significantly associated with FD-Dy. However, CT and TT genotypes of GHRL 2278C/ T (rs1703262), relative to CC genotype, and GA and AA genotypes of GHRL IVS3-1069A/ G (rs42451), relative to GG genotype, were associated with an increased risk of FD-Ul. GC and CC genotypes of GHRL 1062G/C (rs26311), relative to GG genotype, and CT and TT genotypes of GNβ3 2719C/T (rs3759348), relative to CC genotype, were associated with an increased risk of FD-Un. None of the SNPs of CRHR2, ADRA2A, ADRA2C and SLC6A4 genes revealed significant associations with FD or subtypes of FD. Conclusions: GHRL and GNB3 genotypes seem to be implicated in genetic susceptibility to FD or subgroups of FD.
W2055 Race Differences in Symptoms, Health Related Quality of Life and Gastric Emptying in Patients with Gastroparesis Monik Kowalczyk, Susmita Paladugu, Kathleen C. Parkman, John Gaughan, Robert S. Fisher, Henry P. Parkman Gastroparesis, characterized by symptoms of early satiety, nausea, vomiting, and abdominal discomfort, has a negative impact on patients' quality of life. Stroke, diabetes and coronary artery disease have a greater negative impact on quality of life in African-Americans compared to Caucasians. Currently, there are no reported data evaluating the effect of race on the symptoms and quality of life in patients with gastroparesis. PURPOSE: The aim of this study was to assess the relationship of race on severity of symptoms, quality of life, and gastric emptying in patients with gastroparesis. METHODS: All new patients with gastroparesis seen at Temple University Hospital between January 2007 and October 2008 were given the following validated questionnaires: Patient Assessment of Upper Gastrointestinal Disorder Symptoms (SYM); Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (QOL). Gastric emptying (GE) of radiolabeled egg sandwich was measured. Student t-test and Fisher exact test were used to assess differences between white and non-white populations. The effects of other demographic variables (age, gender, education, marital status, income, occupation, diabetes) on symptoms, quality of life, and gastric emptying were assessed using analysis of covariance. RESULTS: 41 non-white patients (mean age 45±2.0 (SEM) years, 83% female; 61% African American, 30% Hispanic, and 7% Asian) and 219 white patients (mean age of 42±1.0 years, 82% female) were studied. There were no significant differences between non-white and white patients with respect to age, gender, education, occupation, diabetes, and marital status. White patients had significantly higher income. Non-white patients reported significantly worse symptoms {SYM total score (2.87±0.14 vs 2.52±0.07, p=0.04), SYM nausea/vomiting score (2.99±0.22 vs 2.11±0.1, p=0.004)}. QOL total score (2.29±0.18 vs 2.67±0.08, p=0.04) and QOL clothing score (2.30±0.28 vs 3.24±0.12, p=0.003) were lower in non-white patients. Non-white patients had slower values of GE at 2 hours (59±3 vs 49±2 percent gastric retention, p=0.01) and 4 hours (36±5 vs 17±2 % retention, p=0.027). Other demographic variables had no consistent effect on these findings. CONCLUSIONS: Non-white patients with gastroparesis have worse symptoms, quality of life, and slower gastric emptying compared to white patients. There was no consistent effect of other demographic variables on symptoms, quality of life, or gastric emptying. Our results suggest that race has an independent effect on severity of symptoms, quality of life and gastric emptying in patients with gastroparesis.
W2058 Associations of the Status of Interstitial Cells of Cajal and Electrogastrogram Parameters, Gastric Emptying and Symptoms in Patients with Gastroparesis Zhiyue Lin, Jameson Forster, Irene Sarosiek, Ivan Damjanov, Richard McCallum The aim of this study was to investigate the association between the status of interstitial cells of Cajal (ICCs) and electrosgastrogram (EGG) parameter, gastric emptying and symptoms in a large cohort of patients with gastroparesis. Forty-one patients with refractory gastroparesis who were referred for gastric electrical stimulation (GES) underwent full thickness gastric (antrum) biopsy during the surgery to place the GES device. The biopsy samples were stained with c-kit and scored for the presence of ICCs. EGG recordings were obtained before surgery in the fasting state and after a test meal. All patients underwent a 4-hour standardized scintigraphic gastric emptying study and symptom assessment prior to surgery. Based on antral biopsy, 15 patients (36%) had almost no ICCs (ICC- group) and 26 patients had adequate cell numbers (ICC+ group). EGG recordings in ICC- group displayed significantly less normal slow waves than in ICC+ group both in the fasting (60±7% vs. 76±3%, p=0.02) and fed states (67±8% vs. 80±2%, p=0.03). Tachygastria in ICC- group was significantly more than in ICC+ group both in the fasting (32±8% vs. 11±2%, p=0.001) and fed states (27±9% vs. 12±2%, p=0.02). There were no statistical differences in gastric emptying and symptom severity of gastroparesis, etiology, age and gender between two groups. Conclusions: 1) absence of ICCs occurs in up to 36% of gastroparetic patients and is correlated with an abnormal EGG; 2) absence of ICCs does not correlate with the degree of gastroparesis as assessed by gastric emptying or symptom severity. These data suggest that the EGG may have a role for predicting ICC status during clinical evaluation of gastroparetic patients.
