Publications by authors named "Michael Vieth"

356 Publications

Interobserver agreement of a gastric adenocarcinoma tumor regression grading system that incorporates assessment of lymph nodes.

Hum Pathol 2021 Jul 17. Epub 2021 Jul 17.

Department of Pathology, Odense University Hospital & Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense C, Denmark.

Perioperative chemotherapy is increasingly used in combination with surgery for the treatment of patients with locally advanced, resectable gastric cancer. Histologic tumor regression grade (TRG) has emerged as an important prognostic factor, however, a common standard for its evaluation is lacking. Moreover, the clinical significance of regressive changes in metastatic lymph nodes (LNs) remains unclear. We conducted an international study to examine the interobserver agreement of a TRG system that incorporates regression grading in LNs. Twenty observers at different levels of experience evaluated the TRG in 60 histologic slides (30 primary tumors and 30 LNs), based on the following criteria: for primary tumors, grade 1 represented complete response (no residual tumor), grade 2 <10%, grade 3 10-50% and grade 4 >50% residual tumor, as described by Becker et al. For LNs, grade "a" represented complete, grade "b" partial and grade "c" no regression. The interobserver agreement was estimated using the Kendall's coefficient of concordance (W). Regarding primary tumors, agreement was good irrespective of level of experience, reaching a W-value of 0.70 overall, 0.71 among subspecialized and 0.71 among non-subspecialized observers. Regarding LNs, interobserver agreement was moderate to good, with W-values of 0.52 overall, 0.64 among subspecialized and 0.45 among non-subspecialized observers. These findings indicate that the combination of the Becker TRG system with a 3-tiered grading of regression in LNs generates a system that is reproducible. Future studies should investigate whether the additional information of TRG in LNs adds to the prognostic value of traditional, primary tumor based, TRG systems.
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http://dx.doi.org/10.1016/j.humpath.2021.07.003DOI Listing
July 2021

Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS).

J Allergy Clin Immunol 2021 Jul 6. Epub 2021 Jul 6.

Inform Diagnostics, Irving, TX, USA; Department of Pathology, Baylor College of Medicine, Houston, TX, USA.

Background: Endpoints used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments.

Objective: To develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE.

Methods: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists.

Results: The COS consists of four outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life (QoL). A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a two-round Delphi process and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, EoE Histology Scoring System, EoE Endoscopic Reference Score, and patient-reported measures of dysphagia and QoL.

Conclusions: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE, which will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
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http://dx.doi.org/10.1016/j.jaci.2021.07.001DOI Listing
July 2021

Targeting of the Tec kinase ITK drives resolution of T cell-mediated colitis and emerges as potential therapeutic option in ulcerative colitis.

Gastroenterology 2021 Jul 3. Epub 2021 Jul 3.

Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany. Electronic address:

Background & Aims: The molecular checkpoints driving T cell activation and cytokine responses in ulcerative colitis are incompletely understood. Here, we studied the Tec kinase ITK in ulcerative colitis.

Methods: We analyzed patients with inflammatory bowel disease (n=223) and evaluated ITK activity as well as the functional effects of Cyclosporine-A (CsA). Moreover, three independent murine colitis models were used to investigate the functional role of ITK. Finally, the activity of ITK was blocked via pharmacological inhibitors and genetically engineered mice. Readout parameters were mini-endoscopy, histopathology, mucosal T cell apoptosis and cytokine production.

Results: We found an expansion of pITK expressing mucosal CD4 T cells in ulcerative colitis rather than Crohn´s disease that correlated with disease severity. CsA suppressed activation of ITK in cultured CD4+ T cells and calcineurin-containing microclusters adjacent to the T cell receptor signaling complex. Functionally, the capacity of CsA to suppress activity of experimental colitis was critically dependent on ITK. Genetic inactivation of Itk via gene targeting or induction of allele-sensitive Itk mutants prevented experimental colitis in three colitis models, while treatment with pharmacological ITK blockers suppressed established colitis. Moreover, ITK controlled apoptosis and activation of mucosal Th2 and Th17 lymphocytes via NFATc2 signaling pathways.

Conclusion: ITK activation was detected in ulcerative colitis and could be downregulated in cultured T cells by CsA administration. Selective targeting of ITK emerges as an attractive approach for treatment of chronic intestinal inflammation and potentially ulcerative colitis by driving resolution of mucosal inflammation.
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http://dx.doi.org/10.1053/j.gastro.2021.06.072DOI Listing
July 2021

Neutrophils, eosinophils and intraepithelial lymphocytes in the squamous esophagus in subjects with and without gastroesophageal reflux symptoms.

Hum Pathol 2021 Jun 25. Epub 2021 Jun 25.

Background: Whilst intraepithelial lymphocytes (IELs) are considered normal within the distal esophageal mucosa, there is an appreciation of the potential role of excess lymphocytic infiltration in the pathogenesis of mucosal damage in reflux esophagitis. Furthermore, the diagnosis of lymphocytic esophagitis depends on quantification of the IEL density. There is a lack of knowledge regarding the upper limit of a normal IEL count in healthy volunteers, and this definition may identify abnormal infiltration in various forms of esophageal inflammation.

