Review article: dyssynergic defaecation and biofeedback therapy in the pathophysiology and management of functional constipation.

BACKGROUND: Functional constipation is a common clinical presentation in primary care. Functional defaecation disorders are defined as the paradoxical contraction or inadequate relaxation of the pelvic floor muscles during attempted defaecation (dyssynergic defaecation) and/or inadequate propulsive forces during attempted defaecation. Prompt diagnosis and management of dyssynergic defaecation is hindered by uncertainty regarding nomenclature, diagnostic criteria, pathophysiology and efficacy of management options such as biofeedback therapy. AIM: To review the evidence pertaining to the pathophysiology of functional defaecation disorders and the efficacy of biofeedback therapy in the management of patients with dyssynergic defaecation and functional constipation. METHODS: Relevant articles addressing functional defaecation disorders and the efficacy of biofeedback therapy in the management of dyssynergic defaecation and functional constipation were identified from a search of Pubmed, MEDLINE Ovid and the Cochrane Library. RESULTS: The prevalence of dyssynergic defaecation in patients investigated for chronic constipation is as many as 40%. Randomised controlled trials have demonstrated major symptom improvement in 70%-80% of patients undergoing biofeedback therapy for chronic constipation resistant to standard medical therapy and have determined it to be superior to polyethylene glycol laxatives, diazepam or sham therapy. Long-term studies have shown 55%-82% of patients maintain symptom improvement. CONCLUSIONS: Dyssynergic defaecation is a common clinical condition in patients with chronic constipation not responding to conservative management. Biofeedback therapy appears to be a safe, successful treatment with sustained results for patients with dyssynergic defaecation. Further studies are required to standardise the diagnosis of dyssynergic defaecation in addition to employing systematic protocols for biofeedback therapy.

Effectiveness of percutaneous tibial nerve stimulation in managing refractory constipation.

AIM: Chronic constipation can be aetiopathogenically classified into slow transit constipation (STC), rectal evacuation difficulty (RED) or a combination (BOTH). Although the efficacy of percutaneous tibial nerve stimulation (PTNS) in faecal incontinence has been well proved, a current literature search identifies only one study which assessed its effect on constipation. We aimed to evaluate the effectiveness of PTNS in patients with different causes of constipation. METHOD: Thirty-four patients [30 women, median age 50 (20-79) years] with constipation who had previously failed maximal laxative and biofeedback therapy participated in the study. All patients underwent a baseline radio-opaque marker transit study and anorectal physiology examination. All had 12 sessions of PTNS of 30 min per session. A fall in the Wexner constipation score to ≤15 or by ≥5 points was taken as the primary outcome. Secondary outcomes included the results of pre- and post- PTNS transit and anorectal physiology studies. RESULTS: Eleven patients had STC, 14 had RED and nine had BOTH. A response was seen in four patients (1/11 STC, 2/14 RED and 1/9 BOTH). Comparing pre- and post- PTNS, there was no significant change in the mean Wexner score (P = 0.10). There was no change in colonic transit time among the whole population (P = 0.56) or among those with STC (P = 0.47). There was no improvement in balloon expulsion in the whole group (P = 0.73) or in patients with RED (P = 0.69). CONCLUSION: PTNS is of no benefit to patients with constipation, whatever aetiopathogenic mechanism is responsible for the symptoms.

Synchronized functional anal sphincter assessment: maximizing the potential of anal vector manometry and 3-D anal endosonography.

