Eosinophilic esophagitis prevalence, incidence, and presenting features: a 22-year population-based observational study from southwest Sweden.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus that affects both children and adults. Symptoms in adults are mainly esophageal dysphagia, which ranges from mild symptoms to acute food bolus obstruction of the esophagus. Diagnosis is defined as symptoms of esophageal dysfunction and ≥ 15 eosinophils/high power field (HPF) in at least one of the biopsies taken from the esophagus. EoE appears to be increasing in both prevalence and incidence. The aim of this study was to investigate the prevalence, incidence, and presenting symptoms of patients with EoE within the catchment area of Northern Älvsborg County Hospital in Trollhättan. Patient records with the ICD code of EoE between 2012 and 2022 and pathology reports from esophageal biopsies from 2000-2022 were examined. Patients with symptoms of esophageal dysfunction and > 15 eosinophils/HPF were classified as having EoE. In total, 409 EoE patients (379 adults and 30 children) fulfilled the diagnostic criteria during the follow-up period. The overall prevalence was 113 cases/100 000 inhabitants (adults 127/100 000 and children 57/100 000) at 31 December 2022. The incidence was 7/100 000 and increased during the observation period. At diagnosis, 46% of the adults and 11% of the children had a history of acute bolus obstruction requiring hospitalization, while 51% of adults and 22% of children exhibited endoscopic findings of fibrosis. The prevalence of EoE is significantly higher than that generally reported in an area of southwest Sweden. The results indicate that the incidence is increasing; however, whether this is due to an actual increase or heightened awareness of EoE is inconclusive. Acute bolus obstruction is a common presenting symptom among EoE patients and is most likely an effect of late diagnosis.

Validation of instruments for the assessment of dysphagia due to malignancy of the esophagus.

The aim of the study was to validate the Watson scale, the Ogilvie scale, and the Goldschmid scale for assessment of dysphagia due to malignancy of the esophagus. After translation of the scales to Swedish, 35 patients with dysphagia due to esophageal malignancy were asked to participate. On day 1, patients were asked to fill in the questionnaires. The patients also kept a food diary for 4 consecutive days, for assessment of actual swallowing ability. On day 10, the patients were asked to fill in the scales again, to control for individual variability. As an external control group, 29 healthy volunteers were asked to fill in the questionnaires once. External validation was done against actual swallowing ability, and against the European Organization for Research and Treatment of Cancer scales QLQ-C30 and QLQ-OG25, which are already validated quality of life scales for malignancy. Reliability in the categorical variables (Ogilvie and Goldschmid) showed weighted kappa values of 0.52 and 0.54, respectively. For the Watson scale and the Dysphagia module of QLQ-OG25, the intraclass correlation coefficients were 0.68 and 0.80, respectively. Correlations between all scales were good to excellent with values of correlation coefficients (rs) between 0.69 and 0.88, with the strongest correlations between the Ogilvie score and the dysphagia module in QLQ-OG25. These latter two scales had the strongest correlation to the food diary (rs = 0.72). Although the Ogilvie scale was superior, all the three scales showed good reliability and are thus judged to have good validity for assessment of dysphagia due to esophageal malignancy.

Eosinophils from eosinophilic oesophagitis patients have T cell suppressive capacity and express FOXP3.

Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (Tregs ). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction. In addition, eosinophilic expression of forkhead box protein 3 (FOXP3), the canonical transcription factor of Tregs , was determined by conventional and imaging flow cytometry, quantitative polymerase chain reaction (qPCR), confocal microscopy and immunoblotting. It was found that blood eosinophils from EoE patients had T cell suppressive capacity, and that a fraction of the eosinophils expressed FOXP3. A comparison of EoE eosinophils with healthy control eosinophils indicated that the patients' eosinophils had inferior suppressive capacity. Furthermore, a higher percentage of the EoE eosinophils expressed FOXP3 protein compared with the healthy eosinophils, and they also had higher FOXP3 protein and mRNA levels. FOXP3 was found in the cytosol and nucleus of the eosinophils from both the patients and healthy individuals, contrasting with the strict nuclear localization of FOXP3 in Tregs . To conclude, these findings suggest that the immunoregulatory function of eosinophils may be impaired in EoE.

