Differentiation of prolonged colonic transit using scintigraphy with indium-111-labeled polystyrene pellets.

UNLABELLED: Prolonged colonic transit can be caused either by slow transit constipation or by pelvic outlet obstruction needing different therapeutic regimes. The aim of this study was to prove the value of scintigraphic assessment. METHODS: Colon scintigraphy was performed in 32 patients (28 women, 4 men; age range 8-68 yr) with idiopathic constipation at 8, 24 and 48 hr in ventral and dorsal projection after oral administration of a pH-sensitive, methacrylate-coated capsule of nonresorbable 111In-labeled polystyrene (cathion exchanger) micropellets (3.5 MBq/capsule). The geometric center (GC) as the sum of products of colon segment activity and colon segment number (1 = colon ascendens; 2 = transverse colon; 3 = colon descendens; 4 = rectosigmoid colon; and 5 = stool) dividing by the total counts was used to determine the velocity of colonic transit at least at 24 hr as the proximal colonic emptying (PCE) rates. Stool activity was evaluated indirectly as decay-corrected colon activity loss between two examinations. Results were compared with data obtained from 22 healthy subjects. RESULTS: Twenty-six patients had a significant prolongation of colonic transit after 24 and 48 hr (the 95% confidence interval of the patient's GC showed no overlap to the 95% confidence interval of GC calculated from 22 healthy controls as normal range) revealing slow transit constipation. Six patients had normal or accelerated transit (GCs and PCE rates) up to the rectum but delayed rectal emptying indicating pelvic outlet obstruction. CONCLUSION: By the help of this method it was possible to differentiate the two subtypes of colon transit prolongation by use of the reported scintigraphic technique, which leads to different therapeutic management of the patients. Compared with x-ray methods (Hinton test), this method has the capability of a continuous observation of colonic transit without increasing radiation exposure.

Altered postprandial motility in chronic pancreatitis: role of malabsorption.

BACKGROUND & AIMS: Intraileal nutrients modulate gastrointestinal motility, but effects of maldigestion on postprandial motility are unknown. The aim of this study was to compare motor responses with ileal nutrient exposure in health and pancreatic insufficiency after a meal or intraluminal perfusion. METHODS: After oroileal multilumen intubation for duodeno-jejuno-ileal sampling, marker perfusion, and motility recording, 14 normal subjects and 12 patients with severe pancreatic insufficiency received a labeled liquid meal twice, either with placebo or pancreatin. Effects of intraileal nutrient perfusion on fed motility induced by duodenal amino acid perfusion were also investigated. RESULTS: Compared with normals, untreated patients had greater cumulative ileal nutrient delivery (69 +/- 21 vs. 487 +/- 232 kJ), shorter fed pattern (196 +/- 22 vs. 131 +/- 14 minutes), greater 90% gastric emptying (163 +/- 12 vs. 128 +/- 10 minutes), and faster small intestinal transit (86 +/- 9 vs. 44 +/- 6 minutes). Pancreatin reversed these changes. Ileal nutrient perfusion converted fed into interdigestive-like motility in normals (7 of 8) and patients (4 of 5). CONCLUSIONS: In subjects with pancreatic insufficiency, a low-energy liquid meal induces shorter fed motor pattern associated with accelerated gastric emptying and intestinal transit compared with healthy subjects. Because changes responded to enzyme treatment and could be reproduced by ileal nutrient perfusion, ileal delivery of malabsorbed chyme may be involved as a mechanism.

Motility and tone of the left colon in constipation: a role in clinical practice?