BACKGROUND: Understanding the association between structure and function is vital before considering surgery involving anal sphincter division. By correlating three-dimensional anal endosonography (AES) and three-dimensional anal canal vector volume manometry (VVM), this study details a method to produce measurements of both sphincter length and pressure leading to identification of the functionally important areas of the anal canal. The aim of this study was to provide combined detailed information on anal canal anatomy and physiology. METHODS: Twelve males and 12 nulliparous females with no bowel symptoms underwent VVM (using a water-perfused, eight-channel radially arranged catheter) and AES. KEY RESULTS: The synchronization of AES and VVM identified that the majority of rest and squeeze anal pressure is present in the portion of the anal canal covered by both anal sphincters. Nearly, 20% of overall resting anal pressure is produced distal to the caudal termination of the internal anal sphincter. Puborectalis accounts for a significantly greater percentage volume of pressure in females both at rest and when squeezing, though the total volume of pressure is not significantly greater. CONCLUSIONS AND INFERENCES: The majority of resting and squeezing pressure and the least asymmetry, in both sexes, is in the portion of the anal canal covered by external anal sphincter. In females, the external anal sphincter is shorter and a proportionately longer puborectalis accounts for a greater percentage of pressure. Sphincter targeted fistula surgery in females must be performed with special caution. A protective role for puborectalis following obstetric anal sphincter injury is suggested.

Global audit on bowel perforations related to transanal irrigation.

PURPOSE: Transanal irrigation is increasingly used against chronic constipation and fecal incontinence in selected patients. The aims were to estimate the incidence of irrigation-related bowel perforation in patients using the Peristeen Anal Irrigation(®) system, and to explore patient- and procedure-related factors associated with perforation. METHODS: External independent expert audit on the complete set of global vigilance data related to Peristeen Anal Irrigation from 2005 to 2013. RESULTS: In total, 49 reports of bowel perforation had been recorded. Based on sales figures, this corresponds to an average risk of bowel perforation of 6 per million procedures. The latest two-year data indicate a risk of 2 per million procedures. In 29 out of 43 evaluable cases (67 %), perforation happened within the first 8 weeks since start of treatment. After 8 weeks, long-term use has an estimated risk of less than 2 per million procedures. Among patients with non-neurogenic bowel dysfunction, 11 out of 15 (73 %) had a history of pelvic organ surgery compared to 5 out of 26 (19 %) in neurogenic bowel dysfunction. In 11 of 46 (24 %) evaluable cases, burst of the rectal balloon was reported. CONCLUSION: Enema-induced perforation is a rare complication to transanal irrigation with Peristeen Anal Irrigation, which increases the benefit risk ratio in support of the further use of transanal irrigation. Increased risk is present during treatment initiation and in patients with prior pelvic organ surgery. Careful patient selection, patient evaluation and proper training of patients are critical to safe practice of this technique.

Randomized clinical trial of sacral versus percutaneous tibial nerve stimulation in patients with faecal incontinence.

BACKGROUND: Sacral nerve stimulation (SNS) is a well established therapy for faecal incontinence (FI). Percutaneous tibial nerve stimulation (PTNS) is a newer, less invasive, treatment. The effectiveness and acceptability of these treatments have not been compared systematically. METHODS: An investigator-blinded randomized pilot trial of PTNS versus SNS with a parallel qualitative study was performed. Quantitative clinical outcomes and qualitative data from patient interviews were collected for both interventions. RESULTS: Forty patients (39 women; mean age 59 years) met the eligibility criteria; 23 were randomized to receive SNS and 17 to PTNS. Fifteen patients progressed to permanent SNS implantation and 16 received a full course of PTNS. Within-group effect sizes were marginally greater for SNS than for PTNS on available-case analysis. Mean(s.d.) FI episodes per week at baseline, and 3 and 6 months of follow-up were: 11·4(12·0), 4·0(4·0) and 4·9(6·9) respectively for SNS compared with 10·6(11·2), 5·8(6·9) and 6·3(6·9) for PTNS. Mean(s.d.) Cleveland Clinic Incontinence Score values at baseline, and 3 and 6 months were: 16·2(3·0), 11·1(5·2) and 10·4(5·6) for SNS versus 15·1(2·7), 11·7(4·4) and 12·1(5·2) for PTNS. Improvement of at least 50 per cent in FI episodes per week at 6 months was seen in 11 of 18 patients in the SNS group compared with seven of 15 in the PTNS group. Effect estimates for SNS with chronic implanted stimulation were larger (10 of 15 patients at 6 months). Disease-specific and generic quality-of-life improvements complemented clinical outcome data. Qualitative analysis of interview data suggested that both treatments had high acceptability amongst patients. CONCLUSION: In the short term, both SNS and PTNS provide some clinical benefit to patients with FI. Registration numbers: 2010-018728-15 and 10479 (http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=10479).