Differences in eosinophil molecular profiles between children and adults with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) afflicts both children and adults. It has been debated whether pediatric EoE and adult EoE represent different disease entities. The objectives of this study were to determine whether the blood eosinophil molecular pattern of children with EoE is (i) distinct from that of healthy children; and (ii) different from that of adults with EoE. METHODS: Blood eosinophils from children and adults with EoE, and healthy controls, were analyzed with flow cytometry regarding levels of CD23, CD44, CD54, CRTH2, FOXP3, and galectin-10. Eosinophil FOXP3 and galectin-10 mRNA levels were determined by qPCR. The data were analyzed using a multivariate method of pattern recognition. RESULTS: An eosinophil molecular pattern capable of distinguishing children with EoE from control children was identified. A smaller fraction of eosinophils from children with EoE expressed CD44 and a larger fraction expressed CRTH2 than the controls. Eosinophils from children with EoE also had higher levels of galectin-10 mRNA and lower levels of FOXP3 mRNA. The eosinophils from children with EoE had lower levels of surface CD54 and of FOXP3 mRNA compared with the eosinophils from the adult patients. A key finding was the detection in healthy individuals of age-related differences in the levels of several eosinophil markers. CONCLUSIONS: Children with EoE can be distinguished from healthy children based on the molecular patterns of their blood eosinophils. Age-related physiologic differences in eosinophil molecular patterns may partly explain the different blood eosinophil phenotypes in children vs adults with EoE.

Grade of eosinophilia versus symptoms in patients with dysphagia and esophageal eosinophilia.

The aim of this study was to assess whether the symptom severity and health-related quality of life (HRQL) of patients with dysphagia and esophageal eosinophilia correlate with disease activity as expressed by the number of eosinophils in the esophageal mucosa. This study included newly diagnosed (n = 58) or relapsed patients (n = 7), where 40% were diagnosed in connection with esophageal bolus impaction. The mean age was 45 years (19-88), and 74% were men. Symptoms and HRQL were recorded using the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Oesophageal Module 18 and the Short Form-36 Questionnaire. Histological samples gathered from the proximal and distal esophageal mucosa were stained using both hematoxylin and eosin (HE) and an immunohistochemical (IHC) technique against 'Eosinophil Major Basic Protein,' and the peak number of eosinophils per high-power field was assessed. More eosinophils were detected after IHC staining than HE staining (P < 0.001). No correlation was found between symptoms or the HRQL and the number of eosinophils. However, higher numbers of eosinophils at the proximal esophagus were found in patients with concomitant bolus impaction (IHC P < 0.05 and HE P < 0.05) and could serve as a risk marker.

Bacterial flora of the human oral cavity, and the upper and lower esophagus.

This reference study aims to survey the bacterial flora of the healthy lower human esophagus and to compare it with that of the upper esophagus and oral mucosa. The use of biopsies, in addition to brush samples, allows inclusion of not only transient bacteria present on the surface but also bacteria residing in the epithelia, and the yield of the two methods can be compared. Forty patients scheduled for surgery for reasons with no known influence on esophageal flora and with no symptoms or endoscopic signs of esophageal disease were included. Samples were collected from the oral, upper esophageal, and lower esophageal mucosa using sealed brushes and biopsy forceps. Colonies cultivated on agar plates were classified and semiquantified. Twenty-three different bacterial species were identified, with similar strains present at the three sites. The most common group of bacteria was viridans streptococci, with an occurrence rate in brush samples and biopsies of 98% and 95%, respectively. The median number of species occurring in the oral cavity, upper esophagus, and lower esophagus was between 3 and 4 (range 0-7). The total number of species in the oral cavity was significantly higher when compared with either level in the esophagus, while the yields obtained by brush and biopsy sampling were highly correlated. Hence, the normal human esophagus is colonized with a resident bacterial flora of its own, which has similarities to that of the oral mucosa. There are diverse species that make up this flora, although in relatively low amounts. The most frequent inhabitants of the esophagus are streptococci, with an occurrence rate in brush samples and biopsies of 95-98%. Comparative studies of patients with eosinophilic esophagitis and gastroesophageal reflux disease are warranted.

Combined stent insertion and single high-dose brachytherapy in patients with advanced esophageal cancer--results of a prospective safety study.

