UNDERSTANDING IBS AND CC Implications for diagnosis and management

UNDERSTANDING IBS AND CC Implications for diagnosis and management J. TACK, M.D., Ph.D. Department of Gastroenterology University Hospitals, K.U. Leuven Leuven, Belgium

TYPES OF GASTROINTESTINAL DISORDERS Organic gastrointestinal disorders Conventional diagnostic means identify underlying disease Functional gastrointestinal disorders In up to 50% of patients seen by gastroenterologists, conventional diagnostic means (endoscopical, radiological, histological, biochemical) fail to explain the symptoms. In these patients symptoms are thought to be caused by disturbances of gastrointestinal motility and perception

ROME PROCESS FUNCTIONAL GASTRODUODENAL DISORDERS FUNCTIONAL ESOPHAGEAL DISORDERS FUNCTIONAL ANORECTAL DISORDERS FUNCTIONAL BOWEL DISORDERS Irritable bowel syndrome; Functional bloating; Functional constipation; Functional diarrhoea

SELF-REPORTED CONSTIPATION Epidemiology Belgian survey N = 1012 Representative sample 40% 35% 30% 35% 31% 31% 29% 25% 20% 23% 21% 15% 10% 5% 0% bloating diarrhoea flatulence abdominal cramps abdominal pain constipation Tack et al., Belgian Week 2008

CHRONIC CONSTIPATION Global prevalence 41 separate adult study populations 261,040 subjects Pooled prevalence ~ 14% (95% CI = 12 17%) Lower prevalence (~ 7%) in studies adopting Rome III criteria Prevalence increases with age and lower socio-economic status Higher in women (OR 2.22) and patients reporting IBS (OR 7.98) Suares & Ford. Am J Gastroenterol 2011;106:1582-91

Age (years) CONSTIPATION EPIDEMIOLOGY Age- and sex-related prevalence Percentage men and women reporting constipation by age 1 85 54,5 54,7 80-84 75-79 70-74 52,2 47,3 42,1 36,4 31,1 44 Older subjects use more laxatives 2,3 65-69 60-64 55-59 50-54 38,6 36,2 35,4 34,1 25,2 21,3 17,8 15,9 The frequency of physician visits for constipation increases with age 5 45-49 30,3 14,5 40-44 27,8 13,6 35-39 27,3 12,8 30-34 27,9 12,5 0 20 40 60 80 100 120 Responders (%) Women Men 1 Hammond. Am J Pub Health 1964;54:11; 2 Harari et al. Arch Intern Med 1996;156:315; 3 Everhart et al. Dig Dis Sci 1989;34:1153 5 Sonnenberg & Koch. Dig Dis Sci 1989;34:606

%patients CHRONIC CONSTIPATION Symptoms in self-reported constipation 100 80 60 40 1149 participants 27.2% self-reported constipation within the past 3 months 16.7% and 14.9% constipation according to Rome I and II Physician s definition and focus: < 3 BM per week 20 0 Straining Hard or lumpy stools Incomplete emptying Stool cannot be passed Abdominal fullness or bloating Need to press on anus Pare et al., Am. J. Gastroenterol. 2001; 96: 3130-7

CHRONIC CONSTIPATION Quality of life Physical Scale Mental Scale Not constipated Constipated * * * * * * * * * * PF = Physical functioning RP = Role Physical BP = Bodily Pain GH = General Health V = Vitality SF = Social functioning RE = Role Emotional MH = Mental Health MCS = Mental Component Score PCS = Physical Component Score * P<0.05 in constipated vs not constipated effect on QoL osteoarthritis, chronic allergies, diabetes, GERD, heart disease, depression 13,875 adults in 7 countries as assessed by SF-36 score Wald et al. APT 2007;26:227 36

CHRONIC CONSTIPATION Causes of constipation Primary Secondary Normal diameter colon Irritable bowel syndrome Chronic functional constipation Disordered defecation Dilated colon Hirschsprung s disease Idiopathic megacolon Chronic intestinal pseudo-obstruction Intrinsic Colorectal cancer Diverticular Disease Metabolic / Endocrine Diabetes Hypercalcaemia Hypothyroidism Neurological Spinal injury Parkinson s Multiple Sclerosis Iatrogenic Drugs Postsurgical Psychological Depression Anorexia nervosa Anorectal Anal fissure Stricture 1 Schiller Aliment Pharmacol Ther 2001; 15: 749 2 Rao. Gastroenterol Clin N Am 2003; 32: 659

CHRONIC CONSTIPATION Rome III definition Must include 2 or more of the following: a. Straining during at least 25% of defecations b. Lumpy or hard stools in at least 25% of defecations c. Sensation of incomplete evacuation for at least 25% of defecations d. Sensation of anorectal obstruction for at least 25% of defecations e. Manual maneuvers to facilitate at least 25% of defecations f. Fewer than 3 defecations per week Loose stools are rarely present without the use of laxatives There are insufficient criteria for IBS Longstreth et al., Gastroenterology. 2006 ;130:1480-91

