Multichannel intraluminal impedance monitoring in the evaluation of patients with non-obstructive Dysphagia

BACKGROUND: Non-obstructive dysphagia (NOD) often poses diagnostic problems. The aim of this study was to evaluate the value of the addition of multichannel intraluminal impedance (MII) recording to esophageal manometry in the work-up of patients with NOD. METHODS: A total of 40 consecutive patients with NOD underwent combined esophageal MII recording and perfusion manometry. Ten liquid and 10 viscous boluses were tested in each patient. Values for bolus presence time (BPT) at each of the four recording sites and total bolus transit time (TBTT) were calculated. Bolus transit (BT) was considered to be normal when BPT at all sites and TBTT were within the normal limits defined in 42 healthy subjects. Patients were judged to have normal transit if >or=80% of liquid and >or=70% of viscous swallows showed normal transit. RESULTS: The following manometric diagnoses were made: normal motility (20), ineffective esophageal motility (IEM) (13), diffuse esophageal spasm (DES) (4), and achalasia (3). Abnormal transit for liquid and/or viscous boluses was found in 35.3% of patients with normal motility, in 66.7% of DES patients, and in 100% of achalasia patients. In patients with achalasia quantification of BT was often made impossible by low initial impedance baseline. Two IEM patients (15.4%) showed normal liquid and viscous transit. Swallows showing normal transit had significantly longer duration of LES relaxation in patients with normal manometry and IEM (p < 0.05). CONCLUSIONS: MII recording identifies esophageal function abnormalities in NOD patients with normal manometry, IEM, and DES. The MII technique seems to be less suitable for the most severe end of the dysphagia spectrum like achalasia.     

Impaired bolus transit across the esophagogastric junction in postfundoplication dysphagia

OBJECTIVES: This study assessed the effect of fundoplication on liquid and solid bolus transit across the esophagogastric junction (EGJ) in relation to EGJ dynamics and dysphagia. METHODS: Twelve patients with gastro-esophageal reflux disease (GERD) were studied before and after fundoplication. Concurrent high-resolution EGJ manometry and fluoroscopy were performed whilst swallowing liquid barium and a solid bolus. The EGJ transit time, EGJ opening duration, transit efficacy, and EGJ relaxation were measured. During the test symptoms of dysphagia were scored using a visual analog scale. RESULTS: The minimal opening aperture at fluoroscopy was located at the manometric EGJ in all subjects. Fundoplication markedly reduced the EGJ opening diameter from 1.0 +/- 0.1 to 0.6 +/- 0.1 cm (p < 0.01) and rendered deglutative EGJ relaxation incomplete. After fundoplication, a higher intrabolus pressure was found (p < 0.05) associated with a reduced axial bolus length (p < 0.001). EGJ transit time increased from 6.9 +/- 0.9 to 9.8 +/- 1.0 s for liquids (p < 0.01) and from 2.8 +/- 0.5 to 5.8 +/- 0.8 s (p < 0.01) for solids after fundoplication. No relation between EGJ transit and dysphagia scores was observed before fundoplication. In contrast, EGJ transit time significantly correlated with dysphagia scores both during liquid (r = 0.84; p < 0.01) and solid (r = 0.69; p < 0.05) bolus transit following fundoplication. CONCLUSIONS: Fundoplication patients exhibit a restricted hiatal opening and an incomplete deglutative EGJ relaxation. To facilitate EGJ transit despite these altered EGJ dynamics a higher intrabolus pressure is created by augmented bolus compression. Fundoplication increases EGJ transit time, the degree of which is associated with postoperative dysphagia.     

Air swallowing, belching, acid and non-acid reflux in patients with functional dyspepsia

BACKGROUND: Frequent belching is a common symptom in patients with functional dyspepsia with a reported incidence up to 80%. We hypothesized that patients with functional dyspepsia possibly have a higher frequency of belching than healthy subjects secondary to frequent air swallowing. AIM: To assess air swallowing, belching, acid and non-acid reflux patterns of patients with functional dyspepsia. METHODS: Combined 24-h oesophageal impedance and pH monitoring was performed in 10 functional dyspepsia patients and 10 controls. Analysis of the impedance-pH signals included incidence of air swallows, belching, acid and non-acid reflux. RESULTS: The incidence of air swallows in functional dyspepsia patients were significantly higher compared with controls (153 +/- 15 vs. 79 +/- 10, P < 0.001), while the incidence of liquid-only swallows were not significantly increased. The proportions of gas-containing reflux episodes (belches) and non-acid reflux episodes in functional dyspepsia patients were significantly higher when compared with controls (66.4 vs. 44.4%, P = 0.04 and 70.1 vs. 45.9%, P = 0.009, respectively). CONCLUSION: Patients with functional dyspepsia swallow air more frequently than controls and this is associated with an increased incidence of non-acid gaseous gastro-oesophageal reflux.     

