Michel Bouchoucha

What is the meaning of colorectal transit time measurement

This study was done to understand the different available methods used to calculate colorectal transit times. A single abdominal radiograph is taken following six successive daily ingestions of the same number of identical radiopaque markers. This method correlates well (P< 0.001) with that using a single ingestion of markers with daily x-ray films until total expulsion. In techniques used to measure colorectal transit time with multiple ingestion of markers, the number of days of ingestion depends on the kinetics of marker defecation. This was found to differ markedly in various groups of control subjects and constipated patients (P< 0.001) and can be used to obtain reliable data, even in subjects with severe constipation. When they ingest 20 markers, constipated patients are found to retain eight or more markers three days after ingestion, and taking a plain film of the abdomen on that day is sufficient to make a diagnosis of constipation. Transit time studies are reproducible from month to month in patients with an irritable bowel syndrome. Control subjects who claim that their bowel habits are not modified by stress have shorter transit times, similar in both sexes, than those who say they are (P<0.001). This may explain why a large percentage of constipated patients have been found by most authors to have “normal” colorectal transit times. The choice of control subjects is thus a key element in studies of functional bowel motor disorders. Stool frequency and consistency, in health, correlate only to rectosigmoid transit time.

Metformin and digestive disorders

Digestive disorders (diarrhoea, vomiting) represent the most common metformin side-effects (around 30%) with this first-line drug treatment for type 2 diabetes. In healthy individuals, metformin affects glucose, vitamin B12 and the digestive uptake of bile salts. In the colon, it acts locally by modifying glucose cell metabolism. Different pathophysiological hypotheses have been proposed to explain the metformin-induced diarrhoea and vomiting, which can sometimes cause the patient to stop an effective treatment. These theories include stimulation of intestinal secretion of serotonin, changes in incretin and glucose metabolism, and bile-salt malabsorption. However, none of these hypotheses can be considered an adequate pathophysiological explanation of metformin digestive side-effects. In addition, there is a lack of experimental data to explain these highly patient-dependent adverse effects.

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Evaluate the Efficacy, Safety, and Tolerability of Prucalopride in Men With Chronic Constipation

OBJECTIVES:Prucalopride is effective at alleviating symptoms of chronic constipation in women. The aim of this study was to assess the efficacy of 12 weeks of prucalopride treatment compared with placebo in men with chronic constipation.METHODS:This was a multicenter, stratified, randomized, parallel-group, double-blind, placebo-controlled, phase 3 study (ClinicalTrials.gov identifier: NCT01147926). The primary end point was the proportion of patients with a mean of three or more spontaneous complete bowel movements (SCBMs) per week across the treatment period. Efficacy end points were assessed using daily electronic diaries, global assessment of the severity of constipation and efficacy of treatment, and Patient Assessment of Constipation—Symptoms (PAC-SYM) and Patient Assessment of Constipation—Quality of Life (PAC-QOL) questionnaires.RESULTS:In total, 374 patients were enrolled in the study. Significantly more patients achieved a mean of three or more SCBMs per week in the prucalopride group (37.9%) than in the placebo group (17.7%, P<0.0001). The proportion of patients rating their constipation treatment as “quite a bit” to “extremely” effective at the final on-treatment visit was 46.7 and 30.4% in the prucalopride and placebo groups, respectively. The difference between treatment groups was statistically significant (P<0.0001). The proportion of patients with an improvement of at least 1 point in PAC-QOL satisfaction subscale score was 52.7 and 38.8% in the prucalopride and placebo groups, respectively (P=0.0035). Prucalopride had a good safety profile and was well tolerated.CONCLUSIONS:Prucalopride is effective, has a good safety profile, and is well tolerated for the treatment of men with chronic constipation.

Different segmental transit times in patients with irritable bowel syndrome and "normal" colonic transit time: is there a correlation with symptoms?