CHRONIC CONSTIPATION Role of fiber intake controls patients Towers 1994 Klauser 1992 Anderson 1986 Preston 1986 0 5 10 15 20 25 fibre intake (g/day)

CHRONIC CONSTIPATION Radiopaque marker study Ingest 24 radiopaque markers on 3 successive days No laxatives, enemas, or medicines that affect bowel function Days 4&7: abdominal plain film Colonic transit = markers (on day 4 and 7), normal <70 markers R L Metcalf, AM et al., Gastroenterology 1987; 92:40

Bristol Stool Chart 1,2 general measurement system to evaluate stool consistency and form. Slow transit Rapid transit Type 1 Type 2 Type 3 Type 4 Type 5 Type 6 Type 7 Separate hard lumps, like nuts (hard to pass) Sausage-shaped but lumpy Like a sausage but with cracks on its surface Like a sausage or snake, smooth and soft Soft blobs with clear-cut edges (passed easily) Fluffy pieces with ragged edges, a mushy stool Watery, no solid pieces. Entirely liquid 1 Adapted from Heaton et al. Gut 1992;33:818 2 Adapted from O Donnell et al. BMJ 1990;300:439 13 13

CHRONIC CONSTIPATION Colonic propulsion: HAPC Corsetti M, unpublished

Schiller LR., Aliment Pharmacol Ther. 2001; 15(6):749 Mertz H, et al., Am J Gastroenterol. 1999; 94(3):609 CHRONIC CONSTIPATION Primary constipation syndromes Normal transit Slow transit

Manometric Expulsion Patterns 50 Normal Dyssynergi a Ineffective Recta l mmhg 0 50 Anal mmhg 0 46

Digital Exam for Continence and Constipation Position 1 Check anal tone and squeeze Symphysis pubis Puborectalis Internal anal sphincter Superficial external anal sphincter (EAS) Superficial external anal sphincter (EAS) Cutaneous EAS 38

Digital Exam Obtuse Angle Position 2 Check puborectalis, squeeze and relax Puborectalis Internal anal sphincter Superficial external anal sphincter (EAS) Obtuse angle ~125 0 39

Digital Exam Acute Angle Position 3 Puborectalis contracts External anal sphincter contracts Puborectalis Internal anal sphincter Superficial external anal sphincter (EAS) Acute angle 40

Digital Exam - Squeeze Position 2a Puborectalis contracts External anal sphincter contracts Puborectalis Internal anal sphincter Superficial external anal sphincter (EAS) 41

Digital Exam Expulsion Effort Position 2b Check puborectalis, squeeze and relax Puborectalis Internal anal sphincter Superficial external anal sphincter (EAS) 42

Digital Exam - Expulsion Puborectalis relaxes Anal canal relaxes Angle widens Perineum decends 43

Schiller LR., Aliment Pharmacol Ther. 2001; 15(6):749 Mertz H, et al., Am J Gastroenterol. 1999; 94(3):609 CHRONIC CONSTIPATION Primary constipation syndromes Defecation disorder ( dyssynergia ) Normal transit Slow transit

Balloon Expulsion Device Polyethylene tube Balloon with 50 cc H 2 O 3-way stopcock 47

CHRONIC CONSTIPATION Balloon expulsion test Normal < 60 seconds Balloon filled with 50 cc water Polyethylene catheter Anal canal closed Patient sits on toilet 3-way stopcock Patient tries to expel balloon to pressure transducers

CHRONIC CONSTIPATION Defaecography Rectocele Rectum Anterior Posterio r 103

CHRONIC CONSTIPATION Role of bacterial flora Chatterjee et al., Am. J. Gastroenterol.. 2007

Detects structural abnormalities and PFD 1 Poor reliability 4 Specific diagnostic tests for Colon transit testing: 1,2 constipation Measures the rate at which stools move through the colon Helps to distinguish between STC and NTC Balloon expulsion test: 1,2 Simple office-based assessment Detects PFD Anorectal manometry: 3 Assesses rectoanal function Detects PFD Defecography: STC, slow-transit constipation; NTC, normal-transit constipation; PFD, pelvic floor dysfunction 1 Lembo & Camilleri. N Engl J Med 2003;349:1360; 2 Eoff. J Manag Care Pharm 2008;14:1 3 Rao et al. Am J Gastroenterol 1999;94:773-83; 4 Pelsang et al. Am J Gastroenterol 1999;94:183-186 28 28

Diagnosis and Treatment of Chronic Constipation European Perspective Tack et al. Neurogastroenterol Motil 2011;

CHRONIC CONSTIPATION Clinical case Woman, 44 years old Divorced, 2 children Works as a teacher Non-smoker No alcohol Medical history: Appendicectomy Depression

CHRONIC CONSTIPATION Clinical case Long-standing history of constipation, approximately 3 BM/week Since one year worsening of constipation; 1 bowel movement now only every 5 6 days Abdominal distension and discomfort, relieved by defecation