OBJECTIVES: Colonic motor mechanisms deranged in constipation are not understood completely. Our aim was to measure left colonic motility and tone, during fasting and postprandially in patients with chronic constipation. METHODS: During 1 h fasting and 2 h postprandially, we measured pressures (multilumen manometry) and tone (barostat) in the left colon of 15 healthy controls and 40 patients with chronic constipation associated with slow (n = 15) or normal colonic transit (n = 12) or outlet obstruction (n = 13). RESULTS: Fasting tone was similar in all groups, and all demonstrated a significant increase in motor activity to food. There was lower postprandial tone (p < 0.05) in the slow transit and outlet obstruction groups. There were no differences in the timing of the tonic response or the number or amplitude of high-pressure propagated contractions. The slow transit group had lower postprandial phasic responses in the rectosigmoid (p < 0.05) and descending (p < 0.1) colon; the outlet obstruction group had lesser descending (p < 0.05) and rectosigmoid (p < 0.1) colon phasic motility. CONCLUSIONS: Colonic intraluminal measurements alone do not discriminate subgroups of chronic constipation more accurately than transit and pelvic floor tests, and currently have a limited role in clinical practice. However, manometry and tone measurements may be helpful in confirming a diagnosis of slow transit constipation (colonic inertia) in patients considered candidates for surgical treatment.

Diarrhoea in patients with diabetes mellitus.

Diarrhoea in patients with diabetes mellitus may be due to anorectal or rectal dysfunction that results in incontinence, intestinal secretion or rapid intestinal transit, or may be associated with disorders that typically cause malabsorption. The latter include small bowel bacterial overgrowth, coeliac sprue and pancreatic insufficiency. A practical algorithm for diagnosis and advances in therapy is discussed.

Ascending colon response to feeding: evidence for a 5-hydroxytryptamine-3 mechanism.

BACKGROUND: The role of serotonergic type-3 receptors in proximal human colon is unclear. Our aims were to assess the postprandial volume and emptying of the ascending colon and to explore the role of 5-hydroxytryptamine-3 (5HT3) mechanisms. METHODS: In healthy subjects with unprepared colons we evaluated in a randomized trial the effects of the 5HT3 antagonist ondansetron (n = 5) or placebo (n = 5) on ascending colon volume and emptying, using a scintigraphic method. RESULTS: Base-line ascending colon volumes were similar and were unaltered by ondansetron. After a 1000-kcal liquid meal the placebo group showed a variable change in volume (P = NS versus base line) during the first 25 min (median, -4%; range, -13% to 135%). Increases in volume during this period coincided with ileal emptying of chyme. During a second phase (30-105 min) there was a significant decrease of ascending colon volume (P = 0.02) relative to the early postprandial volume, but the volume was not significantly different from base line. This second phase was associated with transfer of chyme towards the transverse colon. In the ondansetron group there was an initial modest increase in volume (median, 5%; range, -15% to 14%; P = NS versus base line), and the second phase of contraction was inhibited. CONCLUSIONS: The ascending colon response to a meal in health is characterized by a variable initial change in volume, accommodating ileal chyme in some individuals, and a more consistent reduction in volume from 30 to 105 min postprandially. The latter response is inhibited by ondansetron, suggesting partial control of postprandial colonic motor function by 5HT3 mechanisms.

Differential regional effects of octreotide on human gastrointestinal motor function.

The effects of octreotide on regional motor function in the human gut are unclear. In a randomised, blinded study the effects of octreotide (50 micrograms, subcutaneously, three times daily) and placebo on gastric, small bowel, and colonic transit, and colonic motility and tone were assessed in 12 healthy volunteers whose colon had been cleansed. Octreotide accelerated initial gastric emptying (p = 0.05), inhibited small bowel transit (p < 0.01), and reduced ileocolonic bolus transfers (p < 0.05). Colonic transit was unaltered by octreotide; the postprandial colonic tonic response was inhibited (p < 0.05 v placebo), whereas colonic phasic pressure activity was increased by octreotide (p < 0.05 v placebo). These data support the use of octreotide in diarrhoeal states but not in diseases that cause small bowel stasis and bacterial overgrowth. Simultaneous measurements of colonic transit, tone, and phasic contractility are valid in studying the effects of pharmacological changes and may be applicable to the study of the human colon in health and disease.

A patient with localized megacolon and intractable constipation: evidence for impairment of colonic muscle tone.

