Refractory GERD : case presentation and discussion Ping-Huei Tseng National Taiwan University Hospital May 19, 2018
How effective is PPI based on EGD? With GERD symptom 75% erosive 25% NERD Endoscopy 81% response 19% not response 37% response 63% not response PPI treatment Lee YC, et al. J Gastroenterol Hepatol. 2007;22:1286-92 Tseng PH, et al. J Clin Gastroenterol. 2009;43:920-5
Refractory GERD (PPI failure ) Persistent reflux symptoms or endoscopic visible lesions despite of standard (or double) dose PPI for at least 2 (or 3) months
How common is PPI failure? Persistent symptoms 30-35% of patients with EE 50-55% of patients with NERD Regurgitation > heartburn Atypical > typical symptoms Persistent esophagitis 10-15 % of patients with LA A/B 15-30% of patients with LA C/D Clin Gastroenter Hepatol 2012;10:612-9
Case 1 24 male Heartburn and acid regurgitation for 1 year Not related to meals heartburn when lying flat at night time Poor response to various PPI Smoking -, drinking - BMI: 20.4 EGD: minimal breaks Referred for MII-pH evaluation
Multichannel Intraluminal Impedance and ph monitoring (MII-pH) Impedance: ph: refluxate presence distribution and extent bolus clearing Acidic: ph<4 Weakly acidic: ph 4-7 Non-acidic: ph>7 Symptom association: Symptom index (SI) Symptom association probability (SAP)
MII-pH: equipment and patient diary
24-h MII-pH (on PPI) 8 Many weakly acidic refluxes 24-h ph: ph<4: 0.1% (<1.2%) Demeester score: 1.7 (<14.7) 24-h impedance: Reflux: 85 (<48) Acidic: 4 (<10) Weakly /non-acidic: 67/7 (<35) Symptom association: SI: 0% (>50%), SAP: 0% (95%)
MII-pH: non-acid reflux
Non-Acid Reflux: clinical significance 144 pts refractory to PPI bid Symptom index (SI) Symptoms due to Non-acid reflux: 37% Acid reflux: 11% No association: 52% Mainie et al. Gut 2006;55:1398
Case 2 49 male Acid regurgitation for 7 years Heartburn, mid-sternal pain, globus sensation, poor digestion and postprandial fullness. Sleep disturbance (+) Easy anxiety. He has visited many doctors and undergone EGD several times but no obvious esophageal inflammation was found. PPI has been tried with only partial responses. Smoking -, alcohol -, coffee - BH: 158 cm, BW: 47 kg, BMI: 18.8 kg/m 2
24-h MII-pH (on PPI) Hypersensitive to weakly acidic refluxes 24-h ph: ph<4: 0% (<4.2%) Demeester score: 0.2 (<14.7) 24-h impedance: Reflux: 37 (<75) Acidic: 1, weakly acidic: 36 Symptom association: SI: 63% (>50%), SAP: 100% (95%)
Course of management Lansoprazole 30 mg bid and imipramine 25 mg hs were prescribed. Diet and lifestyle modification. However, no obvious symptom improvement was noted after 4 months. Follow-up EGD showed only mild gastritis.
Case 3: 68 male Globus, throat clearing, cough Smoking (-), drinking (-) BMI: 23.3 ENT: normal EGD: normal RDQ=6; GerdQ=6; RSI=19
24-h MII-pH (off PPI) GERD!! 24-h ph: ph<4: 6.2% (<4.2%) Demeester score: 21.7 (<14.7) 24-h impedance: Reflux: 90 (<75) Acidic: 56, weakly acidic: 34 Symptom association: SI:78 % (>50%), SAP:100% (95%)
Prevalences of extraesophageal symptoms among GERD patients ProGERD study: 6215 patients with EE and NERD Eextraesophageal manifestations: 32.8% Non-cardiac chest pain: 14.5% chronic cough: 13.0% laryngeal disorders: 10.4% Asthma: 4.8% ERD > NERD Aliment Pharmacol Ther 2003;17:1515-1520
Prevalences of extraesophageal symptoms among GERD patients (Korean) ERD > NERD N=1712 J Neurogastroenterol Motil. 2014 Jan;20(1):87-93
Extra-esophageal manifestations Characteristics Non-specific, subjective Persistent, less episodic Higher dose, longer duration and poor response to PPI Other conditions: smoking, allergy, neurogenic, psychogenic Clinical impact: QoL Medical cost Curr Opin Gastroenterol 2010; 26:389-94 Am J Gastroenterol 2013; 108:905 911
GERD and esophageal motility disorder Associated esophageal motility disorder Absent contractility (scleroderma esophagus) Ineffective esophageal motility (IEM) Hypotensive LES Clinical manifestations High grade erosive esophagitis Barrett s esophagus Esophageal stenosis Dysphagia World J Gastrointest Pharmacol Ther 2014; 5: 86-96
Case 4 : 33 female Acid regurgitation for 7 years Esp. waking up in the morning, bitter taste in the mouth. Heartburn also accompanied. She has visited many doctors and undergone EGD several times but only mild esophageal inflammation was found. PPI bid has been tried with no obvious response Smoking -, alcohol -, coffee - BH: 168 cm, BW: 52 kg, BMI: 18.4 kg/m 2
High resolution manometry (HRM) Ineffective esophageal motility (IEM) with 70% failed contractions!!