Methods: We studied 117 non-healthcare seeking adult volunteers from a random community sample (the Kalixanda study) with esophageal biopsies 2cm 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.

Results: 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 symptoms when a normal esophageal mucosa is visualized on endoscopy (sensitivity=100.0%, specificity=35.2%) CONCLUSION: The healthy esophageal mucosa does not contain more than three IELs per five HPF in the distal esophagus, and a higher count is a sensitive but a non-specific marker that can be used to rule out esophageal mucosal inflammation in symptomatic individuals.
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http://dx.doi.org/10.1016/j.humpath.2021.06.004DOI Listing
June 2021

Programmed death ligand 1 (PD-L1) in colon cancer and its interaction with budding and tumor-infiltrating lymphocytes (TILs) as tumor-host antagonists.

Int J Colorectal Dis 2021 Jun 25. Epub 2021 Jun 25.

Institute of Pathology, Klinikum Bayreuth, Preuschwitzer Str. 101, 95445, Bayreuth, Germany.

Purpose: To analyze the role of programmed death ligand 1 (PD-L1) immunohistochemisty in the context of tumor microenvironment in colon cancer (CC) with focus on the interaction between tumor budding and tumor-infiltrating lymphocytes (TILs) and to elucidate its potential value for immunooncologic treatment decisions.

Methods: Three hundred forty seven patients with CC, stages I to IV, were enrolled. PD-L1 immunohistochemistry was performed using two different antibodies (clone 22C3 pharmDx, Agilent and clone QR1, Quartett). Tumor proportion score (TPS) as well as immune cell score (IC) was assessed. Budding and TILs were assessed according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) and International TILs Working Group (ITWG). Correlation analyses as well as survival analyses were performed.

Results: PD-L1 positivity significantly correlated with TILs > 5% and MMR deficiency, and PD-L1-positive cases (overall and IC) showed significantly longer overall survival (OS) with both antibodies.The parameters "high grade," "right-sidedness," and "TILS > 5% regardless of MMR status" evolved as potential parameters for additional immunological treatment decisions. Additionally, TPS positivity correlated with low budding. More PD-L1-positive cases were seen in both high TIL groups. The low budding/high TIL group showed longer disease-free survival and longer OS in PD-L1-positive cases.

Conclusion: Overall, PD-L1 positivity correlated with markers of good prognosis. PD-L1 immunohistochemistry was able to identify parameters as additional potential candidates for immune therapy. Furthermore, it was able to stratify patients within the low budding/high TIL group with significant prognostic impact.
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http://dx.doi.org/10.1007/s00384-021-03985-9DOI Listing
June 2021

Issues in histopathological reporting: a crucial crossroad between surgeons and pathologists after oesophago-gastrectomy.

Dis Esophagus 2021 Jun 23. Epub 2021 Jun 23.

Internal Medicine II, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.

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http://dx.doi.org/10.1093/dote/doab038DOI Listing
June 2021

[The autopsy of Napoleon Bonaparte: Anatomo-pathological assessment for the bicentenary of the death of Napoleon I on the island of Saint Helena in 1821].

Ann Pathol 2021 Jul 20;41(4):381-386. Epub 2021 May 20.

Sorbonne université, AP-HP, hôpital Saint-Antoine, service d'anatomie et cytologie pathologiques, Paris, France.

Napoleon Bonaparte died on 5 May 1821 on the island of St Helena after almost six years of exile. The next day, Dr Francesco Antommarchi, a Corsican doctor chosen by the Bonaparte family to treat the exiled emperor, performed the autopsy in the presence of sixteen people, including seven British doctors. Two hundred years after the event of 6 May 1821, the cause of Napoleon's death is still a mystery. Various hypotheses, such as arsenic intoxication, cardiac arrhythmia or, more recently, anaemia caused by gastrointestinal haemorrhage associated with chronic gastritis, have been put forward in the medical-historical literature. The main reasons for all these debates and misunderstandings are the presence of several autopsy reports, their often unscientific interpretation, as well as a certain taste for mystery. However, from a scientific point of view, the question arises as to whether autopsy reports are really conclusive as to the real cause of death. Thus, on the occasion of the bicentenary of Napoleon I's death in St. Helena, an international group of anatomo-pathologists specialising in digestive pathology set themselves the goal of analysing Napoleon I's autopsy reports according to their level of medical evidence (high, moderate and low). The autopsy reports of 1821 support the hypothesis of advanced malignant neoplasia of the stomach associated with gastric haemorrhage as the immediate cause of Napoleon I's death on 5 May 1821.
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http://dx.doi.org/10.1016/j.annpat.2021.04.004DOI Listing
July 2021

Effect of intravenous dexamethasone on postoperative pain and swelling following periodontal flap surgery: A randomized controlled trial of patient-centered outcomes.

J Periodontol 2021 May 22. Epub 2021 May 22.

Department of Periodontics, UT Health San Antonio School of Dentistry, San Antonio, TX.

Background: This randomized, crossover trial sought to determine if a preoperative intravenous (IV) dose of dexamethasone reduces pain, swelling, and analgesic usage following periodontal surgery.

