Asle W. Medhus

Gastric emptying: the validity of the paracetamol absorption test adjusted for individual pharmacokinetics.

An algorithm for the paracetamol absorption test for gastric emptying, adjusting for individual pharmacokinetics, was recently developed. The aim of the present study was to validate the use of this algorithm. Furthermore, the algorithm was applied to elucidate whether a gastric tube interferes with the rate of gastric emptying. A caloric liquid meal with paracetamol was administered orally to nine healthy volunteers on two separate days. On one occasion, the subjects were intubated with a nasogastric tube and the meal was aspirated from the stomach 45 min after meal intake. The percentage of the meal retained in the stomach at the time of aspiration was determined by analyses of paracetamol in the aspirate and compared with calculations by the algorithm. On the other examination day, the same meal was ingested without tube and aspiration. The median percentage of the meal retained in the stomach at aspiration was 47% (range 33–70%) calculated by the algorithm and 48% (range 23–61%) based on the aspiration data. The correlation between the emptying parameters was r=0.97 (P < 0.001). The median of gastric emptying parameters was similar when the number of samples included in the calculation by the algorithm was reduced, but the range tended to increase. The gastric tube moderately inhibited gastric emptying during the period 20–40 min after meal intake (P < 0.05), but for the period from meal intake until start of aspiration, no inhibition was found. The present study demonstrates that the novel algorithm for the paracetamol absorption test provides valid estimates for gastric emptying.

Switching from Remicade® to Remsima® is well Tolerated and Feasible: A Prospective, Open-label Study

Background and Aims A biosimilar version of infliximab [CT-P13/Remsima®] recently entered the European market. The clinical data on its use in inflammatory bowel disease [IBD] are sparse, especially on switching from the originator Remicade®. In this study, we aimed to prospectively investigate the feasibility, safety and immunogenicity of switching from Remicade to Remsima in a real-life IBD population. Methods All adult patients who were treated with Remicade in the Department of Gastroenterology at Oslo University Hospital were switched to Remsima. The follow-up lasted for 6 months. In addition, a retrospective registration was performed with a start time of 6 months before switching drugs. The primary endpoints were [i] the proportion of patients remaining on medication 6 months after switching and [ii] adverse events during the 6 months after switching. The secondary endpoints included [i] disease activity scores [Harvey-Bradshaw Index and Partial Mayo Score], C-reactive protein, haemoglobin, faecal calprotectin, infliximab dose and interval, and p-infliximab and [ii] the development of antidrug antibodies. Results In total, 143 IBD patients were switched, 99 with Crohns disease and 44 with ulcerative colitis. The large majority [97%] remained on the medication throughout follow-up. A low number of adverse events were observed. No change in disease activity, C-reactive protein, haemoglobin, faecal calprotectin, infliximab dose and interval or p-infliximab was detected. Three patients developed new detectable antidrug antibodies. Conclusions Switching from Remicade to Remsima was feasible and with few adverse events, including very limited antidrug antibody formation and loss of response.

Treatment of malignant gastric outlet obstruction with stents: An evaluation of the reported variables for clinical outcome

BackgroundMalignant gastric outlet obstruction (GOO) is commonly seen in patients with advanced gastric-, pancreatic-, duodenal, hepatobiliary or metastatic malignancies. Ten to 25% of patients with pancreatic cancer will develop duodenal obstruction during the course of the disease. Duodenal stenting with self-expandable metal stents is an alternative treatment to surgical bypass procedures. Our aim was to review the published literature regarding treatment of malignant GOO with stents to reveal whether the information provided is sufficient to evaluate the clinical effects of this treatmentMethodsA literature search from 2000 – 2007 was conducted in Pub Med, Embase, and Cochrane library, combining the following search terms: duodenal stent, malignant duodenal obstruction, gastric outlet obstruction, SEMS, and gastroenteroanastomosis.All publications presenting data with ≥ 15 patients and only articles written in English were included and a review focusing on the following parameters were conducted: 1) The use of graded scoring systems evaluating clinical success; 2) Assessment of Quality of life (QoL) before and after treatment; 3) Information on stent-patency; 4) The use of objective criteria to evaluate the stent effect.Results41 original papers in English were found; no RCTs. 16 out of 41 studies used some sort of graded scoring system. No studies had objectively evaluated QoL before or after stent treatment, using standardized QoL-questionnaires, 32/41 studies reported on stent patency and 9/41 performed an oral contrast examination after stent placement. Objective quantitative tests of gastric emptying had not been performed.ConclusionAvailable reports do not provide sufficient relevant information of the clinical outcome of duodenal stenting. In future studies, these relevant issues should be addressed to allow improved evaluation of the effect of stent treatment.

