Michael Camilleri

Paraneoplastic gastrointestinal motor dysfunction: Clinical and laboratory characteristics

Abstract OBJECTIVES: The aim of this study was to describe the clinical, manometric, and serological characteristics of 12 patients with paraneoplastic GI motor dysfunction and to assess the contributory role of diagnostic tests. METHODS: Twelve patients diagnosed with malignant tumors and GI motor dysfunction were identified at the Mayo Clinic from 1985 to 1996. RESULTS: Cancers identified were: nine small cell lung carcinoma (SCLC), one anaplastic lung adenocarcinoma, one retroperitoneal lymphoma, and one ovarian papillary serous adenocarcinoma. GI symptoms preceded the tumor diagnosis in all cases of SCLC (mean, −8.7 months, range, −1 to −24 months, n = 9). The diagnosis of a malignant tumor preceded the onset of GI symptoms in the three patients with other neoplasms (6, 12, and 24 months). Five of the nine patients found to have SCLC had no evidence of tumor on initial chest x-ray. One or more paraneoplastic autoantibodies were found in 10 of the 11 patients tested by autoimmune serology. Type 1 antineuronal nuclear antibody (ANNA-1 or anti-Hu) was detected in eight of the nine patients with SCLC (one patient was not tested). The patient with ovarian carcinoma had type 1 Purkinje cell cytoplasmic antibody (PCA-1 or anti-Yo). N-type calcium channel antibodies were found in one patient with SCLC, one with a retroperitoneal B cell lymphoma, and one with ovarian carcinoma. Gastric emptying was delayed in 89% (eight of nine tested) and 80% (four of five tested) had esophageal dysmotility. Autonomic reflex tests were abnormal in the seven patients tested. CONCLUSIONS: The diagnosis of paraneoplastic GI motor dysfunction requires a high index of clinical suspicion. A panel of serological tests for paraneoplastic autoantibodies, scintigraphic gastric emptying, and esophageal manometry are useful as first-line screening tests. Seropositivity for ANNA-1, PCA-1, or N-type calcium channel-binding antibodies should prompt further evaluation for an underlying malignancy even when routine imaging studies are negative.

Colonic Tone and Motility in Patients With Irritable Bowel Syndrome

In this study, our aim was to test the hypothesis that colonic tone is abnormal in patients with irritable bowel syndrome (IBS). We studied eight patients with IBS and eight age-matched asymptomatic control subjects, in whom tone and motility were measured by an electronic barostat and by pneumohydraulic perfusion manometry, respectively. Tone and motility were recorded from the descending colon for a 14-hour period--3 hours awake, 7 hours asleep, 2 hours fasting after awakening, and 2 hours postprandially. In patients with IBS and in healthy subjects, colonic tone decreased by up to 50% during sleep and increased promptly on awakening. Fasting colonic tone (as quantified by the volume in the barostat balloon) in the awake state was not significantly higher in patients with IBS than it was in healthy subjects (125 +/- 13 versus 152 +/- 15 ml; P = 0.19). Tone increased postprandially in both study groups, and the increase was greater in healthy subjects than it was in patients with IBS (P < 0.05). The motility index during fasting was greater in patients with IBS than it was in healthy control subjects (3.2 +/- 0.6 versus 1.6 +/- 0.4; P = 0.05), and the postprandial increase in motility index was greater in the healthy subjects. Preprandially and postprandially, we noted a trend for high-amplitude prolonged contractions to be more frequent in patients with IBS than in healthy subjects. We conclude that colonic tone in patients with IBS showed the same nocturnal and postprandial variations as it did in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Sleep disturbances are linked to both upper and lower gastrointestinal symptoms in the general population

Abstract  In tertiary referral patients, there is association between altered sleep patterns, functional bowel disorders and altered gut motor function. Body mass index (BMI) is also associated with gastrointestinal (GI) symptoms including diarrhoea, and with sleep disturbances. Our hypothesis is that sleep disturbances are associated with GI symptoms, and this is not explained by BMI. A 48‐item‐validated questionnaire was mailed to 6939 community participants in Olmsted County, MN. The survey included GI symptoms, sleep disturbance, daily lifestyle and quality of life (QOL). Independent contributions of sleep disturbance to individual symptoms were assessed using logistic regression adjusting for age, gender, lifestyle and mental health status. The association of an overall sleep score with an overall symptom score was examined and the ability of both scores to predict SF‐12 physical and mental functioning scores assessed in multiple linear regression models. Among 3228 respondents, 874 (27%) reported trouble staying asleep. There was a significant correlation of overall sleep scores with overall GI symptom scores (partial r = 0.28, P < 0.001). Waking up once nightly at least four times a month was significantly associated with pain, nausea, dysphagia, diarrhoea, loose stools, urgency and a feeling of anal blockage. Trouble falling asleep was significantly associated with rectal urgency. Associations were independent of gender, age, lifestyle factors and BMI. Overall, sleep scores and GI symptom scores were both significant independent predictors of impaired QOL. In the community, reporting poor sleep is associated with upper and lower GI symptoms, but this is independent of BMI.

Ehlers Danlos syndrome and gastrointestinal manifestations: a 20-year experience at Mayo Clinic.

Gastrointestinal (GI) manifestations are found in Ehlers Danlos syndrome (EDS) hypermobility subtype (HM). We aimed to assess associations between EDS HM and other EDS subtypes with GI manifestations.

