Mogens Bove

Impact of prophylactic percutaneous endoscopic gastrostomy on malnutrition and quality of life in patients with head and neck cancer: a randomized study.

The purpose of this randomized study was to examine if a prophylactic percutaneous endoscopic gastrostomy (PEG) for enteral nutrition could prevent malnutrition, reduce hospital stay, and improve health‐related quality of life (HRQOL).

Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults:

Introduction Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE. Methods General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes. Results The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice. Conclusion Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients’ follow up are proposed in the guideline.

Distinctive blood eosinophilic phenotypes and cytokine patterns in eosinophilic esophagitis, inflammatory bowel disease and airway allergy.

Blood eosinophil numbers may be elevated in allergy, inflammatory bowel disease and eosinophilic esophagitis. The aim of this study was to examine whether circulating eosinophils display distinct phenotypes in these disorders and if different patterns of eosinophilic chemoattractants exist. Blood eosinophils from patients with symptomatic eosinophilic esophagitis (EoE; n = 12), ulcerative colitis (n = 8), airway allergy (n = 10) and healthy controls (n = 10) were enumerated and their surface markers analyzed by flow cytometry. Plasma levels of pro-eosinophilic cytokines were quantified in parallel. Data were processed by multivariate pattern recognition methods to reveal disease-specific patterns of eosinophil phenotypes and cytokines. EoE patients had higher numbers of eosinophils with enhanced expression of CD23, CD54, CRTH2 and CD11c and diminished CCR3 and CD44 expression. Plasma CCL5 was also increased in EoE. Although allergic patients had increased interleukin (IL)-2, IL-3, IL-5 and granulocyte macrophage colony-stimulating factor plasma concentrations, their blood eosinophil phenotypes were indistinguishable from those of healthy controls. Decreased eosinophilic expression of CD11b, CD18, CD44 and CCR3, but no distinctive pattern of eosinophil chemoattractants, characterized ulcerative colitis. We propose that eosinophils acquire varying functional properties as a consequence of distinct patterns of activation signals released from the inflamed tissues in different diseases.

Acid challenge to the human esophageal mucosa: effects on epithelial architecture in health and disease.

The histological changes that occur in the squamous epithelium in response to acute acid challenge was examined in healthy controls and proton pump inhibitor-treated gastroesophageal reflux disease (GERD) patients and related to the state of untreated erosive GERD in a saline-controlled, randomized perfusion study. In the basal state a stepwise significant increase in the thickness of the basal cell layer, papillary length, and dilatation of intercellular spaces (DIS) was seen when the three groups were compared. Acid perfusion induced a slight increase in the height of the basal cell layer mainly in healthy volunteers; this layer appears to be reactive to acute acid challenge as well as to acid suppressive therapy. DIS increases promptly in response to acute acid exposure in the healthy epithelium but no changes were seen in the lengths of the papillae or regarding DIS in the GERD patients. A protective effect of luminal nitric oxide on DIS development is suggested.

Validation of the Swedish M. D. Anderson Dysphagia Inventory (MDADI) in Patients with Head and Neck Cancer and Neurologic Swallowing Disturbances

The aim of this study was to validate the Swedish version of the dysphagia-specific quality-of-life questionnaire, the M. D. Anderson Dysphagia Inventory (MDADI). Patients with oropharyngeal dysphagia due to neurologic disease (nxa0=xa030) and head and neck (H&N) cancer patients with post-treatment subjective dysphagia (nxa0=xa085) were compared to an age- and gender-matched nondysphagic control group (nxa0=xa0115). A formal forward–backward translation was performed and followed international guidelines. Validity and reliability were tested against the Short-Form 36 (SF-36) and Hospital Anxiety and Depression Scale (HADS). Internal-consistency reliability was calculated by means of Cronbach’s α coefficient. Test–retest reliability was assessed by intraclass correlation (ICC). Convergent and discriminant validity were assessed by correlations between MDADI, SF-36, and HADS. Known-group validity was examined and statistically tested. Of 126 eligible patients, 115 agreed to participate (response ratexa0=xa091.3%). The age of the participants ranged between 37 and 92 years. Most of the MDADI items showed good variability and only minor floor or ceiling effects in solitary items were found. The internal-consistency reliability (Cronbach’s α) of the MDADI total score was 0.88 (after correction for systematic errors in the subjects’ responses to two reversed questions). All estimates reached over the satisfactory >0.70 reliability standard for group-level comparison. ICC ranged between 0.83 and 0.97 in the test–retest. The mean MDADI total score was 66.9 (SDxa0=xa014.7) for the H&N cancer patients, 65.0 (16.9) for the neurologic patients, and 97.5 (4.4) for the control group (Pxa0<xa00.001; study patients vs. controls). The MDADI was also sensitive to disease severity as measured by different food textures. The Swedish version of the MDADI showed good psychometric properties and is a valid instrument to assess dysphagia-related quality of life. It was also shown to be a reliable instrument after correction for systematic errors in the subjects’ responses to two reversed questions. Its known-group validity enables the differentiation between dysphagic and nondysphagic patients for group-level research.

