Studies on the Pathophysiology, Risk Factors and Management of Diverticular Disease

Abstract

INTRODUCTION Diverticular disease is a common gastrointestinal condition with significant associated morbidity. The objectives of this thesis are to improve understanding of the role of colonic pressure as a pathophysiological mechanism, predict more severe outcomes in acute diverticulitis and examine the need for antibiotics in uncomplicated acute diverticulitis. METHODS A literature review consolidated information on the terminology and pathophysiology of diverticular disease, and recent changes to the management of uncomplicated acute diverticulitis. A systematic review examined the role of colonic pressure in diverticular disease and an in vivo high resolution manometry study was performed. A survey of Australasian surgeons assessed local diverticular disease management and two retrospective cohort studies identified risk factors for complicated acute diverticulitis and severe clinical course in uncomplicated disease. An international, double-blinded, placebo-controlled, randomised trial investigating the non-inferiority of placebo compared to antibiotic therapy was performed to investigate whether antibiotics are mandatory in this group of patients. RESULTS The terminology and classification of diverticular disease is complex and not applied in a standardised manner. The manometry study found that participants with diverticulosis had fewer propagating contractions and lower intracolonic pressures when compared to controls. The clinician survey revealed a lack of consensus around the management of multiple aspects of diverticular disease, including more conservative and novel approaches. Independent risk factors for complicated acute diverticulitis included systemic inflammatory response syndrome, delayed presentation to hospital and raised C-reactive protein. Independent risk factors for severe course in uncomplicated disease included high self-reported pain score, fever, raised C-reactive protein and regular steroid/immunomodulator use. Non-inferiority between placebo versus antibiotic treatment was demonstrated by the clinical trial which compared length of hospital admission in participants with uncomplicated acute diverticulitis. CONCLUSIONS Evidence supporting the role of motility and pressure in diverticula formation and diverticular disease is limited and not supported by high resolution manometry; risk prediction in acute diverticulitis may be a useful tool for research and clinical practice; and foregoing antibiotics is non-inferior to standard antibiotic therapy in the management of uncomplicated acute diverticulitis.