Chronic loose stools following right-sided hemicolectomy for colon cancer and the association with bile acid malabsorption and small intestinal bacterial overgrowth.

AIM: Patients treated with right-sided hemicolectomy for colon cancer may suffer from long-term bowel dysfunction, including loose stools, urgency and faecal incontinence. The underlying causes are poorly understood. The aim of this case-control study was to investigate the aetiology of chronic loose stools among patients with right-sided hemicolectomy curatively operated for cancer. METHOD: Cases with chronic loose stools (Bristol stool type 6-7) after right-sided hemicolectomy were compared with a control group of patients with right-sided hemicolectomy without loose stools. All patients underwent a selenium-75 homocholic acid taurine (SeHCAT) scan to diagnose bile acid malabsorption (BAM) and a glucose breath test to diagnose small intestinal bacterial overgrowth (SIBO). Gastrointestinal transit time (GITT) was assessed with radiopaque markers. In a subgroup of patients, fibroblast growth factor 19 (FGF19) was measured in fasting blood. SIBO was treated with antibiotics and BAM was treated with bile acid sequestrants. RESULTS: We included 45 cases and 19 controls. In the case group, 82% (n = 36) had BAM compared with 37% (n = 7) in the control group, p < 0.001. SIBO was diagnosed in 73% (n = 33) of cases with chronic loose stools and in 74% (n = 14) of controls, p = 0.977. No association between BAM and SIBO was observed. GITT was similar in cases and controls. No difference in median FGF19 was observed between cases and controls (p = 0.894), and no correlation was seen between FGF19 and SeHCAT retention (rs 0.20, p = 0.294). Bowel symptoms among cases were reduced after treatment. CONCLUSION: BAM and SIBO are common in patients having undergone right-sided hemicolectomy for cancer. Chronic loose stools were associated with BAM but not with SIBO.

Biochemical Diagnosis of Bile Acid Diarrhea: Prospective Comparison With the 75Seleno-Taurohomocholic Acid Test.

INTRODUCTION: The diagnosis of bile acid diarrhea is often missed because the availability of the seleno-taurohomocholic acid (SeHCAT) test is limited. We aimed to compare the biomarkers 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) with the SeHCAT test. METHODS: Patients with chronic diarrhea without intestinal resection referred for SeHCAT were prospectively recruited for this diagnostic accuracy study. Blood was sampled at fasting and after a stimulation meal with chenodeoxycholic acid. SeHCAT retention ≤10% defined bile acid diarrhea and >10% defined miscellaneous diarrhea. Receiver operating characteristics (ROC) were analyzed with SeHCAT as the gold standard. www.clinicaltrials.gov (NCT03059537). RESULTS: Patients with bile acid diarrhea (n = 26) had mean C4 of 30 ng/mL (95% confidence interval: 19-46) vs 8 (7-11; P < 0.001) in the miscellaneous diarrhea group (n = 45). Area under the ROC curve (ROCAUC) for C4 was 0.83 (0.72-0.93). C4 < 15 ng/mL had 85% (74%-96%) negative predictive value; C4 > 48 ng/mL had 82% (59%-100%) positive predictive value. Twenty patients had C4 values 15-48 ng/mL, of whom 11/20 had SeHCAT ≤10%. Median fasting FGF19 was 72 pg/mL (interquartile range: 53-146) vs 119 (84-240) (P = 0.004); ROCAUC was 0.71 (0.58-0.83). Stimulated FGF19 responses did not differ (P = 0.54). DISCUSSION: We identified C4 thresholds with clinically useful predictive values for the diagnosis of and screening for bile acid diarrhea in patients with chronic watery diarrhea. Further validation of the cutoff values with the placebo-controlled effect of sequestrant therapy is warranted (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B603).

The Risk of Second Primary Colorectal Adenocarcinomas Is Not Increased among Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Nationwide Population-Based Study.

