Minelli M. Le nuove Terapie in Oncologia. ASMaD 2016
G.Barbara. Irritable bowel syndrome, An overview
1. Il colon irritabile Giovanni Barbara Dipartimento di Medicina Interna e Gastroenterologia Università di Bologna (1088-2008)
2. Ho la pancia gonfia Sono stitica Ho spesso diarrea Circa il 30% della popolazione generale lamenta sintomi di origine gastrointestinale Ho mal di pancia
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5. Hungin et al., Aliment Pharmacol Ther 2003;17:643-50 The Chief Symptoms in IBS Telephone interviewing 41.984 interviews completed (Italy: 5.082)
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7. Subtyping IBS by predominant stool pattern 0 25 50 75 100 25 50 75 100 % Loose or Watery Stools (type 6, 7) % Hard or Lumpy Stols (type 1, 2) Bristol Stool Form Scale Longstreth et al., Gastroenterology 2006;130:1480-91 IBS-C IBS-M IBS-U IBS-D
10. Psychiatric Comorbidity in IBS 0 50 25 75 100 Anxiety disorders Any psychiatric disorder Other disorders Somatization disorder Affective disorders Subjects with diagnosis (%) = range and weighted mean Data adapted from Walker EA et al. Am J Psychiatry 1990 Studies mainly carried out in tertiary centers !
11. Risposta motoria allo stress Almy TP, Am J Med, 1951 Motilità 3+ 2+ 1+ 0 0 10 20 30 40 Minuti “ Rassicurazione” “ Scoperta del cancro”
12. Intestinal motility and association with symptoms in IBS Clustered contractions Ileum Cecum Abdominal cramps Prolonged propagated Contractions in the ileum Kellow & Phillips, Gastroenterology 1987;92:1885-93
13. Controllo Paziente con gonfiore Salvioli et al., Gastroenterology, 2004 RITENZIONE DI GAS NELL’INTESTINO DI PAZIENTI CON GONFIORE ADDOMINALE
14. Prevalence of rectal hypersensitivity in IBS across (tertiary referral) studies % A biomarker of IBS 17% hyposensitive 95% 88% 61% 50% 33% 21% Revisited over the years Not a biomarker! Patients may overreact during testing
15. Brain activation evoked by GI stimuli in IBS Control IBS Verne et al., Pain 1996 Functional MRI ACC: anterior cingulate; PCC: posterior cingulate; PFC: prefrontal cortex; Ins: insula Mechanical stimulus
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17. An Acute Episode of Infectious Gastroenteritis is a Strong Risk Factor for the Development of IBS Halvorson HA et al., Am J Gastroenterol 2006 0.1 0.5 1 10 50 Odds Ratio Protective Effect Increased Risk Odds Ratio (95% CI) 2.8 (1.0-7.5) 8.7 (3.3-22.6) 10.7 (2.5-45.6) 10.1 (0.6-181.4) 6.6 (2.0-22.3) 2.7 (0.2-30.2) 9.9 (3.2-30.0) 11.3 (6.3-20.1) 7.3 (4.8-11.1) Study (year) Ji (2005) Mearin (2005) Wang (2004) Okhuysen (2004) Cumberland (2003) Ilnyckyj (2003) Parry (2003) Rodriguez (1999) Pooled estimate
18. The immune system in IBS Healthy subject IBS Barbara et al., Gastroenterology 2004 Mast cell
19. IBS is a multifactorial disease: old and new pathophysiological factors Food allergy Inflammation Infections Bile acids Intolerance Microflora Barbara et al., APT 2004 Neurotransmitters Genetic factors Psychosocial factors
37. Pazienti con IBS che rispondono a diete di esclusione (8 studi, 540 pazienti) % responding to diet Park MI, Neurogastroenterol Motil 2006 Vi è limitata evidenza a supporto del beneficio clinico della dieta di esclusione nel trattamento dell’IBS sebbene alcuni pazienti possano benificiare di consigli alimentari