There have been descriptions of a variety of abnormalities in motor function in patients with megacolon; however, colonic tone in megacolon has not been measured to date. Recent data suggest that colonic hypertonicity of carcinoid diarrhea is measurable with an electronic barostat. Using a barostat method, we have evaluated colonic transit, motility, and tone in a patient with severe constipation and localized chronic megacolon. Transit measurements showed a significant delay beyond the mid transverse colon; motility studies in the dilated region of colon showed abnormally low tone but normal phasic contractility, as measured by the barostat. In contrast, manometry showed low amplitude contractions relative to control data; this discrepancy probably results from the large capacity of the segment of colon examined. Chronic megacolon can be associated with abnormal colonic tone, which can be measured by means of an electronic barostat.

Drugs affecting serotonin receptors.

A greater understanding of the various serotonin receptor subtypes has led to a clearer appreciation of the role of serotonin in gastrointestinal motility, sensation and secretion. Serotonin is definitely involved in the aetiopathogenesis of cisplatin-induced emesis and carcinoid diarrhoea. The application of serotonergic drugs in clinical therapeutics for gut disturbances is presently dominated by the use of 5-HT3 antagonists for acute chemotherapy-induced nausea and vomiting, and the use of substituted benzamides which are 5-HT4 agonists stimulating gut motor function through 5-HT4 neuronal receptors. The best-studied 5-HT4 agonist is cisapride, which has been shown to stimulate motility at several levels of the gut. Cisapride is approved for healing and maintenance treatment of reflux oesophagitis and is used in several countries for the alleviation of symptoms consistent with regional stasis, from dyspepsia to constipation. Carcinoid diarrhoea is a prototypic disease associated with deranged serotonin metabolism, and a rationale for using 5-HT3 or 5-HT4 antagonists is based on the recent appreciation of the important role of impaired gut motor function in carcinoid diarrhoea. In the future, greater understanding of the serotonin receptor subtypes and their role in gut disorders may lead to novel approaches to alleviate increased visceral perception of functional gastrointestinal disorders, to correct changes in colonic capacitance, or to alter gastrointestinal motility that contributes to diarrhoea or constipation. However, at the present time, it must be stressed that these uses are still at an experimental stage and that careful validation and proper controlled studies are still required.

A 5HT3 antagonist corrects the postprandial colonic hypertonic response in carcinoid diarrhea.

BACKGROUND/AIMS: Carcinoid patients show a hypertonic colonic motor response postprandially. Ondansetron reduces postprandial colonic tone in health. It was hypothesized that ondansetron, a selective 5HT3 antagonist, corrects the colonic motor response to eating in carcinoid diarrhea. METHODS: The effects of ondansetron and placebo on fasting and postprandial colonic tone and motility in 10 patients with carcinoid diarrhea were compared using a manometry-barostat assembly positioned in the upper descending colon. RESULTS: Fasting colonic tone and motility indices were similar in the placebo and ondansetron groups; ondansetron did not affect fasting motility. The placebo group showed a significant reduction in barostat balloon volume (signifying increased tone) from 207 +/- 29 mL (mean +/- SEM) during fasting to 106 +/- 14 mL postprandially (P = 0.01). With ondansetron, a tonic colonic response was induced postprandially (198 +/- 37 mL to 151 +/- 30 mL; P = 0.053). However, the increment in tone in the ondansetron group (23% +/- 7%) was significantly lower than in the placebo group (48% +/- 5%; P = 0.02) and was similar to that observed in untreated healthy subjects (24% +/- 3%). Postprandial manometric pressure activity increased significantly in the placebo group (P = 0.01); in the ondansetron group there was a trend (P = 0.09) to increased phasic activity. CONCLUSIONS: Ondastetron reduces the postprandial colonic hypertonic response in carcinoid diarrhea to levels previously reported in health; further clinical studies of this class of antagonists in carcinoid diarrhea appear warranted.

Serotonergic mediation of postprandial colonic tonic and phasic responses in humans.