BACKGROUND: Second primary colorectal adenocarcinomas (SPCA) may occur with a higher frequency in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In a nationwide population-based study, we investigated the risk of SPCA in GEP-NEN patients and compared it to the general population. METHODS: Using the nationwide Danish registries, we identified 2,831 GEP-NEN patients (median age 63 years [IQR 50-73 years], 53% women) diagnosed in 1995-2010. We used Cox regression to compare the incidence of SPCA in GEP-NEN patients relative to a gender- and age-matched general population sample of 56,044 persons. RESULTS: We observed 20 SPCAs among the 2,831 GEP-NEN patients with a total time at risk of 14,003 years (incidence = 143 per 100,000 person-years) and 770 colorectal adenocarcinomas in the general population of 56,044 persons with a total time at risk of 466,801 years (incidence = 165 per 100,000 person-years). The hazard ratio (HR) of SPCA from GEP-NEN diagnosis to the end of follow-up was 1.22 (95% CI: 0.78-1.92) in GEP-NEN patients compared to the general population. This nonsignificant association was the result of a strong positive association in the first 6 months after diagnosis of GEP-NEN (HR = 9.43 [95% CI: 4.98-17.86]) followed by a negative association in the remainder of the follow-up period (HR = 0.50 [95% CI: 0.20-1.21]). CONCLUSION: In this population-based study, there was no increased risk of SPCA among GEP-NEN patients. The clinical workup in newly diagnosed GEP-NEN patients likely explains the positive short-term association followed by a negative association.

Prospective comparison of diagnostic tests for bile acid diarrhoea.

BACKGROUND: Bile acid diarrhoea is often missed because gold standard nuclear medicine tauroselcholic [75-Se] acid (SeHCAT) testing has limited availability. Empirical treatment effect has unknown diagnostic performance, whereas plasma 7α-hydroxy-4-cholesten-3-one (C4) is inexpensive but lacks sensitivity. AIMS: To determine diagnostic characteristics of empirical treatment and explore improvements in diagnostics with potential better availability than SeHCAT. METHODS: This diagnostic accuracy study was part of a randomised, placebo-controlled trial of colesevelam. Consecutive patients with chronic diarrhoea attending SeHCAT had blood and stool sampled. Key thresholds were C4 > 46 ng/mL and SeHCAT retention ≤10%. A questionnaire recorded patient-reported empirical treatment effect. We analysed receiver operating characteristics and explored machine learning applied logistic regression and decision tree modelling with internal validation. RESULTS: Ninety-six (38%) of 251 patients had SeHCAT retention ≤10%. The effect of empirical treatment assessed with test results for bile acid studies blinded had 63% (95% confidence interval 44%-79%) sensitivity and 65% (47%-80%) specificity; C4 > 46 ng/mL had 47% (37%-57%) and 92% (87%-96%), respectively. A decision tree combining C4 ≥ 31 ng/mL with ≥1.1 daily watery stools (Bristol type 6 and 7) had 70% (51%-85%) sensitivity and 95% (83%-99%) specificity. The logistic regression model, including C4, the sum of measured stool bile acids and daily watery stools, had 77% (58%-90%) sensitivity and 93% (80%-98%) specificity. CONCLUSIONS: Diagnosis of bile acid diarrhoea using empirical treatment was inadequate. Exploration suggested considerable improvements in the sensitivity of C4-based testing, offering potential widely available diagnostics. Further validation is warranted. CLINICALTRIALS: gov: NCT03876717.

Efficacy and safety of colesevelam for the treatment of bile acid diarrhoea: a double-blind, randomised, placebo-controlled, phase 4 clinical trial.

