| 1. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 2. |
- Spak, Emma, 1977, et al.
(författare)
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Angiotensin II receptor expression following intestinal transplantation in mice.
- 2006
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 0022-4804. ; 135:1, s. 144-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To further improve the success rate of intestinal transplantation there is a need to find early appearing indicators of rejection. The specific aim of this study was to compare Angiotensin (Ang) II type 1 receptor and Ang II type 2 receptor expression in relation to histological signs of rejection. METHODS: Mice of the C57BL6 strain with syngeneic intestinal grafts were compared to mice subjected to allogeneic intestinal transplantation with BalbC strain as donors. Local expression of Ang II type 1 and 2 receptor was evaluated using rt-PCR and Western blot and compared to histological picture in grafts and native intestine. RESULTS: The Ang II type 2 receptor protein expression was markedly up-regulated in the allogeneically transplanted graft from day 1 postoperatively. Histological signs of rejection were not seen until day 6. CONCLUSION: Intestinal allograft transplantation in mice is associated with a marked up-regulation of the Ang II type 2 receptor. However, the detailed role of the renin-angiotensin system in the immune rejection following intestinal transplantation remains to be clarified.
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| 3. |
- Agreus, Lars, et al.
(författare)
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Towards a healthy stomach? : Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community
- 2016
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Ingår i: United European Gastroenterology journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 4:5, s. 686-696
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Tidskriftsartikel (refereegranskat)abstract
- Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden.Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n=145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status.Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p=0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p=0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were 57 years old.Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.
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| 4. |
- Aro, Pertti, et al.
(författare)
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Use of tobacco products and gastrointestinal morbidity : an endoscopic population-based study (the Kalixanda study)
- 2010
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 25:10, s. 741-750
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Tidskriftsartikel (refereegranskat)abstract
- The impact of snus (smokeless tobacco or snuff) on gastrointestinal symptoms and pathological findings is largely unknown. The authors aimed to investigate whether the exposure to different forms of tobacco influences upper gastrointestinal symptoms, histology and frequency of Helicobacter pylori infection. A random sample (n = 2,860) of the adult population of two northern Swedish municipalities Kalix and Haparanda (n = 21,610) was surveyed between December 1998 and June 2001 using a validated postal questionnaire assessing gastrointestinal symptoms (response rate 74.2%, n = 2,122) (The Kalixanda Study). A random sub-sample (n = 1,001) of the responders was invited to undergo an esophagogastroduodenoscopy (participation rate 73.3%) including biopsies, Helicobacter pylori culture and serology and symptom assessment and exploration of present and past use of tobacco products. No symptom groups were associated with snus use. Snus users had a significantly higher prevalence of macroscopic esophagitis univariately but snus use was not associated with esophagitis in multivariate analysis. Snus use was associated with basal cell hyperplasia (OR = 1.74, 95% CI: 1.02, 3.00) and with elongation of papillae (OR = 1.79, 95% CI: 1.05-3.05) of the squamous epithelium at the esophago-gastric junction. Current smoking cigarettes was associated with overall peptic ulcer disease (OR = 2.32, 95% CI: 1.04, 5.19) whereas snus use was not. There were no significant association between current Helicobacter pylori infection and different tobacco product user groups. Snus significantly alters the histology of the distal esophagus but does not impact on gastrointestinal symptoms or peptic ulcer disease.
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| 5. |
- Baldaque-Silva, Francisco, et al.
(författare)
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Endoscopic assessment and grading of Barrett's esophagus using magnification endoscopy and narrow band imaging: Impact of structured learning and experience on the accuracy of the Amsterdam classification system
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:2, s. 160-167
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Several classification systems have been launched to characterize Barrett's esophagus (BE) mucosa using magnification endoscopy with narrow band imaging (ME-NBI). The good accuracy and interobserver agreement described in the early reports were not reproduced subsequently. Recently, we reported somewhat higher accuracy of the classification developed by the Amsterdam group. The critical question then formulated was whether a structured learning program and the level of experience would affect the clinical usefulness of this classification. Material & methods: Two hundred and nine videos were prospectively captured from patients with BE using ME-NBI. From these, 70 were randomly selected and evaluated by six endoscopists with different levels of expertise, using a dedicated software application. First, an educational set was studied. Thereafter, the 70 test videos were evaluated. After classification of each video, the respective histological feedback was automatically given. Results. Within the learning process, there was a decrease in the time needed for evaluation and an increase in the certainty of prediction. The accuracy did not increase with the learning process. The sensitivity for detection of intestinal metaplasia ranged between 39% and 57%, and for neoplasia between 62% and 90%, irrespective of assessor's expertise. The kappa coefficient for the interobserver agreement ranged from 0.25 to 0.30 for intestinal metaplasia, and from 0.39 to 0.48 for neoplasia. Conclusion: Using a dedicated learning program, the ME-NBI Amsterdam classification system is suboptimal in terms of accuracy and inter- and intraobserver agreements. These results reiterate the questionable utility of corresponding classification system in clinical routine practice.
