Prospective assessment of the effect on quality of life of anti-tumour necrosis factor therapy for perineal Crohn's fistulas.

BACKGROUND: Anti-tumour necrosis factor (TNF) therapy effectively treats Crohn's perineal fistulas (CPF); the effect on health-related quality of life (HRQoL) remains unknown. AIMS: To evaluate the effect of anti-TNF therapy on the HRQoL of patients with CPF in daily clinical practice. METHODS: Prospective evaluation of clinical and magnetic resonance imaging (MRI) responses, disease activity (Perianal Disease Activity Index - PDAI), and HRQoL assessment [Inflammatory Bowel Disease Questionnaire (IBDQ)] in patients receiving anti-TNF therapy for CPF treated up to 12 months. RESULTS: In all, 26 patients with CPF were treated (mean age 39 years; 19 infliximab, 7 adalimumab). At baseline, 85% patients had impaired IBDQ scores (mean 137; 'normal' >170). At 12 months, mean increases in IBDQ score for infliximab and adalimumab treated patients were 40 and 41 points respectively (P < 0.05). There were significant improvements in all IBDQ subscores (bowel, emotional, systemic, social) at 12 months (all P < or = 0.003). Fourteen patients (74%) on infliximab and six on adalimumab (86%) achieved IBDQ score > or =170. Mean increase in IBDQ score was 50, 34 and 16 points in patients with clinical fistula closure (P < 0.001), clinical response (P = 0.002) and no response (n = 1) respectively. IBDQ score increased for patients with MRI healing (P < 0.001) and MRI improvement (P = 0.016), but not for those with no MRI change (n = 2). IBDQ correlated significantly with PDAI at baseline and at 12 months. CONCLUSION: Anti-TNF therapy improves HRQoL in patients with CPF at 12 months and this improvement is most pronounced in patients with clinical and MRI healing.

Economic evaluation of sacral nerve stimulation for faecal incontinence.

BACKGROUND: Sacral nerve stimulation (SNS) is an established treatment for faecal incontinence in patients who have failed conservative management. This study established the cost-effectiveness of treating patients with SNS compared with non-surgical treatment. METHODS: A decision analysis model was performed. Data from 70 patients were obtained from medical records, bowel habit diaries and Short Form 36 quality of life questionnaires. Direct medical and non-medical costs were ascertained using the 2005/2006 national tariff, national statistics, and medication, pad and device costs. Indirect non-medical costs were also estimated. RESULTS: Incontinence episodes were reduced from a median of 12 per fortnight at baseline to one per fortnight with SNS. Based on direct medical and non-medical costs, the incremental cost-effectiveness ratio (ICER) for SNS was pound25 070 per QALY gained. It cost pound1038 more per year to treat patients with SNS for a median reduction of 286 incontinence episodes, equating to pound3.63 per episode reduced. When indirect non-medical costs were included the ICER was reduced to pound12 959 per QALY gained. CONCLUSION: The ICER of pound25 070 is within the pound30 000 per QALY threshold recommended by the National Institute for Health and Clinical Excellence as an effective use of National Health Service resources with proper justification.

Review article: Population screening for colorectal cancer.

Colorectal cancer is a common cancer and common cause of death. The mortality rate from colorectal cancer can be reduced by identification and removal of cancer precursors, adenomas, or by detection of cancer at an earlier stage. Pilot screening programmes have demonstrated decreased colorectal cancer mortality; as a result many countries are developing colorectal cancer screening programmes. The most common modalities being evaluated are faecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Implementation of screening tests has been hampered by cost, invasiveness, availability of resources and patient acceptance. New technologies such at computed tomographic colonography and stool screening for molecular markers of neoplasia are in development as potential minimally invasive tools. This review considers who should be screened, which test to use and how often to screen.

Clinical and economic evaluation of surgical treatments for faecal incontinence.

