Søren Kruse-Andersen

Severe gastroesophageal reflux disease and cow milk hypersensitivity in infants and children: disease association and evaluation of a new challenge procedure.

Background: Gastroesophageal reflux disease (GERD) and cow milk hypersensitivity are frequent disorders of infancy. A possible causative association between these two entities has been suggested. Objective: The primary aim was to elucidate whether a causative relationship between the two entities could be established in a population of infants and children. A secondary aim was to evaluate whether cow milk challenge during esophageal pH monitoring is useful as an objective method to identify this subgroup of patients. Methods: Upper endoscopy followed by a 48-hour esophageal pH monitoring with cow’s milk elimination diet at day 1 and challenge at day 2. Cow milk hypersensitivity was later verified by elimination diet and a second open (in patients <3 years of age) or double-blind placebo-controlled (in patients ≥3 years of age) challenge. Skin prick test, specific serum immunoglobulin E and skin patch test were used as supplementary procedures. Follow-up endoscopy and pH monitoring were performed after 3 months of treatment (omeprazole versus elimination diet dependent on evidence of food hypersensitivity). Results: Eighteen of 42 investigated patients had severe GERD, defined as endoscopic esophagitis and/or a reflux index >10%. Among these patients, a group of 10 patients with GERD and cow milk hypersensitivity was identified. This group had a significantly higher reflux index compared with children with primary GERD. No significant increase was noted in reflux index during simultaneous pH monitoring and milk challenge. Conclusions: An association between GERD and cow milk hypersensitivity was observed in both infants and children with severe GERD. Simultaneous cow milk challenge and pH monitoring had limited value as a method to identify this subgroup.

Eosinophilic oesophagitis in infants and children in the region of southern Denmark: a prospective study of prevalence and clinical presentation.

Objective: Eosinophilic oesophagitis (EE) is a clinical entity characterised by a set of symptoms and eosinophilic infiltration of the oesophageal epithelium. Recent reports indicate that EE is increasingly diagnosed in paediatric patients. We aimed to evaluate the epidemiology of paediatric EE in a European population. Design: Infants and children in the Region of Southern Denmark were prospectively referred for further evaluation of symptoms of gastroesophageal reflux disease (GERD) after treatment failure with a proton pump inhibitor. The evaluation included endoscopy, 24-hour oesophageal pH-metry, histology of oesophageal biopsies, and investigations for food allergy (double-blind, placebo-controlled food challenge, skin prick test, S-IgE antibodies, atopy patch test). Results: Of the 78 referred patients, 28 qualified for a diagnosis of GERD. Six children had >15 eosinophils per high-power field in biopsies from the oesophageal mucosa and qualified for the diagnosis of EE. The median age at diagnosis was 9.6 years. In 4 of the 6 patients, food allergy was confirmed by double-blind, placebo-controlled food challenge. In the Region of Southern Denmark with a paediatric population of 256,164 between 0 and 16 years of age, a yearly incidence of EE of 0.16/10,000 was estimated. Conclusion: We report a European prospective study of EE. It was documented in 6 of 78 patients with symptoms of GERD corresponding to an annual incidence of 0.16/10,000 infants and children.

Gastroesophageal reflux disease and eosinophilic esophagitis in infants and children. A study of esophageal pH, multiple intraluminal impedance and endoscopic ultrasound.

Abstract Objective. Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) in childhood share aspects of symptomatology. In order to characterize EE and GERD in infants and children with symptoms of GERD we performed a prospective investigation including prolonged esophageal pH measurement, multiple intraluminal impedance (MII) and esophageal wall estimation by endoscopic ultrasound (EUS). Material and methods. Infants and children (0–15 years) with typical symptoms of GERD persisting after a 14-days proton pump inhibitor trial were included in a prospective study protocol. Upper endoscopy and EUS of the esophageal wall were performed followed by combined esophageal MII and pH measurement for 24 h. Results. A total of 78 infants and children were investigated: EE patients (n = 6), GERD patients (n = 28) and a group of infants and children with normal investigations (n = 44). The GERD group did not show a significantly higher number of non-acid reflux episodes (p = 0.9) than the patients with normal investigations. In all patients gastroesophageal reflux regularly extended into the proximal esophagus. EUS in four EE patients suggested an increased thickness of the mucosal layers both in the distal and in the proximal part of the esophagus. Conclusions. Esophageal MII indicated that neutral non-acid reflux episodes do not occur frequently in pediatric GERD or in EE. MII and pH-metry indicated that the majority of reflux episodes both in patients and controls pass into the proximal esophagus. EUS measurements suggested in EE patients a thickened mucosa both in the proximal and the distal part of the esophagus as compared to children with GERD and disease controls.

