Citations

Background Meckel's diverticulum is present in about 2% of the population. The literature reports 3.2% incidence of tumors within Meckel's diverticulum; the tumors are predominantly benign. Objective and methods The purpose of this study was to evaluate malignant tumors in Meckel's diverticulum through systematic review of the literature and review of electronic medical records including pathology reports over 14 years at the Mayo Clinic, Rochester, USA. Results A literature review over the last 10 years identified 37 citations with 402 patients (median age: 58 years; 68.9% males). The predominant malignancy reported was neuroendocrine tumor 84.6%, followed by gastrointestinal stromal tumor 8.2%, and adenocarcinoma 6%. At the time of diagnosis, 29.5% of patients had metastases. In the Mayo Clinic electronic medical records review, there were 19 patients (5.1% of them surgically removed Meckel's diverticulum) who had a malignancy associated with Meckel's diverticulum: 63.2% neuroendocrine tumor, 10.5% gastrointestinal stromal tumor, 5.3% adenocarcinoma, 5.3% pancreatic epithelial neoplasia, and 15.8% metastases from secondary location. Median size of the malignancy was 7 mm, and 17/19 malignancies were coincidental findings. Most neuroendocrine tumors infiltrated the submucosa, while gastrointestinal stromal tumor and adenocarcinoma invaded the serosa. At the time of diagnosis, 33.3% of patients had metastases. Conclusion About 5% of Meckel's diverticulums resected were associated with malignant tumors, most commonly neuroendocrine tumor, and a significant portion of Meckel's diverticulum malignancy was metastatic at the time of discovery.

Glucagon-like peptide-1 (GLP-1) relaxes the stomach during fasting but decreases hunger and food consumption and retards gastric emptying. The interrelationships between volume, emptying, and postprandial symptoms in response to GLP-1 are unclear. We performed, in healthy human volunteers, a placebo-controlled study of the effects of intravenous GLP-1 on gastric volume using99mTc-single photon emission computed tomography imaging, gastric emptying of a nutrient liquid meal (Ensure) using scintigraphy, maximum tolerated volume (MTV) of Ensure, and postprandial symptoms 30 min after MTV. The role of vagal cholinergic function in the effects of GLP-1 was assessed by human pancreatic polypeptide (HPP) response to the Ensure meal. GLP-1 increased fasting and postprandial gastric volumes and retarded gastric emptying; MTV and postprandial symptoms were not different compared with controls. Effects on postprandial gastric function were associated with reduced postprandial HPP levels. GLP-1 does not induce postprandial symptoms despite significant inhibition of gastric emptying and vagal function; this may be partly explained by the increase in postprandial gastric volume.

Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of99mTc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 ± 11 (SE) ml and mean postprandial volume was 690 ± 32 ml ( P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.

The amylin analog pramlintide delays gastric emptying in type I diabetics. The effects of multiple doses of pramlintide and the mechanism of action in non-amylin-deficient humans are unknown. We investigated the effects of pramlintide on gastrointestinal and colonic transit and on the plasma pancreatic polypeptide response to the meal in a parallel-group dose-response study with subjects randomized to placebo, or 30 or 60 μg (tid, sc) of pramlintide. Pramlintide delayed gastric emptying [half-time ( t½): 112 min (SE 8.7 min), 169 min (SE 12 min), or 177 min (SE 25 min) after placebo or 30- or 60-μg pramlintide treatment, respectively; P = 0.033]. Pramlintide did not significantly affect small bowel or colonic transit. Pancreatic polypeptide concentrations in the first postprandial hour were lower with pramlintide than with placebo ( P < 0.01 for drug effect). An inverse correlation was observed between mean pancreatic polypeptide concentrations in the first postprandial hour and gastric emptying t½[Spearman correlation coefficient ( Rs) = 0.48; P = 0.044]. Pramlintide at 30 and 60 μg delays gastric emptying in healthy humans without affecting small bowel or colonic transit. Vagal inhibition is a potential mechanism of the effects of pramlintide on gastric emptying.

The effects of pharmacological modulation of adrenergic receptors on colonic motor and sensory function are unclear. We studied 40 healthy volunteers in a single-blind design; 12 received saline, and the remaining 28 received either clonidine, yohimbine, phenylephrine, or ritodrine. A barostat-manometric assembly in the left colon recorded drug effects on fasting and postprandial motor function, compliance, and sensation in response to standardized phasic balloon distensions delivered in random order. Clonidine reduced and yohimbine increased fasting, but not postprandial tone, by 63.2 ± 22.3% and 24.8 ± 8.8% (SE), respectively. Clonidine tended to reduce fasting phasic activity in the descending and sigmoid colon. A power exponential model provided the best fit to the compliance curve. Clonidine significantly increased colonic compliance. Clonidine reduced and yohimbine increased colonic perception of pain but not gas sensation during distension. Phenylephrine and ritodrine did not influence colonic motor or sensory function in the present studies. Thus α2-receptors modulate fasting colonic tone and compliance and alter perception of pain but not gas during mechanical stimulation of the colon.