BACKGROUND: Faecal incontinence affects 1-2 per cent of the adult population. While many patients can be managed successfully with conservative therapy, a small proportion require surgery. Improved imaging techniques and technological advances have led to the availability of a wide range of surgical treatments. Decision-makers increasingly require clinical and cost-effectiveness studies of surgical treatments for faecal incontinence. This review examines the practical aspects of undertaking such studies. METHODS: The practical issues related to different aetiologies, different types of treatment, defining outcomes, the hidden costs of the condition and its treatment, the rapid changes in technology and issues of patient choice were all considered. A Medline search was undertaken to identify relevant publications, and the reference lists of identified papers were scanned manually. RESULTS: There are few randomized controlled studies and those that have been performed have been limited in their scope. There has also been very limited health economic analysis undertaken. Strategies for conducting such studies, and the criteria they use, have been outlined. CONCLUSION: Randomized trials have a limited role in this setting because of variations in aetiology, difficulty in standardizing procedures, continuing evolution of devices, small patient numbers, concerns for patient choice and the need for long-term follow-up. Issues to be addressed when evaluating interventions for faecal incontinence include choosing appropriate measures of surgical outcome, using new continence scoring systems and tools for quality-of-life assessment, and choosing appropriate cost perspectives and time horizons for economic evaluation.

Assessment of external anal sphincter morphology in idiopathic fecal incontinence with endocoil magnetic resonance imaging.

The failure of external anal sphincter repair may relate to sphincter atrophy where muscle fibers are replaced by fat, seen on MRI due to the differing signals returned by fat and muscle tissue. Manometry, electrophysiology, and MRI with an endocoil were performed on 34 fecally incontinent patients with intact sphincters on endosonography. The area of the external sphincter was measured in the midcoronal plane, and the percentage fat content calculated. Sphincter muscle area correlated strongly with squeeze pressure (P < 0.001) but not with percentage fat content. There was no relationship between percentage fat and age, weight, anal sensation, squeeze pressure, sphincter length or width, or pudendal nerve terminal motor latency. There was a trend for smaller sphincters to contain a higher percentage fat content (P = 0.059). MRI has established a relationship between function and external sphincter bulk, but not fat content, although smaller muscles may contain more fat.

Prospective assessment of interobserver agreement for endoanal MRI in fecal incontinence.

BACKGROUND: Endoanal magnetic resonance (MR) imaging is a new technique for the assessment of anal sphincter integrity in fecal incontinence and an alternative to anal endosonography. The present study aimed to determine interobserver variation for assessment of anal sphincter integrity using endoanal MR imaging. METHODS: Fifty-two consecutive anally incontinent patients underwent MR imaging by using a purpose-built endoanal receiver coil and static 1.0-T magnet. T2-weighted axial, coronal, and sagittal scans were independently assessed by two radiologists who noted external and internal sphincter integrity. Findings were compared and agreement was assessed with the kappa statistic. RESULTS: There was disagreement in 18 of 49 technically adequate studies (37%; kappa = 0.46), indicating "moderate" agreement. Agreement was strongest if the sphincters were either both intact or both disrupted. Observers agreed in only one diagnosis of an isolated internal sphincter defect and in no diagnosis of an isolated external sphincter defect. CONCLUSION: The overall interobserver agreement for assessment of sphincter integrity using endoanal MR imaging is "moderate." Interobserver agreement using endoanal MR imaging is less than that reported for anal endosonography.

Prospective assessment of accuracy of endoanal MR imaging and endosonography in patients with fecal incontinence.