Consensus review of best practice of transanal irrigation in adults.

STUDY DESIGN: Review article. OBJECTIVES: To provide a consensus expert review of the treatment modality for transanal irrigation (TAI). METHODS: A consensus group of specialists from a range of nations and disciplines who have experience in prescribing and monitoring patients using TAI worked together assimilating both the emerging literature and rapidly accruing clinical expertise. Consensus was reached by a round table discussion process, with individual members leading the article write-up in the sections where they had particular expertise. RESULTS: Detailed trouble-shooting tips and an algorithm of care to assist professionals with patient selection, management and follow-up was developed. CONCLUSION: This expert review provides a practical adjunct to training for the emerging therapeutic area of TAI. Careful patient selection, directly supervised training and sustained follow-up are key to optimise outcomes with the technique. Adopting a tailored, stepped approach to care is important in the heterogeneous patient groups to whom TAI may be applied. SPONSORSHIP: The review was financially supported by Coloplast A/S.

Randomised clinical trial: the efficacy of prucalopride in patients with chronic intestinal pseudo-obstruction--a double-blind, placebo-controlled, cross-over, multiple n = 1 study.

BACKGROUND: Chronic intestinal pseudo-obstruction is a disabling condition for which there are no established drug therapies. The condition is caused by a diverse range of intestinal myopathies and neuropathies. AIM: To assess the therapeutic efficacy of prucalopride, a selective high-affinity 5-HT(4) receptor agonist, we employed a multiple n = 1 study design. Each patient acted as his/her own control, each day counting as one treatment episode, allowing comparison of 168 days on each of active drug and placebo. METHODS: Double-blind, randomised, placebo-controlled, cross-over trial of four 12-week treatment periods, with 2-4 mg prucalopride or placebo daily. In each of the first and second 6 months there was a prucalopride and a placebo treatment. Patients with proven chronic intestinal pseudo-obstruction, including dilated gut, were included. Evaluation was by patient diary and global evaluation. RESULTS: Seven patients participated (mean 42 years, five female, median symptom duration 11 years). Three discontinued, two due to study length, and one on prucalopride due to unrelated malnutrition and bronchopneumonia. Four patients (three visceral myopathy and one visceral neuropathy) completed the study; prucalopride significantly improved pain in three of four patients, nausea in two, vomiting in one, bloating in four and analgesic intake. Bowel function was not changed substantially. CONCLUSIONS: n = 1 studies in rare conditions allow drug efficacy assessment. Prucalopride relieves symptoms in selected patients with chronic pseudo-obstruction.

Vector volume manometry--methods and normal values.

BACKGROUND: Vector volume manometry (VVM) can be used to assess patients with fecal incontinence. The VVM may be performed using a station pull through, or an automated technique. Currently no standard technique or equipment exists to assess anal canal VVM. This study aimed to assess the different techniques to produce repeatable results, and generate normal values for the vector volume profile. METHODS: Anal canal VVM was performed using a water-perfused system on 12 male and 12 nulliparous female volunteers. Manometry was performed with an automated puller withdrawn at 3 and 25mms(-1) using a station technique. The VVM profiles were calculated using 4, 8, and 16 channels. KEY RESULTS: The greatest repeatability of vector volume profile was seen with faster puller speed (25mms(-1) ) and with an 8-channel catheter. Men had higher squeeze volumes, maximal squeeze pressure, average squeeze pressure, and squeeze high pressure zone length. Women had a significantly greater anal canal asymmetry on both station and automated pull through at rest and when squeezing. Squeeze vector volume of pressure, mean maximum squeeze pressure, and the average squeeze pressure were significantly higher when calculated using the station technique. CONCLUSIONS & INFERENCES: The faster puller speed has improved agreement between vector profiles, which is most marked during active contraction. The 8-channel catheters have the greatest agreement between profiles. There is variation in values between automated manometry and the stationary pull through technique. The improved repeatability in automated VVM for healthy controls should improve its diagnostic utility in patients with incontinence.