AbstractBackgroundThe Rome criteria serve as gold standard for establishing a diagnosis of irritable bowel syndrome (IBS), but only represent a cluster of symptoms. On the other hand, measurement of colonic transit time (CTT) with radiopaque markers is a solid and more objective method to quantify functional abnormalities. The goal of this study was to investigate whether the IBS symptoms, as defined in the Rome II criteria, correspond to objective physiological parameters, i.e. CCTs.MethodsThe study enrolled 148 healthy control subjects and 1385 consecutive IBS patients. Transit times were measured for the whole rectocolon (overall CTT) and for 3 segments (right colon, left colon, rectosigmoid area); segmental distribution of markers and diffusion coefficients were also assessed. In order to analyze homogeneous groups, we restricted analysis to subjects with “normal” CTT (≤70 hours).ResultsSix hundred forty four IBS patients (46%) and 14 control subjects (9%) had CTT >70 h and were eliminated. In subjects with CTT ≤70 h, CTT did not follow a normal (Gaussian) distribution. We identified 3 different CTT clusters in healthy controls and 4 clusters in IBS patients. Even if CTT was not significantly different between clusters, each cluster was characterized by a specific pattern of segmental colonic transit. There was a marked gender difference: women had longer overall CTT values than men, both in control and IBS patient groups (p<0.001). However, female IBS patients had significantly shorter colorectal transit times than female controls (p<0.001), as well as faster transit than in men through the left colon and rectosigmoid area. There were no significant differences in transit time between male IBS patients and male controls with the exception of a faster rectal transit in IBS patients (p<0.01). There was no association between segmental colonic transit values and sign or symptoms comprising the Rome II criteria.ConclusionsIn subjects with CTT ≤70 h, CTT does not follow a normal distribution but is clustered in subgroups that can be distinguished only by measuring segmental colonic transit. Within these subgroups, there is a marked difference in transit times between IBS patients and normal subjects, suggesting that IBS patients with “normal” CTT are not “normal”. The Rome II criteria do not reflect differences in segmental transit times in IBS patients with “normal” CTT. We therefore propose to evaluate segmental transit times in IBS patients with “normal” CTT, before and after treatment, in order to correctly interpretate variations in signs and symptoms. These findings have important implications in evaluating the effect of drugs on bowel function and should help define better inclusion criteria for studies evaluating new drugs for the treatment of IBS.

Anismus: a marker of multi-site functional disorders?

PurposeThis study was undertaken to assess the clinical significance of anismus in patients who complain of constipation.Patients and methodsThirty control subjects and 93 consecutive patients complaining of functional constipation took part in the study. Colonic transit time study and anorectal manometry were performed. Questions about depression and urinary and sexual diseases were added to a questionnaire based on the Rome II criteria, and visual analog scales about four items (constipation, diarrhoea, abdominal bloating and abdominal pain).ResultsConstipated patients have lower threshold sensation volume, lower constant sensation volume, and lower maximum tolerable volume than controls. Thirty-seven patients (40%) were found to have anismus, based on anorectal manometry. No significant difference was found between constipated patients with anismus and constipated patients without anismus, using anorectal manometry. Constipated patients had longer colorectal transit time than controls, but neither total nor segmental colonic transit time was correlated with the presence or absence of anismus. In patients with anismus, a higher frequency of oesophageal symptoms, dysmotility-like dyspepsia, aerophagia, functional bowel disorders, functional abdominal pain, soiling, and dyschezia was found. In addition, a higher frequency of urinary complaints, sexual complaints, and depression was found. Anismus was associated with increased awareness of constipation, abdominal bloating, and abdominal pain, but not with diarrhoea.

In vitro analysis of rat intestinal wall movements at rest and during propagated contraction: a new method

Intestinal wall motions are not easily studied and are frequently deduced from manometric and electromyographic measurements. This study aimed to establish a method of wall movement analysis based on an automatic technique of image processing. Segments of rat jejunum were fixed in an organ bath under isometric conditions. A real-time edge-detection algorithm was used to find the contours of the intestine using video imaging. After the measurement, a mapping of intestinal wall movements was performed based on diameter variations. In the 260 experiments without stimulation, intestinal wall activity was always detected. Propagated activity was found in 40% of the experiments and periodic wall motion in 60%, with 0.5-Hz activity found more frequently (41%) than 0.24-Hz activity (19%). These cyclic activities, related to intestinal slow waves, had their amplitude decreased by acetylcholine and were modified by vapreotide. Analysis of a propagated wave after cholinergic stimulation showed that it is characterized by an increase of the diameter of the intestine followed by a decrease. Moreover, this methodology allows analysis of the initiation of a propagated wave.Intestinal wall motions are not easily studied and are frequently deduced from manometric and electromyographic measurements. This study aimed to establish a method of wall movement analysis based on an automatic technique of image processing. Segments of rat jejunum were fixed in an organ bath under isometric conditions. A real-time edge-detection algorithm was used to find the contours of the intestine using video imaging. After the measurement, a mapping of intestinal wall movements was performed based on diameter variations. In the 260 experiments without stimulation, intestinal wall activity was always detected. Propagated activity was found in 40% of the experiments and periodic wall motion in 60%, with 0.5-Hz activity found more frequently (41%) than 0.24-Hz activity (19%). These cyclic activities, related to intestinal slow waves, had their amplitude decreased by acetylcholine and were modified by vapreotide. Analysis of a propagated wave after cholinergic stimulation showed that it is characterized by an increase of the diameter of the intestine followed by a decrease. Moreover, this methodology allows analysis of the initiation of a propagated wave.