OBJECTIVE: Endoanal MR imaging was prospectively compared with anal endosonography to determine any superiority in the characterization of sphincter morphology in fecal incontinence. SUBJECTS AND METHODS: Fifty-two consecutive patients with fecal incontinence were examined with anal endosonography and endoanal MR imaging after a detailed bowel history, clinical examination, and complete anorectal physiologic testing. External and internal anal sphincter integrity was noted on both endosonograms and MR images by two radiologists in consensus, who read individual scans in a random order to avoid recall bias. Imaging findings were subsequently compared, and arbitration of any disagreement between endosonography and MR imaging was made in consensus by a surgeon and a gastroenterologist who also had access to the patient's history, clinical examination, and anorectal physiologic testing results. RESULTS: Complete agreement was found between anal endosonographic and MR imaging interpretations in 32 patients (62%): 10 with combined external and internal sphincter injuries, two with isolated internal sphincter injury, and 20 with intact sphincters. Of 20 patients in whom results of the scans were disparate, incorrect interpretation was found on endosonography in six patients, on MR imaging in 15. Overall, one error relating to the internal sphincter was made on endosonography versus 12 on MR imaging (p = 0.002), and five errors relating to the external sphincter were made on endosonography versus six on MR imaging (p = 1.0). CONCLUSION: This study suggests that endoanal sonography and endoanal MR imaging are equivalent in diagnosing external anal sphincter injury, but MR imaging is inferior in diagnosing internal anal sphincter injury.

Review article: the clinical role of anti-TNFalpha antibody treatment in Crohn's disease.

The recent licensing of anti-TNFalpha antibody treatment offers the potential to radically alter the course of severe Crohn's disease using genetically-engineered drugs directed against a specific inflammatory mediator. Controlled randomized trials have demonstrated clinical benefit associated with tissue healing in patients with active intestinal disease and fistulae, often when conventional therapies were unsuccessful. This therapy is expensive, however, and long-term efficacy and safety data are still awaited. This review considers the nature of this therapy and the current evidence for its clinical benefit and adverse effects. The treatment is also considered in the context of available immunosuppressive agents, with suggestions about its practical application.

Prospective assessment of the clinical value of anorectal investigations.

BACKGROUND/AIM: Anorectal physiological testing and imaging have become part of routine colorectal and gastro-enterological practice, but their clinical value is controversial. We prospectively evaluated the new diagnostic information, impact on management and prognostic information provided by anorectal testing. METHODS: One hundred consecutive patients referred for testing were studied. The referring doctor's diagnosis, reason for referral, planned management and expectation of the value of investigations were recorded. Incontinent patients underwent anorectal physiological testing and endo-anal ultrasound. Patients with constipation underwent anorectal physiological testing and a study of whole-gut transit time to distinguish between slow and normal transit. Constipated patients over age 45, or those younger patients who digitated to assist defaecation, also underwent evacuation proctography to identify large rectoceles. RESULTS: Fifty-one patients had faecal incontinence. Of 12 patients with suspected anterior external anal sphincter obstetric damage, all of whom were planned for surgical repair, 3 were unsuitable for repair, 3 had a normal sphincter, 2 had a weak but structurally intact sphincter, and 1 had internal anal sphincter damage only. Of 6 patients with failed anterior repair, 3 had a defect suitable for repeat repair, 2 had intact repairs and good function, and 1 had extensive damage requiring reconstructive surgery. The tests also influenced management for incontinent patients after haemorrhoidectomy surgery (n = 5), after fistula surgery (n = 5), with congenital abnormalities (n = 3), after cerebrovascular accident (n = 1) and those with no presumptive diagnosis (n = 15). Of the 20 patients referred with constipation, demonstration of a recto-anal reflex in 1 patient with a megarectum excluded the need for full-thickness biopsy. A further patient with altered electrosensation went on to have a neurological lesion defined. Definition of slow transit in some patients did not immediately affect management. New information or a change in management was provided in patients referred for pre-operative assessment (n = 13). Information was gained in only 1 of 7 patients with solitary rectal ulcer and in none of the 8 patients with anal pain. CONCLUSION: Anorectal assessment provides important diagnostic and prognostic information and directly alters management in patients with benign anorectal disorders.

Reproducible assessment of vaginal and rectal mucosal and skin blood flow: laser doppler fluximetry of the pelvic microcirculation.