Esophageal Atresia: Gastroesophageal functional follow-up in 5–15 year old children

PURPOSE Esophageal atresia (EA) is one of the most frequent congenital alimentary tract anomalies with a considerable morbidity throughout childhood. This study evaluates the gastroesophageal problems in 5-15 year old children with EA and aims to identify factors predisposing to esophagitis in EA. MATERIAL AND METHODS Fifty-nine patients primarily operated at Odense University Hospital, Denmark, during 1993-2005 were included in this follow-up study. The patients underwent the following examinations: Interview, upper endoscopy, endoscopic ultrasonography, high-resolution esophageal manometry (HREM), and pH- and multichannel intraluminal impedance (MII) measurements. Twenty-five patients with suspected gastro-esophageal reflux disease (GERD) underwent the same investigations and served as controls. RESULTS Median age was 10.2 years (7.1-13.3). Thirty-three (55.9%) presented with GERD symptoms, 41 (69.5%) with dysphagia, and 33 (55.9%) with respiratory symptoms. Twenty-nine (49.2%) had endoscopic esophagitis, and 26 (44.1%) histological esophagitis. Median reflux index (RI) was 8.3 (4.8-14.9). In 32 (55.2%) RI was above 7. Ten percent had eosinophilic inflammation. HREM showed dysmotility in the esophagus in all EA patients, 83.3% had no propagating swallows. No predictive factors predisposing the development of endoscopic esophagitis were identified. CONCLUSIONS Gastroesophageal problems in children born with EA are common. Routine follow-up with endoscopy and pH-metry in EA patients is warranted.

Effect of Cisapride on the Gastro-Oesophageal Function in Normal Human Subjects

The aim of this study was to investigate oesophageal peristalsis and gastro-oesophageal function in normal subjects after 4 days of cisapride 10 mg p.o. 3 times/day and 10 mg 1.5 h before the investigation. The study was carried out in a double-blind cross-over design with coded cisapride or placebo tablets. Basal sphincter pressure increased after cisapride (p less than 0.002). The peristaltic pressure amplitude in the oesophageal body as well as the duration and velocity of the peristaltic pressure wave were measured after wet swallows. No changes were found. Intragastric pH was unchanged after cisapride. No effect was found on the result of a standard acid clearing test. Plasma concentration of cisapride did not correlate with any of the other variables. Oral cisapride increases fasting gastro-oesophageal sphincter pressure, but does not influence oesophageal peristalsis, acid clearing or intragastric pH in normal subjects.

Serum lactate dehydrogenase isoenzyme 1 as a marker of testicular germ cell tumor

Serum lactate dehydrogenase isoenzyme 1 activity was determined repeatedly in 21 men with testicular germ cell tumors in connection with orchiectomy and in 25 without neoplasia who underwent exploration of the testis. The highest level in the men without malignancy was 109 units per 1. and a higher pre-orchiectomy level was found in 15 of the tumor patients: 7 of 11 with seminoma and 8 of 10 with nonseminomatous tumors. In the patients with stage 3 disease serum lactate dehydrogenase isoenzyme 1 was increased more often and the activity was higher than in the stage 1 and 2 cancer patients. Within 1 month after orchiectomy the initially increased level decreased to less than 109 units per 1. in 8 of 10 patients with a stage 1 tumor and it remained higher in 5 with stage 2 or 3 disease. Serum lactate dehydrogenase isoenzyme 1 seems to be a useful marker of testicular germ cell tumor.