Methods: Thirty-seven patients planned for two similar periodontal flap surgeries under IV sedation were enrolled. Patients were randomized to receive either 2 mL (8 mg) dexamethasone sodium phosphate or 2 mL of IV solution (placebo) before the first surgery, and 2 mL of the other solution before the second surgery. Postoperative discomfort was managed with a standardized regimen of 600 mg ibuprofen and 325 mg acetaminophen. A smartphone application was used to record self-assessed pain and swelling scores using 21-point numerical (NRS-21) and 4-point verbal (VRS-4) rating scales as well as the number of analgesic medications taken at 12-, 24-, 48-, 72-, 168-, and 336-hours following each surgery.

Results: IV dexamethasone was associated with a significant reduction in pain at 12, 24, 48, and 72 hours (P <0.05), and swelling at 12, 24, 48, and 168 hours (P < 0.05) postoperatively when compared with placebo based on NRS-21 responses. VRS-4 data showed significant reductions in pain at 12, 72, and 168 hours and swelling at 12, 24, and 168 hours postoperatively with dexamethasone. No significant differences were found in the number of tablets of ibuprofen or acetaminophen between dexamethasone and placebo surgeries.

Conclusions: Preoperative, intravenously administered dexamethasone reduces pain and swelling within the first postoperative week following periodontal flap surgery and should be considered a useful adjunct for perioperative management.
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http://dx.doi.org/10.1002/JPER.21-0153DOI Listing
May 2021

Computational tissue staining of non-linear multimodal imaging using supervised and unsupervised deep learning.

Biomed Opt Express 2021 Apr 23;12(4):2280-2298. Epub 2021 Mar 23.

Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich-Schiller-University, Jena, Germany.

Hematoxylin and Eosin (H&E) staining is the 'gold-standard' method in histopathology. However, standard H&E staining of high-quality tissue sections requires long sample preparation times including sample embedding, which restricts its application for 'real-time' disease diagnosis. Due to this reason, a label-free alternative technique like non-linear multimodal (NLM) imaging, which is the combination of three non-linear optical modalities including coherent anti-Stokes Raman scattering, two-photon excitation fluorescence and second-harmonic generation, is proposed in this work. To correlate the information of the NLM images with H&E images, this work proposes computational staining of NLM images using deep learning models in a supervised and an unsupervised approach. In the supervised and the unsupervised approach, conditional generative adversarial networks (CGANs) and cycle conditional generative adversarial networks (cycle CGANs) are used, respectively. Both CGAN and cycle CGAN models generate pseudo H&E images, which are quantitatively analyzed based on mean squared error, structure similarity index and color shading similarity index. The mean of the three metrics calculated for the computationally generated H&E images indicate significant performance. Thus, utilizing CGAN and cycle CGAN models for computational staining is beneficial for diagnostic applications without performing a laboratory-based staining procedure. To the author's best knowledge, it is the first time that NLM images are computationally stained to H&E images using GANs in an unsupervised manner.
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http://dx.doi.org/10.1364/BOE.415962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086483PMC
April 2021

Wide-field endoscopic submucosal dissection for the treatment of Barrett's esophagus neoplasia.

Endosc Int Open 2021 May 22;9(5):E727-E734. Epub 2021 Apr 22.

Department of Upper Gastrointestinal Diseases, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.

Implementation of endoscopic submucosal dissection (ESD) for the treatment of Barrett's esophagus neoplasia (BEN) has been hampered by high rates of positive margins and complications. Dissection with wider margins was proposed to overcome these problems, but was never tested. We aim to compare Wide-Field ESD (WF-ESD) with conventional ESD (C-ESD) for treatment of BEN. This was a cohort study of all ESDs performed in our center during 2011 to 2018. C-ESD was the only technique used before 2014, with WF-ESD used beginning in 2014. In WF-ESD marking was performed 10 mm from the tumor margin compared to 5 mm with C-E. ESD was performed in 90 cases, corresponding to 74 patients, 84 % male, median age 69. Of these, 22 were C-ESD (24 %) and 68 were WF-ESD (76 %). The en bloc resection rate was 95 vs 100 % (ns), the positive lateral margin rate was 23 % vs 3 % (  < 0.01), the R0 rate was 73 % vs 90 %, and the curative resection rate was 59 % vs 76 % in the C-ESD and WF-ESD groups, respectively, (both  > 0.05). The procedure speed was 4.4 and 2.3 (min/mm) in the C-ESD and WF-ESD groups (  < 0.01), respectively. WF-ESD was associated with less post-operative strictures, 6 % vs 27 % (  = 0.01), with no local recurrence but no significantly reduced risk of metachronous recurrence (Hazard Ratio = 0.46, 95 %CI = 0.14-1.46), during a follow-up of 13.4 and 9.4 months in the C-ESD and WF-ESD cohorts, respectively. WF-ESD is associated with a reduction in positive lateral margins, faster dissection, and lower stricture rates. Further prospective, multicenter studies are warranted to evaluate its role in clinical practice.
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http://dx.doi.org/10.1055/a-1386-3668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062230PMC
May 2021

Validation of the "Inflammatory Bowel Disease - Distribution, Chronicity, Activity (IBD-DCA) Score" for Ulcerative Colitis and Crohn´s disease.

