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1. Quantification of Mucosal Mast Cells in the Gastrointestinal Tract: A Primer for Practicing Pathologists

Author

Genta, Robert M., Turner, Kevin O., Collins, Margaret H., Wechsler, Joshua B., Arva, Nicoleta C., Pletneva, Maria A., Dellon, Evan S., and Walker, Marjorie M.

Subjects
Gastrointestinal system, Gastrointestinal diseases, Health
Abstract

* Context.--Mast cells are essential components of the immune system and play crucial pathogenetic roles in several digestive diseases, including mastocytic enterocolitis and eosinophilic gastrointestinal disorders. Pathologists have rarely been asked to evaluate the distribution and density of mast cells in gastrointestinal (GI) biopsy specimens. However, such requests are becoming more common because of an increasing awareness of the role of mast cells in functional GI disease and in both esophageal and nonesophageal eosinophilic gastrointestinal disorders. Objective.--To provide pathologists with tools to incorporate the assessment of mast cells in the evaluation of esophageal, gastric, and intestinal specimens by developing a systematic approach to their evaluation, counting, and reporting. Design.--This study consisted of a review of the literature followed by multiple consensus sessions to decide where to count mast cells and what a countable mast cell is. Results.--We reviewed 135 papers addressing the content of mast cells in the digestive tract, selected 21 that detailed how cells were counted (microscope lens, area of high-power fields, locations evaluated, type of cells considered as countable), and summarized their data in a table. Then, drawing from both the acceptable literature and our own extensive experience, we reached a tentative consensus on: (1) the normal numbers in the different segments of the GI tract; (2) the morphology of countable mast cells; and (3) the locations and strategies for counting them. Conclusions.--The result is a set of suggestions for reporting mast cell counts, their distribution, and their location in a way clinicians can understand and use for management decisions. (Arch Pathol Lab Med. 2024; 148:e25-e35; doi: 10.5858/arpa.2023-0070-OA), The discovery of mast cells and the gradual understanding of their role in the immune system have been described in fascinating detail by Blank et al. (1) First reported by [...]

Published
2024
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3. Do General Pathologists Assess Gastric and Duodenal Eosinophilia? A Community-Based Study

Author

Saad, A. Joe, Genta, Robert M., Turner, Kevin O., Kamboj, Amol P., Dellon, Evan S., and Chehade, Mirna

Subjects
Gastrointestinal system -- Analysis, Gastrointestinal diseases -- Analysis, Eosinophilia -- Analysis, Health
Abstract

* Context.--Eosinophilic diseases of the gastrointestinal tract (EGIDs), eosinophilic gastritis (EoG), and eosinophilic duodenitis (EoD) are rarely suspected clinically and infrequently detected by pathologists. Objective.--To determine whether histories of allergic or eosinophilic disorders and requests to rule out EoG and EoD affect pathologists' awareness of eosinophils in gastrointestinal biopsies. Design.--Thirty-one community-based pathologists were given 16 sets of biopsies from gastric and duodenal mucosa with elevated eosinophils, Helicobacter pylori gastritis, atrophic gastritis, normal stomach and duodenum, lymphocytosis, and celiac disease. Participants were assigned to 3 groups: group A did not receive histories of allergic or eosinophilic conditions; group B received similar histories plus a clue of possible allergic or eosinophilic conditions; and group C received the same histories as B and was asked to rule out EoG/EoD. A list of gastric and duodenal diagnoses and a space for comments were provided. Results were analyzed descriptively. Results.--Pathologists correctly diagnosed most non-eosinophilic gastrointestinal disorders, indicating competence in gastrointestinal pathology. With respect to EoG and EoD, pathologists in group C performed significantly better that those in groups A and B. The combined odds ratio with 95% CI was 12.34 (2.87-53.04), P < .001, for A versus C and 4.02 (1.60-10.09), P < .02, for B versus C. Conclusions.--Most pathologists neither reported gastric/duodenal eosinophilia nor diagnosed EoG/EoD, even when provided histories of eosinophilic disorders. Requests to rule out EoG/EoD resulted in only 4 of 11 participants evaluating and counting eosinophils in some cases. Simple evidence-based histopathologic criteria are needed before pathologists can be expected to consider and diagnose EGIDs., The prevalence of nonesophageal eosinophilic gastrointestinal disorders (EGIDs) remains poorly characterized, but is generally believed to be low, (1) and EGIDs are generally considered to be rare diseases. (2) Estimates [...]

Published
2023
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7. High Discovery Rate of Duodenal and Gastric Eosinophilia in Patients With Unexplained Moderate–Severe Abdominal Symptoms: A Prospective US Multisite Study

Author

Talley, Nicholas J., Peterson, Kathryn A., Genta, Robert M., Chang, Alan T., Dellon, Evan S., Sandborn, William J., Lacy, Brian E., Chehade, Mirna, Hirano, Ikuo, Gonsalves, Nirmala, Lembo, Anthony, Schmitt, Colleen M., Rothenberg, Marc E., Jain, Neal, Pletneva, Maria A., Turner, Kevin O., and Youngblood, Bradford A.