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41. Efficacia degli antispastici nel dolore viscerale nell’IBS Jailwala et al., Ann Intern Med 2000 Autore Farmaco # Pz Età media % F Sintomi predominanti Sett Miglioramento globale dei sintomi Dobrilla et al., Gut 1990 Cimetropio 70 45 67 - 12 SI’, dolore addominale , distensione Centonze et al., Am J Gastr 1988 Cimetropio 44 - 50 Dolore addominale, stipsi 24 SI’, dolore addominale , alvo Moshal et al., JIMR 1979 Trimebutina 20 27 65 Dolore addominale, stipsi 4 - dolore addominale , stipsi Awad et al., Act G Lat 1995 Pinaverio 40 31 100 - 3 SI’, dolore addominale , alvo Piai & Mazzacca, Gastroent. 1979 Cimetropio 30 41 37 Dolore addominale 12 SI’, dolore addominale Baldi et al., It J Gastro 1991 Otilonio 72 40 61 - 4 - dolore addominale , gonfiore Battaglia et al., AP&T 1998 Otilonio 325 47 69 - 15 SI’, dolore addominale , distensione
42. Effetto degli Antidepressivi Triciclici sul dolore addominale nell’IBS Jackson et al., Am J Med 2000 - 4 0 1 2 3 4 SMD A favore del placebo A favore del trattamento Greenbaum (1987) Heffner (1978) Loldrup (1989) Mertz (1998) Loldrup (1989) Myren (1984) Rajagopalan (1998) Steinhart (1981) Tanum (1996) Mean
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45. Fibre solubili e insolubili nel trattamento dell’IBS Effetto sulla stipsi Effetto sul miglioramento globale
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47. Effect of prucalopride (5-HT 4 agonist) in patients with chronic constipation Camilleri et al, N Engl J Med 2008 ;358:2344-2354 620 patients
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49. Effect of Lubiprostone on bowel function in IBS-C Johanson et al., APT 2008;27:685-96 Weekly bowel movements
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51. Efficacia dell’Alosetron (antagonista 5-HT 3 ) nell’ IBS Cremonini et al, Neurogastroenterol Motil 2003 Camilleri et al. Jones et al. Bardhan et al. Camilleri et al. Camilleri et al. Lembo et al. Pooled (excl alosetron vs. mebeverine) Pooled (all studies) Studio Odds ratios (95% Cl) 1.28 (0.98-1.67) 1.69 (1.42-2.32) 1.6 (0.93-2.63) 1.35 (0.99-1.83) 1.99 (1.45-2.71) 2.76 (2.04-3.72) 1.85 (1.57-2.18) 1.81 (1.57-2.10) 0.5 1 2 4 A favore del placebo A favore dell’alosetron
55. Proof of concept study on the effect of 5-ASA in IBS Corinaldesi et al., Aliment Pharmacol Ther 2009;30:245-252 p = 0.04 General well being (VAS 0-10) 0 2 4 6 8 10 12 14 16 * (% over lamina propria area) Before placebo After placebo Before mesalazine After mesalazine Mast cells p = 0.08 Abdominal pain Placebo Mesalazine 800 mg t.i.d.
I would like to thank etc… In the previous presentation we have have learned that infectious gastroenteritis is a strong risk factor for the development of infectious GE. This is a recent meta-analysis of the currently available studies showing that on average the risk to develop IBS after GE is increased by on averege 8 times compared to people that do not have GE. I must admit that I am a strong supporter of these novel findings. But preparing thsi lecture I have tried to look at the data from a different perspective, trying to discover the critical and controversial issues that still exist on PI-IBS. Thus,
Finally, we cannot disregard the fact that the role of infectious gastroenteritis in the pthophysiology of IBS should be viewed in a much broader context where a number of other factors contribute to the full expression of the disease. Thes factors include psychosocial facors, genetic factors possibly cahnges in intestinal microflora, I will com back to this concept in a moment, changes in newurotransmitters and in particular serotonin, and anumber of other controversial factors including food allergies and intolerance