J Crohns Colitis 2021 Mar 27. Epub 2021 Mar 27.

Institute of Pathology, Klinikum Bayreuth GmbH, Bayreuth, Germany.

Background And Aims: Histological scoring plays a key role in the assessment of disease activity in ulcerative colitis (UC) and is also important in Crohn´s disease (CD). Currently, there is no common scoring available for UC and CD. We aimed to validate the Inflammatory Bowel Disease (IBD) - Distribution (D), Chronicity (C), Activity (A) score (IBD-DCA score) for histological disease activity assessment in IBD.

Methods: Inter- and intra-rater reliability were assessed by 16 observers on biopsy specimen from 59 patients with UC and 25 patients with CD. Construct validity and responsiveness to treatment were retrospectively evaluated on a second cohort of 30 patients.

Results: Inter-rater reliability was moderate to good for the UC cohort (intraclass correlation coefficients (ICCs) = 0.645, 0.623, 0.767 for D, C and A, respectively) and at best moderate for the CD cohort (ICC = 0.690, 0.303, 0.733 for D, C and A, respectively). Intra-rater agreement ranged from good to excellent in both cohorts. Correlation with the Nancy Histological Index (NHI) was moderate and strong with the Simplified Geboes Score (SGS) and a Visual Analog Scale (VAS). Large effect sizes (ES) were obtained for all three parameters. External responsiveness analysis revealed correlated changes between IBD-DCA score and NHI, SGS and VAS.

Conclusions: The IBD-DCA score is a simple histological activity score for UC and CD, agreed and validated by a large group of IBD specialists. It provides reliable information on treatment response. Therefore, it has potential value for use in routine diagnostics as well as clinical studies.
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http://dx.doi.org/10.1093/ecco-jcc/jjab055DOI Listing
March 2021

Adjuvant chemotherapy in stage II and III colon cancer: the role of the "budding and TILs-(tumor-infiltrating lymphocytes) combination" as tumor-host antagonists.

Int J Colorectal Dis 2021 Aug 20;36(8):1765-1779. Epub 2021 Mar 20.

Institute of Pathology, Klinikum Bayreuth GmbH, Preuschwitzer Str. 101, 95445, Bayreuth, Germany.

Purpose: To analyze the influence of adjuvant chemotherapy on the combination of tumor budding and tumor-infiltrating lymphocytes (TILs) in stage II and III colon cancer and to elucidate its potential value for adjuvant treatment decisions.

Methods: 306 patients with stage II and 205 patients with stage III colon cancer diagnosed between 2005 and 2016 who had undergone surgery in a curative setting were enrolled. Budding and TILs were assessed according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) and the criteria of the International TILs Working Group (ITWG). Combinations of budding and TILs were analyzed, and the influence of adjuvant chemotherapy was assessed.

Results: In stage II colon cancer, stratification into the four budding/TILs groups showed no significant differences in overall survival (OS) between the chemotherapy and the surgery-alone group, not even in cases with high-risk features. In stage III colon cancer, patients with low budding/high TILs benefited significantly from chemotherapy (p=0.005). Patients with high budding/low TILs as well as high budding/high TILs showed a trend to benefit from adjuvant treatment. However, no chemotherapy benefit was seen for the low budding/low TIL group.

Conclusions: The budding/TIL combination identified subgroups in stage II and III colon cancer with and without benefit from adjuvant treatment. The results this study suggest that the combination of budding and TILs as tumor-host antagonists might be an additional helpful tool in adjuvant treatment decisions in stage II and III colon cancer.
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http://dx.doi.org/10.1007/s00384-021-03896-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279987PMC
August 2021

The gastric disease of Napoleon Bonaparte: brief report for the bicentenary of Napoleon's death on St. Helena in 1821.

Virchows Arch 2021 Mar 4. Epub 2021 Mar 4.

Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Service d'Anatomie et cytologie pathologiques, Paris, France.

After the defeat at the battle of Waterloo on June 18, 1815, Napoleon Bonaparte was sent into exile to the Island of St. Helena where he died 6 years later on May 5, 1821. One day after his death, Napoleon's personal physician, Dr. Francesco Antommarchi, performed the autopsy in the presence of Napoleon's exile companions and the British medical doctors. Two hundred years later, mysteries still surround the cause of his death and different hypotheses have been postulated in the medical and historical literature. The main reasons seem to be the presence of several autopsy reports, their interpretation and perhaps the greed for thrill and mystery. Therefore, for the bicentenary of Napoleon's death, an international consortium of gastrointestinal pathologists assembled to analyse Napoleon's autopsy reports based on the level of medical evidence and to investigate if the autopsy reports really do not allow a final statement.
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http://dx.doi.org/10.1007/s00428-021-03061-1DOI Listing
March 2021

Improving tumor budding reporting in colorectal cancer: a Delphi consensus study.

Virchows Arch 2021 Mar 1. Epub 2021 Mar 1.

Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6525 GA, Nijmegen, Netherlands.

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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http://dx.doi.org/10.1007/s00428-021-03059-9DOI Listing
March 2021

Microbiota alteration at different stages in gastric lesion progression: a population-based study in Linqu, China.

