Veerle Boecxstaens

Baclofen Improves Symptoms and Reduces Postprandial Flow Events in Patients With Rumination and Supragastric Belching

BACKGROUND & AIMSnIn patients with clinically suspected rumination, esophageal impedance manometry differentiates episodes of rumination (involuntary straining with intragastric pressure increases) from aerophagia/supragastric belching. Treatment options are limited and focused on behavioral therapy. Baclofen, an agonist of the γ-aminobutyric acid B receptor, increases lower esophageal sphincter pressure and decreases swallowing rate. We investigated its effects in these patients.nnnMETHODSnHigh-resolution manometry-impedance recordings were taken from 12 patients (8 women; mean age, 45 years; range, 18-89 years) with clinically suspected rumination or supragastric belching before and during treatment with baclofen (10 mg, 3 times daily). After 30 minutes of recordings, patients received a 1000-kcal solid meal; recordings were then continued for 1 hour. Patients were asked to register symptoms with an event marker. The number of symptoms registered and number and type of flow events were compared before and during treatment.nnnRESULTSnAn average of 20 symptom markers (range, 14-34) were recorded at baseline (10 [range, 4-25] for belching and 9 [range, 0-11] for regurgitation). This was significantly reduced to 6 (range, 2-22) (3 [range, 1-15] for belching and 1 [range, 0-13] for regurgitation) during baclofen treatment (P = .01). The number of flow events (473 at baseline [42 reflux, 192 rumination, 188 supragastric belching, and 42 aerophagia]) was significantly reduced to 282 (32 reflux, 99 rumination, 123 supragastric belching, and 13 aerophagia) during baclofen therapy (P = .02). The reduction in flow events correlated with the increase in lower esophageal sphincter pressure (r = -0.62; P = .03) and reduction in swallowing frequency (r = 0.64; P = .02).nnnCONCLUSIONSnBaclofen is an effective treatment for patients with rumination or supragastric belching/aerophagia.

Review article: the pathophysiology, differential diagnosis and management of rumination syndrome

Aliment Pharmacol Ther 2011; 33: 782–788

MODULATION OF THE POSTPRANDIAL ACID AND BILE POCKETS AT THE GASTRO-OESOPHAGEAL JUNCTION BY DRUGS THAT AFFECT GASTRIC MOTILITY

Backgroundu2002 Previous studies have established the presence of a postprandial acid pocket at the gastro‐oesophageal junction.

Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers

There are limited data concerning the effects of 5-HT(1A) receptor activation on esophageal motility. Sumatriptan, a 5-HT(1A) receptor agonist, was recently reported to enhance esophageal peristalsis after intravenous administration. Buspirone, an orally available 5-HT(1A) receptor agonist, was shown to modulate gastroduodenal motor function. Our aim was to evaluate the effect of buspirone on esophageal motility of healthy volunteers. On two separate visits, 20 healthy volunteers aged 21-29 years (nine women) underwent esophageal manometry before and 10, 30, and 60 minutes after the administration of buspirone 20-mg or placebo capsule, according to a double-blind crossover design. At each time point, we compared buspirone and placebo effects on: resting pressure of the lower esophageal sphincter (LES); residual pressure and duration of LES relaxation; amplitude, duration, and onset velocity of esophageal body contractions, during 10 swallows of 5 mL of water. Significant analysis of variance differences (P < 0.05) are presented as mean ± standard deviation. Buspirone significantly increased mean distal esophageal wave amplitude (151 vs. 87 mmHg, P < 0.05) and duration (6.1 vs. 4.2 seconds, P < 0.05). Similarly, buspirone significantly increased mean LES resting pressure (26 vs. 21 mmHg, P < 0.05) and mean residual LES pressure (7.9 vs. 2 mmHg, P < 0.05), whereas reduced mean LES relaxation duration (7.2 vs. 8.0 seconds, P < 0.05) and mean distal onset velocity (7.6 vs. 14.7 cm/second, P < 0.05). Buspirone enhances esophageal peristalsis and LES function in healthy volunteers. Further study is warranted on the effects of buspirone on esophageal function and symptoms in patients with ineffective esophageal motility.

Increasing body weight enhances prevalence and proximal extent of reflux in GERD patients 'on' and 'off' PPI therapy

Backgroundu2002 Increased body weight is associated with higher intragastric pressure. Proximal extent of reflux is a determinant of symptoms in patients with gastro‐esophageal reflux disease (GERD). We aimed to investigate the association between body mass index (BMI) and abdominal circumference on the incidence and proximal extent of reflux.

