DYSPEPSIA OR GASTROPARESIS Update 2015 J. TACK, M.D., Ph.D. TARGID University of Leuven Leuven, Belgium www.targid.eu DYSPEPSIA OR GASTROPARESIS Clinical case A 22 year old preschool teacher sees a gastroenterologist with marked early satiety with postprandial epigastric pain, nausea and fullness. Symptoms started with an acute gastroenteritis while on holiday on a Greek island. Diarrhea disappeared rapidly but since then she remained intolerant to food. In total she lost 4 kgs over the last 5 months. Upper endoscopy with biopsies, laboratory testing and abdominal ultrasound are negative. FUNCTIONAL DYSPEPSIA Rome III definition Functional dyspepsia: one or more of bothersome Postprandial fullness, or Early satiety, or Epigastric pain, or Epigastric burning No evidence of organic disease that is likely to explain the symptoms; and Symptoms present during the last 3 months with onset at least 6 months before diagnosis Overlap with GERD and IBS is common and does not exclude the diagnosis. Tack et al., 2006 DYSPEPSIA OR GASTROPARESIS Clinical case Proton pump inhibitors are not helpful. A psychiatrist ruled out an eating disorder. A CT scan of the abdomen was normal Would you do a gastric emptying test? DYSPEPSIA EPIDMIOLOGY Prevalence and health care impact 141 (33.8%) D+R+ 1608 417 4 (1.0%) D+R- D-R- 237 35 (56.8%) (8.4%) P < 0.001 P < 0.001 P < 0.001 100% 100% 100% 90% 90% 90% 80% 80% 80% 70% 70% 70% 60% 60% 60% No No No 50% 50% 50% Yes Yes Yes 40% 40% 40% 30% 30% 30% Medication (% of patients)Medicationof (% Investigationspatients)of (% Doctor's visit (% of patients) Doctor's (% visit 20% 20% 20% 10% 10% 10% 0% 0% 0% GERD+FD+ GERD-FD+ GERD-FD- GERD+FD+ GERD-FD+ GERD-FD- GERD+FD+ GERD-FD+ GERD-FD- 5 Doctor’s visits, Investigations, Medications Piessevaux et al., NMO 2010 MEAL-RELATED DYSPEPSIA Prevalence of delayed gastric emptying Study n Delayed emptying Normal emptying Jian 1989 23 59% 41% Wegener 1989 48 30% 70% Wegener 1989 50 42% 58% Klauser 1993 69 35% 65% Scott 1993 75 28% 72% Stanghellini 1996 343 33% 67% Maes 1997 344 30% 70% Perri 1998 304 33% 67% Sarnelli 2003 392 23% 77% Overall 1648 30% 70% GASTROPARESIS Definition • Delayed gastric emptying in the absence of a mechanical obstruction of the stomach. • Symptoms: – Postprandial fullness – Early satiety – Nausea and vomiting – Bloating – Epigastric pain Parkman et al., Neurogastroenterology and Motility 2010 GASTROPARESIS Causes Pseudo-obstruction Anorexia nervosa 5% 3% Collagen-vascular disease 5% Idiopathic 33% Parkinson’s disease 5% Miscellaneous 6% Postgastric surgery 19% Diabetes mellitus 24% GASTROPARESIS Diagnosis • Gastric emptying test • Rule out mechanical obstruction • Upper g.i. endoscopy • Small bowel x-ray / CT GASTROPARESIS Gastric emptying test • Scintigraphy • Breath test • (Ultrasound) • (Magnetic resonance imaging) • (Paracetamol absorption test) • (Solid markers radiography) • (Gastric aspiration tests) GASTROPARESIS Scintigraphy • 99mTc-containing meal • Scan at 0,1, 2 and 4 hours 100 Tlag 75 Gastric retention (%) 50 T1/2 25 0 0 60 120 180 240 300 360 Time after the meal (min) GASTROPARESIS Breath test • Standardized meal: caloric content, % CH and fat – Scrambled egg and water – Substrate: degraded immediately after emptying from stomach; appearance of labeled CO2 in breath; empyting is rate-limiting step • 13C- or 14C-octanoic acid • 13C- or 14C-glycin • 13C-acetate • 13C-spirulina DYSPEPSIA OR GASTROPARESIS Reasons to do a gastric emptying test Would enter the patient into or would exclude the patient from a different diagnostic category: Gastroparesis Is it present in a subset of patients? Is it stable over time? Does it explain symptoms (better?) Does it determine choice of therapy? Does it determine long-term prognosis? FUNCTIONAL DYSPEPSIA Rome III definitions Functional Dyspepsia Postprandial distress Epigastric pain syndrome (PDS): syndrome (EPS): Meal-related FD Meal-unrelated FD Early satiation Epigastric pain Postprandial fullness Epigastric burning Tack et al., Gastroenterology 2006; 130(5):1466-79 FUNCTIONAL DYSPEPSIA Subgroups 20 Tack and Talley, NRGH 2013 FUNCTIONAL DYSPEPSIA Subgroups 21 Tack and Talley, NRGH 2013 MEAL-RELATED FUNCTIONAL DYSPEPSIA Putative pathophysiological mechanisms Perception Perception Visceral hypersensitivity Fasting Accommodation Emptying Gastric acid secretion Hormone secretion Hormone secretion Duodenal bicarbonate secretion Impaired Gastric Disordered gastric Accommodation emptying 22 MEAL-RELATED DYSPEPSIA Impaired accommodation Presence Health FD Impaired accommodation Troncon et al., 1994 Hausken et al., 1996 Tack et al., 1998 Boeckxstaens et al., 2002 Kim et al., 2001 ……… MEAL-RELATED DYSPEPSIA Prevalence of impaired accommodation Impaired Normal Author Method n accommodation accommodation Scott 1993 Scintigraphy 75 31% 69% Tack 1998 Barostat 40 40% 60% Thumshirn 1999 Barostat 17 70% 30% Kim 2001 SPECT 32 41% 59% Boeckxstaens 2001 Barostat 42 40% 60% Piessevaux 2003 Scintigraphy 40 50% 50% Bredenoord 2003 SPECT 151 43% 57% Overall 397 44% 56% GASTROPARESIS Scintigraphy • 99mTc-containing meal • Scan at 0,1, 2 and 4 hours 100 Tlag 75 Gastric retention (%) 50 T1/2 25 0 0 60 120 180 240 300 360 Time after the meal (min) MEAL-RELATED DYSPEPSIA Prevalence of delayed gastric emptying Study n Delayed emptying Normal emptying Jian 1989 23 59% 41% Wegener 1989 48 30% 70% Wegener 1989 50 42% 58% Klauser 1993 69 35% 65% Scott 1993 75 28% 72% Stanghellini 1996 343 33% 67% Maes 1997 344 30% 70% Perri 1998 304 33% 67% Sarnelli 2003 392 23% 77% Overall 1648 30% 70% MEAL-RELATED DYSPEPSIA Visceral hypersensitivity 100% 80% 60% Normal sensitivity Hypersensitivity 40% 20% Prevalence (% patients) of (% Prevalence 0% Control Organic Functional dyspepsia dyspepsia Mertz et al., 1998 Tack et al., 2001 Rhee et al., 2001 Boeckxstaens et al., 2002 …….. FUNCTIONAL DYSPEPSIA Rome III definitions Functional Dyspepsia Postprandial distress Epigastric pain syndrome (PDS): syndrome (EPS): Meal-related FD Meal-unrelated FD Impaired accommodation 45% Delayed emptying 30% Visceral hypersensitivity 40% … Tack et al., Gastroenterology 2006; 130(5):1466-79 MEAL-UNRELATED FUNCTIONAL DYSPEPSIA Putative pathophysiological mechanisms CNS Non-acid reflux dysfunction Atypical NERD H. pylori Duodenal acid infection exposure Duodenal lipid Gastric hypersensitivity arrhythmia’s Small bowel