W2056 Sepiapterin, a Precursor for Tetrahydrobiopterin (Bh4, a Cofactor for nNOS Activity), Restores Gastric Emptying and nNOS Alpha Protein Expression in Female Diabetic Rats Pandu R. Gangula, Pankaj J. Pasricha Background: Gastroparesis affects females predominantly but the biological basis of this gender bias is unknown. Recently, we have shown that tetrahydrobiopterin (BH4), a major co-factor for nitric oxide synthases is significantly restored gastric emptying and nNOSalpha dimerization in female gastric at the onset of diabetes. Recent studies have been demonstrated that cellular BH4 content is primarily upregulated via salvage pathway. In this study, we have investigated whether supplementation of sepiapterin, a precursor for BH4 biosynthesis via salvage pathway restores gastric emptying and NO synthesis in a time dependent manner in female diabetic rats. Results: In Vitro studies on gastric LM-MPs (longitudinal musclemyenteric plexus) showed that methotrexate, an inhibitor of BH4 synthesis via salvage pathway, significantly (p<0.05) decreased nNOSα protein expression and NO release (0.39±0.03 vs. 1.50±0.38 μmole/mg tissue). In Vivo, diabetic female rats showed a significantly (p<0.05) greater reduction in solid gastric emptying and NO synthesis compared to male diabetics. Supplementation of sepiapterin for 10 days, significantly (75±5.9 %) (p<0.05) attenuated delayed gastric emptying for solids in diabetic female rats. In addition, sepiapterin supplementation restored impaired nitrergic relaxation and gastric nNOSα protein expression in diabetic females. Conclusions: The above data suggests that impaired bioavailability of NO may be associated with decreased BH4 biosynthesis via salvage pathway. Supplementation of sepiapterin accelerated gastric emptying and gastric nNOS alpha expression .Sepiapterin may be beneficial to improve endogenous BH4 content and thus control gastroparesis in female diabetic patents.
AGA Abstracts
W2059 Small Intestinal Bacterial Overgrowth (SIBO) in Patients with Gastroparesis Maryam Khorrami, Javier Gomez, Henry P. Parkman, John Gaughan, Robert S. Fisher Gastroparesis is chronic motility disorder characterized by delayed gastric emptying with symptoms of nausea, vomiting, abdominal pain, and bloating. Some symptoms of gastroparesis are similar to that of small intestinal bacterial overgrowth (SIBO) including bloating and abdominal discomfort. The aims of this study were to determine the prevalence of SIBO in patients with gastroparesis and to determine the most common symptoms suggesting SIBO in gastroparesis patients. Methods: 235 charts of patients (F=153, M=82, mean age= 46±15 yrs) who underwent a lactulose breath test (LBT) for symptoms suggesting SIBO and/or gastroparesis from July 2007 to June 2008 were reviewed. After fasting for 8 hours and filling a modified Patient's Assessment of GI Symptoms (PAGI-SYM) questionnaire, patients underwent LBT consisting of ingestion of 10 gram of lactulose in 150 cc of water with breath samples collection at baseline and 15 minutes intervals for 3 hours. Hydrogen (H2) and Methane (CH4) levels in breath samples were measured using a Quintron DP Microanalyzer. An abnormal LBT was defined according to Quintron criteria as a biphasic pattern in H2/CH4 with an early increase of ≥20 ppm within 120 min followed by a larger peak. The data were also evaluated using two other criteria (Pimentel, King). 169 of these patients had gastric emptying study (GES). Statistical analysis to determine the prevalence of SIBO in gastroparetics was performed utilizing Chi-Square and t-test. Results: Using the Quintron criteria, 23 of 72 (32%) patients with delayed GES had a positive LBT, whereas 27 of 97 patients (28%) had positive LBT (p=0.61). In evaluating the LBT result using Pimentel criteria, 44% patients with delayed GES had positive LBT whereas 38% of patients with normal GES had positive LBT (p=0.43). Furthermore, the King criteria showed 34% of patients with delayed GES had positive LBT and 36% of patients with normal GES had
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on day 1, 6 days (days 2-7) of treatment with clonidine, a second GE test on day 8 with IV infusion of vasopressin (to induce nausea and vomiting), 6 more days (days 9-14) of treatment with clonidine with two-channel GES of dual pulses given for 4 hours after the ingestion of food, a third GE test on day 15 with GES turned on and vasopressin given and a fourth GE test on day 16 with GES on, vasopressin given and atropine injected before GES was turned on. GE was determined by the oral ingestion of boost mixed with phenol red and the amount of phenol red collected from the duodenal cannula. Vomiting and animal behaviors suggestive nausea were recorded using a previously validated method. Results: 1) Clonidine and vasopressin delayed GE at 60min from 81.8±3.2% at baseline to 23.0±5.0% (P<0.001) and increased the symptom score from 0±0 at baseline to 6.8±0.5 (P<0.001). 2) Chronic GES increased GE at 60 min to 66.6±3.7% (P<0.01 vs clonidine/ vasopressin without GES) and decreased the symptom score by 62% to 2.6±0.9 (P<0.01 vs no-GES). 3) The ameliorating effects of GES on gastric emptying and symptoms were blocked by atropine. 4) No adverse events, such as infection or mal-function of device, were noted during the entire study period. Conclusions: The newly developed two-channel dual pulse stimulator is feasible and safe for implantation and chronic GES with two-channel GES is able to improve gastroparesis induced by clonidine and nausea and vomiting induced by vasopressin. This new device may be a better therapy for gastroparesis.
