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

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          Abstract

          Background/Aims

          The paucity of knowledge regarding gastrointestinal motility in patients with neuroendocrine tumors and carcinoid diarrhea restricts 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 investigated 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 colonic 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.

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          Most cited references32

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          Lanreotide in metastatic enteropancreatic neuroendocrine tumors.

          Somatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited. We conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor-positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety. Most patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant between-group differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group). Lanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005-004904-35.).
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            Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue.

            We studied the effects of a long-acting analogue of somatostatin (SMS 201-995, Sandoz) in 25 patients with histologically proved metastatic carcinoid tumors and the carcinoid syndrome. This drug was self-administered by subcutaneous injection at a dose of 150 micrograms three times daily. Flushing and diarrhea associated with the syndrome were promptly relieved in 22 patients. All 25 patients had an elevated 24-hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) (mean, 265 mg per 24 hours; range, 14 to 1079), which served as an objective indicator of disease activity. Eighteen of the 25 patients (72 percent) had a decrease of 50 percent or more in their urinary 5-HIAA levels, as compared with the pretreatment values. The median duration of this biochemical response was more than 12 months (range, 1 to greater than 18). Since no serious toxicity was observed, we conclude that SMS 201-995 may be appropriate for use as early therapy in patients with symptoms due to the carcinoid syndrome who have not responded to simpler measures.
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              Wireless capsule motility: comparison of the SmartPill GI monitoring system with scintigraphy for measuring whole gut transit.

              Assessment of whole gut transit, by radio-opaque markers or scintigraphy, is used to evaluate patients with constipation for slow gastrointestinal transit. Wireless capsule motility, using the SmartPill GI monitoring system, samples and transmits intraluminal pH, pressure, and temperature data from a capsule at regular intervals as it traverses through the gastrointestinal tract; from these, gastric emptying and whole gastrointestinal tract transit can be assessed. The objective of this study was to compare the SmartPill with whole gut transit scintigraphy to determine whether the SmartPill system could serve as a test for measurement of whole gut motility and transit. Ten healthy, asymptomatic subjects underwent simultaneous whole gut scintigraphy and SmartPill assessment of whole gut transit. All subjects completed the study per protocol and experienced natural passage of the pill. Capsule residence time in the stomach correlated very strongly with percent gastric retention of the Tc-99 radiolabel at 120 min (r = 0.95) and at 240 min (r = 0.73). Small bowel contraction-min(-1) measured by the SmartPill correlated with small bowel transit % (r = 0.69; P = 0.05) and with isotopic colonic geometric center at 24 h after ingestion (r = 0.70, P = 0.024). Capsule transit time correlated with scintigraphic assessment of whole gut transit. SmartPill capsule assessment of gastric emptying and whole gut transit compares favorably with that of scintigraphy. Wireless capsule motility shows promise as a useful diagnostic test to evaluate patients for GI transit disorders and to study the effect of prokinetic agents on GI transit.
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                Author and article information

                Journal
                J Neurogastroenterol Motil
                J Neurogastroenterol Motil
                Journal of Neurogastroenterology and Motility
                Korean Society of Neurogastroenterology and Motility
                2093-0879
                2093-0887
                July 2015
                03 July 2015
                : 21
                : 3
                : 423-432
                Affiliations
                [1 ]Neurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
                [2 ]Motilis Medica SA, Lausanne, Switzerland
                Author notes
                [* ]Correspondence: Tine Gregersen, MD, Aarhus University Hospital, Norrebrogade 44, Building 1A, Basement, DK-8000 Aarhus C, Denmark, Tel: +45-2233-4161, Fax: +45-7846-2860, E-mail: tg@ 123456clin.au.dk
                Article
                jnm-21-423
                10.5056/jnm15035
                4496908
                26130638
                cbe91704-0c64-4e0a-8f44-9a0e2d2db538
                © 2015 The Korean Society of Neurogastroenterology and Motility

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 February 2015
                : 04 April 2015
                : 05 April 2015
                Categories
                Original Article

                Neurology
                capsules,carcinoid tumor,diarrhea,gastrointestinal motility
                Neurology
                capsules, carcinoid tumor, diarrhea, gastrointestinal motility

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