Pharmacological management of constipation.

The approach of this review is to give a pragmatic approach to using laxatives, based on a combination of what is known about mechanism of action and the available literature on evidence.

Relationship between gut-specific autonomic testing and bowel dysfunction in spinal cord injury patients.

STUDY DESIGN: Investigation of bowel function in 55 patients and 26 healthy volunteers using radiological, anorectal physiological and laser Doppler blood flow monitoring. OBJECTIVES: Bowel dysfunction is common after spinal cord injury (SCI). We aimed to determine whether hindgut testing of autonomic innervation provides insight into presence of symptoms, altered motor function (transit) and level of injury. SETTING: St Mark's Hospital, UK and The Spinal Injuries Unit, Royal National Orthopaedic Hospital, UK. METHODS: A total of 55 patients with chronic complete SCI and 26 healthy volunteers were studied. Twenty-four patients had lesions above T5 and 31 had lesions below T5. Thirty-five patients complained of constipation: 75% (18/24) of patients with lesions above T5 and 55% (17/31) of those with lesions below T5. Gut transit, rectal electrosensitivity and rectal blood flow were measured. RESULTS: Slow gut transit occurred in 65% of patients and in all the 35 patients complaining of constipation. Delay was pancolonic. All patients had an elevated sensory threshold. The threshold was significantly higher in those with subjective constipation (P<0.01), slow transit (P<0.04) and high SCI (P=0.046). Mucosal blood flow was lower in SCI patients with constipation (P<0.04) and slow transit (P<0.03). It was higher than normal in high-SCI volunteers (P=0.056), reflecting loss of sympathetic inhibition. CONCLUSIONS: In SCI, subjective constipation correlates closely with slow gut transit. Delay is pancolonic, regardless of the site of lesion. Sensory testing provides evidence for completeness of lesion, offering further evidence for pain transmission through sympathetic pathways. Studies in SCI patients provide further evidence of mucosal blood flow as a marker of altered autonomic innervation.

Amitriptyline modifies the visceral hypersensitivity response to acute stress in the irritable bowel syndrome.

BACKGROUND: Acute physical stress causes alteration in gut autonomic function and visceral hypersensitivity in patients with irritable bowel syndrome (IBS). We have developed a model to measure this stress response. AIM: To assess whether treatment with a drug effective in treating IBS (amitriptyline) alters the response to acute stress in IBS patients. METHODS: Nineteen patients with IBS were given amitriptyline 25-50 mg. Patients underwent physical stress (cold pressor) test at baseline and after 3 months of treatment. Physiological parameters measured were: stress perception; systemic autonomic tone [heart rate (HR) and blood pressure (BP)]; gut specific autonomic innervation [rectal mucosal blood flow (RMBF)] and visceral sensitivity (rectal electrosensitivity). RESULTS: Fourteen of 19 (74%) patients improved symptomatically after 3 months of amitriptyline. Acute stress induced increased perception of stress and systemic autonomic tone and reduced RMBF in symptomatic responders and nonresponders (P > 0.05 for all). All nonresponders but only 3 of 14 responders continued to exhibit stress-induced reduced pain threshold at 3 months (change from baseline -31% vs. +2%, P < 0.03 respectively). CONCLUSION: In this open study, amitriptyline appears to decrease stress-induced electrical hypersensitivity; this effect is independent of autonomic tone. The gut response to acute stress deserves further study as a model to study drug efficacy in IBS.

Acid-related oesophageal sensitivity, not dysmotility, differentiates subgroups of patients with non-erosive reflux disease.

