难治性胃食管反流病ppt课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,难治性胃食管反流病,*,Refractory Gastroesophageal reflux disease,难治性胃食管反流病,1,Refractory Gastroesophageal re,Definition of RGERD,RGERD:Patients who are unresponsive to 4-8 weeks treatment with PPIs twice daily or esophageal injury caused by RE can,t 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 sufcient to consider patients as PPI failures.,Any attempt to narrow the denition of refractory GERD might exclude many true sufferers.,Hershcovici T et al. Best Practice& Research Clinical Gastroenterology 2010 (24)923-936,难治性胃食管反流病,2,Definition of RGERDRGERD:Patie,PPI failed in Each of the Gastrooesophageal Reux Disease (GERD) Groups,GERD,NERD,60-70%,EE,20-30%,Barretts oesophagus,6-10%,PPI failure patients,Failure on PPI qd,40-50%,Failure on PPI qd,6-15%,Failure on PPI qd,20%,Fass et al. Aliment Pharmacol Ther 2005; 22(2):79-94.,难治性胃食管反流病,3,PPI failed in Each of the Gast,30%NERD fail to PPI treatment,难治性胃食管反流病,4,30%NERD fail to PPI treatment难,NERD-acid,visceral sensitivity,难治性胃食管反流病,5,NERD-acid,visceral sensitivity,Potential causes of PPI refractoriness in GERD,Neurogastroenterol Motil (2012) 24, 697704,难治性胃食管反流病,6,Potential causes of PPI refrac,难治性胃食管反流病,7,难治性胃食管反流病7,Weakly Acid Reflux,The prevalence of weakly acidic reflux in refractory 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,难治性胃食管反流病,8,Weakly Acid RefluxThe prevalen,Esophageal Hypersensitivity,AM J Gastroenterol ,2012,107, 8-15.,Esophageal,receptor,upregulation and/,or enhanced,signaling,Physiological,stressors,sensitization of,spinal sensory,neurons,.,Potential factors contributing to the spectrum of reflux perception in patients with GERD,难治性胃食管反流病,9,Esophageal HypersensitivityAM,Gastroparesis,Delayed gastric emptying (gastroparesis) may be a factor 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,）,: 2440-2444,难治性胃食管反流病,10,GastroparesisSURGICAL ENDOSCOP,Poor Compliance with PPI Treatment,Compliance to treatment and proper dosing are important.,Timing and frequency of dosing are critical for maximum efcacy of the medication.,Patients dosed optimally the PPIs(%),Proper dosing timing,46%,Patients dosed suboptimally the PPIs(%),60 min before meals,39%,after meals,30%,at bedtime,28%,as-needed,4%,PPI dosing situation in 100 patients with persistent GERD symptoms,Aliment Pharmacol Ther 2006;23:14737,难治性胃食管反流病,11,Poor Compliance with PPI Treat,Nocturnal 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 Ther,2002,16()7:1309-1316.,难治性胃食管反流病,12,Nocturnal Acid BreakthroughNAB,Dilated 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 eliminated,in RGERD patients who fail to PPI treament.,难治性胃食管反流病,13,Dilated intercellular spaces T,Bile Reflux,Gastroenterol 2009 January 21; 15(3): 334-338,230 patients with hear tburn and regurgitation continued to report symptoms,after 8 wk of high-dose PPI therapy (40 mg esomeprazole bid).,难治性胃食管反流病,14,Bile RefluxGastroenterol 2009,Psychological Comorbidities,ALIMENTARY PHARMACOLOGY & THERAPEUTICS,2007,26 (3): 443-452.,Anxiety and depression have been shown to increase GERD-related symptoms report in population-based studies.,难治性胃食管反流病,15,Psychological ComorbiditiesALI,New Mechanism,难治性胃食管反流病,16,New Mechanism难治性胃食管反流病16,A,n inflammatory response,occurs in the squamous epithelium, induced by the release of inflammatory mediators,L,eads to the subsequent chemoattraction and infiltration of immune cells,F,ollowed by the,proliferative response,of the rat epithelium.,Immunity:Mucosal Inflammation,Gastroesophageal reflux disease-from reflux episodes to mucosal inflammation.,Nat. Rev. Gastroenterol. Hepatol.2012,难治性胃食管反流病,17,An inflammatory response Leads,Protease activated receptor 2(PAR2),Gastroesophageal reflux disease-from reflux episodes to mucosal inflammation.,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,neuroinflammatory effects the modulation of,visceral hypersensitivity and pain,generation and increasing epithelial,permeability.,G,ERD,is Immune-mediated esophageal mucosal damage(IL-8,A new targets for GERD drug development.,难治性胃食管反流病,18,Protease activated receptor 2(,Proinflammatory and Neuroinflammatory Aspects,Gastroenterol. Hepatol.