Diversion-related experimental colitis in rats

PURPOSE: Diversion-related colitis is an inflammatory process that affects the colon and/or rectum distal to a colostomy. Its mechanisms are unknown, and many hypotheses have been considered. The aim of the present study was to create an experimental model of diversion-related colitis in rats, so in the future it will be possible to test different hypotheses. METHODS: Three groups of ten male Wistar rats were used for the study. Two groups underwent a colostomy and were kept alive for 6 or 17 weeks. One group of rats was killed at the onset of the experiment. Specimens were taken in bypassed segments in the rats who had had a colostomy and in the sigmoid colon for the control group. Histologic analysis using standard coloration, histochemical techniques, and bacterial preparation was used to find histologic or changes of colonic histology or flora. RESULTS: Exclusion was associated with vascular congestion, a decrease in length of glandular crypts (P< 0.01), and an erosion of surface epithelium; inflammation of the mucosa was absent in all control animals and present in all test animals. In contrast, the number of goblet cells was not changed by the procedure. There was also a significant change in distribution and intensity of sulfomucins and sialomucins and quantitative and qualitative changes of the colonic flora. CONCLUSION: This experimental model of diversion colitis is characterized by histologic and bacteriologic modifications comparable with those reported in humans but with different histochemical changes.

Effect of an oral bulking agent and a rectal laxative administered alone or in combination for the treatment of constipation.

OBJECTIVES The aim of the present study was to search for a synergetic action between psyllium and a defecation-inducing drug, Eductyl, for symptom relief in patients suffering from chronic constipation. METHODS Twenty healthy volunteers and 20 patients complaining of chronic constipation were included in a randomized crossover study. The study was divided into four 2-weeks periods: pre-inclusion and three periods of treatment with psyllium, Eductyl, and Eductyl + psyllium respectively. Colonic transit time was determined at the end of each period of treatment. During each of the four periods, a self-administered questionnaire was used to assess symptoms of constipation. RESULTS For constipated patients, treatment with Eductyl and Eductyl-psyllium improved clinical symptoms of constipation: increased stool frequency, resulted in fewer hard stools and less sensation of incomplete evacuation and less straining to defecate. The improvement was associated with a decrease in total and segmental colonic transit time. The Eductyl-psyllium combination did not exhibit any synergetic effect. CONCLUSION Treatment with Eductyl alone is more efficient than with psyllium alone in providing symptom relief. Combination with psyllium is not synergetic.

Colonic response to food in constipation

ObjectivesColonic response to food is possibly abnormal in constipation.MethodsThe colonic response to food was evaluated in 323 patients and 60 healthy subjects by following the movements of radiopaque markers after ingestion of a standard 1,000-cal test meal. Constipated patients were divided into four groups: one with a normal, and three with a delayed colorectal transit time. When the delay was found mainly in the ascending colon, the group was labeled as suffering from “colonic inertia”. In “hindgut dysfunction”, the delay was predominantly found in the descending colon, whereas the term “outlet obstruction” was reserved for constipated patients whose major site of delay was the rectosigmoid area. Colonic response to food was quantified by evaluating the variation of markers in a given abdominal region and the evolution of the geometric center on the entire plain film of the abdomen.ResultsEmptying of the caecum-ascending colon and filling of the rectosigmoid area characterize the colonic response to food in healthy subjects. Constipated patients also filled the rectosigmoid, but different patterns were found in the colon. In constipated patients with transit in the normal range, there was a frequent (41%) absence of colonic response to food as compared to controls (13%) and constipated patients with delayed transit (p<0.0001). The response to food of patients with colonic inertia was similar to that of healthy subjects in terms of distal progression, but less marked. The hindgut dysfunction group emptied the entire left colon but failed to empty the caecum and ascending colon. In the outlet obstruction group, there was no distal progress of the geometric center after meal.ConclusionsAbnormal colonic response to food is frequently found in constipated patients, with different patterns according to the type of constipation.

Treatment of refractory irritable bowel syndrome with visceral osteopathy: Short-term and long-term results of a randomized trial

In light of the low efficiency of available drugs in treating irritable bowel syndrome (IBS), there has been a growing interest in its alternative therapies. The aim of this study was to evaluate the effectiveness of visceral osteopathy for IBS.