BACKGROUND: Patients with non-erosive reflux disease can experience reflux symptoms with similar frequency and severity as those with erosive reflux disease. Oesophageal motility and acid sensitivity are thought to influence symptom occurrence. AIM: To compare the effect of infused hydrochloric acid on oesophageal physiology in patients with non-erosive reflux disease and erosive reflux disease. METHODS: Twelve healthy controls and 39 patients with reflux disease [14 erosive reflux disease, 11 non-erosive reflux disease with normal (functional heartburn) and 14 non-erosive reflux disease with excess acid exposure] had hydrochloric acid and saline infused into distal and then proximal oesophagus. Oesophageal contraction amplitude, lower oesophageal sphincter pressure and pain intensity were documented at baseline and during each infusion. RESULTS: Patients with non-erosive reflux disease had higher pain sensitivity to acid than those with erosive reflux disease and controls. Proximal acid infusion caused greater pain than distal in patients with non-erosive reflux disease. Acid and saline sensitivity were more pronounced in patients with functional heartburn. Lower oesophageal sphincter pressure and oesophageal contraction amplitudes were lower in the erosive reflux disease and non-erosive reflux disease groups, but did not change during infusions. CONCLUSIONS: Patients with non-erosive reflux disease and, to a lesser extent, patients with erosive reflux disease, are sensitive to acid in the oesophagus, being more sensitive to proximal acid. Hypersensitivity is most marked in functional heartburn patients. This acid sensitivity is not associated with motility change.

Normal ranges for anorectal manometry and sensation in women of reproductive age.

OBJECTIVE: To derive a range of normal values for anal sphincter resting and squeeze pressure, and anorectal sensation in healthy women without anorectal disease before and after their first childbirth. METHOD: Nulliparous women undergoing anal physiology testing in the third trimester of pregnancy and 12 weeks after delivery. All were asked to undergo anal manometry and anorectal electrosensation testing. Maximum resting pressure, maximum squeeze pressure and anal thresholds to electrical current were assessed at 1 cm intervals down the anal canal. Rectal electrosensitivity thresholds were assessed 10 cm from the anal verge. RESULTS: A total of 286 women attended for antenatal investigations and 161 (56%) returned postpartum. The anal canal length was 3.9 +/- 0.6 cm antenatally and 3.9 +/- 0.6 cm postnatally. During pregnancy the 95% normal range for anal resting and squeeze pressures, anal and rectal sensation were 29-90 mmHg, 50-163 mmHg, 2-31 mA and 3-33 mA respectively. Post delivery the 95% normal ranges were 27-98 mmHg, 43-156, 2-12 mA and 0.1-34 mA respectively. Both antenatally and postnatally the manometry and sensitivity values were similar in women with and without bowel symptoms. CONCLUSION: This study is the largest series of normative data for anal manometry, and anorectal sensation in women before and after their first delivery. The antenatal values can serve to represent ranges for nulliparous women and the postnatal values ranges in primiparous women.

Pharmacological modulation of gut mucosal and large vessel blood flow.

BACKGROUND: Constipation, diminished gut blood flow, ischaemic colitis and drug therapy may be associated. AIM: To study the effect of constipating medication on, and the regulation of, gut blood flow. METHODS: 24 healthy females (mean age 30) received, in a double-blind, three-way crossover study: (i) placebo, (ii) ipratropium 40 microg by inhalation (positive control known to reduce rectal mucosal blood flow) and (iii) oral loperamide 4 mg. Mucosal blood flow was measured at the splenic flexure and rectum using laser Doppler flowmetry. Blood flow in the superior and inferior mesenteric arteries was measured by trans-abdominal Doppler ultrasound. RESULTS: Ipratropium decreased rectal mucosal blood flow by 16% (P=0.009) and splenic flexure mucosal blood flow by 8% (P=0.075). Loperamide caused no change in rectal (P=0.40) or splenic flexure mucosal blood flow (P=0.73). Neither treatment changed superior or inferior mesenteric artery blood flow. Splenic flexure mucosal blood flow showed a positive correlation with rectal mucosal blood flow (r=0.69; P<0.0001). CONCLUSIONS: Vasoactive agents may reduce gut mucosal blood flow in the absence of reduced large vessel flow. Constipating drugs do not necessarily reduce gut blood flow. Rectal mucosal blood flow correlates with splenic flexure mucosal flow, and potentially may be used as a more convenient surrogate for studying splenic flexure blood flow.

Faecal incontinence.