24-h MII-pH (on PPI) No pathological reflux by ph and impedance monitoring 24-h ph: ph<4: 0% (<4.2%) Demeester score: 0.2 (<14.7) 24-h impedance: Reflux: 0 Symptom association: negative
Course of management Dexilant 60 mg qd and mosapride were prescribed. Diet and lifestyle modification. Education and reassurance was also given. However, she only have minimal symptom improvement PPI may be limited for reflux patients with esophageal dysmotility!
Mrs Lee, 64 female Dermatomyositis Smoking/alcohol (-) ; BMI: 19.4 Acid regurgitation at night, especial after 0.5-1 hr going to bed Poor sleep Swallowing disturbance(+) EGD: Reflux esophagitis, LA Gr. D Refractory acid reflux under PPI Referred for pre-op evaluation
High resolution manometry (HRM) Absent contractility with 100% failed peristalsis and hypotensive LES!!
24-h Impedance-pH (on PPI) Extreme low impedance at lower esophagus: fluid accumulation Esophageal acid exposure: 17.3% (<4.2%) Supine: 39.2% upright: 1.1% Gastric ph: median 2.7 Scleroderma esophagus!!
53F, acid reflux for 1.5 years Mild dysphagia EGD: GERD A? PPI with poor response Aggravated dysphagia, weight loss 8 kg/1 yr Resting pressure: 31 mmhg IRP-4s: 7.7 mmhg 100% failed contraction 30% panesophageal pressurization Achalasia, type II
Ms Lin, 32 female Acid reflux, heartburn, hoarseness Smoking (-), drinking (-) BMI: 45.2 Upper endoscopy: normal Poor response to PPI Pre-OP evaluation RDQ=40; GerdQ=11; RSI=28
24-h MII-pH (off PPI) No GERD!! Functional heartburn!! 24-h ph: ph<4: 0.7% (<4.2%) Demeester score: 2.2 (<14.7) 24-h impedance: Reflux: 35 (<75) Acidic: 13, weakly acidic: 20 Gas reflux: 141 Symptom association: 5 episodes of chest pain SI: 0% (>50%), SAP: 0% (95%)
GERD subgroups: endoscopic and MII-pH categorization Nat. Rev. Gastroenterol Hepatol 2013;10:371 80
Patients with refractory reflux symptoms N=106; all received MII-pH and gastroscopy (excluding esophagitis and BE) Hiatal hernia: 46 (43%) Neurogastroenterol Motil 2015; 27: 1267 73
Algorithm for refractory GERD GERD Symptoms EGD Barrett s, malignancy Response + PPI Diet and life style modification Maintenance, On demand Response MII-pH + manometry (HRM) Motility disorder Acid reflux Weakly acid/ non-acid reflux Negative Specific Tx compliance, Dosing, timing, change Rx, H2RA Baclofen, surgery, endoscopic Tx Pain modulator, Psychological consultation 33 Modified from Fass CGH 2008
2017 年新增健保給付項目 多管腔食道內阻抗及酸鹼度測定
Take Home Message Refractory reflux symptoms are increasingly common in our clinical practice The pathogenesis of refractory reflux symptoms is complex, ranging from mechanically impaired barrier to dysmotility to visceral hypersensitivity Application of esophageal motility studies, including HRM and MII-pH, may help to clarify the underlying mechanism of refractory reflux symptoms and tailor further treatment strategies (personalized medicine)
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