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| 6. |
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| 7. |
- Bokhorst, John-Melle, et al.
(författare)
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Deep learning for multi-class semantic segmentation enables colorectal cancer detection and classification in digital pathology images
- 2023
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- In colorectal cancer (CRC), artificial intelligence (AI) can alleviate the laborious task of characterization and reporting on resected biopsies, including polyps, the numbers of which are increasing as a result of CRC population screening programs ongoing in many countries all around the globe. Here, we present an approach to address two major challenges in the automated assessment of CRC histopathology whole-slide images. We present an AI-based method to segment multiple (n=14 ) tissue compartments in the H &E-stained whole-slide image, which provides a different, more perceptible picture of tissue morphology and composition. We test and compare a panel of state-of-the-art loss functions available for segmentation models, and provide indications about their use in histopathology image segmentation, based on the analysis of (a) a multi-centric cohort of CRC cases from five medical centers in the Netherlands and Germany, and (b) two publicly available datasets on segmentation in CRC. We used the best performing AI model as the basis for a computer-aided diagnosis system that classifies colon biopsies into four main categories that are relevant pathologically. We report the performance of this system on an independent cohort of more than 1000 patients. The results show that with a good segmentation network as a base, a tool can be developed which can support pathologists in the risk stratification of colorectal cancer patients, among other possible uses. We have made the segmentation model available for research use on .
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| 8. |
- Bokhorst, John-Melle, et al.
(författare)
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Fully Automated Tumor Bud Assessment in Hematoxylin and Eosin-Stained Whole Slide Images of Colorectal Cancer
- 2023
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Ingår i: Modern Pathology. - : ELSEVIER SCIENCE INC. - 0893-3952 .- 1530-0285. ; 36:9
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Tidskriftsartikel (refereegranskat)abstract
- Tumor budding (TB), the presence of single cells or small clusters of up to 4 tumor cells at the invasive front of colorectal cancer (CRC), is a proven risk factor for adverse outcomes. International definitions are necessary to reduce interobserver variability. According to the current international guidelines, hotspots at the invasive front should be counted in hematoxylin and eosin (H & E)-stained slides. This is time-consuming and prone to interobserver variability; therefore, there is a need for computer-aided diagnosis solutions. In this study, we report an artificial intelligence-based method for detecting TB in H & E-stained whole slide images. We propose a fully automated pipeline to identify the tumor border, detect tumor buds, characterize them based on the number of tumor cells, and produce a TB density map to identify the TB hotspot. The method outputs the TB count in the hotspot as a computational biomarker. We show that the proposed automated TB detection workflow performs on par with a panel of 5 pathologists at detecting tumor buds and that the hotspot-based TB count is an independent prognosticator in both the univariate and the multivariate analysis, validated on a cohort of n 1/4 981 patients with CRC. Computer-aided detection of tumor buds based on deep learning can perform on par with expert pathologists for the detection and quantification of tumor buds in H & E-stained CRC histopathology slides, strongly facilitating the introduction of budding as an independent prognosticator in clinical routine and clinical trials. & COPY; 2023 THE AUTHORS. Published by Elsevier Inc. on behalf of the United States & Canadian Academy of Pathology. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).
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| 9. |
- Bokhorst, John-Melle, et al.