Previous randomized studies comparing the two commonly used palliative treatments for incurable esophageal cancer, i.e. stent insertion and intraluminal brachytherapy, have revealed the pros and cons of each therapy. While stent treatment offers a more prompt effect, brachytherapy results in more long-lasting relief of dysphagia and a better health-related quality of life (HRQL) in those living longer. This prospective pilot study aimed to explore the feasibility and safety of combining these two regimes and incorporating a single high dose of internal radiation. Patients with newly diagnosed, incurable cancer of the esophagus and dysphagia were eligible for inclusion, and stent insertion followed by a single dose (12 Gy) of brachytherapy was performed as a two-stage procedure. Clinical parameters including HRQL and adverse events were registered at inclusion, and 1, 2, 3, 6, and 12 months later. Twelve patients (nine males) with a median age of 73 years (range 54-85) were included. Stent insertion followed by a single dose of brachytherapy was successfully performed in all but one patient who was treated with stent only. Relief of dysphagia was achieved in the majority of cases (10/11, P < 0.05), but HRQL did not improve except for dysphagia-related items. Only minor adverse events, including chest pain, reflux, and restenosis, were reported. The median survival time after inclusion was 6.6 months. Our conclusion is that the combination of stent insertion and single high-dose brachytherapy seems to be a feasible and safe palliative regime in patients with advanced esophageal cancer. Randomized trials comparing the efficacy of this strategy to stent insertion or brachytherapy alone are warranted.

The pharyngeal mucosa is not involved in eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis is thought to be an isolated oesophageal disease associated with biopsy-verified eosinophilia of the squamous cell epithelium of the oesophagus. Food- or aeroallergens have been suggested to be the cause of eosinophilic oesophagitis; however, as these allergens pass through the pharynx sharing the same squamous cell epithelium, eosinophilic infiltration could be expected also here. Whether this is true or not has hitherto not been clarified. AIM: To find out whether eosinophilia is present also within the pharyngeal epithelium in patients with eosinophilic oesophagitis. METHODS: In all, 10 patients (median age 34, range 15-70) with biopsy-verified eosinophilic oesophagitis [peak count >20 eosinophils per high power field (hpf)] were biopsied also in the pharynx. The biopsies underwent histopathological examination and at each level, the peak number of eosinophils per hpf was counted. RESULTS: None of the patients examined was found to have eosinophilia within the squamous cell epithelium of the pharynx (median peak count 0, range 0-1). CONCLUSIONS: The pronounced eosinophilic infiltration in eosinophilic oesophagitis appears to be an isolated oesophageal phenomenon not shared by the adjoining organ sites and in particular, not by the pharynx. This may have implications for future research.

Factors predicting survival in patients with advanced oesophageal cancer: a prospective multicentre evaluation.

BACKGROUND: Oesophageal cancer is often diagnosed at an advanced stage, with poor prognosis and severe morbidity. In majority of cases, palliative treatment is the only option available. AIM: To find factors that can predict survival for patients with incurable cancer of the oesophagus or gastro-oesophageal junction and hence aid in the choice of treatment. METHODS: Ninety-six patients were included. Health-related quality of life questionnaires (EORTC QLQ C-30 and QLQ OES18) were administered and computerized tomography-derived size assessment of the primary tumours was performed. Univariate and multivariate Cox-regression analyses were used to determine potential predictors of survival. RESULTS: Karnofsky Index, occurrence of metastases (M-stage), Union International Contre le Cancer-stage, computerized tomography-derived tumour size assessment and 10 of 25 scales and single items from the health-related quality of life questionnaires were found to be related to survival. In the multivariate analysis, three of the health-related quality of life questionnaire scales (physical functioning, fatigue and reflux) were found to add prognostic information to M-stage, the single strongest predictor (HR 1.9, P < 0.01). CONCLUSION: In addition to M-stage, the outcome of health-related quality of life questionnaires can sharpen the prediction of survival in patients with advanced cancer of the oesophagus or gastro-oesophageal junction and thus aid in the choice of palliative treatment strategy.

Psychiatric morbidity among patients with cancer of the esophagus or the gastro-esophageal junction: a prospective, longitudinal evaluation.