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 patients,NGF,GNDF,难治性胃食管反流病,19,Proinflammatory and Neuroinfla,Esophageal Eosinophilia,American 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/HPF,难治性胃食管反流病,20,Esophageal EosinophiliaAmerica,Erosive esophagitis may be related to small intestinal bacterial overgrowth S,candinavian Journal of Gastroenterology. 2012,GERD and SIBO,Overlap of GERD and IBS,Lactulose,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 Bacterial Overgrowth,难治性胃食管反流病,21,Erosive esophagitis may be rel,Diagnosis tests,难治性胃食管反流病,22,Diagnosis tests难治性胃食管反流病22,Upper Gastrointestinal Endoscopy,Gastrointest Endosc 2007;66:21924,Commonly used in clinical,practice to evaluate patients,with GERD who failed PPI,treatment.,The value of endoscopy in,patients with refractory GERD,is very low,Eosinophilic oesophagitis was,found in only 0.9% of RGERD,patients,and NERD and,functional heartburn patients,take a big part.,难治性胃食管反流病,23,Upper Gastrointestinal Endosco,A new method in the diagnosis of reflux esophagitis:,confocal laser endomicroscopy. GIE.2012,Confocal laser endomicroscopy,，,CLE,A,new method to test GERD,The distance between the,surface to papillary (S-P) tip,can be measured by using CLE,.,S,-P distance : 0.19um/cm in,RE ,0.44um/cm in control.,黏膜表面,毛细血管袢,难治性胃食管反流病,24,A new method in the diagnosis,共聚焦激光显微内镜诊断,NERD,N,ERD patients had more,intrapapillary capillary,loops(IPCLs) than control.,IPCLs number increased;,IPCLs diameter become bigger;,IPCLs extended to mucosal,surface;,The intercellular spaces of,squamous cells was enlarged.,Am J Gastroenterol. 2012 Mar 13,.,难治性胃食管反流病,25,共聚焦激光显微内镜诊断NERDNERD patients h,NERD diagnosed by CLE-,Dilated DIC,Am J Gastroenterol. 2012 Mar 13.,;,Control:figuer a, b,e;,NERD:figure c,d,f,（,DIS,）,难治性胃食管反流病,26,NERD diagnosed by CLE-Dilated,Esophageal pH monitoring allow the quantication of esophageal acid,exposure and the assessment of the temporal relationship between symptoms,and acid reux events.,PH monitoring can be performed off PPI to test if the initial diagnosis was,correct (i.e., heartburn was due to acid reux) or on PPI to test whether the,symptoms are due to residual acid reux.,Remote,proximal,acid reux,Remote,proximal,acid reux,Ambulatory 24h Esophageal pH Monitoring,难治性胃食管反流病,27,Remote proximalRemote,Ambulatory 24h Esophageal pH Monitoring- Graphs,难治性胃食管反流病,28,Ambulatory 24h Esophageal pH M,Esophageal Bilitec,Bilitec detects bilirubin in,the reuxate that is used as a surrogate marker for bile reux. One has to recall that non-acidic and bile reux are two distinct phenomena.,Esophageal exposure to bile acids can result in heartburn symptoms.,Dig Dis Sci 2005;50:815,.,难治性胃食管反流病,29,Esophageal Bilitec Dig Dis,Treament of RGERD,难治性胃食管反流病,30,Treament of RGERD难治性胃食管反流病30,Therapeutic options for RGERD patients,Gastroenterology and Hepatology 27 (2012) Suppl. 3; 37,难治性胃食管反流病,31,Therapeutic options for RGERD,GERD and PPI,Paul Moayyedi et al, Lancet, 2006, June 24(367):2086-2100,难治性胃食管反流病,32,GERD and PPIPaul Moayyedi et a,New PPIs,Dis. Esophagus 2005; 18: 3703.,Gastroenterol,，,2010; 105: 23416,In Process,难治性胃食管反流病,33,New PPIsDis. Esophagus 2005; 1,Histamine 2 receptor antagonist (H2RA),Histamine 2 receptor antagonist,given in divided doses may also be used and are effective treatment in many patients with less severe GERD.,American guidelines for diagnosis and treatment of GERD,难治性胃食管反流病,34,Histamine 2 receptor antagonis,Promotility therapy,Regurgitation may