CHRONIC CONSTIPATION Clinical case X-ray of the colon, ordered by the GP, was normal. Tried PEG preparation, but this worsened abdominal distension and caused nausea Tried bisacodyl, which was effective, but this also induced severe cramps

CHRONIC CONSTIPATION Clinical case Current therapy: Trazodone 100 mg/day Omeprazole 40 mg/day Phosphate enema every 4 days Clinical examination: 55 kg, 161 cm Normal cardiopulmonary examination Normal abdominal examination Normal rectal examination; empty rectum

CHRONIC CONSTIPATION Laxative use - Europe Muller-Lissner et al., APT 2013

CHRONIC CONSTIPATION Laxative satisfaction - Europe Muller-Lissner et al., APT 2013

CHRONIC CONSTIPATION Treatment satisfaction 1.Efficacy-related reasons does not work well (60%) inconsistent results (71%) does not resolve all symptoms (44%) 2.Safety-related concerns 3.Adverse-effect concerns Johansson, 2004

CHRONIC CONSTIPATION Traditional treatments GUT WALL Water binding in stool Stool softening & lowers surface tension of stool Salts, Sugars and Osmotic agents Fibre and Bulking agents Docusate and Stool softeners Peristalsis Senna and Stimulant agents 1 Tack & Müller-Lissner. Clin Gastroenterol Hepatol 2009;7:502

Diagnosis and Treatment of Chronic Constipation: European Perspective Tack et al. Neurogastroenterol Motil 2011;

ROME PROCESS Functional dyspepsia; Belching disorders; Nausea and vomiting disorders; Rumination syndrome Functional heartburn; Chest pain of presumed esophageal origin; Function dysphagia; Globus Functional fecal incontinence; Functional anorectal pain; Functional defecation disorders Irritable bowel syndrome; Functional bloating; Functional constipation; Functional diarrhoea

IBS: Rome III criteria Recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months, associated with 2 or more of: Improvement with defecation Onset associated with a change in frequency of stool Onset associated with a change in form (appearance) of stool * Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis Longstreth et al., 2006

Bristol Stool Chart 1,2 general measurement system to evaluate stool consistency and form. Slow transit Rapid transit Type 1 Type 2 Type 3 Type 4 Type 5 Type 6 Type 7 Separate hard lumps, like nuts (hard to pass) Sausage-shaped but lumpy Like a sausage but with cracks on its surface Like a sausage or snake, smooth and soft Soft blobs with clear-cut edges (passed easily) Fluffy pieces with ragged edges, a mushy stool Watery, no solid pieces. Entirely liquid 1 Adapted from Heaton et al. Gut 1992;33:818 2 Adapted from O Donnell et al. BMJ 1990;300:439 41 41

IRRITABLE BOWEL SYNDROME (ROME III) Subgroups Longstreth et al., 2006

Colonic transit time (h) IRRITABLE BOWEL SYNDROME Abnormal motility 140 120 100 80 60 40 20 0 Men Women Men Women Men Women DIARRHOEA CONSTIPATION CONTROL Sadik et al., 2007

IRRITABLE BOWEL SYNDROME Abnormal motility Tornblom et al., 2011

Transit time (hours) IRRITABLE BOWEL SYNDROME Abnormal motility 100 90 80 70 60 50 40 30 20 10 * p=0,003 IBS-C CC 0 CTT Rectosigmoid TT Ansari et al., 2010

IRRITABLE BOWEL SYNDROME Anorectal function Prott et al., 2013

IRRITABLE BOWEL SYNDROME Rectal barostat

IRRITABLE BOWEL SYNDROME Abnormal sensitivity

IRRITABLE BOWEL SYNDROME Abnormal sensitivity % 80 70 60 50 40 30 20 10 0 ** **** ** ** **** Altered perception (n=68) Normal perception (n=41) pain bloating constipation diarrhea satiety GI sx anxiety depression ** Posserud et al., 2007

CHRONIC CONSTIPATION Rectal sensitivity Rectal hyposensitivity Rectal normosensitivity Gladman et al., 2007

CHRONIC CONSTIPATION Rectal hyposensitivity Gladman et al., 2009

IRRITABLE BOWEL SYNDROME Pain exacerbations Survey in 374 Acute exacerbations present in 42% Prospective diary-based study on «pain attacks» Hellstrom et al., DDW 2010

IRRITABLE BOWEL SYNDROME Meal-induced symptoms Posserud et al., UEGJ 2013

CONSTIPATION IBS-C versus CC IBS-C CC Infrequentstools + ++ Hard stools ++ ++ Incomplete evacuation ++ ++ Slow transit + +(+) Slow rectosigmoid transit - + Disordered defecation + + Abdominal pain ++ + Pain relieved by defecation ++ + Pain after meals ++? Bloating ++ ++ Rectal hypersensitivity ++ - Rectal hyposensitivity - ++