(författare)
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Semi-Supervised Learning to Automate Tumor Bud Detection in Cytokeratin-Stained Whole-Slide Images of Colorectal Cancer
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- Tumor budding is a histopathological biomarker associated with metastases and adverse survival outcomes in colorectal carcinoma (CRC) patients. It is characterized by the presence of single tumor cells or small clusters of cells within the tumor or at the tumor-invasion front. In order to obtain a tumor budding score for a patient, the region with the highest tumor bud density must first be visually identified by a pathologist, after which buds will be counted in the chosen hotspot field. The automation of this process will expectedly increase efficiency and reproducibility. Here, we present a deep learning convolutional neural network model that automates the above procedure. For model training, we used a semi-supervised learning method, to maximize the detection performance despite the limited amount of labeled training data. The model was tested on an independent dataset in which human- and machine-selected hotspots were mapped in relation to each other and manual and machine detected tumor bud numbers in the manually selected fields were compared. We report the results of the proposed method in comparison with visual assessment by pathologists. We show that the automated tumor bud count achieves a prognostic value comparable with visual estimation, while based on an objective and reproducible quantification. We also explore novel metrics to quantify buds such as density and dispersion and report their prognostic value. We have made the model available for research use on the grand-challenge platform.
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| 10. |
- Elfvin, Anders, 1971, et al.
(författare)
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Helicobacter pylori induces gastritis and intestinal metaplasia but no gastric adenocarcinoma in Mongolian gerbils.
- 2005
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 40:11, s. 1313-20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The Mongolian gerbil is considered as the model of choice when studying adenocarcinoma related to Helicobacter pylori infection. The purpose of this study was to compare two different H. pylori strains and elucidate whether adenocarcinomas developed in gerbils. MATERIAL AND METHODS: Male gerbils were separated into three groups: one control and two groups infected with two different strains of H. pylori, TN2GF4 and SS1. At 3, 6, 12 or 18 months after inoculation 5 animals from each group were sacrificed. The stomach was used for culture, and for histology. RESULTS: Inflammation was seen after 3 months in all the infected animals. In the controls no pathology was found at any time. Intestinal metaplasia was found in both the infected groups. Glands buried in the submucusal layer, changes that might be misinterpreted as adenocarcinoma, were found in 10% of the SS1 and in 65% of the TN2GF4 animals. Adenocarcinoma was not found in any of the gerbils. CONCLUSIONS: All studies claiming to have found H. pylori-induced adenocarcinomas in gerbils describe atypical glands penetrating into the muscularis propria and interpret these as invasive growths due to cancer. An alternative interpretation is that the deranged glandular structures grow in and below the submucosa. It is suggested that atypical glands in the muscularis layer are not enough as a diagnostic criterion for gastric adenocarcinoma. It is concluded that adenocarcinoma has not yet been shown convincingly to develop in Mongolian gerbils infected with H. pylori. Nevertheless, it is a model well suited for studying gastritis, gastric ulcer and premalignant changes such as metaplasia.
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| 11. |
- Fiehn, Anne-Marie Kanstrup, et al.
(författare)
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Distribution of histopathological features along the colon in microscopic colitis
- 2021
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 36, s. 151-159
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The diagnosis microscopic colitis (MC) consisting of collagenous colitis (CC) and lymphocytic colitis (LC) relies on histological assessment of mucosal biopsies from the colon. The optimal biopsy strategy for reliable diagnosis of MC is controversial. The aim of this study was to evaluate the distribution of histopathological features of MC throughout the colon. Methods Mucosal biopsies from multiple colonic segments of patients with MC who participated in one of the three prospective European multicenter trials were analyzed. Histological slides were stained with hematoxylin-and-eosin, a connective tissue stain, and CD3 in selected cases. Results In total, 255 patients were included, 199 and 56 patients with CC and LC, respectively. Both groups exhibited a gradient with more pronounced inflammation in the lamina propria in the proximal colon compared with the distal colon. Similarly, the thickness of the subepithelial collagenous band in CC showed a gradient with higher values in the proximal colon. The mean number of intraepithelial lymphocytes was > 20 in all colonic segments in patients within both subgroups. Biopsies from 86 to 94% of individual segments were diagnostic, rectum excluded. Biopsies from non-diagnostic segments often showed features of another subgroup of MC. Conclusion Conclusively, although the severity of the histological changes in MC differed in the colonic mucosa, the minimum criteria required for the diagnosis were present in the random biopsies from the majority of segments. Thus, our findings show MC to be a pancolitis, rectum excluded, questioning previously proclaimed patchiness throughout the colon.
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| 12. |
- Haddad, Tariq Sami, et al.
