231 Upper and Lower Gastrointestinal Safety Profile of Celecoxib: Patient-Level Pooled Analysis of...
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AGA Abstracts agreed that colon cancer screening is part of good overall health care) and 90% thought that colonoscopy was the most effective CRC screening test. Only 47%, however, were compliant with colonoscopy screening recommendations at baseline (every 1-2 years for HNPCC; every 5 years for HR). The most commonly reported barriers to colonoscopy screening were lack of symptoms (34%), being too busy (26%) and concern about the preparation (25%). Of the 632 subjects randomized, 570 (90%) completed the 24 month follow-up. Colonoscopy compliance increased from 43% to 59% in the intensive intervention group but only from 52% to 55% in the minimal intervention group (OR 1.6: 95% CI 0.9- 1.8). The intervention was comparably effective in the HNPCC and HR groups. Conclusions: Compliance with colonoscopy screening is surprisingly low in unaffected members of HNPCC and HR families and a telephone-based intervention may be able to improve colonoscopy screening in this group. 230 Long Term Outcome of Early Colorectal Cancer Treated With Local Excision or Radical Resection Monique E. van Leerdam, Thomas C. Smyrk, Felicity Enders, Sara Holton, Petrus C. de Groen BACKGROUND: Treatment of early stage colorectal cancer (CRC) with minimally invasive techniques decreases morbidity but carries the risk of incomplete local excision. AIM: To compare long term outcome in a large cohort of patients with non-invasive intramucosal (NIIM) or T1 CRC treated with local excision (LE) or radical surgical resection (RSR). METHODS: Mayo Clinic databases were used to select patients with NIIM and T1 CRC who were diagnosed between 1/1994 and 1/2004 to ensure at least 5 years of follow up (FU). Patients with prior or synchronous CRC, IBD, FAP or incomplete data were excluded. Tumor characteristics (stage, grade, depth submucosal invasion, angiolymphatic invasion, tumor budding) were reviewed. Overall and disease free survival were determined only in patients without metastatic disease at the time of diagnosis. Breslow statistics and Cox proportional Hazard Ratios (HR) were used to compare overall and disease free survival and to determine risk factors for recurrent disease (local recurrence, lymph node or distant metastases). RESULTS: A total of 569 eligible patients were included in the study. NIIM CRC cases (N=52): 54% were treated with LE and 46% with RSR. No recurrent disease occurred during mean FU of 127 ± 8.5 months. Overall survival was equal for both treatment groups. T1 CRC cases (N=517): 25% were treated with LE and 75% with RSR. LE was more often performed for rectal lesions and RSR more often for proximal lesions (p<0.001). 50 patients had metastatic disease at the time of diagnosis and 9 patients developed metachronous CRC during FU. CRC recurrence during mean FU of 134 ± 3.1 months was more often seen in the LE group (13% vs 3% in RSR, p<0.001). Recurrence occurred more often in rectal than in non-rectal CRC (81% vs 19% p<0.001). After adjusting for age, gender and co-morbidity, overall survival was better in the RSR group than in the LE group (HR 1.42, 95% CI 1.0-2.0, p=0.05). Disease free survival was also better in the RSR group (HR 1.62, 95% CI 1.15-2.28). After adjusting for age and gender, rectal location (HR 4.3, 95%CI 1.4- 13.7), tumor budding (HR 3.5, 95%CI 1.4-8.9) and LE (HR 4.2, 95%CI 1.5-11.6) were significantly associated with recurrent disease, whereas angiolymphatic invasion, submucosal invasion and tumor grade were not. CONCLUSIONS: Disease free survival among NIIM patients is 100% and among T1 CRC patients is significantly better in those who were treated with surgical resection rather than local excision. Rectal location of cancer, tumor budding and LE were associated with recurrent disease. Better criteria are needed to identify those T1 CRC patients who can safely be treated with local excision. 