Am J Cancer Res 2021 1;11(2):561-575. Epub 2021 Feb 1.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute Beijing, China.

In addition to Helicobacter pylori (H.pylori), gastric microbiota may be involved in carcinogenesis process. However, the longitudinal study to assess changes in the gastric microbiota associated with the development of gastric carcinogenesis is still limited. The aim of this study is to explore dynamic microbial alterations in gastric cancer (GC) development based on a 4-year endoscopic follow-up cohort in Linqu County, China. Microbial alterations were investigated by deep sequencing of the microbial 16S ribosomal RNA gene in 179 subjects with various gastric lesions, and validated in paired gastric biopsies prospectively collected before and after lesion progression and in non-progression controls. Significant differences were found in microbial diversity and community structure across various gastric lesions, with 62 candidate differential taxa between at least two lesion groups. Further validations identified Helicobacter, Bacillus, Capnocytophaga and Prevotella to be associated with lesion progression-to-dysplasia (DYS)/GC (all P < 0.05), especially for subjects progressing from intestinal metaplasia (IM) to DYS/GC. The combination of the four genera in a microbial dysbiosis index showed a significant difference after lesion progression-to-DYS/GC compared to controls (P = 0.027). The panel including the four genera identified subjects after progression-to-DYS/GC with an area under the receiver-operating curve (AUC) of 0.941. Predictive significance was found before lesion progression-to-DYS/GC with an AUC = 0.776 and an even better AUC (0.927) for subjects progressing from IM to DYS/GC. Microbiota may play different roles at different stages in gastric carcinogenesis. A panel of bacterial genera associated with gastric lesions may help to assess gastric microbial dysbiosis and show potential predictive values for lesion progression. Our findings provide new clues for the microbial mechanism of H.pylori-associated carcinogenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868750PMC
February 2021

Helicobacter Infection and Gastric Adenoma.

Microorganisms 2021 Jan 5;9(1). Epub 2021 Jan 5.

Institute of Pathology, Universitätsklinikum Erlangen, Krankenhausstr. 8-10, 91054 Erlangen, Germany.

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 () gastritis in 23.9%, Ex- 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.
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http://dx.doi.org/10.3390/microorganisms9010108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824786PMC
January 2021

Possible tumour cell reimplantation during curative endoscopic therapy of superficial Barrett's carcinoma.

Gut 2021 Jan 13. Epub 2021 Jan 13.

Department of Interdisciplinary Endoscopy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Background And Aims: Endoscopic resection has been established as curative therapy for superficial cancer arising from Barrett's oesophagus (BE); recurrences are very rare. Based on a case series with unusual and massive early recurrences, we analyse the issue of tumour cell reimplantation.

Methods: This hypothesis was developed on the basis of two out of seven patients treated by circumferential (n=6) or nearly circumferential (n=1) en bloc and R0 endoscopic resection of T1 neoplastic BE. Subsequently, a prospective histocytological analysis of endoscope channels and accessories was performed in 2 phases (cytohistological analysis; test for cell viability) in 22 different oesophageal carcinoma patients undergoing endoscopy. Finally, cultures from two oesophageal adenocarcinoma cell lines were incubated with different triamcinolone concentrations (0.625-10 mg/mL); cell growth was determined on a Multiwell plate reader.

Results: Cancer regrowth in the two suspicious cases (male, 78/71 years) occurred 7 and 1 months, respectively, after curative tumour resection. Subsequent surgery showed advanced tumours (T2) with lymph node metastases; one patient died. On cytohistological examinations of channels and accessories, suspicious/neoplastic cells were found in 4/10 superficial and in all 5 advanced cancers. Further analyses in seven further advanced adenocarcinoma cases showed viable cells in two channel washing specimens. Finally, cell culture experiments demonstrated enhanced tumour cell growth by triamcinolone after 24 hours compared with controls.

Conclusions: Tumour cell reimplanation from contaminated endoscopes and accessories is a possible cause of local recurrence after curative endoscopic therapy for superficial Barrett carcinoma; also, corticosteroid injection could have promoted tumour regrowth in these cases.
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http://dx.doi.org/10.1136/gutjnl-2020-322723DOI Listing
January 2021

The epigenetic regulator Mll1 is required for Wnt-driven intestinal tumorigenesis and cancer stemness.

Nat Commun 2020 12 21;11(1):6422. Epub 2020 Dec 21.

Cancer Research Program, Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Society, 13125, Berlin, Germany.