(författare)
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Improving tumor budding reporting in colorectal cancer: a Delphi consensus study
- 2021
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Ingår i: Virchows Archiv. - : SPRINGER. - 0945-6317 .- 1432-2307. ; 479:3, s. 459-469
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Tidskriftsartikel (refereegranskat)abstract
- Tumor budding is a long-established independent adverse prognostic marker in colorectal cancer, yet methods for its assessment have varied widely. In an effort to standardize its reporting, a group of experts met in Bern, Switzerland, in 2016 to reach consensus on a single, international, evidence-based method for tumor budding assessment and reporting (International Tumor Budding Consensus Conference [ITBCC]). Tumor budding assessment using the ITBCC criteria has been validated in large cohorts of cancer patients and incorporated into several international colorectal cancer pathology and clinical guidelines. With the wider reporting of tumor budding, new issues have emerged that require further clarification. To better inform researchers and health-care professionals on these issues, an international group of experts in gastrointestinal pathology participated in a modified Delphi process to generate consensus and highlight areas requiring further research. This effort serves to re-affirm the importance of tumor budding in colorectal cancer and support its continued use in routine clinical practice.
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| 13. |
- Hansdotter, Ida, et al.
(författare)
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Hill classification is superior to the axial length of a hiatal hernia for assessment of the mechanical anti-reflux barrier at the gastroesophageal junction
- 2016
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Ingår i: Endoscopy International Open. - : Georg Thieme Verlag KG. - 2364-3722 .- 2196-9736. ; 4:3, s. E311-E317
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Tidskriftsartikel (refereegranskat)abstract
- Background and study aims: The pathogenesis of gastroesophageal reflux disease (GERD) is multifactorial, including the mechanical anti-reflux barrier of the gastroesophageal junction. This barrier can be evaluated endoscopically in two ways: by measuring the axial length of any hiatal hernia present or by assessing the gastroesophageal flap valve. The endoscopic measurement of axial length is troublesome because of the physiological dynamics in the area. Grading the gastroesophageal flap valve is easier and has proven reproducible. The aim of the present study was to compare the two endoscopic grading methods with regard to associations with GERD. Patients and methods: Population-based subjects underwent endoscopic examination assessing the axial length of hiatus hernia, the gastroesophageal flap valve using the Hill classification, esophagitis using the Los Angeles (LA) classification, and columnar metaplasia using the Z-line appearance (ZAP) classification. Biopsies were taken from the squamocolumnar junction to assess the presence of intestinal metaplasia. Symptoms were recorded with the validated Abdominal Symptom Questionnaire. GERD was defined according to the Montreal definition. Results: In total, 334 subjects were included in the study and underwent endoscopy; 86 subjects suffered from GERD and 211 presented no symptoms or signs of GERD. Based on logistic regression, the estimated area under the curve statistic (AUC) for Hill (0.65 [95 % CI 0.59-0.72]) was higher than the corresponding estimate for the axial length of a hiatal hernia (0.61 [95 % CI 0.54-0.68]), although the difference was not statistically significant (P=0.225). Conclusion: From our data, and in terms of association with GERD, the Hill classification was slightly stronger compared to the axial length of a hiatal hernia, but we could not verify that the Hill classification was superior as a predictor. The Hill classification may replace the axial length of a hiatal hernia in the endoscopic assessment of the mechanical anti-reflux barrier of the gastroesophageal junction.
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| 14. |
- Irani, Mudar Zand, et al.