Increased use of laxatives and constipation are more common among people with diabetes mellitus than matched nondiabetic people in the same community. The mechanism of constipation in diabetes is unclear. Acute hyperglycemia was previously reported to reduce the gastrocolonic response. Our aim was to determine the effects of acute hyperglycemia on the colon compliance and motor response to feeding and on the sensory function of the colon and rectum in healthy human subjects. Eleven healthy individuals were studied under conditions of hyperglycemia (mean blood glucose 280 ± 13 mg/dl) and euglycemia. We evaluated three parameters: 1) colonic motility and compliance by a multilumen manometry and barostatic balloon assembly in the descending colon (motility was studied during fasting and for 2 h postprandially); 2) perception of isobaric distensions of polyethylene balloons in the rectum and colon; and 3) rectal compliance. Initial tonic response to meal ingestion (0–5 min) was slightly lower during hyperglycemia ( P = 0.3). However, colonic tone, motility, compliance, and sensation, as well as rectal compliance and sensation, were not significantly different under the conditions of euglycemia and acute hyperglycemia. In healthy individuals, acute hyperglycemia does not significantly change colonic or rectal motor functions or the perception of mechanosensory stimuli in the colon or rectum compared with euglycemia. These results do not support the hypothesis that hyperglycemia abolishes the colonic response to feeding.

To characterize α2-adrenergic control of motor and sensory functions of gastrointestinal tract and colon, we studied dose-related effects of clonidine (placebo or up to 0.3 mg po) by random assignment in 55 healthy humans. Gastrointestinal transit was measured in all subjects; in 35, we assessed colonic compliance, tone, and sensations of gas and pain during phasic distensions. Clonidine did not significantly alter gastrointestinal or colonic transit, but it increased colonic compliance and reduced fasting tone without altering colonic response to a meal. Clonidine significantly reduced aggregate sensation to distensions overall and had significant linear dose-related sensory effects at 8- and 24-mmHg distensions. Effect on pain (including dose-response relationship) was due to 0.3-mg dose for distensions at 24 mmHg. We confirmed that clonidine relaxes fasting colonic tone and reduces sensation of pain. In this study, gut transit was not altered by clonidine, and novel dose-response characteristics and clonidine's effect on gas sensation are provided. Doses as low as 0.05 mg may be effective and potentially useful in reducing colonic tone and gas sensation.

Central processing of visceral information in humans is incompletely understood. We aimed to demonstrate the feasibility of single photon emission computed tomography (SPECT) and to quantitate the changes in regional cerebral blood flow during rectal distension. Ten healthy volunteers underwent randomized sham and active rectal distensions on separate days, during which cerebral blood flow was assessed by intravenous technetium-99m ethyl cysteinate dimer (99mTc-ECD) SPECT. Three-dimensional coregistration of brain images was used to quantitate activation in four preselected cerebral foci and two control regions. Paired analysis compared blood flow during sham and active distensions. There was increased right anterior cingulate gyrus activity (6.5 ± 2.9%, P = 0.03) with active rectal distension. A 5.4 ± 2.4% reduction in blood flow in the superior parieto-occipital control region ( P = 0.04) suggested blood “redistribution” during stimulation. Marked variability in activation of the frontal cortex, thalamus/basal ganglia complex, and mesiotemporal lobe was noted. Thus rectal distension increases activity in the right anterior cingulate gyrus on average; other foci of cerebral activation are quite variable, suggesting a lack of specific cerebral projections during rectal stimulation.

Increasing interest is focusing on the role of intestinal tone, distensibility, and mechanosensation in the genesis of abdominal symptoms. Experimental approaches usually feature balloon distension of the bowel with measurements of perception, tone, and compliance and/or elastance; however, the methodologies are standardized incompletely. We examined the reproducibility of repeated assessments of sensory perception, basal tone, and compliance and/or elastance of the rectum during distension. We also evaluated the response to inflations that varied in regard to control of pressure or volume, pattern of distension, and rate of inflation. Five healthy volunteers were studied under two separate protocols. The first featured a series of experiments on each of 5 days; the other consisted of 2 separate days of study. Repeated distensions evoked reproducible responses of sensation and compliance and/or elastance on a single day, providing a conditioning distension preceded them. Day-to-day variability was also sufficiently small to allow valid comparisons to be made on different days in healthy persons. The configuration of the distension profile (phasic, staircase, or ramp) and the rate of inflation (from 1 to 40 ml/s) had little effect on distensibility or perception. Perceptions were sometimes transient and sometimes constant, but no relationship was found between these temporal features and the magnitude of the stimulus. These observations help provide a basis as to how the responses to rectal distension can be best studied.

Our first aim was to compare 111In-labeled Amberlite IR-12OP resin pellets and 131I-labeled fiber in the assessment of gastric and small bowel transit and colonic filling in healthy humans. Both radiolabels were highly stable for 3 h in an in vitro stomach model and remained predominantly bound to solid phase of stools collected over 5 days [90.5 +/- 2.1 (SE)% for 131I and 87.4 +/- 1.4% for 111In). The lag phase of gastric emptying was shorter for 111In-pellets (30 +/- 11 min compared with 58 +/- 12 min for 131I-fiber, P less than 0.05). However, the slope of the postlag phase of gastric emptying and the half time of small bowel transit were not significantly different for 111In-pellets and 131I-fiber. Filling of the colon was characterized by bolus movements of the radiolabel (10-80% range, 26% mean) followed by plateaus (periods of no movement of isotope into colon lasting 15-120 min, range; 51 min, mean). Half of the bolus movements occurred within 1 h of the intake of a second meal. Thus 111In-labeled Amberlite pellets provide an excellent marker for the study of gastric and small bowel transit and colonic filling in humans. The ileum acts as a reservoir and transfers boluses of variable sizes into the colon, often soon after the intake of a subsequent meal.