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

( Tine Gregersen ),( Anne Mette Haase ),( Vincent Schlageter ),( Henning Gronbaek ),( Klaus Krogh ) 대한소화기기능성질환·운동학회 2015 Journal of Neurogastroenterology and Motility (JNM Vol.21 No.3

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. (J Neurogastroenterol Motil 2015;21:423-432)

Effects of Naloxegol on Gastrointestinal Transit and Colonic Fecal Volume in Healthy Participants Receiving Oxycodone

Anne E Olesen,Debbie Grønlund,Esben B Mark,Klaus Krogh,Jens B Frøkjær,Asbjørn M Drewes 대한소화기 기능성질환∙운동학회 2019 Journal of Neurogastroenterology and Motility (JNM Vol.25 No.4

Background/Aims Opioids cause gastrointestinal (GI) dysmotility, decrease gut secretion, and affect gut sphincters. Symptoms of opioid-induced bowel dysfunction may be alleviated by peripherally acting opioid antagonists like naloxegol, but detailed knowledge on GI effects of this drug is lacking. We hypothesized that naloxegol, compared to placebo, would reduce GI transit time and colonic fecal volume in opioid-treated healthy participants. Methods We conducted a randomized, double-blinded, single-center, 2-way cross-over study in 24 healthy males, randomized to a 6 day treatment period of oxycodone (15 mg twice a day) co-administered with either naloxegol (25 mg once a day) or matching placebo. Participants swallowed an electromagnetic capsule which determined GI transit times. Colonic fecal volume was quantified with magnetic resonance imaging both pre-treatment and post-treatment. Results Naloxegol reduced total GI transit time by 21% (56 hours vs 71 hours, P = 0.02) and colonic transit time by 23% (45 hours vs 59 hours, P < 0.01), compared to placebo. However, no difference in colonic fecal volume was found (818 mL vs 884 mL, P = 0.20). Conclusions Short-term administration of naloxegol in healthy participants reverses the retardation of total GI and colonic transit induced by oxycodone. This supports the use of naloxegol in the treatment of GI side effects to opioid treatment, and add knowledge to the current understanding of mechanisms behind peripherally-acting opioid antagonists.

Colorectal Transit and Volume During Treatment With Prolonged-release Oxycodone/Naloxone Versus Oxycodone Plus Macrogol 3350

( Jakob L Poulsen ),( Esben B Mark ),( Christina Brock ),( Jens B Frøkjær ),( Klaus Krogh ),( Asbjørn M Drewes ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.1

Background/Aims Opioid-induced constipation (OIC) is the most common gastrointestinal (GI) side effect to opioid treatment. Opioid receptor antagonists against OIC have been introduced, but their efficacy has not been directly compared to conventional laxatives. Our aim was to compare symptoms and objective parameters of gut function in an experimental model of OIC during treatment with the opioid antagonist naloxone and oxycodone in prolonged-release (PR) formulation versus oxycodone plus macrogol 3350. Methods In this randomized, double-blind, crossover trial 20 healthy men received a 5-day treatment of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Regional GI transit times and segmental colorectal transit were assessed with the Motilis 3D-Transit electromagnetic capsule system. Colorectal volumes were determined by MRI. OIC symptoms were assessed with validated questionnaires, along with stool frequency and consistency. Results Total colorectal volume did not change after 5 days’ treatment with PR oxycodone/naloxone (941 vs 1036 mL; P = 0.091), but increased significantly after PR oxycodone plus macrogol treatment (912 vs 1123 mL; P < 0.001). Neither regional GI transit times nor segmental colorectal transit differed between the treatments (all P > 0.05). The Patient Assessment of Constipation Symptom Questionnaire abdominal symptoms score was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (0.2 vs 3.2; P = 0.002). Stool frequency was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (4.2 vs 5.4; P = 0.035). Conclusions PR oxycodone plus macrogol increases colorectal volume, but does not improve GI transit compared to PR oxycodone/naloxone. However, PR oxycodone/naloxone results in a lower abdominal symptom burden, despite higher stool frequency during macrogol treatment. (J Neurogastroenterol Motil 2018;24:119-127)

Axial Movements and Length Changes of the Human Lower Esophageal Sphincter During Respiration and Distension-induced Secondary Peristalsis Using Functional Luminal Imaging Probe

( Donghua Liao ),( Christian Lottrup ),( Lotte Fynne ),( Barry P Mcmahon ),( Klaus Krogh ),( Asbjørn M Drewes ),( Jingbo Zhao ),( Hans Gregersen ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.2