be the main symtom of refractory GERD ,compare with those who are without treatment.,GERD is a disorder of gastrointestinal motility,Defects in esophagogastric motility (LES incompetence,poor esophageal clearance, and delayed gastric emptying),are central to the pathogenesis of GERD .,If these defects could be corrected, then GERD would be controlled,making suppression of normal amounts of gastric acid unnecessary,.,American guidelines for diagnosis and treatment of GERD,难治性胃食管反流病,35,Promotility therapyRegurgitati,Transient lower esophageal sphincterrelaxation (TLESR) reducers,Gamma-aminobutyric acid B (GABAB) receptor agonists(Baclofen),Metabotropic glutamate receptor 5(mGluR5) antagonists(ADX10059),Am J Physiol 2001;281:G3115.,Gastroenterology 2005;129:9951004.,难治性胃食管反流病,36,Transient lower esophageal sph,Gastroesophageal reflux disease-from reflux episodes to mucosal inflammation. Nat. Rev. Gastroenterol. Hepatol.2012,Cannabinoids (CB1) antagonist,:,(rimonabant),Decreased meal-induced TLESR;,The total number of postprandial TLESR episodes,acid reflux episodes was markedly reduced in,healthy volunteers after treatment with,rimonabant.,Drug Therapy-In Process,难治性胃食管反流病,37,Gastroesophageal reflux diseas,Gastroesophageal reflux disease-from reflux episodes to mucosal inflammation.,Nat. Rev. Gastroenterol. Hepatol.2012,mGluR5 antagonist,（,ADX10059,）,ADX10059 has a different pharmacodynamic,approach to TLESR reduction than the above,medications, and has been shown to reduce both,acidic and nonacidic reflux events.,After an increase in abnormal laboratory test,results (liver enzymes) and a few cases of,hepatic failure, the further development of,ADX10059 was also discontinued.,Drug Therapy-In Process,难治性胃食管反流病,38,Gastroesophageal reflux diseas,Aliment. Pharmacol. Ther. 33, 11131122 (2011).,TRPV1,antagonist,（,AZD1386,),：,TRPV 1 channel is responsive to noxious heat,and acid.,TRPV 1 antagonist(AZD1386)increased oesophageal,and skin heat pain thresholds.,It is a potential drug class for GERD treatment,.,Drug Therapy-In Process,难治性胃食管反流病,39,Aliment. Pharmacol. Ther. 33,Visceral pain modulators,Most of the patients who fail PPI treatment originate from the NERD group,more than 50% of the PPI failure (twice daily) subjects demonstrate lack of either weakly or acidic reux, the usage of these agents is highly attractive,.,Tricyclic antidepressants,Trazodone (a tetracyclic antidepressants),Selective serotonin reuptake inhibitors (SSRIs),Gut,，,2006,，,55:1398402,难治性胃食管反流病,40,Visceral pain modulatorsMost o,Antireux Surgery,Gastrointest Surg (2010) 14:14341441,Gut,2011;60:435e441.,Refractory GERD was the most common (88%) indication for antireux surgery,and the most common preoperative symptom reported under failure of medical,antireux treatment was regurgitation (54%).,难治性胃食管反流病,41,Antireux SurgeryGastrointest,Endoscopic therapy,Radiofrequency therapy : Stretta procedure;,Injection therapy:Enteryx ,GK, Stem cell injection;,Suturing/plication therapy,LINX reux management system,难治性胃食管反流病,42,Endoscopic therapyRadiofrequen,LINX reux management system,Surg Endosc,，,2012 April,J Gastrointest Surg (2008),The device consists of a series of,interlinked titanium beads,containing a magnetic core, is,placed laparoscopically around,the external esophagus at the,gastroesophageal junction (EGJ),Improve the reux barrier,(reduced esophageal acid,exposure), improved GERD-,related quality of life, and,cessation of dependence on PPIs,难治性胃食管反流病,43,LINX reux management systemSu,Management algorithm of GERD patient who failed PPI once daily,Best Practice & Research Clinical Gastroenterology 24 (2010) 923936,难治性胃食管反流病,44,Management algorithm of GERD p,Thank you for your attention!,难治性胃食管反流病,45,Thank you for your attention!,此课件下载可自行编辑修改，供参考！,感谢您的支持，我们努力做得更好！,难治性胃食管反流病,46,此课件下载可自行编辑修改，供参考！难治性胃食管反流病46,