BACKGROUND: Bile acid diarrhoea is a common but overlooked cause of chronic watery diarrhoea. Plasma 7α-hydroxy-4-cholesten-3-one (C4) is an alternative to the gold standard tauroselcholic [75Se] acid (SeHCAT) test. Low-certainty evidence supports sequestrant treatment, including colesevelam. We aimed to determine the efficacy and safety of colesevelam in bile acid diarrhoea. METHODS: In this randomised, double-blind, placebo-controlled, investigator-initiated phase 4 trial of the sequestrant colesevelam in bile acid diarrhoea (SINBAD), we enrolled consecutive patients aged 18-79 years without inflammatory bowel disease attending SeHCAT testing for suspected bile acid diarrhoea at four Danish secondary care centres. Participants were randomly allocated 1:1 to receive 12 days of treatment with colesevelam (overencapsulated tablets of 625 mg) or placebo, with the starting dose of two capsules twice daily and titrated to effect during the first 5 days of treatment. A pharmacist independent of the clinical investigators generated a randomisation list on the web page randomization.com using block randomisation (randomisation was not stratified). C4 and SeHCAT diagnostic results were blinded during treatment. We treated all patients with diarrhoea, with a daily mean of 3·0 or more bowel movements or 1·0 or more watery bowel movements (Bristol stool scale type 6 and 7). Remission was defined as the absence of both these criteria during treatment days 6-12. The primary outcome was the intention-to-treat remission rate in bile acid diarrhoea diagnosed by C4 concentration greater than 46 ng/mL. A secondary outcome was the intention-to-treat remission rate in bile acid diarrhoea diagnosed by SeHCAT retention of 10% or less. This trial is registered with ClinicalTrials.gov, NCT03876717. FINDINGS: Between Oct 25, 2018, and July 1, 2021, 168 patients were randomly assigned to receive colesevelam (n=84) or placebo (n=84). 41 patients had C4 concentration greater than 46 ng/mL (22 assigned to the colesevelam group and 19 to the placebo group). For the C4-defined primary outcome, 14 (64%) of 22 participants receiving colesevelam versus three (16%) of 19 participants receiving placebo achieved remission (adjusted odds ratio 9·1, 95% CI 1·9-62·8; p=0·011). For the SeHCAT-defined secondary outcome, 75 of the 168 participants had retention of less than 10% (37 assigned to the colesevelam group and 38 assigned to the placebo group); 22 (59%) of 37 participants receiving colesevelam achieved remission versus five (13%) of 38 participants receiving placebo (adjusted odds ratio 11·1, 95% CI 3·4-45·6; p=0·00020). There were no serious adverse events. Common adverse events were transient. For patients receiving colesevelam within the primary outcome population, five had abdominal pain, nine had bloating, and four had nausea. For patients receiving placebo, four had abdominal pain, four had bloating, and one had nausea. No participants with bile acid diarrhoea withdrew due to adverse events. INTERPRETATION: Colesevelam was superior to placebo at inducing remission of bile acid diarrhoea diagnosed with C4 concentration greater than 46 ng/mL. Secondary outcome data suggest similar efficacy treating SeHCAT-defined bile acid diarrhoea. Colesevelam was safe during the treatment. FUNDING: Fabrikant Vilhelm Pedersen og hustrus mindelegat; recommended by the Novo Nordisk Foundation.

Gastrointestinal transit times and motility in patients with cystic fibrosis.

OBJECTIVE: Patients with cystic fibrosis (CF) often suffer from gastrointestinal (GI) dysfunction including obstructive symptoms, malabsorption and pain, but the underlying pathophysiology remains obscure. AIM: To compare GI motility and transit times in CF patients and healthy controls. MATERIAL AND METHODS: Ten CF patients (five women, median age 23) with pancreatic insufficiency were studied. Total gastrointestinal transit time (GITT) and segmental colonic transit times (SCTT) were assessed by radiopaque markers. Gastric emptying and small intestinal transit were evaluated using the magnet-based motility tracking system (MTS-1). With each method patients were compared with 16 healthy controls. RESULTS: Basic contraction frequencies of the stomach and small intestine were normal, but the pill reached the cecum after 7 h in only 20% of CF patients while in 88% of controls (p = 0.001). Paradoxically, velocity of the magnetic pill through the upper small intestine tended to be faster in CF patients (median 1.1 cm/min, range 0.7-1.7) compared with controls (median 1.0 cm/min, range 0.6-1.7) (p = 0.09). No statistically significant differences were found in median gastric emptying time (CF: 58 min, range 6-107 vs. healthy: 41 min, range 4-125 (p = 0.24)), GITT (CF: 2 days, range 0.5-3.3 vs. healthy: 1.5 days, range 0.7-2.5 (p = 0.10)), right SCTT (CF: 0.5 day, range 0-1.1 vs. healthy: 0.4 day, range 0-1.0 (p = 0.85)), or left SCTT (CF: 1.0 day, range 0-2.2 vs. healthy 0.6 day, range 0.2-1.2 (p = 0.10)). CONCLUSIONS: In spite of normal contraction patterns, overall passage through the small intestine is significantly delayed in CF patients while upper small intestinal transit may be abnormally fast.

Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland.

AIM: Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this treatment option still needs clinical evaluation. METHODS: In this study, we evaluated the PRRT treatment response of 69 Danish patients with NET mainly originating from the gastroenteropancreatic system. Fifty-six patients (81%) were referred for PRRT to the Department of Nuclear Medicine, University Hospital Basel, Switzerland, between 2004 and 2008 due to progression assessed by the referring physicians. However, when retrospectively evaluated, only 42 of the 69 patients (61%) had progression according to RECIST (Response Evaluation Criteria in Solid Tumors). Most patients were treated with 9°Y-DOTATOC. RESULTS: Based on RECIST, a complete response was observed in 5 patients (7.4%), a partial response in 11 patients (16.2%) and stable disease in 42 patients (61.8%). Progressive disease after completed therapy was observed in 10 patients (14.7%). The median progression-free survival was 29 months (95% CI: 22-36 months). Pancreatic NET seemed to respond better to PRRT than small intestinal carcinoid tumors (p = 0.03). The overall frequency of serious adverse events was low. CONCLUSION: Implementation of PRRT in clinical routine has provided a valuable new therapeutic option for the treatment of advanced NET. We suggest that PRRT may advance from second- or third-line to first- or second-line therapy in inoperable/unresectable NET patients.

Effects of Sandostatin LAR on gastrointestinal motility in patients with neuroendocrine tumors.

BACKGROUND: Diarrhea is part of the carcinoid syndrome and a significant clinical problem in neuroendocrine tumor (NET) patients. Somatostatin analog (SA) treatment usually alleviates carcinoid diarrhea, but little is known about the objective effects of SA on gastrointestinal transport. AIM: To compare gastrointestinal motility in healthy subjects and NET patients before and during SA treatment. METHODS: Twelve NET patients were studied before and during 4 weeks of SA treatment and were compared with 12 healthy controls. Radio-opaque markers were used for the assessment of total gastrointestinal transit time (GITT). Gastric and small intestinal (SI) transit patterns were described via the external tracking of a small magnetic pill ingested by the subjects. RESULTS: Compared with controls, NET patients had a significantly shorter GITT (0.7 days (0.5-1.5) vs. 1.9 days (1.0-2.3)), a shorter SI transit time (184 min (74-307) vs. 322 min (131-376)), and a faster SI velocity (2.16 cm/min (0.91-3.66) vs. 1.29 cm/min (0.76-2.60)) (all p < 0.05) but a similar gastric emptying time. SA treatment was followed by a reduction in bowel movements (five per day (3-12) vs. four per day (1-7; p < 0.02)) as well as an increase in GITT (1.4 days (0.5-2.2; p < 0.05)). Further, a trend was observed toward increased SI transit time (253 min (145-344; p = 0.08)). Gastric emptying time increased during SA treatment (19 min (4-200) vs. 179 min (5-389; p < 0.02)). Elevated chromogranin A (CgA), serotonin, and urinary 5-hydroxyindoleacetic acid (U-5HIAA) levels decreased during SA treatment. CONCLUSION: NET patients have faster than normal total GITT and SI transit times. SA treatment prolongs gastric emptying and GITT, thereby reducing the number of bowel movements.