W2060 A Single Centre Audit of the Indications and Clinical Impact of Prolonged Ambulatory Small Intestinal Manometry Daphne Ang, Rita Vos, Antoine Degreef, Raf Bisschops, Jan F. Tack Background: Small bowel manometry is an investigative modality available only in a few specialised referral centres. Its exact place in the management of refractory symptoms is controversial. Aims: To provide a re-appraisal of the role of ambulatory small bowel manometry today in the assessment of small intestinal motor function. Methods: The records of all patients who underwent 24 hour ambulatory duodenojejunal manometry from January 2000 to June 2007 were retrospectively reviewed. We studied the clinical indications for small bowel manometry, and reviewed the impact of manometric findings on the patients' subsequent clinical outcome. A total of 146 studies were performed for 137 patients (46M, 91F) with a mean age of 44.9 ± 15.7 years (range 14-79 years). Mean follow-up duration was 15.1±22.6 months. Appropriate endoscopic, radiological and gastric scintigraphic studies were performed in all patients prior to small bowel manometry. Criteria for abnormal motor activity was based on the classification by Bharucha. (Gut 1993). Results: The indications for small bowel manometry were chronic abdominal pain (n=43), slow-transit constipation (n=17), refractory gastroparesis(n=16), chronic diarrhoea (n=7), recurrent episodes of subacute small intestinal obstruction(n=16), post-surgical evaluation (n=36), suspicion of gut involvement in systemic disease (n=9) and unexplained nausea (n=2). The most common finding was a normal 24 hour ambulatory small bowel manometry (n=113). A total of 33 studies yielded abnormal findings which included extrinsic neuropathy (n=6), intrinsic neuropathy (n=18), intestinal myopathy (n=2) and mechanical subocclusion (n=7).The impact of small bowel manometry is illustrated in the table. In patients who had undergone prior extensive investigations, ambulatory small bowel manometry excluded a generalised motility disorder in 77% and had a significant impact on the subsequent clinical course in 23%. Conclusions: Ambulatory small bowel manometry is a useful and safe diagnostic tool to complement traditional investigative modalities in patients with unexplained abdominal symptoms.
W2062 Value of Liquid Gastric Emptying in Addition to Solid Gastric Emptying for Evaluation for Gastroparesis Priyanka Sachdeva, Umar Khayyam, Alan H. Maurer, Robert S. Fisher, Henry P. Parkman Gastric emptying scintigraphy (GES) of solids is traditionally used to evaluate patients with dyspeptic symptoms to assess for delayed gastric emptying. Liquid emptying is thought to be preserved until late stages of gastroparesis, and not needed for evaluation for delayed gastric emptying. At our institution, radiolabeled water is often used simultaneously during GES for evaluation of liquid gastric emptying and small bowel transit (SBT). Aim: To determine the value of measuring gastric emptying of liquids in addition to solids for assessing patients for delayed gastric emptying. Methods: 178 patients were referred to our institution from 9/2007 to 9/2008, for GES with assessment of liquid gastric emptying and SBT. An EggBeaters meal radiolabeled with Tc-99m was used for solid GES and 300cc of water radiolabeled with In-111 for liquid GES and SBT. Imaging was performed at 0,0.5,1,2,3,4 hrs for solids and 0.5,1,2,6 hrs for liquids. A modified Patient Assessment of GI Symptoms (PAGI-SYM) questionnaire was used to record symptoms and the total Gastroparesis Cardinal Symptom Index (GCSI) score was calculated to assess symptom severity. Results: 117 patients met inclusion criteria (not on medications affecting gastric motility in 48 hrs prior to test or prior gastric surgery). Solid and liquid gastric emptying were significantly correlated at 30 min (r =0.684; p<0.001), 60 min (r =0.686; p<0.001) and 120 min (r= 0.793; p<0.001). The table below shows patient distribution based on GES results. Of note, there were 10 patients who had normal solid GES but showed delayed liquid emptying. These represent 8.5% of all 117 patients, but 16% of the 62 patients with normal GES. This group had 9 females and 1 male; none had diabetes and hence also represents 13% of all non-diabetics and 30% of non-diabetic patients with normal solid GES. Using the modified PAGI-SYM, liquid gastric retention at 30 min was correlated with loss of appetite (r=-0.215; p=0.036), and liquid gastric retention at 30 min and 60 min was correlated with the number of bowel movements per week (r=-0.292; p=0.009 and r=-0.280, p=0.012 respectively). Conclusions: Gastric emptying of liquids has a good correlation with gastric emptying of solids. However, there is additional value in measuring liquid gastric emptying for evaluating patients with gastroparesis, particularly in non-diabetic patients where 30% of patients with normal solid phase emptying can demonstrate delayed emptying of liquids.
