难治性胃食管反流病RGERD-参考幻灯片课件.ppt
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- 难治 食管 反流病 RGERD 参考 幻灯片 课件
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1、1Definition of RGERD?RGERD:Patients who are unresponsive to 4-8 weeks treatment with PPIs twice daily or esophageal injury caused by RE cant to be healing.Richter JE Natl Clin Gastroenterol 2007;4:658?Others suggest that lack of satisfactory symptomatic response to PPI once a day is suf?cient to con
2、sider patients as PPI failures.?Any attempt to narrow the de?nition of refractory GERD might exclude many true sufferers.Hershcovici T et al. Best Practice& Research Clinical Gastroenterology 2010 (24)923-936 Remains an area of controversy22020/2/14PPI failed in Each of the Gastrooesophageal Re?ux D
3、isease (GERD) GroupsGERDNERD60-70% EE 20-30% Barretts oesophagus6-10% Failure on PPI qd40-50%40-50%Failure on PPI qd6-15%Failure on PPI qd20%Fass et al. Aliment Pharmacol Ther 2005; 22(2):79-94. 32020/2/1430%NERD fail to PPI treatment42020/2/14NERD-acid,visceral sensitivity52020/2/14Potential causes
4、 of PPI refractoriness in GERDNeurogastroenterol Motil (2012) 24, 697704 62020/2/14MechanismWeakly acid refluxNABDilated intercellular spaces DGEREsophageal hypersensitivityGastroparesisPoor compliance with PPI treatment Psychological 7Weakly Acid Reflux?The prevalence of weakly acidic reflux in ref
5、ractory GERD is 30-40%. ?When the esophageal pH falls by 1 unit, but remains 4, it is considered “weakly acidic reflux”.Gut,2004,53:1024-1031? Esophageal distension ? Persistent impaired mucosal integrity? Esophageal hypersensitivity82020/2/14Esophageal HypersensitivityAM J Gastroenterol ,2012, 107
6、, 8-15. Esophageal receptor upregulation and/or enhanced signalingPhysiological stressors, sensitization of spinal sensory neuronsPotential factors contributing to the spectrum of reflux perception in patients with GERD 92020/2/14GastroparesisDelayed gastric emptying (gastroparesis) may be a factor
7、associated with severe reflux, dyspepsia, or both. Gastroparesis, concomitant in 25% of patients with gastroesophageal reflux disease (GERD), has been shown to improve after Nissen fundoplication. SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES ,2008,22 (11)2440-2444102020/2/14Poor Compliance
8、 with PPI Treatment ?Compliance to treatment and proper dosing are important. ?Timing and frequency of dosing are critical for maximum ef?cacy of the medication.Patients dosed optimally the PPIs(%)Properdosing timing 46%Patientsdosed suboptimally the PPIs(%)60 min before meals39%after meals30%at bed
9、time28%as-needed4%PPI dosing situation in 100 patients with persistent GERD symptomsAliment Pharmacol Ther 2006;23:14737112020/2/14Nocturnal Acid Breakthrough?NAB: Gastric pH below 4 over 60 consecutive minutes at night-time in subjects who take proton pump inhibitors twice daily.Aliment Pharmacol T
10、her,2002,16()7:1309-1316.122020/2/14Dilated intercellular spaces ? The dilation of esophageal intercellular spaces (ICS) is considered an early morphologic marker of acid damage in patients with GERD. ? ICS will be difficult to eliminatedin RGERD patients who fail to PPI treament. 132020/2/14Bile Re
11、fluxGastroenterol 2009 January 21; 15(3): 334-338230 patients with hear tburn and regurgitation continued to report symptoms after 8 wk of high-dose PPI therapy (40 mg esomeprazole bid).142020/2/14Psychological ComorbiditiesALIMENTARY PHARMACOLOGY & THERAPEUTICS ,2007,26 (3): 443-Anxiety and depress
12、ion have been shown to increase GERD-related symptoms report in population-based studies. 152020/2/1416An inflammatory response occurs in the squamous epithelium, induced by the release of inflammatory mediatorsLeads to the subsequent chemoattraction and infiltration of immune cellsFollowed by the p
13、roliferative response of the rat epithelium.Immunity:Mucosal InflammationGastroesophageal reflux disease-from reflux episodes to mucosal inflammation. Nat. Rev. Gastroenterol. Hepatol.2012172020/2/14Protease activated receptor 2(PAR2)Gastroesophageal reflux disease-from reflux episodes to mucosal in
14、flammation. Nat. Rev. Gastroenterol. Hepatol.2012? Activated by serine proteases ? Upregulated in patients with GERD and induced by acid conditions in cell culture models? PAR2 activation :? Leads to epithelial IL - 8 release and contributes to the pathogenesis of GERD?Implicated in inflammatory and
15、 neuroinflammatory effects the modulation of visceral hypersensitivity and pain generation and increasing epithelial permeability.G GERD is Immune-mediated esophageal mucosal damage(IL-8 A new targets for GERD drug development.182020/2/14Proinflammatory and Neuroinflammatory AspectsGastroenterol. He
16、patol.2012?TRPV1(transient receptor potential cation channel subfamily V member 1)?TRPV1 is involved in the inflammatory epithelial response ,that is supposed to be involved in GERD- related symptom generation.?EE or NERD patients with high expression level of TRPV?Nuroinflammatory aspects in GERD p
17、atients ? NGF?GNDF192020/2/14Esophageal EosinophiliaAmerican Journal of Gastroenterology,2008,435-442?High intraepithelial eosinophil counts in esophageal squamous epithelium are not specific for eosinophilic esophagitis .?Eos20/HPF in GERD patients suggest it may be RGERD. 20/HPF202020/2/14Erosive
18、esophagitis may be related to small intestinal bacterial overgrowth Scandinavian Journal of Gastroenterology. 2012GERD and SIBOOverlap of GERD and IBSLactulose hydrogen breath test (LHBT)In Abnormal LHBT,67% in EE,37% in control (P=0.024)65% in EE,31% in control(without IBS)(P=0.032)Small Intestinal
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