Cancer of the esophagus is often diagnosed at a late stage and is related to severe morbidity and a low 5-year survival rate. Previous studies have reported low health-related quality of life and high suicide rates for these patients. The occurrence of psychiatric morbidity and thus the potential need for psychological support may vary over time after diagnosis. This has not been adequately studied in patients with newly diagnosed cancer of the esophagus or gastro-esophageal junction. The present study therefore aimed to prospectively evaluate the prevalence of psychiatric morbidity in 94 consecutive patients (median age 66, range 45-88 years) with all stages of disease. Psychiatric morbidity was evaluated with the Hospital Anxiety and Depression Scale (HADS) questionnaire at inclusion and 1, 2, 3, 6 and 12 months later. At inclusion, 42% of the patients had HADS scores indicating possible or probable anxiety disorder and/or depression. At all follow-ups except at 3 months, proportions of patients with possible/probable anxiety disorder were significantly lower than at inclusion. Among patients with a duration of tumor-specific symptoms exceeding 6 months pre-diagnosis, larger proportions of patients with a possible/probable anxiety disorder were found at the 1- and 6-month follow ups. The prevalence of possible/probable depression was greater among patients treated with a palliative intent than among those with a curative intent at inclusion. Patients who died during the study period scored worse for depression compared to the survivors. Apart from this, the proportion of patients with possible/probable psychiatric morbidity (anxiety and/or depression) was relatively stable over time and was unrelated to patient characteristics or clinical background, including the treatment regime. In conclusion, psychiatric morbidity is common among esophageal cancer patients, both at inclusion and over time, regardless of the cancer therapy given. The findings stress the importance of monitoring the patients' mental health and of offering adequate psychological care when needed.

Functional and radiological evaluation of free jejunal transplant reconstructions after radical resection of hypopharyngeal or proximal esophageal cancer.

Cancer of the pharyngoesophageal junction (PEJ) is associated with late onset of symptoms, high morbidity, and a dismal prognosis. Radical surgery with pharyngolaryngectomy and reconstruction with a free vascularized jejunal transplant has been increasingly practiced in the treatment of these patients. This strategy is not devoid of challenges, and the present study is aimed at evaluating the long-term functional outcome among patients who have undergone such surgical treatment. Ten patients (mean age 59 years) with a mean follow-up time of 54 months were included. Clinical assessment, health-related quality of life (HRQL) questionnaires, and a standardized radiography examination were used for evaluation. The Karnofsky index ranged from 60 to 90 (mean 82). Global QL scores (EORTC QLQ-C30) had a mean value of 74, and the mean scores for dysphagia-related items of the EORTC QLQ OES-18 questionnaire were within the lower range. Radiographic signs of disturbed bolus transport through the jejunal transplant were found in all patients examined despite the grading of dysphagia from 0 to 1. The Watson dysphagia score varied between 0.5 and 45.0 (mean 16.2). No correlations were found between radiographic findings and the clinical evaluations or the outcomes assessed by the HRQL questionnaires. HRQL was found to be generally good after cancer of the PEJ and jejunal transplant insertion. Most patients reported mild dysphagia. Radiologic signs of disturbed bolus passage were common, but their clinical impact seemed questionable.

Stent insertion or endoluminal brachytherapy as palliation of patients with advanced cancer of the esophagus and gastroesophageal junction. Results of a randomized, controlled clinical trial.

SUMMARY: Esophageal cancer often presents as advanced stage disease with a dismal prognosis, with only 10-15% of patients surviving 5 years. Therefore, in a large proportion of patients, palliative treatment is the only option available. The aim of this study was to prospectively compare the palliative effect of self-expandable stent placement with that of endoluminal brachytherapy regarding the effect on quality of life and on specific symptoms. Sixty-five patients with advanced cancer of the esophagus or gastroesophageal junction were randomized to treatment with either an Ultraflex expandable stent or high-dose-rate endoluminal brachytherapy with 7 Gy x 3 given in 2-4 weeks. Clinical assessment and health-related quality of life (HRQL) were measured at inclusion and 1, 3, 6, 9 and 12 months later. The HRQL was measured with standardized questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Oesophageal Module and Hospital Anxiety and Depression Scale). Twenty-eight patients completed the stent treatment and 24 patients the brachytherapy. The group of patients treated with stent reported significantly better HRQL scores for dysphagia (P < 0.05) at the 1-month follow-up, but most other HRQL scores, including functioning and symptom scales, deteriorated. Among brachytherapy-treated patients, improvement was found for the dysphagia-related scores at the 3-months follow-up, whereas other significant changes of scores were few. The median survival time was comparable in the two groups (around 120 days). In conclusion, insertion of self-expandable metal stents offered a more instant relief of dysphagia compared to endoluminal brachytherapy, but HRQL was more stable in the brachytherapy group.