Gastrointestinal transit in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis and collagen deposits. Gastrointestinal symptoms of SSc, including abdominal pain, bloating and discomfort, are common but diffuse and their pathophysiology remains obscure. AIM: To investigate the pathophysiology of abdominal pain and discomfort in individuals with SSc. METHODS: A total of 15 individuals with SSc (13 women, median age 58 years), all suffering from diffuse abdominal symptoms, and 17 healthy volunteers (12 women, median age 52 years) were evaluated with the Motility Tracking System, MTS-1, measuring gastric emptying (GE) and velocity through the small intestine. SSc patients were also examined for bacterial overgrowth using the hydrogen breath test and with radiopaque markers to determine the total gastrointestinal transit time (GITT). RESULTS: Assessed with the MTS-1, the velocity through the proximal small intestine was significantly reduced in SSc patients (median 0.525 m/h, range 0.11-1.15) when compared to healthy subjects (median 0.91 m/h, range 0.51-1.74) (p = 0.02). Prolonged GE was found in 4 SSc patients (27%) but in none of the healthy volunteers (p = 0.04). Only 3 SSc patients (21%) had positive breath tests for small intestinal bacterial overgrowth. GITT was >3 days in 8 patients (53%). Slow small intestinal transit was associated with a prolonged GITT (p < 0.05). CONCLUSION: Velocity through the small intestine is significantly reduced in SSc patients with diffuse abdominal symptoms.

Gastric transit and small intestinal transit time and motility assessed by a magnet tracking system.

BACKGROUND: Tracking an ingested magnet by the Magnet Tracking System MTS-1 (Motilis, Lausanne, Switzerland) is an easy and minimally-invasive method to assess gastrointestinal transit. The aim was to test the validity of MTS-1 for assessment of gastric transit time and small intestinal transit time, and to illustrate transit patterns detected by the system. METHODS: A small magnet was ingested and tracked by an external matrix of 16 magnetic field sensors (4 × 4) giving a position defined by 5 coordinates (position: x, y, z, and angle: θ, φ). Eight healthy subjects were each investigated three times: (1) with a small magnet mounted on a capsule endoscope (PillCam); (2) with the magnet alone and the small intestine in the fasting state; and (3) with the magnet alone and the small intestine in the postprandial state. RESULTS: Experiment (1) showed good agreement and no systematic differences between MTS-1 and capsule endoscopy when assessing gastric transit (median difference 1 min; range: 0-6 min) and small intestinal transit time (median difference 0.5 min; range: 0-52 min). Comparing experiments (1) and (2) there were no systematic differences in gastric transit or small intestinal transit when using the magnet-PillCam unit and the much smaller magnetic pill. In experiments (2) and (3), short bursts of very fast movements lasting less than 5% of the time accounted for more than half the distance covered during the first two hours in the small intestine, irrespective of whether the small intestine was in the fasting or postprandial state. The mean contraction frequency in the small intestine was significantly lower in the fasting state than in the postprandial state (9.90 min-1 vs. 10.53 min-1) (p = 0.03). CONCLUSION: MTS-1 is reliable for determination of gastric transit and small intestinal transit time. It is possible to distinguish between the mean contraction frequency of small intestine in the fasting state and in the postprandial state.

Implications of rectal preconditioning for interpretation of sensory-motor data.

Testing of biomechanical properties of intestine requires the tissue to be preconditioned by applying cyclic loading to obtain repeatable mechanical data. However, little is known about the mechanosensory properties during intestinal preconditioning. We aimed to study the relationship between mechanical preconditioning of the human rectum and sensory response. Three fast rectal bag distensions to the pain threshold were done in seven healthy females. A visual analog scale (VAS) was used for sensory assessment. At each distension, we determined (1) time, bag cross-sectional area (CSA), radius (r), r/r0, pressure and tension to reach VAS = 1, 3 and 5 (pain threshold); (2) the same parameters at induced contraction start; (3) CSA where the pressure started to increase (CSAP>baseline) and (4) the number of contractions. The time, CSA, r/r0 and tension to reach VAS = 1 and VAS = 3 increased from distension 1 to 3 (4.9 < F < 11.5, 0.05 > P > 0.007), primarily due to difference between the first and second distension. For VAS = 5, r/r0 was smaller in distension 3 than distension 1 (P < 0.05), whereas time, CSA and tension did not differ between distensions (P > 0.5). Compared with distension 1, CSA, r/r0 and tension at contraction start, and CSAP>baseline were bigger in distensions 2 and 3 (5.5 < F < 10.9, 0.05 > P > 0.009). The pressure to reach the VAS levels, the contraction numbers and pressure at contraction start did not differ among distensions (P > 0.6). During mechanical preconditioning, CSA, tension and deformation increased at sub-pain levels, reflecting sensory adaptation. The data point to acute remodeling of a strain-dependent mechanism in the rectal wall.