(författare)
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Neutrophils, eosinophils, and intraepithelial lymphocytes in the squamous esophagus in subjects with and without gastroesophageal reflux symptoms
- 2021
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Ingår i: Human Pathology. - : Elsevier BV. - 0046-8177 .- 1532-8392. ; 115, s. 112-122
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Tidskriftsartikel (refereegranskat)abstract
- Whilst intraepithelial lymphocytes (IELs) are considered normal within the distal esophageal mucosa, they have an increasingly recognised role in the pathogenesis of reflux esophagitis, and IEL quantification establishes the diagnosis of lymphocytic esophagitis. Knowledge regarding the upper limit of a normal IEL count in health is lacking. We studied 117 non-healthcare seeking adult volunteers from a random community sample (the Kalixanda study) with esophageal biopsies 2 cm above the gastroesophageal junction. Subjects were divided into four groups based on the presence or absence of gastro-esophageal reflux symptoms and/or esophagitis on endoscopy. Asymptomatic subjects with no endoscopic esophagitis were selected as controls, and the cell counts in this group were used to define the upper limit of normal of IELs, eosinophils and neutrophils. The entire sample was used to identify independent predictors of increased cellular counts by logistic regression analysis. None of the healthy controls had an IEL count of more than three per five high power fields (HPF), and therefore this was considered as the upper limit of normal; no controls had eosinophils or neutrophils in esophageal biopsies. Independent predictors of an elevated IEL count were spongiosis on histology (OR 11.17, 95% CI 3.32–37.58, P < 0.01) and current smoking (OR 4.84, 95% CI 1.13–2.71, P = 0.03). A receiver operating characteristics analysis concluded that a threshold of 3 IELs/5HPFs performs best in predicting reflux symptoms when a normal esophageal mucosa is visualized on endoscopy (sensitivity = 100.0%, specificity = 35.2%). The healthy esophageal mucosa does not contain more than three IELs per five HPF in the distal esophagus.
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| 15. |
- Koch, Raphael, et al.
(författare)
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Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial
- 2023
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 29:24, s. 5057-5068
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The phase III, open-label, prospective, multicenter, randomized Ewing 2008R1 trial (EudraCT2008-003658-13) was conducted in 12 countries to evaluate the effect of zoledronic acid (ZOL) maintenance therapy compared with no add-on regarding event-free survival (EFS, primary endpoint) and overall survival (OS) in standard-risk Ewing sarcoma (EWS). PATIENTS AND METHODS: Eligible patients had localized EWS with either good histologic response to induction chemotherapy and/or small tumors (<200 mL). Patients received six cycles of VIDE induction and eight cycles of VAI (male) or eight cycles of VAC (female) consolidation. ZOL treatment started parallel to the sixth consolidation cycle. Randomization was stratified by tumor site (pelvis/other). The two-sided adaptive inverse-normal four-stage design (planned sample size 448 patients, significance level 5%, power 80%) was changed after the first interim analysis using the Müller-Schäfer method. RESULTS: Between April 2010 and November 2018, 284 patients were randomized (142 ZOL/142 no add-on). With a median follow-up of 3.9 years, EFS was not significantly different between ZOL and no add-on group in the adaptive design (HR, 0.74; 95% CI, 0.43-1.28, P = 0.27, intention-to-treat). Three-year EFS rates were 84.0% (95% CI, 77.7%-90.8%) for ZOL vs. 81.7% (95% CI, 75.2%-88.8%) for no add-on. Results were similar in the per-protocol collective. OS was not different between groups. The 3-year OS was 92.8% (95% CI, 88.4%-97.5%) for ZOL and 94.6% (95% CI, 90.9%-98.6%) for no add-on. Noticeable more renal, neurologic, and gastrointestinal toxicities were observed for ZOL (P < 0.05). Severe renal toxicities occurred more often in the ZOL arm (P = 0.003). CONCLUSIONS: In patients with standard-risk localized EWS, there is no additional benefit from maintenance treatment with ZOL.
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| 16. |
- Ludvigsson, Jonas F., et al.
(författare)
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Celiac disease, eosinophilic esophagitis and gastroesophageal reflux disease, an adult population-based study
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 48:7, s. 808-814
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Celiac disease (CD) has been linked to gastroesophageal reflux disease (GORD) and eosinophilic esophagitis (EoE), but population-based studies of the prevalence of CD in these conditions are lacking, that is, the aim of this study. Materials and methods. An endoscopic study was carried out in 1000 randomly selected adults from the general population. CD was defined on the basis of positive serology in parallel with mucosal abnormalities of the small intestine. Any eosinophil infiltration of the esophageal epithelium was defined as esophageal eosinophilia and EoE was defined as having at least 15 eosinophils/high-power field in biopsies from the distal esophagus. We used Fisher's exact test to compare the prevalence of GORD, esophageal eosinophilia, and EoE in subjects with CD versus controls. Results. Four hundred subjects (40%) had gastroesophageal reflux symptoms (GORS), 155 (15.5%) had erosive esophagitis, 16 (1.6%) had Barrett's esophagus, 48 (4.8%) had esophageal eosinophilia, and 11 (1.1%) had EoE. CD was diagnosed in 8/400 (2.0%) individuals with GORS (vs. controls: 10/600 (1.7%), p = 0.81), in 3/155 (1.9%) with erosive esophagitis (vs. 15/845 controls (1.8%), p = 0.75), and in 2/48 (4.2%) individuals with esophageal eosinophilia (controls: 16/952 (1.7%), p = 0.21), but in none of those 16 with Barrett's esophagus (vs. 18/984 controls (1.8%), p = 1.0) or of the 11 individuals with EoE (controls: 18/989 (1.8%), p = 1.0). Conclusions. This population-based study found no increased risk of CD among individuals with GORD, esophageal eosinophilia, or EoE. CD screening of individuals with GORD or EoE of individuals with CD cannot be recommended.