BACKGROUND: Faecal incontinence is a life style-limiting condition with multiple aetiologies. Surgical cure is not often possible. METHODS AND RESULTS: A review of the literature was undertaken using Medline, Cochrane database and standard textbooks. Advanced imaging techniques now inform the treatment algorithm and objectively assess success. The long-term outcome of anal surgery is uncertain. Modern approaches favour conservative measures, such as biofeedback, and less invasive surgical procedures. Stoma formation is a definitive option for some patients. CONCLUSION: Current treatment of faecal incontinence is evolving from a sphincter-focused view to a more holistic one, recognizing the influence of the pelvic floor and psyche in maintaining continence. Modern imaging modalities direct treatment strategies.

Ghrelin augments afferent response to distension in rat isolated jejunum.

Ghrelin has been shown to decrease firing of gastric vagal afferents at doses comparable with circulating levels in the fasted state. This raises the possibility that ghrelin may have a hormonal action on other vagal afferent populations. The aim of this study was to determine the effects of ghrelin on jejunal afferent activity; including responses to distension, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) and cholecystokinin (CCK) in both naïve and vagotomized rats. Ghrelin significantly augmented the afferent response to distension. No effect was observed on baseline afferent discharge, or the response to 2-methyl-5-HT and CCK. The effect of ghrelin was more pronounced at lower ramp distending pressures (0-30 mmHg). Similarly, ghrelin augmented the jejunal afferent responses to phasic distension at 10-30 mmHg, but had no effect at higher pressures. Chronic subdiaphragmatic vagotomy and administration of the growth hormone secretagogue receptor (GHS-R) antagonist [D-Lys3]-GHRP-6 prevented the augmentation of the afferent responses to distension indicating ghrelin is acting through the GHS-R on vagal afferent fibres. Ghrelin augments the mechanosensation of jejunal vagal afferents and hence may lead to increased perception of hunger contractions.

Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study.

BACKGROUND: Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In animals, ghrelin increases gastric emptying and reverses postoperative ileus. We present the results of a double blind, placebo controlled, crossover study of ghrelin in gastric emptying in patients with diabetic gastroparesis. METHODS: Ten insulin requiring diabetic patients (five men, six type I) referred with symptoms indicative of gastroparesis received a two hour infusion of either ghrelin (5 pmol/kg/min) or saline on two occasions. Blood glucose was controlled by euglycaemic clamp. Gastric emptying rate (GER) was calculated by real time ultrasound following a test meal. Blood was sampled for ghrelin, growth hormone (GH), and pancreatic polypeptide (PP) levels. Cardiovagal neuropathy was assessed using the Mayo Clinic composite autonomic severity score (range 0 (normal)-3). RESULTS: Baseline ghrelin levels were mean 445 (SEM 36) pmol/l. Ghrelin infusion achieved a peak plasma level of 2786 (188) pmol/l at 90 minutes, corresponding to a peak GH of 70.9 (19.8) pmol/l. Ghrelin increased gastric emptying in seven of 10 patients (30 (6)% to 43 (5)%; p = 0.04). Impaired cardiovagal tone correlated inversely with peak postprandial PP values (p < 0.05) but did not correlate with GER. CONCLUSIONS: Ghrelin increases gastric emptying in patients with diabetic gastroparesis. This is independent of vagal tone. We propose that analogues of ghrelin may represent a new class of prokinetic agents.

Azathioprine dose escalation in inflammatory bowel disease.