W2063 Functional Dyspepsia in Patients with GERD Before and After Fundoplication Robert Scheffer, Hilda G. Rijnhart-de Jong, Hein G. Gooszen Functional dyspepsia (FD) is highly prevalent in patients with gastroesophageal reflux disease (GERD). The pathogenesis of FD is still unclear. Several pathophysiological mechanisms currently proposed to be involved in FD symptom generation include delayed gastric emptying and impaired gastric accommodation to a meal. Whilst fundoplication impairs gastric accommodation and accelerates gastric empyting, it's effect on functional dyspeptic symptoms, especially epigastric pain syndrome and postprandial distress syndrome, has not yet been investigated. Fifty patients (36 men, 18 women) with endoscopically and/or pHmetrically proven GERD were included in this study. Functional dyspeptic symptoms were scored using a visual analogue scale before, at 3 months and at 12 months after laparoscopic Nissen fundoplication. The diagnosis of functional dyspepsia was assessed according to the Rome III criteria. Symptom relief was reported in 84.5 and 91.5% at 3 months and 96.1 and 94.5% at 1 year after fundoplication for pyrosis and regurgitation respectively. Mean epigastric pain or burning (epigastric pain syndrome) symptoms were markedly more severe before (44.3, 32.6% resp.) than at 3 months (17.3, 6.3% resp.; both P< 0.001) and at 1 year (14.3, 6.8% resp.; both P<0.001) after fundoplication. Mean severity of meal-related symptoms such as fullness and early satiety (postprandial distress syndrome) decreased from (41.3, 24.2% resp.) to (18.3, 20.9% resp.; P=0.001 and P=0.44) at 3 months and (16.1, 13.9% resp.; P<0.001 and P=0.12) at 1 year. Conclusions: 1. Epigastric and meal-related dyspeptic symptoms are prevalent in GERD. 2. Both epigastric and meal-related symptoms diminish after a successful fundoplication. 3. Both epigastric pain syndrome and postprandial distress syndrome are not a contraindication for antireflux surgery.
W2061 A Newly Developed Implantable Two-Channel Stimulator with Dual Pulses Improves Both Gastric Emptying and Nausea and Vomiting in Dogs Geng-Qing Song, Yong Lei, Robert A. Ross, Jiande Chen The Enterra therapy (gastric electrical stimulation, GES with short pulses) has been shown to improve nausea and vomiting without consistent effects on gastric emptying, and is the only commercially able implantable stimulator. Recent animal studies have revealed improvement in both symptoms and gastric emptying with GES of dual pulses (combination of short and long pusles). The aims of this study were to develop an implantable stimulator capable of generating dual pulses and to investigate the efficacy of this novel implantable stimulator on emetic symptoms and gastric emptying in a chronic canine model. Methods: An implantable stimulator was designed and developed that was able to generate twochannel dual pulses and programmable remotely using a special wander. The test of the device was performed in five female dogs with chronically implanted with a duodenal cannula (for assessing gastric emptying) and two pairs of electrodes placed along the greater curvature at an interval of 8-10cm and connected to the stimulator that was implanted in a subcutaneous pouch. The study protocol included a baseline gastric emptying (GE) test
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AGA Abstracts
AGA Abstracts
positive LBT (p=1.0). In most cases, there was an agreement in determining an abnormal LBT (κ =0.78). There was no difference in symptoms in the gastroparetic patients with positive or negative LBT using the Quintron criteria. However, early satiety (p=0.04) and upper abdominal pain (p= 0.02) in Pimentel's criteria and regurgitation (p=0.05) in King's criteria were statistically associated with a positive LBT. Conclusions: This study shows a 32% prevalence of a positive LBT in patients with delayed GES, a slightly higher value than the 28% prevalence in patients with normal GES, both higher than the 4-10% prevalence of SIBO in the general population. Symptoms did not reliably predict a positive LBT in patients with delayed GES.
(p=0.60) between both groups, 270±38 ml and 278±46 ml for HS and FD resp. The lower range of normal (mean-2SD) for accommodation volume was 194 ml in HS. None of the patients with functional dyspepsia had an accommodation volume lower than 194 ml. Accommodation ratio did not differ significantly (p=0.072) between both groups, 11±7 en 8±2 for HS and FD resp. After meal intake (0-15 min) an increase in intragastric contents, apart from the meal, was observed in both groups, 18±33 ml and 11±44 ml for HS and FD resp., only significant in HS (p<0.05). Hereafter (15-30 min) a significant decrease in intragastric contents was observed in both groups, -31±32 ml and -23±24 ml for HS and FD resp. (p<0.05). Conclusions: Using Magnetic Resonance Imaging we did not observe a difference in volume response to a liquid meal between healthy subjects and patients with functional dyspepsia, nor did we observe a difference in accommodation response. These results are in contrast to various barostat studies. After meal intake intragastric contents increased most likely due to gastric secretion. Only in healthy subjects this increase was significant, that might reflect impairment in gastric secretion in patients with functional dyspepsia.