Gastrointestinal Motility Considerations in Patients with Short-Bowel Syndrome

Short-bowel syndrome results from large resections of the small intestine that result in the malabsorption of nutrients and fluids. Following intestinal resection both morphological and functional adaptations of the residual intestine occur. While we have witnessed progress in the understanding of morphological adaptation, little is known about the effects of gastrointestinal motility in short-bowel syndrome. This article reviews what is currently known about gastrointestinal motility in the context of short-bowel syndrome and the motility considerations that impact on clinical management.

Does co-administration of a non-selective opiate antagonist enhance acceleration of transit by a 5-HT4 agonist in constipation-predominant irritable bowel syndrome? A randomized controlled trial.

Abstract  Opioid neurons exhibit tonic restraint on intestinal motility; opioid antagonists stimulate peristalsis and increase transit. In vitro, 5‐hydroxytryptamine (5‐HT4) agonists combined with selective opioid antagonists significantly increased colonic propulsion relative to a 5‐HT4 agonist alone. We hypothesized that the combination of 5‐HT4 agonist and non‐selective opioid antagonist enhances intestinal transit more than either treatment alone in female constipation‐predominant irritable bowel syndrome (C‐IBS) patients. Our aim was to examine the effect of tegaserod 6 mg b.i.d. alone and combined with naltrexone 50 mg on intestinal transit and stool characteristics in females with C‐IBS. Forty‐eight patients were randomized to tegaserod alone, naltrexone alone or in combination with tegaserod or placebo for 6 days. Small bowel, ascending colon half‐life (in pharmacokinetics) (t1/2), and colonic geometric centre (8, 24, 48 h) were assessed by scintigraphy. Tegaserod increased small bowel (P < 0.01) and colon transit (P < 0.01). Naltrexone did not accelerate colonic transit relative to placebo. Combination treatment did not significantly accelerate transit relative to tegaserod alone. Tegaserod and tegaserod with naltrexone resulted in looser stool form (P < 0.01). In female C‐IBS patients, tegaserod accelerates small bowel and colon transit and contributed to looser stool consistency. Use of naltrexone, 50 mg, does not support the hypothesis that combination of 5‐HT4 agonist and non‐selective opioid antagonist enhances intestinal transit.

Axial forces during gastric emptying in health and models of disease

The propulsive forces involved in gastric emptying of solid and liquid chyme are incompletely characterized, and the contribution of the proximal region of the stomach to overall propulsion has not been quantifiable. We have used an axial force catheter to characterize longitudinally directed forces during gastric emptying in man. The topography of these forces has been described relative to circumferential contractions, and the contribution of axial forces in experimental models of dumping and gastric stasis were quantified by assessing the effects of intravenous erythromycin and intraduodenal lipid, respectively. There is an excellent correlation between axial forces and gastric emptying of solids in health and in models of gastric dysmotility, suggesting that the axial force catheter semiquantitatively measures propulsive forces during emptying of the human stomach.

Balance Studies and Polymeric Glucose Solution to Optimize Therapy After Massive Intestinal Resection

The aim of this study was to determine whether fluid homeostasis could be maintained by using a hypo-osmolar (200 to 221 mosmol/kg), relatively low-sodium (50 to 52 mmol/liter) solution that contained a glucose polymer in a 54-year-old patient with high ileostomy output attributed to short-gut syndrome and resultant prerenal azotemia. Sequential balance studies were performed to assess stool and urinary output, stool fat, and urinary electrolytes initially during intravenous rehydration and subsequently during administration of the necessary fluids and nutrients exclusively by oral supplementation. The additional effects of high-fat and low-fat diet, loperamide hydrochloride, and octreotide acetate were evaluated. When the patient sipped a hypo-osmolar oral rehydration solution while she was awake during the day and received a high dose of loperamide and a 40-g fat, disaccharide-free diet, salt and water homeostasis was maintained. The addition of octreotide did not substantially enhance fluid balance; rather, it increased fecal fat and fluid losses from the small bowel. Thus, hypo-osmolar polymeric glucose solutions maintain fluid homeostasis in patients with the short-gut syndrome. In such patients, simple balance studies are useful for assessing the absorptive capacity of the residual intestine, for developing an optimal individualized treatment, and for eliminating the need for costly, long-term home parenteral nutrition.

Audit of the Treatment of Malnutrition Due to Chronic Intestinal Pseudo-Obstruction With Enteral Nutrition

Purpose: Chronic intestinal pseudo-obstruction (CIP) can result in significant malnutrition and weight loss. Although parenteral nutrition can be a useful adjunct in the management of CIP, it is expensive and not without complications. Aim: To determine the outcome of enteral nutrition with nonelemental isotonic formulas in patients with CIP in a tertiary referral center, over the time period 1980 to 1998. Methods: A retrospective medical record review of patients with CIP receiving enteral nutrition. Median follow-up was 3 years (range, 1 to 8 years) Results: 30 patients (20 women, 10 men; mean age at diagnosis, 49 years) with scleroderma (n = 10), amyloidosis (n = 10), and idiopathic CIP (n = 10) were studied. All had failed oral feeding and had a feeding tube placed. Jejunal tubes were placed in 19 patients and gastric tubes in 11 patients. Continuous feedings were used in 24 patients, and 6 patients received intermittent gravity feedings. Initially, the goal rate of delivery using a standard isotonic ...