BACKGROUND: Forty per cent of patients with inflammatory bowel disease fail to respond to standard dose azathioprine (2 mg/kg/day). AIMS: To evaluate the efficacy and safety of increasing the azathioprine dose according to a fixed schedule and guided by clinical response and adverse effects. METHODS: We reviewed the records of all patients with inflammatory bowel disease treated by a single clinician over 6 years, unresponsive to at least 3 months treatment with standard dose azathioprine, and whose dose was subsequently increased. RESULTS: Forty patients (27 male; 24 Crohn's, 16 ulcerative colitis) with chronic active disease or recurrent flares despite standard dose azathioprine for a median 8 months (range 3-114) increased their dose from a median 2.02 (1.61-3.19) mg/kg/day to 2.72 (2.37-3.99) mg/kg/day in one to four increments of 0.5 mg/kg/day, and were followed over a median 6 (0.5-54) months. Eleven of the 40 patients (seven Crohn's, four ulcerative colitis) responded or had reduced frequency of flare-ups at the end of follow-up, while 17 of the 40 patients had no benefit. Response was more likely for maximum doses < or =2.5 mg/kg/day (six of 11 patients) than for doses >2.5 mg/kg/day (five of 29 patients) (P = 0.042). Twelve patients (11 of whom received maximum doses >2.5 mg/kg/day) were unable to maintain an increased azathioprine dose because of leukopenia in eight, nausea in three, and raised liver enzymes in one (all transient and reversible). CONCLUSIONS: Increasing the azathioprine dose up to 2.5 mg/kg/day appears beneficial in patients who have not responded to 2 mg/kg/day. Further increase above 2.5 mg/kg/day is less likely to be efficacious, and is associated with a substantial risk of adverse reactions.

Erythromycin for the treatment of chronic intestinal pseudo-obstruction: description of six cases with a positive response.

BACKGROUND: Chronic intestinal pseudo-obstruction, due to intestinal myopathy or neuropathy, is characterized by the signs and symptoms of intestinal obstruction in the absence of true obstruction. Episodes are resistant to medical therapy. AIM: To determine the value of erythromycin treatment in chronic intestinal pseudo-obstruction. METHODS: All patients with proven chronic intestinal pseudo-obstruction treated with erythromycin were reviewed. Patients with symptomatic benefit are described in detail. Responders were compared with non-responders to identify the factors associated with benefit. RESULTS: Fifteen consecutive patients (nine females; median age, 37 years; median follow-up, 41 months) were treated with oral erythromycin, 1.5-2.0 g/day. Six patients (three primary visceral myopathy, two normal histology on light microscopy, one visceral myopathy secondary to scleroderma) responded, with decreased pain and vomiting, normalized bowel dysfunction and decreased episodes of ileus. Five of the six patients (83%) who responded to erythromycin were male, compared with two of the nine non-responders (22%) (P = 0.04). Four of the six responders (67%) had histological or immunohistological visceral myopathy, compared with three of the nine patients (33%) who failed to respond. Responders were less likely than non-responders to be taking long-term opiates. CONCLUSIONS: Erythromycin is effective for acute episodes of ileus and chronic symptoms in some patients with chronic intestinal pseudo-obstruction.

Behavioural therapy (biofeedback) for solitary rectal ulcer syndrome improves symptoms and mucosal blood flow.

AIMS: The aim of the study was to determine if there is a permanent disorder of mucosal blood flow in patients with solitary rectal ulcer syndrome (SRUS) or a disorder related to autonomic gut innervation and physiological function that is reversible concomitant with successful treatment. Rectal mucosal blood flow was used as a validated measure of extrinsic autonomic nerve function. METHODS: Sixteen consecutive patients with SRUS (12 women; mean age 35 years) and 26 healthy controls (17 women; mean age 36 years) were studied. Laser Doppler mucosal flowmetry was performed before and after biofeedback treatment. Symptoms were documented before and after biofeedback treatment using a standardised prospectively applied questionnaire. RESULTS: Twelve of 16 patients (75%) reported subjective symptomatic improvement after treatment. Five of the 16 patients (31%) had sigmoidoscopic ulcer resolution. Pretreatment rectal mucosal blood flow was significantly lower in patients with SRUS compared with controls (163 (27) v 186 (14) flux units (FU) (mean (SD)); p<0.01). Biofeedback resulted in a significant improvement in rectal mucosal blood flow in subjects who felt subjectively better after biofeedback (p = 0.001), from 165 (30) FU to 190 (40) FU. CONCLUSION: Gut directed biofeedback is an effective behavioural treatment for the majority of patients with SRUS. Mucosal blood flow is reduced to a similar level seen in normal transit constipation, suggesting similar impaired extrinsic autonomic cholinergic nerve activity. Successful outcome following biofeedback is associated with increased rectal mucosal blood flow, suggesting that improved extrinsic innervation to the gut may be partially responsible for the response to treatment.