Hypopharyngeal Acid Exposure: An Independent Risk Factor for Laryngeal Cancer?

Objectives/Hypothesis Gastroesophageal reflux disease has in recent years been linked to a variety of extraesophageal conditions including laryngeal cancer. However, whether a causal relationship exists is still under debate. The present study aimed to compare the occurrence and severity of gastroesophago‐hypopharyngeal reflux in patients with laryngeal cancer with those of healthy volunteers.

Topical Corticosteroids Do Not Revert the Activated Phenotype of Eosinophils in Eosinophilic Esophagitis but Decrease Surface Levels of CD18 Resulting in Diminished Adherence to ICAM-1, ICAM-2, and Endothelial Cells

Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients’ eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.

Sources of Intra-Oesophageal Nitric Oxide Production Following Intraluminal Acid Exposure

Background: The aim of the present study was to assess luminal nitric oxide (NO) levels in the oesophagus during baseline and acidic conditions and to clarify the sources of such oesophageal NO formation. Methods: Healthy volunteers received an intra-oesophageal infusion of either HCl (100 mM) or NaCl (150 mM) on two separate study days. After a low nitrate diet, nitrate load or no dietary restrictions/pretreatment, direct intraluminal measurements of NO formation were performed using a tonometric technique. Endoscopy was performed and mucosal biopsies were taken and analysed by means of immunohistochemistry, Western blot and RT-PCR. Results: No intra-oesophageal NO was detected during baseline conditions with pH neutrality. During the infusion of HCl the NO levels rose dramatically to around 12000 ppb. This high rate of NO formation fell by 95% following deviation of saliva. NO formation after an acute nitrate load was almost doubled during acid perfusion compared to control. Immunohistochemistry demonstrated distinct staining for iNOS in the oesophageal squamous epithelial cells, and Western blot and RT-PCR confirmed the presence of iNOS. Conclusion: Two sources exist for intra-oesophageal NO formation, both dependent on the luminal acidity: 1) chemical reduction of salivary nitrite, a mechanism related to dietary intake of nitrate, and 2) NO formation within the oesophageal mucosal epithelium by enzymatic degradation of L-arginine. In the latter case, the NO synthase has antigenic characteristics, indicating the inducible isoform, although a functional behaviour suggests an unconventional subtype.

Pharyngeal reflux episodes at pH 5 in healthy volunteers

Objective. The clinically used cut-off limit in reflux disease is pH 4. Yet, earlier studies have shown a poor correlation between pharyngeal reflux episodes and symptoms or laryngeal findings, and treatment results have been suboptimal. Moreover, recent data suggest that pepsin is still active at pH 5. The aim of this study was to evaluate the occurrence of pharyngeal pH 5 reflux episodes in healthy controls and to correlate these to the pH monitoring results with a cut-off limit of pH 4. Material and methods. The results of double-probe 24-h pH monitoring from 35 healthy controls were reanalysed concerning the occurrence of pH decreases to pH 5. Results. Pharyngeal pH 5 reflux episodes occurred in 32 healthy controls (91%). The median number of pharyngeal reflux episodes at pH 5 was 4.0. The vast majority of these reflux episodes (92%) occurred in the upright position, especially in the postprandial period. The median time pHu200a<u200a5 in the pharynx was 0.1% while the upper limit of normality was 1.5%. Pharyngeal pH 5 reflux episodes were 5 times more common than pH 4 reflux episodes. There was a significant positive correlation between hypopharyngeal and oesophageal acid exposure time at both pH 4 and 5 (p<0.01).Conclusions. Pharyngeal pH 5 reflux episodes are present in most healthy adults, mainly in upright position and in the postprandial period. The importance of these episodes for the occurrence of laryngeal symptoms and signs and for treatment response needs to be prospectively assessed.

Acid Challenge to the Esophageal Mucosa: Effects on Local Nitric Oxide Formation and Its Relation to Epithelial Functions

To evaluate the effect of esophageal acid exposure on epithelial function, transmucosal potential, histopathological markers of acute tissue damage, and local nitric oxide production were examined in healthy volunteers treated with proton pump inhibitors (group I), patients with treated reflux disease (group II), and patients with untreated erosive reflux disease (group III). The participants were randomized to esophageal perfusion with either saline or HCl. Denominators of acute acid exposure were balloon cells in superficial layers and superficial densification. The nitric oxide concentrations in groups I to III increased from < 1, 10.0± 10.0, and 20.6± 19.9 ppb, respectively, to 300± 80, 1360± 1080, and 920± 700 ppb after HCl infusion (P < 0.001). Inducible nitric oxide synthase was consistently expressed in the epithelium. Blood flow was lower among reflux patients but did not correlate with acid exposure or nitric oxide. Nitric oxide is formed following acid perfusion and predominantly in gastroesophageal reflux disease.