dysmotility 32 IDIOPATHIC GASTROPARESIS Overlap with FD Idiopathic gastroparesis N= 243 Overlapping FD: 86% PDS: 91% Parkman et al., Neurogastroenterology and Motility 2010 DYSPEPSIA OR GASTROPARESIS Reasons to do a gastric emptying test Is it present in a subset of patients? Is it stable over time? FUNCTIONAL DYSPEPSIA Reproducibility of emptying rate 350 300 250 200 150 100 Half emptying Half emptying time (min) 50 0 Baseline 1 month Measurement of gastric emptying Arts et al., 2005 IDIOPATHIC GASTROPARESIS Tegaserod and emptying rate 25% Baseline (%) hours 4 20% 8 weeks (%) 15% * “normal” post meal 10% gastric retention rate % retention% at 5% at 4 hours is 6.3% 0% 24 18 12 6 Placebo Tegaserod daily dose Tougas et al DDW 2003 DYSPEPSIA OR GASTROPARESIS Reasons to do a gastric emptying test Is it present in a subset of patients? Is it stable over time? Does it explain symptoms (better?) FUNCTIONAL DYSPEPSIA Symptoms and delayed emptying 100 90 Normal emptying (77%) * Delayed emptying (23%) 80 70 * 60 50 * 40 30 Prevalence Prevalence (% of patients) 20 10 0 Fullness Bloating Pain Early Nausea Belching Weight Epigastric Vomiting satiety loss burning Sarnelli et al., 2003 ROME II DYSPEPSIA AND GASTROPARESIS Symptom patterns 100% 90% 80% 70% 60% Absent or Functional dyspepsia 50% mild 40% Relevant or severe 30% Prevalence (% (% of patients) Prevalence 20% 10% 0% FullnessBloating Pain Early satietyNausea BelchingWeight EpigastricVomiting loss burning 100% 90% 80% 70% 60% Absent or mild Idiopathic gastroparesis 50% Moderate = severely delayed emptying 40% or severe on at least 2 occasions 30% Prevalence (%of (%of patients) Prevalence 20% 10% Tack et al., 2005 0% FullnessBloating Pain Early Nausea Belching WeightEpigastric Vomiting Karamanolis et al., 2007 satiety loss burning ROME II DYSPEPSIA AND GASTROPARESIS Symptom patterns 100 Dyspepsia normal emptying 90 Dyspepsia delayed emptying Idiopathic gastroparesis 80 70 60 50 40 30 20 Prevalence (% patients)(% of Prevalence 10 0 Fullness Bloating Pain Early Belching Nausea Epigastric Weight Vomiting satiety burning loss Sarnelli et al., 2003 Karamanolis et al., 2007 IDIOPATHIC GASTROPARESIS Symptom severity and emptying rate 40 35 30 25 20 15 10 Symptom Symptom severity score 5 0 100 120 140 160 180 200 220 240 260 280 300 Solid half emptying time (min) Karamanolis et al., 2007 IDIOPATHIC GASTROPARESIS Symptom severity and gastric sensitivity 40 35 30 25 20 15 10 Symptom Symptom severity score 5 0 0 5 10 15 20 25 Discomfort pressure (mm Hg above MDP) Karamanolis et al., 2007 DYSPEPSIA OR GASTROPARESIS Reasons to do a gastric emptying test Is it present in a subset of patients? Is it stable over time? Does it explain symptoms (better?) Does it determine choice of therapy? FUNCTIONAL DYSPEPSIA Management algorithm (in the West) Chronic dyspeptic symptoms Endoscopy 70% Functional Organic dyspepsia dyspepsia Eradicate if H.pylori positive POSTPRANDIAL EPIGASTRIC PAIN DISTRESS SYNDROME SYNDROME (PDS) (EPS) 44 FUNCTIONAL DYSPEPSIA Response to proton pump inhibitors Patient subgroup Risk ratio (95% c.I.) 0.76 (0.66, 0.88) GERD: Reflux group EPS: Epigastric pain group 0.85 (0.79, 0.92) PDS: Dysmotility