231 Upper and Lower Gastrointestinal Safety Profile of Celecoxib: Patient-Level Pooled Analysis of 51,048 Patients in Randomized, Double-Blinded, Parallel- Group Clinical Trials Gurkirpal Singh, George Triadafilopoulos, Naurang M. Agrawal, Geoff Makinson, Mark (Chunming) Li, Ha Nguyen Background: While nonsteroidal anti-inflammatory drug (NSAID)-related serious upper and lower gastrointestinal (UGI/LGI) complications are well-recognized, most clinical trials of cyclooxygenase (COX)-2 selective NSAIDs have focused on UGI outcomes as their primary endpoints. By using a novel composite endpoint measuring injury in the entire GI tract— clinically significant upper and lower GI events (CSULGIEs)—we aimed to compare GI outcomes in patients enrolled in celecoxib clinical trials, using individual patient-level data. Methods: 52 randomized, double-blind, parallel group studies were identified from the Celecoxib Clinical Database and included in this patient-level pooled analysis. All studies had a planned duration of continuous treatment with celecoxib and either a nsNSAID (ibuprofen, naproxen, diclofenac, ketoprofen, ioxoprofen), rofecoxib or a placebo comparator arm for ≥ than 4 weeks. All included studies had their final study reports completed by October 1st, 2007. Open-label and cross-over trials, and all healthy volunteer studies were excluded from the analysis. The primary endpoint was the cumulative incidence of CSULGIEs (including perforations, obstructions, clinically significant bleeds, decrease in hemoglobin ≥2g/dL) or symptomatic ulcers as adjudicated by an independent blinded committee. Adjudication was based on predefined criteria and available reported adverse events, laborat- ory data and narratives. The stratified log rank test was used to compare treatments, adjusting for studies. All doses of celecoxib (from <200 to 800 mg total daily dose) and nsNSAIDS were pooled. Results: 51,048 patients were included: 28,614 patients were randomized to celecoxib (mean age 60.1 years), 15,278 to nsNSAIDs (mean age 59.3 years), 1,329 to rofecoxib (mean age 70.6 years) and 5,827 to placebo (mean age 57.2 years). A total of 803 cases of serious UGI/LGI complications (or decrease in hemoglobin level ≥2g/dL) were reviewed by the adjudication committee who confirmed 511 CSULGIEs. 220 GI events were in the celecoxib group with an incidence rate of 1.8 per 100 person-years; 244 events were in the nsNSAID group with an incidence rate of 5.3 per 100 person-years; the rofecoxib and placebo arms had 2 and 45 events and incidence rates of 1.3 and 1.2 per 100 person- years, respectively.The difference between celecoxib and nsNSAIDs was statistically signific- ant, using a stratified log-rank test (p<0.0001). Conclusion: The known UGI safety of S-44 AGA Abstracts celecoxib is also associated with a lower risk of all clinically significant GI events throughout the entire GI tract compared to patients treated with nsNSAIDs. 244 Evidence for Involvement of the Cysteinyl Leukotriene Receptor Type 2 (cysLTR2) in the Regulation of Food Intake and Body Weight and Possible Role for Vagal Afferents Ala'a Al-Helaili, Sung Jin Park, Donna M. Daly, Michael Beyak A variety of lipid mediators are known to be involved in satiety signaling and body weight. For example endocannabinoids and related compounds have profound effects on food intake, via vagal afferent pathways. More recently evidence has emerged for eicosanoids such as prostaglandins and leukotrienes in the regulation of body weight. For example, 5-lipoxygen- ase deficient mice are obese and glucose intolerant, and mice deficient in the EP3 prostanoid receptor are obese and have increased food intake. The aim of the present study was to examine the role of cysLTR2 receptors in regulation of food intake and body weight. Methods: cysLTR2-/- lacZ transgenic mice (-/-) and wild type controls (+/+) on a C57Bl6j background were used for this study. Mice were housed and fed identically from the time of weaning to the end of the study. Food intake was measured using specialized cages equipped with a continuously weighed food reservoir, connected to a computer interface. Food and body weight were measured from 7 to 25 weeks of age. X-Gal staining was used to visualize sites of cysLTR2 expression in nodose ganglion and vagus nerve. For calcium imaging, nodose ganglia were isolated, and neurons dissociated and plated on glass coverslips for 18-24h prior to experimentation. Fluorescent calcium imaging experiments were performed on fura2-AM loaded dissociated nodose ganglion cells. Results: Body weight increased more over time in -/- mice compared to +/+ (maximal at 25 weeks, 50.3±1.2g vs. 47.0±0.49 g p<0.05), as did food intake (maximal at 25 weeks 4.8±0.14g/d vs. 3.9±0.29g/d, p<0.05 n= 4 mice each group). Meal