Background/Aims Efficient transport through the esophago-gastric junction (EGJ) requires synchronized circular and longitudinal muscle contraction of the esophagus including relaxation of the lower esophageal sphincter (LES). However, there is a scarcity of technology for measuring esophagus movements in the longitudinal (axial) direction. The aim of this study is to develop new analytical tools for dynamic evaluation of the length change and axial movement of the human LES based on the functional luminal imaging probe (FLIP) technology and to present normal signatures for the selected parameters. Methods Six healthy volunteers without hiatal hernia were included. Data were analyzed from stepwise LES distensions at 20, 30, and 40 mL bag volumes. The bag pressure and the diameter change were used for motion analysis in the LES. The cyclic bag pressure frequency was used to distinguish dynamic changes of the LES induced by respiration and secondary peristalsis. Results Cyclic fluctuations of the LES were evoked by respiration and isovolumetric distension, with phasic changes of bag pressure, diameter, length, and axial movement of the LES narrow zone. Compared to the respiration-induced LES fluctuations, peristaltic contractions increased the contraction pressure amplitude (P < 0.001), shortening (P < 0.001), axial movement (P < 0.001), and diameter change (P < 0.01) of the narrow zone. The length of the narrow zone shortened as function of the pressure increase. Conclusions FLIP can be used for evaluation of dynamic length changes and axial movement of the human LES. The method may shed light on abnormal longitudinal muscle activity in esophageal disorders. (J Neurogastroenterol Motil 2018;24:255-267)

The Impact of Opioid Treatment on Regional Gastrointestinal Transit

( Jakob L Poulsen ),( Matias Nilsson ),( Christina Brock ),( Thomas H Sandberg ),( Klaus Krogh ),( Asbjørn M Drewes ) 대한소화기기능성질환·운동학회 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.2

Background/Aims To employ an experimental model of opioid-induced bowel dysfunction in healthy human volunteers, and evaluate the impact of opioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility assessed by questionnaires and regional GI transit times using the 3-dimensional (3D)-Transit system. Methods Twenty-five healthy males were randomly assigned to oxycodone or placebo for 5 days in a double blind, crossover design. Adverse GI effects were measured with the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipation symptom questionnaire, and Bristol stool form scale. Regional GI transit times were determined using the 3D-Transit system, and segmental transit times in the colon were determined using a custom Matlab® graphical user interface. Results GI symptom scores increased significantly across all applied GI questionnaires during opioid treatment. Oxycodone increased median total GI transit time from 22.2 to 43.9 hours (P < 0.001), segmental transit times in the cecum and ascending colon from 5.7 to 9.9 hours (P = 0.012), rectosigmoid colon transit from 2.7 to 9.0 hours (P = 0.044), and colorectal transit time from 18.6 to 38.6 hours (P = 0.001). No associations between questionnaire scores and segmental transit times were detected. Conclusions Self-assessed GI adverse effects and increased GI transit times in different segments were induced during oxycodone treatment. This detailed information about segmental changes in motility has great potential for future interventional head-to-head trials of different laxative regimes for prevention and treatment of constipation. (J Neurogastroenterol Motil 2016;22:282-291)

Rectal Mechano-sensory Function in Patients with Carcinoid Diarrhea

( Tine Gregersen ),( Christina Brock ),( Anne Mette Haase ),( Søren Laurberg ),( Asbjørn M Drewes ),( Henning Grønbæk ),( Klaus Krogh ) 대한소화기기능성질환·운동학회 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.2

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 several other groups of patients, diarrhea may be associated with rectal hypersensitivity and increased rectal tone. Therefore, the aim of the present 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 ± 3.1oC in patients vs 44.7 ± 4.7oC 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 normal rectal 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. (J Neurogastroenterol Motil 2016;22:264-271)

Early Assessment of Cost-effectiveness of Gastric Electrical Stimulation for Diabetic Nausea and Vomiting

( Mette W Klinge ),( Peter Rask ),( Lene S Mortensen ),( Kathrine Lassen ),( Niels Ejskjaer ),( Lars H Ehlers ),( Klaus Krogh ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2017 Journal of Neurogastroenterology and Motility (JNM Vol.23 No.4

Background/Aims Recurrent nausea and/or vomiting are common complications of diabetes mellitus. The conditions severely impact the quality of life of patients and often cause repeated admissions to hospital incurring significant healthcare costs. If standard treatment fails, gastric electrical stimulation (GES) may be offered in selected cases, as a minimally invasive, but expensive, therapeutic option. Our aims are to evaluate the clinical effect and the cost-utility of GES as a treatment for severe diabetic recurrent nausea and/or vomiting. Methods Among 33 diabetes patients implanted with GES because of recurrent nausea and/or vomiting, 30 were available for evaluation. The effect of treatment was assessed prospectively using symptom-diaries and the SF-36 questionnaires at baseline, after 6 and 12 months, and thereafter yearly. The number of days in hospital due to symptoms related to gastrointestinal dysfunction was calculated using hospital records 12 months prior to and 12 months after implantation. Results The surgical procedures were performed without mortality or major complications. Six months after surgery 78% of the respondents had at least 50% reduction in time with nausea and 48% had at least 50% reduction in days with vomiting. Symptom relief persisted at follow-up after at least 4 years. Quality adjusted life years improved after GES, which was cost-effective after 24 months. Conclusions GES reduces symptoms and improves quality of life in diabetes patients with recurrent nausea and/or vomiting. The procedure is supposed as cost-effective over a 2-year time horizon. (J Neurogastroenterol Motil 2017;23:541-549)