DIVERTICULAR DISEASE Practical Advances in Internal Medicine Symposium April 2016 Evolving concepts We fundamentally know very little about this common diagnosis New insights and questions What causes diverticulosis and? Changing spectrum of diverticular disease Not just abrupt, isolated attacks Chronic illness Overlap with IBS and IBD Changing management 1
Nomenclature DIVERTICULOSIS Diverticular disease (DD) Asymptomatic diverticulosis Diverticulitis SUDD SUDD = symptomatic uncomplicated diverticular disease Acute Chronic Chronic recurrent SCAD SCAD = segmental colitis associated with diverticulosis Epidemiology Developed western countries Age >60 years: 60% Age >80 years: 70+% Asia, Africa, & Indian subcontinent Much lower prevalence Burden of disease in US 3 rd most common GI disorder requiring hospitalization $2.6 billion dollars per year Everhart, Gastroenterol 2009 Fong, Colorectal Dis 2011 Goenka, Indian J Gastroentol 1994 2
Risk of 15 25% over lifetime Review by Parks 1975 Postmortem & BE studies in 1940 1950 s 4% over 11 years Shahedi 2013 : retrospective study of >2000 patients My quote: 5 10% Pathophysiology A = mucosa B = submucosa C = muscularis D = serosa/adventitia Pseudodiverticula Thin walled Wikipedia.org 3
Pathophysiology Barostat manometry studies Compliance lowest in sigmoid and descending colon, partly accounts for left sided predominance Extracellular matrix Collagen, elastin, proteoglycans Breakdown in connective tissue diseases and aging Ford, Gut 1995 Colonoscopy Lumen daveproject.org 4
What causes diverticulosis? We don t know! The fiber hypothesis The Industrial Revolution Painter & Burkitt 1971 Changes in dietary habits Ground flour Refined carbohydrates Red meat Diverticulosis A deficiency disease of Western civilization 5
The fiber hypothesis Low fiber intake Slower transit times, constipation Increased intraluminal pressure Forceful contractions Diverticula formation The fiber hypothesis Makes sense! Fiber derived from plants binds water and salt in the colon bulkier and more voluminous stools decreased contractions But, where is the evidence? Motility & manometry studies Inconsistent results No statistical analyses 6
The fiber hypothesis Peery 2012 Colonoscopy based cross sectional study n = 2104 Low fiber intake not a risk factor for diverticulosis Constipation also not a risk factor for diverticulosis Positive correlation between high fiber intake and diverticulosis? The fiber hypothesis Aldoori 1994 n = 47,888, US male health professionals Followed for 4 years Low fiber diet associated with symptomatic DD Crowe 2011 n = 47,033, England & Scotland Followed for 12 years High fiber intake associated with fewer hospital admissions and deaths from DD 7
The fiber hypothesis Take home messages Fiber may decrease the risk of symptoms and complications in patients with diverticulosis Fiber likely does not prevent the development of diverticulosis Nuts & seeds You have diverticulosis, don t eat nuts, corn and seeds! Theoretical mechanism Particulate matter obstruction barotrauma, mucosal abrasion inflammation, bleed Where s the evidence? 8
Nuts and seeds Strate 2008 Prospective cohort study Male health professionals n = 47,228; age 40 75 Followed for 18 years No association with or bleed Other risk factors Smoking NSAIDs Genetic factors Obesity 9
Proposed mechanisms in chronic symptoms Low grade inflammation Abnormal motility Chronic sxs Altered microbiome Visceral hypersensitivity Chronic DD subtypes No inflammation SUDD Inflammation present SCAD 10
Nomenclature DIVERTICULOSIS Diverticular disease (DD) Asymptomatic diverticulosis Diverticulitis SUDD SUDD = symptomatic uncomplicated diverticular disease Acute Chronic Chronic recurrent SCAD SCAD = segmental colitis associated with diverticulosis SUDD SUDD = symptomatic uncomplicated diverticular disease Recurrent, chronic gastrointestinal symptoms No overt or colitis 11
SUDD & IBS Overlap with IBS Jung 2010: diarrhea predominant IBS Cohen 2013: IBS symptoms after Shared symptoms Abdominal pain, gas/bloating, urgency, diarrhea, constipation SUDD & IBS Differentiating from IBS Cuomo 2013: Rome III criteria Abdominal pain characteristics PAIN Location Improves w/ BM Lasts > 24h Severe IBS Diffuse Yes No Less SUDD LLQ No Yes More Tursi 2014: Fecal calprotectin increased in SUDD 12
SCAD SCAD = segmental colitis associated with diverticulosis Chronic inflammation Usually in the left colon In the inter diverticular areas Rectum is always spared Tursi, Colorectal Dis 2010 SCAD & IBD Likely a subset of IBD TNF α expression is higher than controls Infliximab improves SCAD symptoms Responds to steroids and 5 ASA Tursi, Dig Dis Sci 2008 Rutgeerts, Aliment Pharmacol Ther 2006 Hassan, Gut 2006 13
SCAD & IBD Differentiating from IBD Distribution DISTRIBUTION Colonic segment(s) Rectum involved SCAD Inter diverticula Never UC With & without Yes diverticula Crohn s colitis With & without diverticula No Management of acute 7 10 days of broad spectrum abx Obstruction barotrauma, mucosal abrasion bacterial translocation inflammation Micro perforation Infectious in nature Inflammatory not infectious? 14
Management of acute AVOD and DIABOLO trials Large multicenter RCT s in Sweden, Iceland, and the Netherlands Uncomplicated, documented by CT Abx vs. IVF No difference in pain, temperature, tenderness No difference in mean hospital stay, complications, or recurrence in 1 year Management of acute Danish national guidelines do not recommend antibiotics for uncomplicated American Gastroenterological Association (AGA) November 2015: antibiotics should be used selectively, rather than routinely, in patients with acute uncomplicated 15
Management of chronic DD Rifaximin Alters gut flora, corrects dysbiosis 64% vs. 35% symptom free at 1 year (Bianchi 2011) Mesalamine (5 ASA) Anti inflammatory May improve chronic symptoms, but does not seem to prevent recurrent (Gatta 2010, PREVENT 1, PREVENT 2) Management of chronic DD Probiotics and antispasmodics Weak evidence from small & uncontrolled studies Fiber May improve symptomatic DD and prevent complications from DD (Crowe 2011, Aldoori 1994) The National Diverticulitis Study Group recommends dietary fiber >10 g/d, preferably 20 30 g/d, in all patients with diverticular disease except for acute 16
My recommendations Asymptomatic diverticulosis fiber Acute +/ antibiotics After an episode of acute 1) Fiber 2) Avoid NSAIDs 3) No smoking 4) Lose weight if BMI > 30 kg/m 2 Chronic symptoms mesalamine, rifaximin Questions? 17