frequency was no different between groups, suggesting an overall increase in meal size. X-Gal staining of nodose ganglia from -/- mice revealed widespread staining in the nodose ganglion and vagus nerve. Calcium imaging experiments were per- formed on isolated nodose ganglion neurons, and responses to the cysLTR2 agonists LTC4 and LTD4 (100nM) were assessed. In +/+ mice, LTC4 caused an increase in intracellular calcium in 37% of cells tested, 48.5±14.9% (n=11) of the response to high potassium (80mM), and LTD4 in 25% of cells tested, with a magnitude of 61.4±22% (n=7) of the high potassium response. Conclusions: cysLTR2-/- mice gain more weight and have higher food intake compared to wildtype controls. This appears to be due to an increase in meal size rather than frequency. The cysLTR2 receptor is expressed in vagal afferents, and these afferents can be activated by LTC4 and LTD4, suggesting a possible role for vagal satiety signals. The endogenous source and stimulus for release of leukotrienes as it relates to food intake remains to be determined. 245 Does the Preload of a Non-Caloric Carbonated Beverage, During a Standardized Solid and Liquid Meal, Affect Gastric Volume and Energy Intake in Healthy Subjects? Maria Flavia Savarese, Emanuele Nicolai, Adriana Aragri, Giovanni Sarnelli, Elisabetta Atteo, Ivana Giusy Savino, Maxime E. Buyckx, Rosario Cuomo Background and Aim: Carbon dioxide (CO2), contained in carbonated beverages, could increase gastric volume inducing epigastric discomfort and reducing meal intake. We aimed to verify effect of a sugar-free carbonated beverage (CB) preload compared to a CB without CO2 (DCB) and water (W) during a standardized solid (SM) and liquid (LM) meal on gastric volume, gastrointestinal symptoms and eating perceptions. Subjects & Methods: After 300 ml of CB, DCB and W a standardized SM or LM was administered at constant rate (100 kcal/5 min) to ten healthy subjects (4 females, aged 22-30 years; BMI 21-24) on six days in a random order (D1: CB+SM; D2: DCB+SM; D3: W+SM; D4: CB+LM; D5: DCB+LM; D6: W+LM). Gastrointestinal symptoms (bloating and epigastric pain), eating perceptions (desire to eat, hunger, prospective of food consumption) and maximum satiety (MS) as total kcals intake were measured. Total gastric (TGV) and gas volumes by MRI after the beverages and at MS were also evaluated. All data are expressed as mean±SD. Results: Epigastric pain was absent in all experiment. A slight presence of epigastric bloating was found during the SM and LM without differences among beverages. Desire to eat, hunger and prospective of food consumption were not different among beverages and meals. TGV and gas volumes after beverages were significantly higher with CB than DCB and W (TGV: 715±194 ml, 521±83, 478±63, p<0.01; gas: 306±107, 101±29, 107±40, p<0.01). TGV at MS were not different during SM (665±129; 670±147; 664±167; ) and LM (702±252; 674±206; 709±264) respectively. Gas volumes at MS markedly decrease (p<0.01) respect to evalution after beverage and were not different among beverages during SM (20±8, 13±7, 12±5) and LM (15±12, 22±19, 17±17) respectively. Total kcal intakes at MS were not different among beverages during SM (D1: 774±209; D2:837±208; D3: 783±244) and LM (D4: 585±299; D5:585±280; D6: 630±353) respectively. However kcal intakes were higher with SM than LM (p<0.01) independently of beverage preload. Conclusions: A preload of 300 ml of non caloric carbonated beverage does not determine gastrointestinal symptoms and does not affect satiety ratings and eating perceptions in healthy subjects. Other factors as time of administration, volume and carbon dioxide concentration of carbonated beverage must be explored to exclude interference with gastric function. 246 Role of Ghrelin and Ghrelin Receptors in the Effect of Bitter Taste Receptor Agonists on Food Intake and Gastric Emptying Sara Janssen, Pieter-Jan Verhulst, Jorien Laermans, Jan F. Tack, Inge Depoortere Background: Ghrelin is an orexigenic hormone with gastroprokinetic properties, mainly produced by the stomach. Ghrelin secretion depends on the nutritional composition of the meal but the factors involved in chemosensation of the ghrelin cell are not known. Transcripts
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Transcript of 231 Upper and Lower Gastrointestinal Safety Profile of Celecoxib: Patient-Level Pooled Analysis of...