This study examined the hypothesis that 5HT3 mechanisms mediate the postprandial gastrocolonic response in humans. Fasting and postprandial colonic tone and motility were studied in 12 healthy volunteers and the effects of a selective 5HT3 antagonist, ondansetron assessed in a double blind, randomised, placebo controlled fashion. A manometry barostat assembly was positioned in the transverse or descending colon to quantitate contractile activity fasting, after drug infusion and postprandially after a 1000 kcal meal. Fasting colonic tone and motility indices were similar in the placebo and ondansetron groups; ondansetron did not affect fasting motility. The placebo group showed a significant reduction in barostat balloon volume (signifying increased tone) from 232 ml (median, interquartile range (IQR) 179-261) during fasting to 181 ml (median, IQR 128-208) (postprandially) (p = 0.02). In contrast, the ondansetron group did not have a tonic colonic response (median 248 ml (IQR 199-300) fasting to median, 226 ml (IQR 185-290) postprandially) after the meal. Phasic volume events measured by the barostat increased postprandially in both groups. Postprandial motor activity measured by manometry increased significantly in the placebo group, but not in the ondansetron group. In conclusion, a 5HT3 mechanism participates in the physiological contractile responses in the human transverse and descending colon after ingestion of a high energy meal.

Motor dysfunction of the small bowel and colon in patients with the carcinoid syndrome and diarrhea.

BACKGROUND AND METHODS: The pathophysiology of diarrhea in patients with the carcinoid syndrome is not understood. Possible causes include tumor production of neurohumoral substances, such as serotonin and substance P, which stimulate small-bowel and colonic motility, and intestinal abnormalities, such as lymphangiectasia and bacterial overgrowth. We undertook this study to determine whether carcinoid diarrhea is associated with abnormal motor function in the small intestine and colon. We measured the gastric, small-bowel, and colonic transit of radiolabeled solid residue and estimated the volume of the ascending colon in 16 patients with the carcinoid syndrome and diarrhea and 16 normal subjects. We also measured colonic tone and phasic pressure activity by intracolonic multilumen manometry and with an electronic barostat in seven patients and six normal subjects. RESULTS: The patients with the carcinoid syndrome had elevated 24-hour urinary excretion of 5-hydroxyindoleacetic acid and elevated fasting plasma serotonin concentrations. Transit times in the small bowel and colon were two times (P < 0.001) and six times (P = 0.001) faster in the patients than in the normal subjects. The volume of the ascending colon was approximately 50 percent smaller in the patients than in the normal subjects (P < 0.001). The patients had normal fasting colonic tone; their mean postprandial colonic tone was markedly increased as compared with the values in the normal subjects (mean increase, 41 percent vs. 24 percent; P = 0.03). CONCLUSIONS: Patients with the carcinoid syndrome who have diarrhea have major alterations in gut motor function that affect both the small intestine and colon.

Measurement of small bowel and colonic transit: indications and methods.

In this article, we review the currently available techniques for measuring small intestinal and colonic transit. In addition, we describe the characteristics of an ideal test that provided the rationale for the development and validation of a gastrointestinal and colonic transit test at the Mayo Clinic. This new technique assesses regional transit of solid radiolabeled particles of the same size through the entire digestive tract and provides further insights into motor physiologic processes of the gut. By means of a delayed-release methacrylate-coated capsule, isotopically labeled pellets are delivered to the colon as a single bolus; thereby, dispersion of isotope throughout the small bowel is avoided because of the gradual emptying of chyme from the stomach. Similar pellets labeled with a different isotope can be used to assess gastric and small bowel transit. These new methods for measuring transit have also led to insights into the pathogenesis of unexplained gastrointestinal symptoms and disease states. Thus, we demonstrated that in healthy subjects, ileocolonic transfer of chyme occurs in boluses; this transfer is impaired in patients with myopathic pseudo-obstruction. The emptying rate of the proximal colon is an important determinant of the pathophysiologic features of colonic disease; thus, colonic transit is delayed in cases of severe idiopathic constipation. In contrast, rapid emptying of the proximal colon influences stool weight in diarrhea-predominant irritable bowel syndrome. An integrated approach for studying gastric, small bowel, and colonic transit by using the same radiolabeled particle provides a useful, clinically applicable method for evaluating gastrointestinal symptoms and for measuring motor function of the entire digestive tract without need for intubation; cost and radiation exposure are acceptable.