W2057 Growth Hormone Secretagogue Receptor Ligand (GHRL) Gene and G-Protein β3 Subunit (GNB3) Gene Polymorphisms Are Associated with Functional Dyspepsia Kwang Jae Lee, Marie Yeo, Sung Won Cho Background/Aims: Studies on the genetic variation associated with functional gastrointestinal disorders have shown inconsistent results, which is probably attributed to complex multifactorial pathophysiology and ethnic differences. The genotype of GNB3 C825T polymorphism associated with an increased risk of functional dyspepsia (FD) is not consistent in previous studies. Various candidate genes may be relevant to FD. There may be a ethnic difference of genetic susceptibility of FD. Thus, we aimed to examine genetic variations of candidate genes, including ADRA2A, ADRA2C, GNB3, GHRL, and SLC6A4, in FD patients and in healthy subjects. Methods: 140 patients with FD, diagnosed by the Rome II criteria and 139 healthy controls who had no chronic or recurrent GI symptoms participated in the study. FD was subcategorized into dysmotility-like dyspepsia (FD-Dy), ulcer-like dyspepsia (FD-Ul) and unclassified (FD-Un). Thirty-two validated single nucleotide polymorphisms (SNPs) were selected from a public SNP database, based on the previous reports and the functional location within the gene. Genotyping was performed using multiplex PCR and the complementary oligonucleotides arrayed on the microplates (SNPware Tag array). Genetic association analysis by presuming the four genetic models and performing logistic regression was carried out. Results: Twenty-five SNPs were polymorphic, defined by a minor allele frequency > 0.05, in healthy controls, which were not significantly deviated from the HardyWeinberg equilibrium. GA and AA genotypes of GHRL IVS3-1069G/A (rs42451), relative to GG genotype, and CC genotype of GNβ3 1569A/C (rs5439), relative to AA and AC genotypes, were associated with a decreased risk of FD. There was no genotype of candidate genes significantly associated with FD-Dy. However, CT and TT genotypes of GHRL 2278C/ T (rs1703262), relative to CC genotype, and GA and AA genotypes of GHRL IVS3-1069A/ G (rs42451), relative to GG genotype, were associated with an increased risk of FD-Ul. GC and CC genotypes of GHRL 1062G/C (rs26311), relative to GG genotype, and CT and TT genotypes of GNβ3 2719C/T (rs3759348), relative to CC genotype, were associated with an increased risk of FD-Un. None of the SNPs of CRHR2, ADRA2A, ADRA2C and SLC6A4 genes revealed significant associations with FD or subtypes of FD. Conclusions: GHRL and GNB3 genotypes seem to be implicated in genetic susceptibility to FD or subgroups of FD.
W2055 Race Differences in Symptoms, Health Related Quality of Life and Gastric Emptying in Patients with Gastroparesis Monik Kowalczyk, Susmita Paladugu, Kathleen C. Parkman, John Gaughan, Robert S. Fisher, Henry P. Parkman Gastroparesis, characterized by symptoms of early satiety, nausea, vomiting, and abdominal discomfort, has a negative impact on patients' quality of life. Stroke, diabetes and coronary artery disease have a greater negative impact on quality of life in African-Americans compared to Caucasians. Currently, there are no reported data evaluating the effect of race on the symptoms and quality of life in patients with gastroparesis. PURPOSE: The aim of this study was to assess the relationship of race on severity of symptoms, quality of life, and gastric emptying in patients with gastroparesis. METHODS: All new patients with gastroparesis seen at Temple University Hospital between January 2007 and October 2008 were given the following validated questionnaires: Patient Assessment of Upper Gastrointestinal Disorder Symptoms (SYM); Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (QOL). Gastric emptying (GE) of radiolabeled egg sandwich was measured. Student t-test and Fisher exact test were used to assess differences between white and non-white populations. The effects of other demographic variables (age, gender, education, marital status, income, occupation, diabetes) on symptoms, quality of life, and gastric emptying were assessed using analysis of covariance. RESULTS: 41 non-white patients (mean age 45±2.0 (SEM) years, 83% female; 61% African American, 30% Hispanic, and 7% Asian) and 219 white patients (mean age of 42±1.0 years, 82% female) were studied. There were no significant differences between non-white and white patients with respect to age, gender, education, occupation, diabetes, and marital status. White patients had significantly higher income. Non-white patients reported significantly worse symptoms {SYM total score (2.87±0.14 vs 2.52±0.07, p=0.04), SYM nausea/vomiting score (2.99±0.22 vs 2.11±0.1, p=0.004)}. QOL total score (2.29±0.18 vs 2.67±0.08, p=0.04) and QOL clothing score (2.30±0.28 vs 3.24±0.12, p=0.003) were lower in non-white patients. Non-white patients had slower values of GE at 2 hours (59±3 vs 49±2 percent gastric retention, p=0.01) and 4 hours (36±5 vs 17±2 % retention, p=0.027). Other demographic variables had no consistent effect on these findings. CONCLUSIONS: Non-white patients with gastroparesis have worse symptoms, quality of life, and slower gastric emptying compared to white patients. There was no consistent effect of other demographic variables on symptoms, quality of life, or gastric emptying. Our results suggest that race has an independent effect on severity of symptoms, quality of life and gastric emptying in patients with gastroparesis.