Ambulatory assessment of colonic motility using the electromagnetic capsule tracking system.

BACKGROUND: The Motilis 3D-Transit system tracks electromagnetic capsules as they traverse the gastrointestinal tract. The method is minimally invasive and ambulatory. Analysis has previously been limited to regional gut transit times, but new methods may allow detailed analysis of colonic motility. METHODS: Parameters of colonic motility were analyzed from 34 3D-Transit recordings performed in healthy volunteers (median age 28 years; 8 F). Characteristic propulsive velocities and lengths of movement were determined to quantify common movement patterns. Data from seven patients with severe chronic diarrhea were included for comparison. KEY RESULTS: Lack of capsule motion accounted for 82% (75%-87%) of total colonic transit time. Propulsive velocities were distributed with peaks at 0.5 cm/min (antegrade or retrograde) and 50 cm/min (antegrade). Based on velocity and length of propagation, five motor patterns were identified; (a) long fast antegrade, (b) fast antegrade, (c) slow antegrade, (d) slow retrograde, and (e) fast retrograde movements. Long fast antegrade movements were median 21 cm (10-96 cm). Capsule progression was faster during daytime than at night (5.9 cm/h vs 0.8 cm/h; P < 0.01). Colonic transit was faster in patients with chronic diarrhea than in healthy volunteers (5.4 h vs 18.2 h; P = 0.04), with higher capsule velocity (20.4 cm/h vs 4.4 cm/h; P < 0.01). CONCLUSIONS AND INFERENCES: The 3D-Transit system now allows detailed description of colonic motility and our results are supported by those previously suggested by manometry. It holds promise for future assessment of movement patterns to characterize different diseases and effects of treatment.

Rectal Mechano-sensory Function in Patients with Carcinoid Diarrhea.

BACKGROUND/AIMS: In patients with neuroendocrine tumors, excessive production of serotonin and other amines may cause the carcinoid syndrome,which is mainly characterized by diarrhea and flushing. Little is known about the pathophysiology of carcinoid diarrhea. In severalother groups of patients, diarrhea may be associated with rectal hypersensitivity and increased rectal tone. Therefore, the aim of thepresent study was to compare rectal sensitivity and compliance in patients with carcinoid diarrhea and in healthy subjects. METHODS: Twelve patients (6 males, aged 54-78 years, median 65 years), with carcinoid diarrhea and 19 healthy subjects (7 males, aged 50-78 years, median 61 years) were included. Rectal mechanical and heat stimulation was used for assessment of rectal mechano-sensory properties. RESULTS: Overall, 5.3% higher temperatures were needed to elicit sensory responses in patients with carcinoid diarrhea than in healthy subjects (P = 0.015). Posthoc analyses revealed that the sensory threshold to heat was 48.1 ± 3.1°C in patients vs 44.7 ± 4.7°C in healthy subjects (P = 0.041). In contrast, patients and healthy subjects showed no overall differences in rectal sensory response to mechanical distension (P = 0.731) or rectal compliance (P = 0.990). CONCLUSIONS: Patients with carcinoid diarrhea have higher sensory thresholds to heat stimulation in comparison to healthy subjects, but normalrectal sensation to mechanical distension and normal compliance. Therefore, treatment of carcinoid diarrhea should aim at prolonging gastrointestinal transit and decreasing secretion, rather than modifying rectal mechano-sensory function.

Regional Gastrointestinal Transit Times in Patients With Carcinoid Diarrhea: Assessment With the Novel 3D-Transit System.