Contributions of mucosal immune cells to methotrexate-induced mucositis

The use of high doses of the anti-cancer drug methotrexate (MTX) is associated with intestinal damage. As a result, mucosal immune cells become increasingly exposed to a vast amount of microbial stimuli. We aimed at determining whether these cells are still functional during MTX treatment. Furthermore, we assessed if activation of the mucosal immune system would play a role in the pathogenesis of mucositis. A contributive role to mucositis for the adaptive immune system was established by showing that mucosal lymphocytes from MTX-treated mice secreted enhanced amounts of cytokines upon ex vivo polyclonal stimulation. Next, in vitro experiments revealed that macrophages were not affected by MTX in the capacity to produce tumor necrosis factor-alpha (TNF-alpha) and IL-10 after LPS exposure. Moreover, peritoneal macrophages from MTX-treated mice produced more IL-10 and TNF-alpha upon LPS stimulation, compared with cells derived from control mice. These data indicate a persistence of both innate and adaptive immune responses in this model. The clinical relevance of these findings was further established by the fact that LPS exposure prior to MTX treatment aggravated the course of mucositis. Furthermore, LPS-responsive mice recovered more slowly compared with LPS-unresponsive mice from MTX treatment. Finally, we found an increase in weight loss and intestinal damage upon MTX treatment in IL-10-deficient mice in comparison to wild-type controls, suggesting a protective role for IL-10 in mucositis. We conclude that mucosal immune responses remain resilient during MTX-induced mucositis. Whereas TNF-alpha production may contribute to mucosal damage, IL-10 may regulate by restricting excessive mucositis.     

Fundal dysaccommodation in functional dyspepsia: head-to-head comparison between the barostat and three-dimensional ultrasonographic technique

BACKGROUND: Recently, non-invasive techniques such as 3 dimensional ultrasonography (3DUS) have been developed to assess gastric wall characteristics and to investigate their relationship with upper gastrointestinal sensations. To date, no head-to-head comparison has been carried out between the barostat and the 3DUS technique. AIM: To compare barostat and 3DUS and to investigate the relationship between gastric volumes and sensations in patients with functional dyspepsia and in healthy subjects. PATIENTS AND METHODS: Gastric accommodation was studied in 15 patients with functional dyspepsia and in 15 healthy subjects after ingestion of a liquid nutrient (300 kcal) using barostat and 3DUS in random order for 60 min. Proximal gastric relaxation was measured using barostat and gastric volume using 3DUS. Change in gastric volume, acquired by 3DUS, was expressed as total gastric volume/proximal volume ratio (TGV/PV) and compared with changes in barostat volume (fundal accommodation). RESULTS: Patients with functional dyspepsia showed a smaller change in proximal gastric volume than healthy subjects using barostat (mean (SD) 82 (61) v 205 (79) ml, p<0.01) and 3DUS (118 (41) v 199 (39) ml, p<0.01). Dysaccommodation of the proximal stomach was observed in 7 of 15 (46%) patients using the barostat technique. 10 of 15 (67%) patients were found to have an abnormal change in proximal gastric volume using TGV/PV ratio. At 5 min postprandially, fullness was related to the change in distal gastric volume (r = 0.51, p = 0.006) in the 3DUS study, whereas no relationship was observed in the barostat study. CONCLUSION: 3DUS is a feasible non-invasive technique to measure gastric volumes and shows a distinct overlap with barostat data in healthy subjects and patients with functional dyspepsia. Fullness relates to distal gastric volumes when assessed by non-invasive 3DUS.     