W2058 Associations of the Status of Interstitial Cells of Cajal and Electrogastrogram Parameters, Gastric Emptying and Symptoms in Patients with Gastroparesis Zhiyue Lin, Jameson Forster, Irene Sarosiek, Ivan Damjanov, Richard McCallum The aim of this study was to investigate the association between the status of interstitial cells of Cajal (ICCs) and electrosgastrogram (EGG) parameter, gastric emptying and symptoms in a large cohort of patients with gastroparesis. Forty-one patients with refractory gastroparesis who were referred for gastric electrical stimulation (GES) underwent full thickness gastric (antrum) biopsy during the surgery to place the GES device. The biopsy samples were stained with c-kit and scored for the presence of ICCs. EGG recordings were obtained before surgery in the fasting state and after a test meal. All patients underwent a 4-hour standardized scintigraphic gastric emptying study and symptom assessment prior to surgery. Based on antral biopsy, 15 patients (36%) had almost no ICCs (ICC- group) and 26 patients had adequate cell numbers (ICC+ group). EGG recordings in ICC- group displayed significantly less normal slow waves than in ICC+ group both in the fasting (60±7% vs. 76±3%, p=0.02) and fed states (67±8% vs. 80±2%, p=0.03). Tachygastria in ICC- group was significantly more than in ICC+ group both in the fasting (32±8% vs. 11±2%, p=0.001) and fed states (27±9% vs. 12±2%, p=0.02). There were no statistical differences in gastric emptying and symptom severity of gastroparesis, etiology, age and gender between two groups. Conclusions: 1) absence of ICCs occurs in up to 36% of gastroparetic patients and is correlated with an abnormal EGG; 2) absence of ICCs does not correlate with the degree of gastroparesis as assessed by gastric emptying or symptom severity. These data suggest that the EGG may have a role for predicting ICC status during clinical evaluation of gastroparetic patients.
W2056 Sepiapterin, a Precursor for Tetrahydrobiopterin (Bh4, a Cofactor for nNOS Activity), Restores Gastric Emptying and nNOS Alpha Protein Expression in Female Diabetic Rats Pandu R. Gangula, Pankaj J. Pasricha Background: Gastroparesis affects females predominantly but the biological basis of this gender bias is unknown. Recently, we have shown that tetrahydrobiopterin (BH4), a major co-factor for nitric oxide synthases is significantly restored gastric emptying and nNOSalpha dimerization in female gastric at the onset of diabetes. Recent studies have been demonstrated that cellular BH4 content is primarily upregulated via salvage pathway. In this study, we have investigated whether supplementation of sepiapterin, a precursor for BH4 biosynthesis via salvage pathway restores gastric emptying and NO synthesis in a time dependent manner in female diabetic rats. Results: In Vitro studies on gastric LM-MPs (longitudinal musclemyenteric plexus) showed that methotrexate, an inhibitor of BH4 synthesis via salvage pathway, significantly (p<0.05) decreased nNOSα protein expression and NO release (0.39±0.03 vs. 1.50±0.38 μmole/mg tissue). In Vivo, diabetic female rats showed a significantly (p<0.05) greater reduction in solid gastric emptying and NO synthesis compared to male diabetics. Supplementation of sepiapterin for 10 days, significantly (75±5.9 %) (p<0.05) attenuated delayed gastric emptying for solids in diabetic female rats. In addition, sepiapterin supplementation restored impaired nitrergic relaxation and gastric nNOSα protein expression in diabetic females. Conclusions: The above data suggests that impaired bioavailability of NO may be associated with decreased BH4 biosynthesis via salvage pathway. Supplementation of sepiapterin accelerated gastric emptying and gastric nNOS alpha expression .Sepiapterin may be beneficial to improve endogenous BH4 content and thus control gastroparesis in female diabetic patents.
AGA Abstracts
W2059 Small Intestinal Bacterial Overgrowth (SIBO) in Patients with Gastroparesis Maryam Khorrami, Javier Gomez, Henry P. Parkman, John Gaughan, Robert S. Fisher Gastroparesis is chronic motility disorder characterized by delayed gastric emptying with symptoms of nausea, vomiting, abdominal pain, and bloating. Some symptoms of gastroparesis are similar to that of small intestinal bacterial overgrowth (SIBO) including bloating and abdominal discomfort. The aims of this study were to determine the prevalence of SIBO in patients with gastroparesis and to determine the most common symptoms suggesting SIBO in gastroparesis patients. Methods: 235 charts of patients (F=153, M=82, mean age= 46±15 yrs) who underwent a lactulose breath test (LBT) for symptoms suggesting SIBO and/or gastroparesis from July 2007 to June 2008 were reviewed. After fasting for 8 hours and filling a modified Patient's Assessment of GI Symptoms (PAGI-SYM) questionnaire, patients underwent LBT consisting of ingestion of 10 gram of lactulose in 150 cc of water with breath samples collection at baseline and 15 minutes intervals for 3 hours. Hydrogen (H2) and Methane (CH4) levels in breath samples were measured using a Quintron DP Microanalyzer. An abnormal LBT was defined according to Quintron criteria as a biphasic pattern in H2/CH4 with an early increase of ≥20 ppm within 120 min followed by a larger peak. The data were also evaluated using two other criteria (Pimentel, King). 