The migrating motor complex modulates intestinal motility response and rate of gastric emptying of caloric meals

Abstract The present study elucidates whether the phase of the migrating motor complex (MMC) present at the moment of food intake modulates postprandial motor response and rate of gastric emptying of caloric meals. Eight healthy male volunteers with a mean age of 26 years were examined twice. During water‐perfused gastroduodenal manometry, a liquid meal with paracetamol added as a marker was orally administered during phase I and late phase II. Paracetamol appeared in serum 14.1 ± 3.8 min and 9.1 ± 4.0 (mean ± SD) min, respectively, after intake of the meal (P < 0.02). The area under the curve of s‐paracetamol until 25 min after intake was 232 ± 169 μmoll‐1 min and 362 ± 130 (P < 0.05), respectively. When taken during late phase II, a phase III‐like activity occurred within 2.1 ± 1.3 min in the duodenum, and was succeeded by quiescence. During phase I, the meal invariably initiated irregular contractions within 4 min. The phase of MMC during which a caloric meal is ingested modulates duodenal motor response and rate of gastric emptying during the initial postprandial period. Initial postprandial motor activity thus represents the combined effect of nutrient stimulation and the underlying enteric biorhythm as reflected by phase of MMC.

The influence of the migrating motor complex on the postprandial endocrine response.

BACKGROUND The phase of the migrating motor complex (MMC) in the proximal small intestine at meal intake modulates gastric emptying, which is accelerated after intake during phase II. In the present study the relationship between phase of the MMC at meal intake and the postprandial endocrine response was studied. METHODS Eight healthy subjects ingested a caloric liquid meal of 2020 kJ during phase I and late phase II of the intestinal MMC, respectively, in a randomized order. Blood samples were drawn at regular intervals after meal intake and analysed for insulin, gastrin, neurotensin, cholecystokinin, motilin, and somatostatin by radioimmunoassays. RESULTS The area under the curve (AUC) until 15 min for serum insulin (P<0.05) and plasma neurotensin (P<0.02) and AUC until 120 min for serum gastrin (P<0.05) were higher after intake during late phase II than after phase I. Plasma cholecystokinin increased earlier (P<0.05) after intake during late phase II than after phase I. Plasma motilin and somatostatin were not influenced by preceding phase of the MMC. CONCLUSIONS This study shows that the phase of intestinal MMC at meal intake modulates the postprandial endocrine response, which may be explained by the prior entry of nutrients to the small intestine after intake during phase II.

Stimulation of the Small Intestine by Nutrients in Relation to Phase of the Migrating Motor Complex

Background: The relationship between the preceding phase of the migrating motor complex (MMC) and postprandial motility in the small intestine was studied. Methods: In eight healthy subjects small-bowel manometry was performed, and a 55-ml caloric liquid bolus (280 kJ) containing paracetamol and 14C-D-xylose was instilled into the duodenum during phase I and late phase II of the intestinal MMC, respectively, in randomized order. Blood samples were drawn at regular intervals and analysed for insulin, gastrin, glucose, paracetamol, and 14C-D-xylose. Results: After bolus administration during late phase II a phase-III-like activity succeeded by quiescence occurred in the duodenum in seven of eight subjects, whereas administration during phase I initiated irregular contractions in seven of eight subjects (P < 0.05). The caloric bolus induced a significant increase in serum insulin and gastrin. Areas under the curves for serum insulin, gastrin, glucose, paracetamol, and 14C-D-xylose were not modulated by the preceding phase of the MMC. Conclusions: The present study shows that a nutrient bolus instilled into the intestinal lumen induces MMC-like activity when administered during late phase II. These findings provide further evidence of interference between MMC and postprandial motility.BACKGROUND The relationship between the preceding phase of the migrating motor complex (MMC) and postprandial motility in the small intestine was studied. METHODS In eight healthy subjects small-bowel manometry was performed, and a 55-ml caloric liquid bolus (280 kJ) containing paracetamol and 14C-D-xylose was instilled into the duodenum during phase I and late phase II of the intestinal MMC, respectively, in randomized order. Blood samples were drawn at regular intervals and analysed for insulin, gastrin, glucose, paracetamol, and 14C-D-xylose. RESULTS After bolus administration during late phase II a phase-III-like activity succeeded by quiescence occurred in the duodenum in seven of eight subjects, whereas administration during phase I initiated irregular contractions in seven of eight subjects (P < 0.05). The caloric bolus induced a significant increase in serum insulin and gastrin. Areas under the curves for serum insulin, gastrin, glucose, paracetamol, and 14C-D-xylose were not modulated by the preceding phase of the MMC. CONCLUSIONS The present study shows that a nutrient bolus instilled into the intestinal lumen induces MMC-like activity when administered during late phase II. These findings provide further evidence of interference between MMC and postprandial motility.

Gastric emptying in children with gastroesophageal reflux and in healthy children.