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sagreed that colon cancer screening is part of good overall health care) and 90% thoughtthat colonoscopy was the most effective CRC screening test. Only 47%, however, werecompliant with colonoscopy screening recommendations at baseline (every 1-2 years forHNPCC; every 5 years for HR). The most commonly reported barriers to colonoscopyscreening were lack of symptoms (34%), being too busy (26%) and concern about thepreparation (25%). Of the 632 subjects randomized, 570 (90%) completed the 24 monthfollow-up. Colonoscopy compliance increased from 43% to 59% in the intensive interventiongroup but only from 52% to 55% in the minimal intervention group (OR 1.6: 95% CI 0.9-1.8). The intervention was comparably effective in the HNPCC and HR groups. Conclusions:Compliance with colonoscopy screening is surprisingly low in unaffectedmembers of HNPCCand HR families and a telephone-based intervention may be able to improve colonoscopyscreening in this group.
230
Long Term Outcome of Early Colorectal Cancer Treated With Local Excisionor Radical ResectionMonique E. van Leerdam, Thomas C. Smyrk, Felicity Enders, Sara Holton, Petrus C. deGroen
BACKGROUND: Treatment of early stage colorectal cancer (CRC) with minimally invasivetechniques decreases morbidity but carries the risk of incomplete local excision. AIM: Tocompare long term outcome in a large cohort of patients with non-invasive intramucosal(NIIM) or T1 CRC treated with local excision (LE) or radical surgical resection (RSR).METHODS: Mayo Clinic databases were used to select patients with NIIM and T1 CRCwho were diagnosed between 1/1994 and 1/2004 to ensure at least 5 years of follow up(FU). Patients with prior or synchronous CRC, IBD, FAP or incomplete data were excluded.Tumor characteristics (stage, grade, depth submucosal invasion, angiolymphatic invasion,tumor budding) were reviewed. Overall and disease free survival were determined only inpatients without metastatic disease at the time of diagnosis. Breslow statistics and Coxproportional Hazard Ratios (HR) were used to compare overall and disease free survivaland to determine risk factors for recurrent disease (local recurrence, lymph node or distantmetastases). RESULTS: A total of 569 eligible patients were included in the study. NIIMCRC cases (N=52): 54% were treated with LE and 46% with RSR. No recurrent diseaseoccurred during mean FU of 127 ± 8.5 months. Overall survival was equal for both treatmentgroups. T1 CRC cases (N=517): 25% were treated with LE and 75% with RSR. LE was moreoften performed for rectal lesions and RSR more often for proximal lesions (p<0.001). 50patients hadmetastatic disease at the time of diagnosis and 9 patients developedmetachronousCRC during FU. CRC recurrence during mean FU of 134 ± 3.1 months was more oftenseen in the LE group (13% vs 3% in RSR, p<0.001). Recurrence occurred more often inrectal than in non-rectal CRC (81% vs 19% p<0.001). After adjusting for age, gender andco-morbidity, overall survival was better in the RSR group than in the LE group (HR 1.42,95% CI 1.0-2.0, p=0.05). Disease free survival was also better in the RSR group (HR 1.62,95% CI 1.15-2.28). After adjusting for age and gender, rectal location (HR 4.3, 95%CI 1.4-13.7), tumor budding (HR 3.5, 95%CI 1.4-8.9) and LE (HR 4.2, 95%CI 1.5-11.6) weresignificantly associated with recurrent disease, whereas angiolymphatic invasion, submucosalinvasion and tumor grade were not. CONCLUSIONS: Disease free survival among NIIMpatients is 100% and among T1 CRC patients is significantly better in those who weretreated with surgical resection rather than local excision. Rectal location of cancer, tumorbudding and LE were associated with recurrent disease. Better criteria are needed to identifythose T1 CRC patients who can safely be treated with local excision.