The impact of goitre and its treatment on the trachea, airflow, oesophagus and swallowing function. A systematic review

In this systematic review, we investigated the effects of goitre and its treatment on the trachea and the oesophagus. A total of 6355 papers were screened in scientific databases, which disclosed 40 original studies (nine descriptive and 31 interventional). Although most studies are hampered by a number of methodological shortcomings, it is uncontested that goitre affects the trachea as well as the oesophagus in a large proportion of people. This leads to upper airway obstruction, swallowing dysfunction, or both, which may remain undisclosed unless specifically investigated for. Assessment of the tracheal dimensions should be done by magnetic resonance imaging or computed tomography, and detection of upper airway obstruction by flow volume loops, with focus on the inspiratory component. A clinical evaluation of the oesophageal function is difficult to implement and could be replaced by available and validated questionnaires on swallowing. Although radioiodine therapy and thyroidectomy relieve the negative effect of goitre on the trachea and the oesophagus, many issues remain unexplored.

Acid Gastro-Oesophageal Reflux and Oesophageal Pressure Activity during Postprandial and Nocturnal Periods: A Study in Subjects with and without Pathologic Acid Gastro-Oesophageal Reflux

The aim of the investigation was to evaluate the relative quantity of acid gastrooesophageal reflux during different time periods in subjects with and without pathologic reflux. Twenty duodenal ulcer patients, 10 with and 10 without pathologic acid gastro-oesophageal reflux, and 26 asymptomatic volunteers were subjected to 12 h of simultaneous monitoring of pH and pressure activity in the oesophagus. The monitoring period was divided into a 3-h postprandial period, a night period of 6 h, and a 3-h period in the morning. The highest reflux frequency and the longest duration of oesophageal acid exposure were found in the postprandial hours (p less than 0.001). Thereafter, all groups had an even reduction in reflux rate. A greater absolute reduction in the duration of oesophageal acid exposure could be measured in patients with pathologic reflux as compared with the other groups (p less than 0.001). In spite of this, both reflux frequency and time with acid in the oesophagus were increased during the night in patients with pathologic reflux (p less than 0.001). Pathologic refluxers had in total 11 times as much reflux as normal subjects, and in addition 37.9% of the reflux took place during the 6 night hours. In contrast, only 5.4% of the reflux recorded in normal subjects occurred during this period. The pressure activity during periods with a normal intraoesophageal pH was reduced in all three groups during the night (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Long‐term pulmonary function in esophageal atresia—A case‐control study

Esophageal atresia (EA) is a congenital anomaly associated with substantial pulmonary morbidity throughout childhood.

Acid Gastro-Oesophageal Reflux Episodes as Related to the Quality of Preceding Peristalsis: A Study in Normal Subjects

It has earlier been demonstrated after long-term monitoring of pH and peristalsis in the oesophagus that episodes of acid gastro-oesophageal reflux occur in normal volunteers. To determine whether there is a connection between gastro-oesophageal reflux and prior peristalsis, pH and peristalsis were monitored for 12 h in 26 asymptomatic subjects. The recorded peristalsis was divided into brief bursts of peristaltic contractions (less than or equal to 60 sec) and more prolonged continuous activity. Peristaltic periods were limited to prior and subsequent peristalsis by a non-peristaltic course of greater than 30 sec. Continuous peristalsis was defined as a sequence of peristaltic contractions with a mutual distance between individual peristaltic waves of greater than or equal to 30 sec. A total of 81 episodes of reflux were recorded, of which 67 were preceded by peristaltic activity. Brief bursts of peristalsis, unrelated to reflux episodes, were frequently terminated by bolus-transporting peristaltic waves (p less than 0.001). When the last contraction before reflux was considered, an increased frequency of non-propagating peristalsis was found (p less than 0.01). In addition, a closer time relationship was observed between peristalsis and reflux if the last contraction was of the upper segmentary type, as compared with propagating activity (p less than 0.001). In conclusion, reflectory sphincter relaxation producing reflux may possibly be triggered by contractions in the upper part of the oseophagus, not followed by a bolus-transporting peristaltic wave.