PURPOSE The aim of this report is to examine whether children with gastroesophageal reflux (GER) have delayed gastric emptying compared to healthy children. METHODS All patients had GER verified by 24-hour pH monitoring. Gastric emptying of cows milk was examined by radionuclide scintigraphy in 51 patients with GER and in 24 controls. Gastric emptying rate was expressed as exponential half time (T1/2). RESULTS Median age was 4.4 years [range 0.1-15.4] in patients and 6.1 years [range 2.5-10.0] in controls (p=.10). A wide range of gastric emptying rates was observed both in GER patients [range 16-121] and controls [range 29-94]. One GER patient (2%) had slower gastric emptying (T1/2=121 min) than the healthy child with the longest T1/2 (94 min). Mean T1/2 was 49 minutes (SD 20.1) and 46 minutes (SD 14.2) in GER patients and controls, respectively (p=.51). CONCLUSIONS Gastric emptying rate of milk was not significantly different between children with GER and healthy children. A wide range of gastric emptying rates was observed in both groups.

Long-term outcome of palliative treatment with self-expanding metal stents for malignant obstructions of the GI tract

Abstract Background. Self-expanding metal stents (SEMS) are commonly used in the palliative treatment of malignant gastrointestinal (GI) obstructions with favorable short-term outcome. Data on long-term outcome are scarce, however. Aim. To evaluate long-term outcome after palliative stent treatment of malignant GI obstruction. Method. Between October 2006 and April 2008, nine Norwegian hospitals included patients treated with SEMS for malignant esophageal, gastroduodenal, biliary, and colonic obstructions. Patients were followed for at least 6 months with respect to stent patency, reinterventions, and readmissions. Results. Stent placement was technically successful in 229 of 231 (99%) and clinically successful after 1 week in 220 of 229 (96%) patients. Long-term follow-up was available for 219 patients. Of those, 72 (33%) needed reinterventions. Stent occlusions or migrations (92%) were the most common reasons. Esophageal stents required reinterventions most frequently (41%), and had a significantly (p = 0.02) shorter patency (median 152 days) compared to other locations (gastroduodenal, 256 days; colon, 276 days; biliary, 460 days). Eighty percent of reinterventions were repeated endoscopic procedures that successfully restored patency. Readmissions were required for 156 (72%) patients. Progression of the underlying cancer was the most common reason, whereas 24% were readmitted due to stent complications. Conclusions. Long-term outcome after palliative treatment with SEMS for malignant GI and biliary obstruction shows that 70% had a patent stent until death, and that most reobstructions could be solved endoscopically. Hospital readmissions were mainly related to progression of the underlying cancer disease.

Liquid and solid gastric emptying in adults treated for Hirschsprung's disease during early childhood.

Objective. Dysmotility of the upper gastrointestinal tract has been reported in children with Hirschsprungs disease. In the present study, gastric emptying was studied in adult patients with Hirschsprungs disease to elucidate whether there is a persisting involvement of the upper gastrointestinal tract in this group of patients. Material and methods. Gastric emptying of caloric liquids and solids was studied in 16 adult patients with surgically treated Hirschsprungs disease during early childhood and in age-matched controls. To examine liquid emptying, the paracetamol absorption test was applied using a meal containing glucose, lactose, maize oil, water (2020 kJ) and paracetamol. To examine solid emptying, the 13C gastric emptying breath test was applied using a meal containing white bread, margarine, a one-egg omelette (1050 kJ) and [13C]-octanoic acid. Gastrointestinal symptoms were recorded according to a standardized questionnaire. Results. For liquid meal emptying, the time until emptying commenced was 8.1±1.9 and 2.9±0.9 min (mean±SE) in patients and controls, respectively (p=0.02). Thereafter, the first 25% of the meal emptied in 6.8±0.8 and 12.1±1.1 min in patients and controls, respectively (p=0.0005). The overall emptying rate tended to be delayed in patients compared with controls (p=0.06). For the solid meal, a delay in emptying was evident (p=0.02). The patients reported more symptoms from the upper gastrointestinal tract than the controls, but the symptoms were not significantly related to the emptying pathology demonstrated. Conclusions. The present study demonstrates that adult patients with Hirschsprungs disease have an abnormal pattern of gastric emptying, indicating persisting involvement of the upper gastrointestinal tract.

Motility of the oesophagus and small bowel in adults treated for Hirschsprung’s disease during early childhood

Background  Dysmotility of the upper gastrointestinal (GI) tract has been reported in children with Hirschsprung’s disease (HD). In the present study, motility of the oesophagus and the small bowel was studied in adults treated for HD during early childhood to elucidate whether there are alterations in motility of the upper GI tract in this patient group. [Correction added after online publication 15 Sep: The preceding sentence has been rephrased for better clarity.]