Pelvic venous congestion is a common cause of chronic pelvic pain in women of reproductive age. Although this condition represents a functional disturbance of the pelvic circulation which is related to the menstrual cycle, its aetiology remains unknown. Indirect techniques demonstrate that the vasoconstrictive reflex response of the microcirculation of the foot to a rise in venous pressure is attenuated throughout the menstrual cycle. We wished to develop a simple and non-invasive direct measure of pelvic blood flow to aid diagnosis of this condition. Laser doppler blood flux measurements of the skin of the big toe and of the vaginal and rectal mucosa in the follicular and luteal phases of the menstrual cycle in 12 healthy asymptomatic premenopausal women (mean age 30 years) with regular cycles and in four healthy asymptomatic postmenopausal women (mean age 59 years) were carried out both in the supine position and in response to 40 degrees head-up tilt. The coefficient of variation of resting vaginal flux was lower for measurements in postmenopausal women (0.04) and in premenopausal women in the follicular phase (0. 07) compared with those in the luteal phase (0.16). At rest, vaginal blood flow was higher than rectal and skin flux in both premenopausal and postmenopausal women. In the follicular phase a decrease in flow was observed in response to head-up tilt in the skin (-32.0%), vagina (-34.3%) and rectum (-9.4%). In the luteal phase this reflex was attenuated at these three sites (-8.6%, +6.7% and +7.4% respectively). There were no significant reflex changes in postmenopausal women. Thus laser doppler fluximetry is a reproducible method for comparing the flux of blood in the microcirculation of the skin and of the vaginal and rectal mucosa. The skin is the least sensitive site for testing vascular reactivity in response to cyclical changes. The vaginal and rectal microcirculations are the most sensitive sites for testing visceral cyclical reactivity, and have the advantage of direct anatomical relevance. The follicular phase of the menstrual cycle is associated with greatest vascular reactivity and is the most appropriate phase during which to test for abnormal vascular responses.

Transperineal repair of symptomatic rectocele with Marlex mesh: a clinical, physiological and radiologic assessment of treatment.

BACKGROUND: The aim of this study was to evaluate the operative repair of rectoceles in a defined group of women by a technique designed to deal with the cause (failure of the rectovaginal septum) rather than the effect (rectal and vaginal wall bulging). STUDY DESIGN: Only women whose defecation was aided by vaginal digitation and who had large rectoceles on proctography were included. Any other clinical symptoms in the absence of vaginal digitation, even when proctography demonstrated a rectocele, were not taken as indicators for surgery in this study. There were nine women, median age 50 years (range, 32 to 61). The rectovaginal septum was repaired with Marlex mesh through a perineal approach by one surgeon. The median follow-up period was 29 months. RESULTS: Eight of the nine women achieved successful evacuation after surgery without the need for vaginal digitation. Rectocele size, depth, and the percent of barium trapped in the rectocele on proctography were all improved. Anorectal physiology measurements were unchanged by surgery. CONCLUSIONS: Operative repair of the rectovaginal septum removes the need for vaginal digitation in most women with large rectoceles on proctography. Further studies in well-defined groups of women are needed to establish how well rectocele repair aids women with a variety of other pelvic and perineal symtoms.

Rectal sensory evoked potentials: an assessment of their clinical value.

To assess abnormalities of sensory conduction in anorectal disease we have evaluated peripheral sensory perception and somatosensory evoked potentials produced by rectal stimulation in control subjects and patients with either constipation or idiopathic faecal incontinence. Evoked potentials were also recorded after posterior tibial and dorsal genital nerve stimulation. Rectal sensation was also assessed using electrical stimulation. Reproducible evoked potential recordings after anorectal stimulation were possible in only a minority of subjects and when recorded showed intersubject and intrasubject variation. In the constipated group there was a significant difference in rectal electrical sensation (P < 0.05) from controls. We conclude that peripheral sensory testing demonstrates an abnormality in severe constipation. However, cerebral evoked potentials cannot be reliably recorded after rectal stimulation, and when recorded the latencies are of too broad a range to discriminate between health and disease. This probably relates to the difference between somatic and visceral pathways.