169 of these patients had gastric emptying study (GES). Statistical analysis to determine the prevalence of SIBO in gastroparetics was performed utilizing Chi-Square and t-test. Results: Using the Quintron criteria, 23 of 72 (32%) patients with delayed GES had a positive LBT, whereas 27 of 97 patients (28%) had positive LBT (p=0.61). In evaluating the LBT result using Pimentel criteria, 44% patients with delayed GES had positive LBT whereas 38% of patients with normal GES had positive LBT (p=0.43). Furthermore, the King criteria showed 34% of patients with delayed GES had positive LBT and 36% of patients with normal GES had
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on day 1, 6 days (days 2-7) of treatment with clonidine, a second GE test on day 8 with IV infusion of vasopressin (to induce nausea and vomiting), 6 more days (days 9-14) of treatment with clonidine with two-channel GES of dual pulses given for 4 hours after the ingestion of food, a third GE test on day 15 with GES turned on and vasopressin given and a fourth GE test on day 16 with GES on, vasopressin given and atropine injected before GES was turned on. GE was determined by the oral ingestion of boost mixed with phenol red and the amount of phenol red collected from the duodenal cannula. Vomiting and animal behaviors suggestive nausea were recorded using a previously validated method. Results: 1) Clonidine and vasopressin delayed GE at 60min from 81.8±3.2% at baseline to 23.0±5.0% (P<0.001) and increased the symptom score from 0±0 at baseline to 6.8±0.5 (P<0.001). 2) Chronic GES increased GE at 60 min to 66.6±3.7% (P<0.01 vs clonidine/ vasopressin without GES) and decreased the symptom score by 62% to 2.6±0.9 (P<0.01 vs no-GES). 3) The ameliorating effects of GES on gastric emptying and symptoms were blocked by atropine. 4) No adverse events, such as infection or mal-function of device, were noted during the entire study period. Conclusions: The newly developed two-channel dual pulse stimulator is feasible and safe for implantation and chronic GES with two-channel GES is able to improve gastroparesis induced by clonidine and nausea and vomiting induced by vasopressin. This new device may be a better therapy for gastroparesis.
W2060 A Single Centre Audit of the Indications and Clinical Impact of Prolonged Ambulatory Small Intestinal Manometry Daphne Ang, Rita Vos, Antoine Degreef, Raf Bisschops, Jan F. Tack Background: Small bowel manometry is an investigative modality available only in a few specialised referral centres. Its exact place in the management of refractory symptoms is controversial. Aims: To provide a re-appraisal of the role of ambulatory small bowel manometry today in the assessment of small intestinal motor function. Methods: The records of all patients who underwent 24 hour ambulatory duodenojejunal manometry from January 2000 to June 2007 were retrospectively reviewed. We studied the clinical indications for small bowel manometry, and reviewed the impact of manometric findings on the patients' subsequent clinical outcome. A total of 146 studies were performed for 137 patients (46M, 91F) with a mean age of 44.9 ± 15.7 years (range 14-79 years). Mean follow-up duration was 15.1±22.6 months. Appropriate endoscopic, radiological and gastric scintigraphic studies were performed in all patients prior to small bowel manometry. Criteria for abnormal motor activity was based on the classification by Bharucha. (Gut 1993). Results: The indications for small bowel manometry were chronic abdominal pain (n=43), slow-transit constipation (n=17), refractory gastroparesis(n=16), chronic diarrhoea (n=7), recurrent episodes of subacute small intestinal obstruction(n=16), post-surgical evaluation (n=36), suspicion of gut involvement in systemic disease (n=9) and unexplained nausea (n=2). The most common finding was a normal 24 hour ambulatory small bowel manometry (n=113). A total of 33 studies yielded abnormal findings which included extrinsic neuropathy (n=6), intrinsic neuropathy (n=18), intestinal myopathy (n=2) and mechanical subocclusion (n=7).The impact of small bowel manometry is illustrated in the table. In patients who had undergone prior extensive investigations, ambulatory small bowel manometry excluded a generalised motility disorder in 77% and had a significant impact on the subsequent clinical course in 23%. Conclusions: Ambulatory small bowel manometry is a useful and safe diagnostic tool to complement traditional investigative modalities in patients with unexplained abdominal symptoms.