231
Upper and Lower Gastrointestinal Safety Profile of Celecoxib: Patient-LevelPooled Analysis of 51,048 Patients in Randomized, Double-Blinded, Parallel-Group Clinical TrialsGurkirpal Singh, George Triadafilopoulos, Naurang M. Agrawal, Geoff Makinson, Mark(Chunming) Li, Ha Nguyen
Background: While nonsteroidal anti-inflammatory drug (NSAID)-related serious upper andlower gastrointestinal (UGI/LGI) complications are well-recognized, most clinical trials ofcyclooxygenase (COX)-2 selective NSAIDs have focused on UGI outcomes as their primaryendpoints. By using a novel composite endpoint measuring injury in the entire GI tract—clinically significant upper and lower GI events (CSULGIEs)—we aimed to compare GIoutcomes in patients enrolled in celecoxib clinical trials, using individual patient-level data.Methods: 52 randomized, double-blind, parallel group studies were identified from theCelecoxib Clinical Database and included in this patient-level pooled analysis. All studieshad a planned duration of continuous treatment with celecoxib and either a nsNSAID(ibuprofen, naproxen, diclofenac, ketoprofen, ioxoprofen), rofecoxib or a placebo comparatorarm for ≥ than 4 weeks. All included studies had their final study reports completed byOctober 1st, 2007. Open-label and cross-over trials, and all healthy volunteer studies wereexcluded from the analysis. The primary endpoint was the cumulative incidence of CSULGIEs(including perforations, obstructions, clinically significant bleeds, decrease in hemoglobin≥2g/dL) or symptomatic ulcers as adjudicated by an independent blinded committee.Adjudication was based on predefined criteria and available reported adverse events, laborat-ory data and narratives. The stratified log rank test was used to compare treatments, adjustingfor studies. All doses of celecoxib (from <200 to 800 mg total daily dose) and nsNSAIDSwere pooled. Results: 51,048 patients were included: 28,614 patients were randomized tocelecoxib (mean age 60.1 years), 15,278 to nsNSAIDs (mean age 59.3 years), 1,329 torofecoxib (mean age 70.6 years) and 5,827 to placebo (mean age 57.2 years). A total of 803cases of serious UGI/LGI complications (or decrease in hemoglobin level ≥2g/dL) werereviewed by the adjudication committee who confirmed 511 CSULGIEs. 220 GI events werein the celecoxib group with an incidence rate of 1.8 per 100 person-years; 244 events werein the nsNSAID group with an incidence rate of 5.3 per 100 person-years; the rofecoxiband placebo arms had 2 and 45 events and incidence rates of 1.3 and 1.2 per 100 person-years, respectively.The difference between celecoxib and nsNSAIDs was statistically signific-ant, using a stratified log-rank test (p<0.0001). Conclusion: The known UGI safety of
S-44AGA Abstracts
celecoxib is also associated with a lower risk of all clinically significant GI events throughoutthe entire GI tract compared to patients treated with nsNSAIDs.
244
Evidence for Involvement of the Cysteinyl Leukotriene Receptor Type 2(cysLTR2) in the Regulation of Food Intake and Body Weight and PossibleRole for Vagal AfferentsAla'a Al-Helaili, Sung Jin Park, Donna M. Daly, Michael Beyak
A variety of lipid mediators are known to be involved in satiety signaling and body weight.For example endocannabinoids and related compounds have profound effects on food intake,via vagal afferent pathways. More recently evidence has emerged for eicosanoids such asprostaglandins and leukotrienes in the regulation of body weight. For example, 5-lipoxygen-ase deficient mice are obese and glucose intolerant, and mice deficient in the EP3 prostanoidreceptor are obese and have increased food intake. The aim of the present study was toexamine the role of cysLTR2 receptors in regulation of food intake and body weight. Methods:cysLTR2-/- lacZ transgenic mice (-/-) and wild type controls (+/+) on a C57Bl6j backgroundwere used for this study. Mice were housed and fed identically from the time of weaningto the end of the study. Food intake was measured using specialized cages equipped witha continuously weighed food reservoir, connected to a computer interface. Food and bodyweight were measured from 7 to 25 weeks of age. X-Gal staining was used to visualize sitesof cysLTR2 expression in nodose ganglion and vagus nerve. For calcium imaging, nodoseganglia were isolated, and neurons dissociated and plated on glass coverslips for 18-24hprior to experimentation. Fluorescent calcium imaging experiments were performed onfura2-AM loaded dissociated nodose ganglion cells. Results: Body weight increased moreover time in -/- mice compared to +/+ (maximal at 25 weeks, 50.3±1.2g vs. 47.0±0.49 gp<0.05), as did food intake (maximal at 25 weeks 4.8±0.14g/d vs. 3.9±0.29g/d, p<0.05 n=4 mice each group). Meal frequency was no different between groups, suggesting an overallincrease in meal size. X-Gal staining of nodose ganglia from -/- mice revealed widespreadstaining in the nodose ganglion and vagus nerve. Calcium imaging experiments were per-formed on isolated nodose ganglion neurons, and responses to the cysLTR2 agonists LTC4and LTD4 (100nM) were assessed. In +/+ mice, LTC4 caused an increase in intracellularcalcium in 37% of cells tested, 48.5±14.9% (n=11) of the response to high potassium(80mM), and LTD4 in 25% of cells tested, with a magnitude of 61.4±22% (n=7) of thehigh potassium response. Conclusions: cysLTR2-/- mice gain more weight and have higherfood intake compared to wildtype controls. This appears to be due to an increase in mealsize rather than frequency. The cysLTR2 receptor is expressed in vagal afferents, and theseafferents can be activated by LTC4 and LTD4, suggesting a possible role for vagal satietysignals. The endogenous source and stimulus for release of leukotrienes as it relates to foodintake remains to be determined.