Wnt/β-catenin signaling is crucial for intestinal carcinogenesis and the maintenance of intestinal cancer stem cells. Here we identify the histone methyltransferase Mll1 as a regulator of Wnt-driven intestinal cancer. Mll1 is highly expressed in Lgr5 stem cells and human colon carcinomas with increased nuclear β-catenin. High levels of MLL1 are associated with poor survival of colon cancer patients. The genetic ablation of Mll1 in mice prevents Wnt/β-catenin-driven adenoma formation from Lgr5 intestinal stem cells. Ablation of Mll1 decreases the self-renewal of human colon cancer spheres and halts tumor growth of xenografts. Mll1 controls the expression of stem cell genes including the Wnt/β-catenin target gene Lgr5. Upon the loss of Mll1, histone methylation at the stem cell promoters switches from activating H3K4 tri-methylation to repressive H3K27 tri-methylation, indicating that Mll1 sustains stem cell gene expression by antagonizing gene silencing through polycomb repressive complex 2 (PRC2)-mediated H3K27 tri-methylation. Transcriptome profiling of Wnt-mutated intestinal tumor-initiating cells reveals that Mll1 regulates Gata4/6 transcription factors, known to sustain cancer stemness and to control goblet cell differentiation. Our results demonstrate that Mll1 is an essential epigenetic regulator of Wnt/β-catenin-induced intestinal tumorigenesis and cancer stemness.
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http://dx.doi.org/10.1038/s41467-020-20222-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752919PMC
December 2020

An International Multicenter Real-Life Prospective Study of Electronic Chromoendoscopy Score PICaSSO in Ulcerative Colitis.

Gastroenterology 2021 Apr 6;160(5):1558-1569.e8. Epub 2021 Feb 6.

Institute of Immunology and Immunotherapy, NIHR Wellcome Trust Clinical Research Facilities, University of Birmingham, and University Hospitals Birmingham NHS Trust, Birmingham, United Kingdom; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Birmingham, United Kingdom; Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Canada.

Background & Aims: Endoscopic and histologic remission are important goals in the treatment of ulcerative colitis (UC). We investigated the correlation of the recently developed Paddington International Virtual ChromoendoScopy ScOre (PICaSSO) and other established endoscopic scores against multiple histological indices and prospectively assessed outcomes.

Methods: In this prospective multicenter international study, inflammatory activity was assessed with high-definition and virtual chromoendoscopy in the rectum and sigmoid using the Mayo Endoscopic Score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO. Targeted biopsies were taken for assessment using Robarts Histological Index (RHI), Nancy Histological index (NHI), ECAP (Extent, Chronicity, Activity, Plus score), Geboes, and Villanacci. Follow-up data were obtained at 6 and 12 months after colonoscopy.

Results: A total of 307 patients were recruited. There was strong correlation between PICaSSO and histology scores, significantly superior to correlation coefficients of MES and UCEIS with histology scores. A PICaSSO score of ≤3 detected histologic remission by RHI (≤3 + absence of neutrophils) with area under the receiver operating characteristic curve (AUROC) 0.90 (95% confidence interval [CI] 0.86-0.94) and NHI (≤1) AUROC 0.82 (95% CI 0.77-0.87). The interobserver agreement for PICaSSO was 0.88 (95% CI 0.83-0.92). At 6- and 12-months follow-up, PICaSSO score ≤3 predicted better outcomes than PICaSSO >3 (hazard ratio [HR] 0.19 [0.11-0.33] and 0.22 [0.13-0.34], respectively),} as well as PICaSSO 4-8 (HR 0.25 [0.12-0.53] and 0.22 (0.12-0.39), respectively) and similar to histologic remission.

Conclusion: In this first real-life multicenter study, the PICaSSO score correlated strongly with multiple histological indices. Furthermore, PICaSSO score predicted specified clinical outcomes at 6 and 12 months, similar to histology. Thus, PICaSSO can be a useful endoscopic tool in the therapeutic management of UC.
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http://dx.doi.org/10.1053/j.gastro.2020.12.024DOI Listing
April 2021

Gastric hyperplastic polyps (hyperplasiogenic polyps): a constant debate!

Endoscopy 2021 01 17;53(1):100. Epub 2020 Dec 17.

Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutsches Zentrum Immuntherapie DZI, Kussmaul Campus for Medical Research & Translational Research Center, Erlangen, Germany.

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http://dx.doi.org/10.1055/a-1217-0521DOI Listing
January 2021

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Carcinogenesis 2021 04;42(3):369-377

Department of Medicine, Institute of Clinical Science, Royal Victoria Hospital, Belfast, UK.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
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http://dx.doi.org/10.1093/carcin/bgaa132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052954PMC
April 2021

Mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon: detailed molecular characterisation of two cases indicates a distinct colorectal cancer entity.

J Pathol Clin Res 2021 01 16;7(1):75-85. Epub 2020 Nov 16.

Institute of Pathology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany.