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| 17. |
- Ndegwa, Nelson, et al.
(författare)
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Gastric Microbiota in a Low-Helicobacter pylori Prevalence General Population and Their Associations With Gastric Lesions
- 2020
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Ingår i: Clinical and Translational Gastroenterology. - : LIPPINCOTT WILLIAMS & WILKINS. - 2155-384X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION:Non-Helicobacter pylori microbiota might account for some cases with unexplained chronic gastritis that may in a minority eventually progress to gastric cancer through the Correa cascade. We characterized gastric microbiota by describing the normal stomach, compared it with early precancerous lesions and other disease states, and assessed whether H. pylori status affects bacterial diversity.METHODS:In a population-based study of those with and without gastrointestinal symptoms, cytology brush samples were collected during endoscopy from 316 individuals. Mucosal status was classified as normal mucosa (171), nonatrophic H. pylori gastritis (33), atrophic gastritis (12), or antral chemical gastritis (61). The 16S rRNA gene sequencing and analysis were performed to characterize the microbiota.RESULTS:Microbiota in atrophic gastritis and nonatrophic H. pylori gastritis stomachs were dysbiotic and differed from those in the normal stomach (P = 0.001). The normal stomach had the highest microbial diversity, followed by antral chemical gastritis. The atrophic gastritis and chronic H. pylori gastritis groups had the lowest diversity, a difference that was statistically significant (P = 0.01). Besides H. pylori, non-H. pylori bacteria accounted for group differences. Microbial network analysis showed that the normal group network was most highly connected, whereas the H. pylori gastritis group had the lowest connection. We found an increasing positive co-occurrence of oral bacteria in the stomach because samples deviated from the normal network, some of which were pathogens. The H. pylori-negative group had the highest microbial diversity (Shannon index) compared with the H. pylori-positive group (P = 0.001).DISCUSSION:In this low-H. pylori prevalence general population, the gastric mucosal microbiota of the normal stomach differed significantly from those with nonatrophic or atrophic gastritis. There was an increasing abundance of pathogenic bacteria from the normal state to early precancerous states.
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| 18. |
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| 19. |
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| 20. |
- Spak, Emma, 1977, et al.
(författare)
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Changes in the mucosa of the Roux-limb after gastric bypass surgery.
- 2010
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Ingår i: Histopathology. - : Wiley. - 1365-2559 .- 0309-0167. ; 57:5, s. 680-8
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Roux-en-Y gastric bypass surgery is the most efficient treatment of morbid obesity, but the mechanisms of action are still poorly understood. The aim of this study was to explore the Roux-limb mucosa after gastric bypass surgery, focusing upon basic morphology and inflammation. METHODS AND RESULTS: Jejunal mucosal samples from the Roux-limb were gathered from eight patients at time of surgery and 6-8 months postsurgery. Histological evaluation of inflammation and morphometric investigations were performed, cell proliferation was assessed using immunohistochemistry and inflammatory markers and angiotensin (Ang) II receptors were detected using Western blot. Cell proliferation increased and villous surface area decreased in the Roux-limb mucosa but no signs of active inflammation were observed after surgery. Protein analyses showed increased levels of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, myeloperoxidase (MPO) and the Ang II type 1(AT(1)) receptor after surgery, whereas the levels of inducible nitric oxide synthase (iNOS), nitrotyrosine and the Ang II type 2(AT(2)) receptor remained constant. CONCLUSION: These results indicate that the phenotype of the jejunal mucosa changes once exposed to undigested food and the increased microbial load in the Roux-limb after surgery.