245
Does the Preload of a Non-Caloric Carbonated Beverage, During aStandardized Solid and Liquid Meal, Affect Gastric Volume and Energy Intakein Healthy Subjects?Maria Flavia Savarese, Emanuele Nicolai, Adriana Aragri, Giovanni Sarnelli, ElisabettaAtteo, Ivana Giusy Savino, Maxime E. Buyckx, Rosario Cuomo
Background and Aim: Carbon dioxide (CO2), contained in carbonated beverages, couldincrease gastric volume inducing epigastric discomfort and reducing meal intake. We aimedto verify effect of a sugar-free carbonated beverage (CB) preload compared to a CB withoutCO2 (DCB) and water (W) during a standardized solid (SM) and liquid (LM) meal on gastricvolume, gastrointestinal symptoms and eating perceptions. Subjects & Methods: After 300ml of CB, DCB and W a standardized SM or LM was administered at constant rate (100kcal/5 min) to ten healthy subjects (4 females, aged 22-30 years; BMI 21-24) on six daysin a random order (D1: CB+SM; D2: DCB+SM; D3: W+SM; D4: CB+LM; D5: DCB+LM;D6: W+LM). Gastrointestinal symptoms (bloating and epigastric pain), eating perceptions(desire to eat, hunger, prospective of food consumption) and maximum satiety (MS) as totalkcals intake were measured. Total gastric (TGV) and gas volumes by MRI after the beveragesand at MS were also evaluated. All data are expressed as mean±SD. Results: Epigastric painwas absent in all experiment. A slight presence of epigastric bloating was found during theSM and LM without differences among beverages. Desire to eat, hunger and prospective offood consumption were not different among beverages and meals. TGV and gas volumesafter beverages were significantly higher with CB than DCB and W (TGV: 715±194 ml,521±83, 478±63, p<0.01; gas: 306±107, 101±29, 107±40, p<0.01). TGV at MS were notdifferent during SM (665±129; 670±147; 664±167; ) and LM (702±252; 674±206; 709±264)respectively. Gas volumes at MS markedly decrease (p<0.01) respect to evalution afterbeverage and were not different among beverages during SM (20±8, 13±7, 12±5) and LM(15±12, 22±19, 17±17) respectively. Total kcal intakes at MS were not different amongbeverages during SM (D1: 774±209; D2:837±208; D3: 783±244) and LM (D4: 585±299;D5:585±280; D6: 630±353) respectively. However kcal intakes were higher with SM thanLM (p<0.01) independently of beverage preload. Conclusions: A preload of 300 ml of noncaloric carbonated beverage does not determine gastrointestinal symptoms and does notaffect satiety ratings and eating perceptions in healthy subjects. Other factors as time ofadministration, volume and carbon dioxide concentration of carbonated beverage must beexplored to exclude interference with gastric function.
246
Role of Ghrelin and Ghrelin Receptors in the Effect of Bitter Taste ReceptorAgonists on Food Intake and Gastric EmptyingSara Janssen, Pieter-Jan Verhulst, Jorien Laermans, Jan F. Tack, Inge Depoortere
Background: Ghrelin is an orexigenic hormone with gastroprokinetic properties, mainlyproduced by the stomach. Ghrelin secretion depends on the nutritional composition of themeal but the factors involved in chemosensation of the ghrelin cell are not known. Transcripts