We present two rare cases of mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon. A literature search revealed only three published cases with similar histology but none of these reports provided profound molecular and mutational analyses. Our two cases exhibited a distinct, colon-like immunophenotype with strong nuclear CDX2 and β-catenin expression in more than 90% of the tumour cells of both components. We analysed the two carcinomas regarding microsatellite stability, RAS, BRAF and PD-L1 status. In addition, next-generation panel sequencing with Ion AmpliSeq™ Cancer Hotspot Panel v2 was performed. This approach revealed mutations in FBXW7, CTNNB1 and PIK3CA in the first case and FBXW7 and RB1 mutations in the second case. We looked for similar mutational patterns in three publicly available colorectal adenocarcinoma data sets, as well as in collections of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) and colorectal neuroendocrine carcinomas. This approach indicated that the FBXW7 point mutation, without being accompanied by classical adenoma-carcinoma sequence mutations, such as APC, KRAS and TP53, likely occurs at a relatively high frequency in mixed neuroendocrine and squamous cell carcinoma and therefore may be characteristic for this rare tumour type. FBXW7 codifies the substrate recognition element of an ubiquitin ligase, and inactivating FBXW7 mutations lead to an exceptional accumulation of its target β-catenin which results in overactivation of the Wnt-signalling pathway. In line with previously described hypotheses of de-differentiation of colon cells by enhanced Wnt-signalling, our data indicate a crucial role for mutant FBXW7 in the unusual morphological switch that determines these rare neoplasms. Therefore, mixed large cell neuroendocrine and a squamous cell carcinoma can be considered as a distinct carcinoma entity in the colon, defined by morphology, immunophenotype and distinct molecular genetic alteration(s).
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http://dx.doi.org/10.1002/cjp2.183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737761PMC
January 2021

Loss of RNF43 Function Contributes to Gastric Carcinogenesis by Impairing DNA Damage Response.

Cell Mol Gastroenterol Hepatol 2021 11;11(4):1071-1094. Epub 2020 Nov 11.

Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich, Munich, Germany. Electronic address:

Background & Aims: RING finger protein 43 (RNF43) is a tumor suppressor that frequently is mutated in gastric tumors. The link between RNF43 and modulation of Wingless-related integration site (WNT) signaling has not been shown clearly in the stomach. Because mutations in RNF43 are highly enriched in microsatellite-unstable gastric tumors, which show defects in DNA damage response (DDR), we investigated whether RNF43 is involved in DDR in the stomach.

Methods: DDR activation and cell viability upon γ-radiation was analyzed in gastric cells where expression of RNF43 was depleted. Response to chemotherapeutic agents 5-fluorouracil and cisplatin was analyzed in gastric cancer cell lines and xenograft tumors. In addition, involvement of RNF43 in DDR activation was analyzed upon Helicobacter pylori infection in wild-type and Rnf43 mice. Furthermore, a cohort of human gastric biopsy specimens was analyzed for RNF43 expression and mutation status as well as for activation of DDR.

Results: RNF43 depletion conferred resistance to γ-radiation and chemotherapy by dampening the activation of DDR, thereby preventing apoptosis in gastric cells. Upon Helicobacter pylori infection, RNF43 loss of function reduced activation of DDR and apoptosis. Furthermore, RNF43 expression correlated with DDR activation in human gastric biopsy specimens, and RNF43 mutations found in gastric tumors conferred resistance to DNA damage. When exploring the molecular mechanisms behind these findings, a direct interaction between RNF43 and phosphorylated H2A histone family member X (γH2AX) was observed.

Conclusions: We identified a novel function for RNF43 in the stomach as a regulator of DDR. Loss of RNF43 function in gastric cells confers resistance to DNA damage-inducing radiotherapy and chemotherapy, suggesting RNF43 as a possible biomarker for therapy selection.
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http://dx.doi.org/10.1016/j.jcmgh.2020.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898035PMC
November 2020

Towards an Interpretable Classifier for Characterization of Endoscopic Mayo Scores in Ulcerative Colitis Using Raman Spectroscopy.

Anal Chem 2020 10 7;92(20):13776-13784. Epub 2020 Oct 7.

Department of Internal Medicine IV (Gastroenterology, Hepatology, Infectious Disease), Jena University Hospital, 07747 Jena, Germany.

Ulcerative colitis (UC) is one of the main types of chronic inflammatory diseases that affect the bowel, but its pathogenesis is yet to be completely defined. Assessing the disease activity of UC is vital for developing a personalized treatment. Conventionally, the assessment of UC is performed by colonoscopy and histopathology. However, conventional methods fail to retain biomolecular information associated to the severity of UC and are solely based on morphological characteristics of the inflamed colon. Furthermore, assessing endoscopic disease severity is limited by the requirement for experienced human reviewers. Therefore, this work presents a nondestructive biospectroscopic technique, for example, Raman spectroscopy, for assessing endoscopic disease severity according to the four-level Mayo subscore. This contribution utilizes multidimensional Raman spectroscopic data to generate a predictive model for identifying colonic inflammation. The predictive modeling of the Raman spectroscopic data is performed using a one-dimensional deep convolutional neural network (1D-CNN). The classification results of 1D-CNN achieved a mean sensitivity of 78% and a mean specificity of 93% for the four Mayo endoscopic scores. Furthermore, the results of the 1D-CNN are interpreted by a first-order Taylor expansion, which extracts the Raman bands important for classification. Additionally, a regression model of the 1D-CNN model is constructed to study the extent of misclassification and border-line patients. The overall results of Raman spectroscopy with 1D-CNN as a classification and regression model show a good performance, and such a method can serve as a complementary method for UC analysis.
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http://dx.doi.org/10.1021/acs.analchem.0c02163DOI Listing
October 2020

Toll-like Receptor 5 Activation by the CagY Repeat Domains of Helicobacter pylori.