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| 21. |
- Wallner, Bengt, 1962-, et al.
(författare)
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Z-line alterations and gastroesophageal reflux : an endoscopic population-based prospective cohort study
- 2019
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Ingår i: Scandinavian Journal of Gastroenterology. - : TAYLOR & FRANCIS LTD. - 0036-5521 .- 1502-7708. ; 54:9, s. 1065-1069
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Tidskriftsartikel (refereegranskat)abstract
- Background and study aims: Barrett's esophagus is a premalignant condition in the distal esophagus associated with esophageal adenocarcinoma. Since gastroesophageal reflux is known to be of etiological importance in both Barrett's esophagus and esophageal adenocarcinoma, we aimed to study which endoscopic alterations at the Z-line can be attributed to a previous history of reflux symptoms. Patients and methods: From 1988, a population cohort in Sweden has been prospectively studied regarding gastrointestinal symptoms, using a validated questionnaire. In 2012, the population was invited to undergo a gastroscopy and participate in the present study. In order to determine which endoscopic alterations that can be attributed to a previous history of gastroesophageal reflux, three different endoscopic definitions of columnar-lined esophagus (CLE) were used: (1) ZAP I, An irregular Z-line with a suspicion of tongue-like protrusions; (2) ZAP II/III, Distinct, obvious tongues of metaplastic columnar epithelium; (3) CLE >= 1 cm, The Prague C/M-classification with a minimum length of 1 cm. Results: A total of 165 community subjects were included in the study. Of these, 40 had CLE >= 1 cm, 99 had ZAP I, and 26 had ZAP II/III. ZAP II/III was associated with an over threefold risk of previous GER symptoms (OR: 3.60, CI: 1.49-8.70). No association was found between gastroesophageal reflux and ZAP I (OR: 2.06, CI: 0.85-5.00), or CLE >= 1 cm (OR: 1.64, CI: 0.77-3.49). Conclusions: In a general community, the only endoscopic alteration to the Z-line definitely linked to longstanding GER symptoms was the presence of obvious tongues of metaplastic columnar epithelium (ZAP II/III).
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| 22. |
- Zuzek, Rachael, et al.
(författare)
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Prevalence of Histological Gastritis in a Community Population and Association with Epigastric Pain
- 2024
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Ingår i: Digestive Diseases and Sciences. - 0163-2116 .- 1573-2568. ; 69, s. 528-537
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Gastritis is a common histological diagnosis, although the prevalence is decreasing in developed populations, alongside decreasing prevalence of H. pylori infection. We sought to determine the prevalence of the etiology of gastritis in a Swedish population sample and to analyze any associations with symptoms, an area of clinical uncertainty. Methods Longitudinal population-based study based in osthammar, Sweden. A randomly sampled adult population completed a validated gastrointestinal symptom questionnaire (Abdominal Symptom Questionnaire, ASQ) in 2011 (N = 1175). Participants < 80 years of age and who were eligible were invited to undergo esophagogastroduodenoscopy (EGD) (N = 947); 402 accepted and 368 underwent EGD with antral and body biopsies (average 54.1 years, range 20-79 years; 47.8% male) with H. pylori serology. Results Gastritis was found in 40.2% (148/368; 95% CI 35.2-45.2%). By rank, the most common histological subtype was reactive (68/148; 45.9%), then H. pylori (44/148; 29.7%), chronic non-H. pylori (29/148; 19.6%), and autoimmune (4/148; 2.7%). Gastritis was significantly associated with older age and H. pylori status (p < 0.01). Gastritis subjects were divided into three histological categories: chronic inactive inflammation, autoimmune gastritis, and active inflammation; there was no difference in the presence of upper gastrointestinal symptoms when categories were compared to cases with no pathological changes. Functional dyspepsia or gastroesophageal reflux were reported in 25.7% (38/148) of those with gastritis (any type or location) versus 34.1% (75/220) with no pathological changes (p = 0.32). Epigastric pain was more common in chronic H. pylori negative gastritis in the gastric body (OR = 3.22, 95% CI 1.08-9.62). Conclusion Gastritis is common in the population with a prevalence of 40% and is usually asymptomatic. Chronic body gastritis may be associated with epigastric pain, but independent validation is required to confirm these findings. Clinicians should not generally ascribe symptoms to histological gastritis.
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