Lack of Relationship Between Chronic Upper Abdominal Symptoms and Gastric Function in Functional Dyspepsia

To determine the relationship between gastric function and upper abdominal sensations we studied sixty FD patients (43 female). All patients underwent three gastric function tests: ¹³C octanoic gastric emptying test, three-dimensional ultrasonography (proximal and distal gastric volume), and the nutrient drink test. Upper abdominal sensations experienced in daily life were scored using questionnaires. Impaired proximal gastric relaxation (23%) and a delayed gastric emptying (33%) are highly prevalent in FD patients; however, only a small overlap exists between the two pathophysiologic disorders (5%). No relationship was found between chronic upper abdominal symptoms and gastric function (proximal gastric relaxation, gastric emptying rate, or drinking capacity) (all P > 0.01). Proximal gastric relaxation or gastric emptying rate had no effect on maximum drinking capacity (P > 0.01). The lack of relationship between chronic upper abdominal sensations and gastric function questions the role of these pathophysiologic mechanisms in the generation of symptoms.     

Hyperglycemia attenuates the gastrokinetic effect of erythromycin and affects the perception of postprandial hunger in normal subjects.

OBJECTIVE: The major aims of this study were to determine in normal subjects whether the effects of erythromycin on gastric emptying, postprandial hunger, and fullness are modified by the blood glucose concentration. RESEARCH DESIGN AND METHODS: A total of 10 normal subjects (aged 20-39 years) underwent concurrent measurements of gastric emptying, blood glucose, hunger, and fullness on four separate occasions: twice during euglycemia (approximately 4 mmol/l) and twice during hyperglycemia (approximately 15 mmol/l). Either erythromycin (3 mg/kg) or saline (0.9%) was administered intravenously immediately before ingestion of a radioisotopically labeled solid meal. RESULTS: Gastric emptying was slower (P < 0.0001) during hyperglycemia when compared with euglycemia after both erythromycin and saline administration. During hyperglycemia, erythromycin reduced the lag phase (77.8 +/- 12.6 vs. 20.3 +/- 7.3 min; P < 0.05) but had no effect on the postlag emptying rate (0.32 +/- 0.077% per min vs. 0.24% per min). Hunger decreased (P < 0.001) and fullness increased (P < 0.001) after the meal. Postprandial hunger was less during hyperglycemia after saline infusion (P < 0.05) but not after erythromycin. Hunger was greater after erythromycin during both hyperglycemia and euglycemia (P < 0.05). CONCLUSIONS: At a blood glucose concentration of approximately 15 mmol/l, 1) gastric emptying of a solid meal is slower, when compared with euglycemia, even after administration of erythromycin; 2) the effect of erythromycin on gastric emptying of a solid meal is attenuated; and 3) the perception of postprandial hunger is reduced.     

Pragmatic trials in primary care. Methodological challenges and solutions demonstrated by the DIAMOND-study

Background  

Pragmatic randomised controlled trials are often used in primary care to evaluate the effect of a treatment strategy. In these trials it is difficult to achieve both high internal validity and high generalisability. This article will discuss several methodological challenges in designing and conducting a pragmatic primary care based randomised controlled trial, based on our experiences in the DIAMOND-study and will discuss the rationale behind the choices we made. From the successes as well as the problems we experienced the quality of future pragmatic trials may benefit.     

Gastric emptying of a solid meal starts during meal ingestion: combined study using 13C-octanoic acid breath test and Doppler ultrasonography. Absence of a lag phase in 13C-octanoic acid breath test

Scintigraphy and the 13C-octanoic acid breath test are both applied to assess gastric emptying. Using the 13C-octanoic acid breath test, excretion curves show 13C excretion immediately after ingestion of a solid egg meal, in contrast with scintigraphy where gastric emptying is observed after a lag phase. The aim of our study was to investigate whether transpyloric flow occurs during and directly after meal ingestion. Therefore, transpyloric flow was measured during and after ingestion of an egg meal labeled with 13C-octanoic acid, using Doppler ultrasonography. The breath test was performed simultaneously, with samples taken at regular intervals. The first emptying episode was observed 6.9 (3.9-16.2) min after start of meal ingestion. A significant relation between recovery of 13C and total duration of gastric emptying during the first 20 min was observed (partial correlation coefficient r = 0.80, p < 0.001). In conclusion, transpyloric flow starts during ingestion of a solid egg meal and results in detectable excretion of 13C.