W2062 Value of Liquid Gastric Emptying in Addition to Solid Gastric Emptying for Evaluation for Gastroparesis Priyanka Sachdeva, Umar Khayyam, Alan H. Maurer, Robert S. Fisher, Henry P. Parkman Gastric emptying scintigraphy (GES) of solids is traditionally used to evaluate patients with dyspeptic symptoms to assess for delayed gastric emptying. Liquid emptying is thought to be preserved until late stages of gastroparesis, and not needed for evaluation for delayed gastric emptying. At our institution, radiolabeled water is often used simultaneously during GES for evaluation of liquid gastric emptying and small bowel transit (SBT). Aim: To determine the value of measuring gastric emptying of liquids in addition to solids for assessing patients for delayed gastric emptying. Methods: 178 patients were referred to our institution from 9/2007 to 9/2008, for GES with assessment of liquid gastric emptying and SBT. An EggBeaters meal radiolabeled with Tc-99m was used for solid GES and 300cc of water radiolabeled with In-111 for liquid GES and SBT. Imaging was performed at 0,0.5,1,2,3,4 hrs for solids and 0.5,1,2,6 hrs for liquids. A modified Patient Assessment of GI Symptoms (PAGI-SYM) questionnaire was used to record symptoms and the total Gastroparesis Cardinal Symptom Index (GCSI) score was calculated to assess symptom severity. Results: 117 patients met inclusion criteria (not on medications affecting gastric motility in 48 hrs prior to test or prior gastric surgery). Solid and liquid gastric emptying were significantly correlated at 30 min (r =0.684; p<0.001), 60 min (r =0.686; p<0.001) and 120 min (r= 0.793; p<0.001). The table below shows patient distribution based on GES results. Of note, there were 10 patients who had normal solid GES but showed delayed liquid emptying. These represent 8.5% of all 117 patients, but 16% of the 62 patients with normal GES. This group had 9 females and 1 male; none had diabetes and hence also represents 13% of all non-diabetics and 30% of non-diabetic patients with normal solid GES. Using the modified PAGI-SYM, liquid gastric retention at 30 min was correlated with loss of appetite (r=-0.215; p=0.036), and liquid gastric retention at 30 min and 60 min was correlated with the number of bowel movements per week (r=-0.292; p=0.009 and r=-0.280, p=0.012 respectively). Conclusions: Gastric emptying of liquids has a good correlation with gastric emptying of solids. However, there is additional value in measuring liquid gastric emptying for evaluating patients with gastroparesis, particularly in non-diabetic patients where 30% of patients with normal solid phase emptying can demonstrate delayed emptying of liquids.
W2063 Functional Dyspepsia in Patients with GERD Before and After Fundoplication Robert Scheffer, Hilda G. Rijnhart-de Jong, Hein G. Gooszen Functional dyspepsia (FD) is highly prevalent in patients with gastroesophageal reflux disease (GERD). The pathogenesis of FD is still unclear. Several pathophysiological mechanisms currently proposed to be involved in FD symptom generation include delayed gastric emptying and impaired gastric accommodation to a meal. Whilst fundoplication impairs gastric accommodation and accelerates gastric empyting, it's effect on functional dyspeptic symptoms, especially epigastric pain syndrome and postprandial distress syndrome, has not yet been investigated. Fifty patients (36 men, 18 women) with endoscopically and/or pHmetrically proven GERD were included in this study. Functional dyspeptic symptoms were scored using a visual analogue scale before, at 3 months and at 12 months after laparoscopic Nissen fundoplication. The diagnosis of functional dyspepsia was assessed according to the Rome III criteria. Symptom relief was reported in 84.5 and 91.5% at 3 months and 96.1 and 94.5% at 1 year after fundoplication for pyrosis and regurgitation respectively. Mean epigastric pain or burning (epigastric pain syndrome) symptoms were markedly more severe before (44.3, 32.6% resp.) than at 3 months (17.3, 6.3% resp.; both P< 0.001) and at 1 year (14.3, 6.8% resp.; both P<0.001) after fundoplication. Mean severity of meal-related symptoms such as fullness and early satiety (postprandial distress syndrome) decreased from (41.3, 24.2% resp.) to (18.3, 20.9% resp.; P=0.001 and P=0.44) at 3 months and (16.1, 13.9% resp.; P<0.001 and P=0.12) at 1 year. Conclusions: 1. Epigastric and meal-related dyspeptic symptoms are prevalent in GERD. 2. Both epigastric and meal-related symptoms diminish after a successful fundoplication. 3. Both epigastric pain syndrome and postprandial distress syndrome are not a contraindication for antireflux surgery.
W2061 A Newly Developed Implantable Two-Channel Stimulator with Dual Pulses Improves Both Gastric Emptying and Nausea and Vomiting in Dogs Geng-Qing Song, Yong Lei, Robert A. Ross, Jiande Chen The Enterra therapy (gastric electrical stimulation, GES with short pulses) has been shown to improve nausea and vomiting without consistent effects on gastric emptying, and is the only commercially able implantable stimulator. Recent animal studies have revealed improvement in both symptoms and gastric emptying with GES of dual pulses (combination of short and long pusles). The aims of this study were to develop an implantable stimulator capable of generating dual pulses and to investigate the efficacy of this novel implantable stimulator on emetic symptoms and gastric emptying in a chronic canine model. Methods: An implantable stimulator was designed and developed that was able to generate twochannel dual pulses and programmable remotely using a special wander. The test of the device was performed in five female dogs with chronically implanted with a duodenal cannula (for assessing gastric emptying) and two pairs of electrodes placed along the greater curvature at an interval of 8-10cm and connected to the stimulator that was implanted in a subcutaneous pouch. The study protocol included a baseline gastric emptying (GE) test
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positive LBT (p=1.0). In most cases, there was an agreement in determining an abnormal LBT (κ =0.78). There was no difference in symptoms in the gastroparetic patients with positive or negative LBT using the Quintron criteria. However, early satiety (p=0.04) and upper abdominal pain (p= 0.02) in Pimentel's criteria and regurgitation (p=0.05) in King's criteria were statistically associated with a positive LBT. Conclusions: This study shows a 32% prevalence of a positive LBT in patients with delayed GES, a slightly higher value than the 28% prevalence in patients with normal GES, both higher than the 4-10% prevalence of SIBO in the general population. Symptoms did not reliably predict a positive LBT in patients with delayed GES.