BACKGROUND/AIMS: The paucity of knowledge regarding gastrointestinal motility in patients with neuroendocrine tumors and carcinoid diarrhea re-stricts targeted treatment. 3D-Transit is a novel, minimally invasive, ambulatory method for description of gastrointestinal motility. The system has not yet been evaluated in any group of patients. We aimed to test the performance of 3D-Transit in patients with carcinoid diarrhea and to compare the patients' regional gastrointestinal transit times (GITT) and colonic motility patterns with those of healthy subjects. METHODS: Fifteen healthy volunteers and seven patients with neuroendocrine tumor and at least 3 bowel movements per day were inves-tigated with 3D-Transit and standard radiopaque markers. RESULTS: Total GITT assessed with 3D-Transit and radiopaque markers were well correlated (Spearman's rho = 0.64, P = 0.002). Median total GITT was 12.5 (range: 8.5-47.2) hours in patients versus 25.1 (range: 13.1-142.3) hours in healthy (P = 0.007). There was no difference in gastric emptying (P = 0.778). Median small intestinal transit time was 3.8 (range: 1.4-5.5) hours in patients versus 4.4 (range: 1.8-7.2) hours in healthy subjects (P = 0.044). Median colorectal transit time was 5.2 (range: 2.9-40.1) hours in patients versus 18.1 (range: 5.0-134.0) hours in healthy subjects (P = 0.012). Median frequency of pansegmental co-lonic movements was 0.45 (range: 0.03-1.02) per hour in patients and 0.07 (range: 0-0.61) per hour in healthy subjects (P = 0.045). CONCLUSIONS: Three-dimensional Transit allows assessment of regional GITT in patients with diarrhea. Patients with carcinoid diarrhea have faster than normal gastrointestinal transit due to faster small intestinal and colorectal transit times. The latter is caused by an increased frequency of pansegmental colonic movements.

Magnet tracking allows assessment of regional gastrointestinal transit times in children.

BACKGROUND: Data on small intestinal transit time in healthy children are lacking, and normal values for gastric emptying and colonic transit time are sparse. Conventional methods, including radiopaque markers, scintigraphy, and PillCam™ involve radiation or require the child to swallow a large pill. The minimally invasive, radiation-free Motility Tracking System-1 (MTS-1) has been introduced for description of gastrointestinal motility in adults. The aim of the study was to evaluate the MTS-1 for assessment of gastrointestinal transit times and motility patterns in healthy children. METHODS: Twenty-one healthy children (nine girls), median age 10 (range 7-12) years were included. For evaluation with MTS-1, a small magnetic pill was ingested and tracked through the gastrointestinal tract by a matrix of 16 magnetic sensors placed behind a nonmagnetic bed. The children were investigated for 8 hours after swallowing the magnetic pill and again for 4 hours the following morning. After leaving the unit, each child came back after every bowel movement to determine if the pill had been expelled. RESULTS: Nineteen children could swallow the pill. Characteristic contraction patterns were identified for the stomach (three per minute), small intestine (9-11 per minute), and colon (4-5 per minute). Median total gastrointestinal transit time was 37.7 (range 9.5-95.8) hours, median gastric emptying time was 37 (range 2-142) minutes, median small intestinal transit time was 302 (range 164 to >454) minutes, and median colorectal transit time was 38.1 (range 5.6-90.0) hours. CONCLUSION: MTS-1 allows minimally invasive evaluation of gastrointestinal motility in children. Use of the method is, however, restricted by the nonambulatory setup.

Goblet cell carcinoid in a patient with neurofibromatosis type 1: a rare combination.

Neuroendocrine tumors are rare tumors primarily located in the gastrointestinal tract. Goblet cell carcinoid is a rare subgroup of neuroendocrine tumors located in the appendix. Neurofibromatosis type 1 is an autosomal dominant disorder caused by a mutation in the NF1 gene. Patients with neurofibromatosis type 1 have an increased incidence of typical neuroendocrine tumors, but it is unknown if this is the case with goblet cell carcinoids. We describe a patient with both neurofibromatosis type 1 and goblet cell carcinoid, that according to literature would occur in 0.00017 per million per year. This may suggest a previously unknown association between neurofibromatosis type 1 and goblet cell carcinoids.