Henrik Bergquist

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.

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.

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.

Health economic evaluation of stent or endoluminal brachytherapy as a palliative strategy in patients with incurable cancer of the oesophagus or gastro-oesophageal junction: results of a randomized clinical trial.

Objective To relieve dysphagia is the main goal in palliative treatment of patients with incurable cancer of the oesophagus or the gastro-oesophageal junction. The aim of this prospective, randomized multicentre study was to compare stent placement and brachytherapy regarding health economy and clinical outcomes. Methods Patients with incurable cancer of the oesophagus or gastro-oesophageal junction were randomized to receive a self-expandable metallic stent or 3×7 Gy brachytherapy. At clinical follow-up visits, dysphagia was scored and health care consumptions were recorded. Costs were based on hospital debits. Total lifetime healthcare consumption costs and costs for the initial treatments were calculated and a sensitivity analysis was conducted. Results Thirty patients were randomized to each treatment group. There was no difference in survival or complication rates between the two treatment strategies. There was a significant difference in the change of dysphagia scores between the time of inclusion and the 1-month follow-up visit, in favour of the stented group (P=0.03). This difference had disappeared at 3 months. Median total lifetime costs were &U20AC;17 690 for the stented group compared with &U20AC;33 171 for the brachytherapy group (P=0.005). This difference was due to higher costs for the initial treatment (&U20AC;4615 versus &U20AC;23 857, P<0.0001). Sensitivity analyses showed that the charges for a brachytherapy session had to be reduced from &U20AC;6092 to &U20AC;4222 (31%) to make this therapeutic concept cost-competitive. Conclusion Stenting is currently more cost-effective compared with fractionated 3×7 Gy brachytherapy for patients with incurable cancer of the oesophagus and gastro-oesophageal junction.

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 Incidence of Esophageal Bolus Impaction Is There a Seasonal Variation

Objectives. Eosinophilic esophagitis is a disease associated with dysphagia and has a seasonal variation in incidence. The primary aim of this study was to search for a potential seasonal variation in the incidence of esophageal foreign bodies or food impaction. In addition, after exclusion of structural or accidental causes, the authors sought to explore if such a variation would differ between patients with or without atopic disorders. Study Design. Case series with chart review. Setting. NÄL Medical Centre Hospital, a secondary referral hospital. Subjects and Methods. A total of 314 consecutive cases of esophageal bolus impaction from 2004 through 2009 were included and analyzed regarding seasonal variation in incidence. The analysis was repeated after exclusion of cases with sharp items, cancer, or atresia and again separately after subdividing this group according to presence of atopy. Results. The overall incidence of esophageal bolus impaction was significantly higher during summer and fall than during the corresponding winter and spring period. In cases with atopic disorders and soft foods or meat bolus obstruction (n = 90), the incidence during the fall was significantly higher than that during the winter, and the incidence during the summer and fall was significantly higher than the corresponding incidence during the winter and spring. This variation was not present in patients without any signs or symptoms of atopy. Conclusions. There was a significant seasonal variation in the incidence of acute esophageal bolus impaction. This variation was pronounced in patients with a coexisting atopic diathesis but was nonsignificant in patients without atopy.

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.

Dysphagia and Quality of Life May Improve with Mometasone Treatment in Patients with Eosinophilic Esophagitis A Pilot Study

Objective. The treatment of adult patients with eosinophilic esophagitis remains challenging. The aim was to assess dysphagia and health-related quality of life (HRQL) using validated scales and questionnaires before and after treatment with mometasone furoate. Study Design. Case series with planned data collection. Setting. University hospital and secondary referral hospital. Subjects and Methods. Newly diagnosed patients with eosinophilic esophagitis were included and given 200 µg of orally administered topical mometasone furoate 4 times daily. Questionnaires incorporating the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life–Oesophageal Module 18 (EORTC QLQ-OES18), and the Short Form–36 (SF-36) were completed before the initiation of treatment and after 2 months of treatment. Results. Thirty-one consecutive patients (23 men; mean age, 45 years; range, 18-89 years) completed the trial. At inclusion, the mean scores of the WDS, the EORTC QLQ-OES18 dysphagia scale, the eating scale and choking item, and the global health and social functioning dimensions of the SF-36 were 21.3, 20.4, 35.0, 38.6, 71.1, and 82.3, respectively. Posttreatment, these scores improved to 8.9 (P < .0001), 4.6 (P < .00001), 17.8 (P < .001), 16.0 (P < .01), 76.1 (P < .05), and 91.9 (P = .0001), respectively. Except for 1 case of oral candidiasis, no significant side effects were reported. Conclusion. The dysphagia and impaired HRQL found in untreated patients with eosinophilic esophagitis improved significantly after 2 months of mometasone furoate treatment. A randomized placebo-controlled trial is warranted to assess causality. The scales and questionnaires used are sensitive instruments appropriate for symptom surveillance in individuals with eosinophilic esophagitis.

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.

Functional long-term outcome of a free jejunal transplant reconstruction following chemoradiotherapy and radical resection for hypopharyngeal and proximal oesophageal carcinoma

Background/Aims: To evaluate the functional outcome of a reconstruction by a free vascularized jejunal transplant combined with a voice prosthesis after chemoradiotherapy and surgery for proximal oesophageal or hypopharyngeal cancer. Methods: Seven patients (6 men, mean age 52 years, range 28–70) with squamous cell cancer in the proximal oesophagus (n = 6) or the hypopharynx received preoperative chemoradiotherapy (40.8 Gy, cisplatinum and 5-FU) followed by a circumferential pharyngolaryngectomy and resection of the proximal oesophagus. A single-stage reconstruction was carried out with a free jejunal transplant using a microsurgical technique. A tracheojejunal puncture and insertion of a voice prosthesis (Provox I) was performed after 3 months in suitable cases. Results: All operations had a per- and postoperative uneventful course. Five patients were alive after a mean follow-up time of 5 years and 7 months after surgery (range 3 years 4 months to 7 years 10 months), while 2 patients died from metastases within 2 years after surgery. Postoperative examination showed histopathological down-staging in all cases. Relief of dysphagia was achieved in most cases. Good or average speech was recorded in 3 patients. Conclusion: Reconstruction after radical resection for proximal oesophageal and hypopharyngeal cancer can be carried out with low mortality, acceptable morbidity and a promising functional outcome.