Cell Rep 2020 09;32(11):108159

Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen-Nuremberg, 91058 Erlangen, Germany. Electronic address:

Helicobacter pylori (Hp) is an important human pathogen associated with gastric inflammation and neoplasia. It is commonly believed that this bacterium avoids major immune recognition by Toll-like receptors (TLRs) because of low intrinsic activity of its flagellin and lipopolysaccharides (LPS). In particular, TLR5 specifically detects flagellins in various bacterial pathogens, while Hp evolved mutations in flagellin to evade detection through TLR5. Cancerogenic Hp strains encode a type IV secretion system (T4SS). The T4SS core component and pilus-associated protein CagY, a large VirB10 ortholog, drives effector molecule translocation. Here, we identify CagY as a flagellin-independent TLR5 agonist. We detect five TLR5 interaction sites, promoting binding of CagY-positive Hp to TLR5-expressing cells, TLR5 stimulation, and intracellular signal transduction. Consequently, CagY constitutes a remarkable VirB10 member detected by TLR5, driving crucial innate immune responses by this human pathogen.
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http://dx.doi.org/10.1016/j.celrep.2020.108159DOI Listing
September 2020

Distribution of histopathological features along the colon in microscopic colitis.

Int J Colorectal Dis 2021 Jan 12;36(1):151-159. Epub 2020 Sep 12.

Gastroenterology and Hepatology in Linköping, and Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden.

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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http://dx.doi.org/10.1007/s00384-020-03747-zDOI Listing
January 2021

Sporadic adenoma or ulcerative colitis associated neoplasia? The endoscopist's information has an impact on diagnosis and patient management.

Pathol Res Pract 2020 Nov 15;216(11):153162. Epub 2020 Aug 15.

Institute of Pathology, Klinikum Bayreuth GmbH, Bayreuth, Germany.

Background: Diagnosing low grade intraepithelial neoplasia (LGIN) in patients with ulcerative colitis (UC) is difficult. Distinguishing between sporadic adenoma (SA) and UC associated LGIN is even more challenging but has clinical impact. We aimed to examine, if the morphological distinction between both entities is reliably possible, how it influences patient's outcome and the role of the endoscopist in this decision with respect to current endoscopy classification schemes.

Methods: Seven pathologists retrospectively reevaluated 425 cases of LGIN in UC patients, diagnosed between 2009 and 2017 with preceding expert consensus and follow up in two separate readings, based on published morphological differentiation criteria. In the first evaluation, the observers were blinded to any clinical data. In the second evaluation, they knew patients' age as well as endoscopic features. They also rated their subjective diagnostic certainty.

Results: Diagnostic correctness improved significantly in the second assessment as did the pathologists' confidence in their diagnoses (p < 0.001 - p = 0.019). Knowledge of clinical and endoscopical data led to a higher percentage of SA (71.8% vs. 85.6%). UC associated LGIN showed significant earlier LGIN relapse as well as more high grade intraepithelial neoplasia and carcinoma during follow up (p < 0.001, p < 0.001, p = 0.005).

Conclusions: Distinction between SA and UC associated LGIN is important as it has an impact on patients' follow up and treatment. Morphological distinction remains difficult with moderate interobserver variability. Adequate clinical information significantly improves pathologists' diagnoses as well as their confidence in their diagnoses.
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http://dx.doi.org/10.1016/j.prp.2020.153162DOI Listing
November 2020

Gastric Microbiota in a Low-Helicobacter pylori Prevalence General Population and Their Associations With Gastric Lesions.

Clin Transl Gastroenterol 2020 07;11(7):e00191

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

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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http://dx.doi.org/10.14309/ctg.0000000000000191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431247PMC
July 2020

Topical application of Chlorin e6-PVP (Ce6-PVP) for improved endoscopic detection of neoplastic lesions in a murine colitis-associated cancer model.

Sci Rep 2020 08 4;10(1):13129. Epub 2020 Aug 4.

Department of Medicine 1, University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Screening colonoscopy is crucial in reducing the mortality of colorectal cancer. However, detecting adenomas against the backdrop of an inflamed mucosa (e.g. in ulcerative colitis) remains exceedingly difficult. Therefore, we aimed to improve neoplastic lesion detection by employing a fluorescence-based endoscopic approach. We used the well-established murine AOM/DSS model to induce inflammation-driven carcinogenesis in the colon. In our diagnostic approach, we evaluated Chlorin e6 polyvinylpyrrolidone (Ce6-PVP)-based fluorescence endoscopy in comparison to standard white-light endoscopy. A specialized pathologist then analyzed the histology of the detected lesions. Complementary in vitro studies were performed using human cell lines and a murine organoid system. Ce6-PVP-based fluorescence endoscopy had an improved detection rate of 100% (8/8) in detecting high-grade dysplasias and carcinomas over white-light detection alone with 75% (6/8). Trade-off for this superior detection rate was an increased rate of false positive lesions with an increase in the false discovery rate from 45% for white-light endoscopy to 81% for fluorescence endoscopy. We demonstrate in a proof-of-concept study that Ce6-PVP-based fluorescence endoscopy is a highly sensitive red flag technology to identify biopsy-worthy lesions in the colon.
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http://dx.doi.org/10.1038/s41598-020-69570-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403373PMC
August 2020