Quality of life, physiological evaluation and novel treatment in refractory constipation : a study of patients from a specialist clinic in the North East of England

PhD ThesisBackground Severe idiopathic constipation is a disorder that can significantly impair Quality of Life (QOL). Idiopathic constipation refers to the situation where no organic, biochemical, structural, endocrine or neurological explanations can be found to account for symptoms. Little is known about the factors that predict poor QOL in such patients. The pathophysiological processes involved are not fully understood, particularly with reference to subsets of patients defined by their symptoms (such as the urge to defecate). A proportion of patients remain unresponsive to treatment with life style changes, high fibre diet, laxatives and non-invasive therapies. They can be regarded as having severe refractory idiopathic constipation. They may ultimately be considered for surgical intervention. The main aims of this thesis were to examine three key themes regarding severe refractory idiopathic constipation; 1) To identify factors that can predict disease-specific QOL. 2) To explore the pathophysiology of the urge to defecate and determine whether there are differences between patient groups defined by this symptom. 3) To prospectively evaluate the efficacy of a novel therapy that is a potential alternative to surgery. Predictors of Disease specific QOL: This study involved gathering data with QOL questionnaires (PAC-QOL and SF-36). Before identifying predictors, it was necessary to evaluate the psychometric properties (validity and reliability) of the QOL measures. It was important to confirm that their use was appropriate in patients with severe refractory idiopathic constipation. Confirming the psychometric properties of the measures was a prerequisite secondary aim of the study. Determining predictors of poorer QOL could enable clinicians to identify patients in whom the impact and severity of constipation is greatest. Predictors could be used to target therapies to those with greatest need. The relationships between demographics, symptoms assessed by clinician, symptoms assessed by the patient, results of objective tests and the patient's perception of health were studied. Psychometric testing of the QOL and health perception measures validated their use in patients with severe refractory idiopathic constipation. Multiple linear regression suggested that symptom intensity assessed by the patient and patient perception of mental health were the main predictors of disease specific QOL. With these results in mind, it is possible that therapeutic strategies that reduce symptoms and address problems of mental health may improve QOL. Pathophysiology of the urge to defecate: Approximately 60% of patients with idiopathic constipation have a reduced rectal urge to defecate (RRUD). They may represent a distinct group with differences in the properties and motility of the anorectum including a reduced frequency of the sampling reflex. This reflex describes relaxation of the anal sphincter allowing rectal contents to come into contact with sensory receptors in the proximal anal canal prior to defecation. The frequency of sampling events in patients with reduced urge and normal rectal urge to defecate (NRUD) was measured in a prospective comparative study using solid state, semi-ambulatory continuous anorectal manometry. The mean frequency of sampling events was 8.91/hr (sd 5.9) in the normal rectal urge group and 8.77/hr (sd 7.2) in the reduced urge group (NS). No differences in anorectal sensation or colonic transit time were found. The explanation for the noticeable division of patients into those with NRUD and RRUD remains unclear. Frequency of sampling is no different between the groups and is unlikely that sampling dictates a RRUD. Further study is required to evaluate the role of other potential determinants such as rectal compliance, rectosigmoid motility and central processing of sensory perceptions. Evaluation of a novel therapy: Percutaneous Endoscopic Colostomy (PEC) in the left colon is a minimally invasive endoscopic technique that can be used to irrigate the left colon and relieve constipation. The technique offers a potential alternative to Quality of Life, physiological evaluation and novel treatment in refractory constipation: A study of patients from a specialist clinic in the North East of England. surgery in severe cases. The aim was to perform a prospective efficacy study in refractory idiopathic constipation. The initial step was a retrospective data analysis of patients who had PEC inserted at our unit over a four year period. This is presented in the thesis. The results were to be used to inform the design of a prospective study. Over the 4 year period 31 patients attended for PEC. Indications included idiopathic constipation, recurrent sigmoid volvulus, colonic pseudo-obstruction and neurological constipation. Although symptoms were improved in the majority of patients and recurrent sigmoid volvulus prevented, complications were common. Infection and abdominal pain necessitated the removal of PEC in the majority of patients. Patients with refractory idiopathic constipation were particularly susceptible to these complications. Two deaths occurred due to faecal peritonitis occurring after insertion. Insertion was associated with significant morbidity and mortality. The widespread use of PEC is not recommended and insertion should be restricted to specially selected cases. The results did not support the initiation of a prospective study of efficacy. Consequently, this aim of the thesis was not fulfilled. Conclusions By producing this thesis, predictors of disease specific QOL have been identified. These predictors could be studied in future hypothesis testing studies of QOL. Experience has been gained in the use of physiological techniques that could be utilised in further studies of pathophysiology in idiopathic constipation. Evaluation of PEC has added valuable information to the existing literature and has directly influenced clinical practice