Helicobacter Infection and Gastric Adenoma

Background: We aimed to provide insight into the actual frequencies of gastric adenoma types and their association with gastritis status and associated mucosal changes with a focus on Helicobacter infection and the operative link on gastritis assessment (OLGA)/operative link on gastric intestinal metaplasia assessment (OLGIM) staging. Methods: From the archive of the Institute of Pathology in Bayreuth, we collected a consecutive series of 1058 gastric adenomas diagnosed between 1987 and 2017. Clinicopathological parameters retrieved from diagnostic reports included adenoma type and localization, associated mucosal changes in antrum and corpus (i.e., type of gastritis, the extent of intestinal metaplasia and atrophy), gender, date of birth, and date of diagnosis. Results: Intestinal-type adenoma was the most frequent adenoma (89.1%), followed by foveolar-type adenoma (4.3%), pyloric gland adenoma (3.4%), adenomas associated with hereditary tumor syndromes (2.8%), and oxyntic gland adenoma (0.4%). Adenomas were found in the background of Helicobacter pylori (H. pylori) gastritis in 23.9%, Ex-H. pylori gastritis in 36.0%, autoimmune gastritis in 24.8%, chemical reactive gastritis in 7.4%, and others in 0.1%. More than 70% of patients with gastric adenomas had low-risk stages in OLGA and OLGIM. Conclusions: We found a higher frequency of foveolar-type adenoma than anticipated from the literature. It needs to be questioned whether OLGA/OLGIM staging can be applied to all patients

KRAS, EGFR, PDGFR-α, KIT and COX-2 status in carcinoma showing thymus-like elements (CASTLE)

Background CASTLE (Carcinoma showing thymus-like elements) is a rare malignant neoplasm of the thyroid resembling lymphoepithelioma-like and squamous cell carcinoma of the thymus with different biological behaviour and a better prognosis than anaplastic carcinoma of the thyroid. Methods We retrospectively investigated 6 cases of this very rare neoplasm in order to investigate the mutational status of KRAS, EGFR, PDGFR-α and KIT, as well as the immunohistochemical expression pattern of CD117, EGFR and COX-2, and possibly find new therapeutic targets. Results Diagnosis was confirmed by a moderate to strong expression of CD5, CD117 and CK5/6, whereas thyroglobulin, calcitonin and TTF-1 were negative in all cases. Tumors were also positive for COX-2 and in nearly all cases for EGFR. In four cases single nucleotide polymorphisms (SNPs) could be detected in exon 12 of the PDGFR-α gene (rs1873778), in three cases SNPs were found in exon 20 of the EGFR gene (rs1050171). No mutations were found in the KIT and KRAS gene. Conclusions All tumors showed a COX-2 expression as well as an EGFR expression except for one case and a wild-type KRAS status. No activating mutations in the EGFR, KIT and PDGFR-α gene could be detected. Our data may indicate a potential for targeted therapies, but if these therapeutic strategies are of benefit in CASTLE remains to be determined

Assessing the suitability of formalin-fixed paraffin-embedded (FFPE) tissue for genome-wide association studies (GWAS)

Objective The power of genome-wide association studies (GWAS) to identify common disease variants depends primarily on the number of included samples. The availability of formalin-fixed paraffin-embedded (FFPE) samples in pathology institutes provides a valuable resource for GWAS, but the use of this material poses significant challenges. To explore the suitability of utilizing FFPE tissue for GWAS, we analysed the genotyping concordance between corresponding FFPE and blood samples. We evaluated both microarray technology and low-coverage whole-genome sequencing (lcWGS) to determine whether there were differences between genotyping methods. Results In our concordance study, FFPE tissue showed high recall and precision values across both genotyping methods when compared to matched blood samples for single nucleotide polymorphisms. This demonstrates that FFPE samples are suitable for GWAS and that both methods are viable options for genotyping. However, microarray technology outperformed lcWGS, as evidenced by significantly higher recall ( p  = 0.005) and precision ( p  = 0.003) values. This, together with the lower cost of genotyping and computational efficiency, makes microarray technology currently the superior method for GWAS using FFPE tissue. Nevertheless, lcWGS has shown reliable results and holds the potential to provide more comprehensive and unbiased genetic variant analysis across diverse populations in the future. Our results show that the large number of FFPE samples stored in pathology institutes can significantly increase the power of future GWAS.Open Access funding enabled and organized by Projekt DEAL.Philipps-Universität Marburg (1009

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study.

BACKGROUND & AIMS: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC. RESULTS: Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P = .41). The odds ratio for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P = .18). CONCLUSIONS: In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC

eQTL set-based association analysis identifies novel susceptibility loci for Barrett's esophagus and esophageal adenocarcinoma

Acknowledgements J.Y. Dai and X. Wang were supported by the National Cancer Institute (NCI) grant R01CA222833. M.F. Buas was supported by NCI grant R03CA223731. Computation is in part supported by National Institutes of Health grant S10OD028685 to Fred Hutch Cancer Research Center. A full list of acknowledgments for consortia data used for this study is provided in the Supplementary Data.Peer reviewe

Analysis of failed rotator cuff repair – Retrospective survey of revisions after open rotator cuff repair

Background Rotator cuff defects are frequently occurring shoulder pathologies associated with pain and movement impairment. Aims The aim of the study was to analyse the pathologies that lead to operative revisions after primary open rotator cuff repair. Methods In 216 patients who underwent primary rotator cuff repair and later required operative revision between 1996 to 2005, pathologies found intraoperatively during the primary operation and during revision surgery were collected, analysed and compared. Results The average age at the time of revision surgery was 54.3 years. The right shoulder (61.6 per cent) was more often affected than the left, males (63.4 per cent) more often than females. At primary operation – apart from rotator cuff repair – there were the following surgical procedures performed: 190 acromioplasty, 86 Acromiclavicular joint resections, 68 tenodesis, 40 adhesiolysis and 1 tenotomy. If an ACJ-resection had been performed in the primary operation, ACJ-problems were rare in revision surgery (p<0.01). Primary gleno-humeral adhesions were associated with a significant rise in re-tearing rate (p=0.049). Primary absence of adhesions went along with a significant lower rate of adhesions found at revision (p=0.018). Primary performed acromioplasty had no influence on re-tearing rate (p=0.408) or on the rate of subacromial impingement at revision surgery (p=0.709). Conclusion To avoid operative revision after rotator cuff repair relevant copathologies of the shoulder have to be identified before or during operation and treated accordingly. Therefore, even during open rotator cuff repair, the surgeon should initially start with arthroscopy of the shoulder joint and subacromial space to recognise co-pathologies