Effect of baclofen on gastric acid pocket in subjects with gastroesophageal reflux disease symptoms

Postprandial gastroesophageal reflux (PGER) in the distal esophagus (DE) is associated with a gastric juice acid pocket (AP). Baclofen reduces AP extension into the DE in healthy volunteers, in part through increased lower esophageal sphincter (LES) pressure. We aimed to verify whether baclofen also affects postprandial AP location and extent in gastroesophageal reflux disease (GERD) patients. Thirteen treatment-naive heartburn-prevalent GERD patients underwent two AP studies, after pretreatment with baclofen 40u2009mg or placebo 30u2009minutes preprandially. We performed pH-probe stepwise pull-throughs (PT) (1u2009cm/min, LES -10 to +5u2009cm) before and every 30 minutes from 30u2009minutes before up to 150u2009minutes after a test meal. After the meal, both after placebo and baclofen, gastric pH significantly dropped at 30, 60, 90u2009minutes postprandially (P: nadir pHs of 3.9 ± 0.6, 2.3 ± 0.6, 2.1 ± 0.4; B: nadir pHs of 2.5 ± 0.4, 2.8 ± 0.4, 2.5 ± 0.3; all P < 0.05). After placebo, LES pressure decreased at 60, 90 and 120 minutes postprandially (32.7 ± 6.1 vs. 24.5 ± 3.1, 27.3 ± 5.9, 27.3 ± 6.0u2009mmHg; analysis of variance [ANOVA], P = 0.037), but this was prevented by baclofen (25.4 ± 3.4 vs. 29.4 ± 2, 32.2 ± 1.4, 35.5 ± 1.7u2009mmHg, ANOVA, P = not significant (NS)). Baclofen did not significantly decrease the postprandial AP extent above the LES but prevented the postprandial increase in transient lower esophageal sphincter relaxations (TLESRs) (preprandial vs. postprandial, placebo: 1.1 ± 0.3 vs. 3.7 ± 0.7, P < 0.05; baclofen: 1.4 ± 0.4 vs. 2 ± 0.5, P = NS). In GERD patients, baclofen significantly increases postprandial LES pressure, prevents the increase TLESRs but, unlike in healthy volunteers, does not affect AP extension into the DE.

Vitamin D supplementation in cutaneous malignant melanoma outcome (ViDMe): a randomized controlled trial

BackgroundPrevious studies have investigated the protective effect of vitamin D serum levels, at diagnosis and during the follow-up period after treatment, on melanoma outcome. In the present study we assess whether vitamin D supplementation, in the follow-up period after diagnosis and surgical resection of the primary tumor, has a protective effect on relapse of cutaneous malignant melanoma and whether this protective effect correlates with vitamin D levels in serum and Vitamin D Receptor immunoreactivity in the primary tumor.Methods/designThis study is a multicenter randomized double blind placebo- controlled phase III trial. Patients between the age of 18 and 80xa0years diagnosed and treated surgically for a melanoma stage IB-III are eligible for randomization in a 1:1 ratio to active treatment or placebo. The study drug is taken each month and consists of either 100,000 International Unit cholecalciferol or arachidis oleum raffinatum used as a placebo. The primary endpoint is relapse free survival. The secondary endpoints are 25 hydroxyvitamin D3 serum levels at diagnosis and at 6xa0month intervals, melanoma subtype, melanoma site and stage of melanoma at diagnosis according to the 2009 American Joint Committee on Cancer melanoma staging and classification. At randomization a bloodsample is taken for DNA analysis. The study is approved by the local Ethics Committees.DiscussionIf we can confirm our hypothesis that vitamin D supplementation after removal of the tumor has a protective effect on relapse of cutaneous malignant melanoma we may reduce the burden of CMM at several levels. Patients, diagnosed with melanoma may have a better clinical outcome and improved quality of life. There will be a decrease in health care costs related to treatment of metastatic disease and there will be a decrease in loss of professional years, which will markedly reduce the economic burden of the disease.Trial registrationClinical Trial.gov, NCT01748448, 05/12/2012

Severely impaired gastric accommodation is a hallmark of post-Nissen functional dyspepsia symptoms

Laparoscopic Nissen fundoplication is a commonly performed antireflux surgery, after which reflux symptoms are well controlled, however, complications such as inability to belch or dyspeptic symptoms (mimicking those of functional dyspepsia [FD]) might occur. The aim of the study was to prospectively evaluate symptom pattern and underlying pathophysiological mechanisms in patients with post‐Nissen dyspepsia.

The optimal order of stimulation modalities and reproducibility of the multimodal esophageal stimulation paradigm

Esophageal hypersensitivity can be triggered by different stimuli. We use a multimodal stimulation model to study esophageal sensitivity to four sensory modalities: thermal, mechanical, electrical, and chemical stimulation. The optimal order of these stimulations needs further validation.

Response to targeted therapy in two patients with metastatic melanoma carrying rare BRAF exon 15 mutations: A598_T599insV and V600_K601delinsE

Concurrent BRAF-MEK inhibition improves clinical outcomes in patients with advanced BRAF V600E/K-mutant melanoma. There is currently less evidence for the efficacy of this treatment in patients with rare BRAF non-V600E/K genotypes. We report on two patients with rare BRAF exon 15 mutations – BRAF A598_T599insV and V600_K601delinsE – obtaining clinical benefit and a radiological response to inhibitors directed against the mitogen-activated protein kinase pathway. This highlights the importance of using tests that detect both V600E/K and non-V600E/K BRAF mutations to keep open the possibility of treatment with targeted therapy in patients with uncommon, yet potentially actionable, BRAF exon 15 mutations.