Published
2023
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9. International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature

Author

Dellon, Evan S., Gonsalves, Nirmala, Abonia, J. Pablo, Alexander, Jeffrey A., Arva, Nicoleta C., Atkins, Dan, Attwood, Stephen E., Auth, Marcus K.H., Bailey, Dominique D., Biederman, Luc, Blanchard, Carine, Bonis, Peter A., Bose, Paroma, Bredenoord, Albert J., Chang, Joy W., Chehade, Mirna, Collins, Margaret H., Di Lorenzo, Carlo, Dias, Jorge Amil, Dohil, Ranjan, Dupont, Christophe, Falk, Gary W., Ferreira, Cristina T., Fox, Adam T., Genta, Robert M., Greuter, Thomas, Gupta, Sandeep K., Hirano, Ikuo, Hiremath, Girish S., Horsley-Silva, Jennifer L., Ishihara, Shunji, Ishimura, Norihisa, Jensen, Elizabeth T., Gutiérrez-Junquera, Carolina, Katzka, David A., Khoury, Paneez, Kinoshita, Yoshikazu, Kliewer, Kara L., Koletzko, Sibylle, Leung, John, Liacouras, Chris A., Lucendo, Alfredo J., Martin, Lisa J., McGowan, Emily C., Menard-Katcher, Calies, Metz, David C., Miller, Talya L., Moawad, Fouad J., Muir, Amanda B., Mukkada, Vincent A., Murch, Simon, Nhu, Quan M., Nomura, Ichiro, Nurko, Samuel, Ohtsuka, Yoshikazu, Oliva, Salvatore, Orel, Rok, Papadopoulou, Alexandra, Patel, Dhyanesh A., Pesek, Robert D., Peterson, Kathryn A., Philpott, Hamish, Putnam, Philip E., Richter, Joel E., Rosen, Rachel, Ruffner, Melanie A., Safroneeva, Ekaterina, Schreiner, Philipp, Schoepfer, Alain, Schroeder, Shauna R., Shah, Neil, Souza, Rhonda F., Spechler, Stuart J., Spergel, Jonathan M., Straumann, Alex, Talley, Nicholas J., Thapar, Nikhil, Vandenplas, Yvan, Venkatesh, Rajitha D., Vieira, Mario C., von Arnim, Ulrike, Walker, Marjorie M., Wechsler, Joshua B., Wershil, Barry K., Wright, Benjamin L., Yamada, Yoshiyuki, Yang, Guang-Yu, Zevit, Noam, Rothenberg, Marc E., Furuta, Glenn T., and Aceves, Seema S.

Published
2022
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10. A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions

Author

Dellon, Evan S., Khoury, Paneez, Muir, Amanda B., Liacouras, Chris A., Safroneeva, Ekaterina, Atkins, Dan, Collins, Margaret H., Gonsalves, Nirmala, Falk, Gary W., Spergel, Jonathan M., Hirano, Ikuo, Chehade, Mirna, Schoepfer, Alain M., Menard-Katcher, Calies, Katzka, David A., Bonis, Peter A., Bredenoord, Albert J., Geng, Bob, Jensen, Elizabeth T., Pesek, Robert D., Feuerstadt, Paul, Gupta, Sandeep K., Lucendo, Alfredo J., Genta, Robert M., Hiremath, Girish, McGowan, Emily C., Moawad, Fouad J., Peterson, Kathryn A., Rothenberg, Marc E., Straumann, Alex, Furuta, Glenn T., and Aceves, Seema S.

Published
2022
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12. Impressions and aspirations from the FDA GREAT VI Workshop on Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis and Perspectives for Progress in the Field

Author

Rothenberg, Marc E., Hottinger, Shawna K.B., Gonsalves, Nirmala, Furuta, Glenn T., Collins, Margaret H., Talley, Nicholas J., Peterson, Kathryn, Menard-Katcher, Calies, Smith, Macie, Hirano, Ikuo, Genta, Robert M., Chehade, Mirna, Gupta, Sandeep K., Spergel, Jonathan M., Aceves, Seema S., and Dellon, Evan S.

Published
2022
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13. Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS)

Author

Ma, Christopher, Schoepfer, Alain M., Dellon, Evan S., Bredenoord, Albert J., Chehade, Mirna, Collins, Margaret H., Feagan, Brian G., Furuta, Glenn T., Gupta, Sandeep K., Hirano, Ikuo, Jairath, Vipul, Katzka, David A., Pai, Rish K., Rothenberg, Marc E., Straumann, Alex, Aceves, Seema S., Alexander, Jeffrey A., Arva, Nicoleta C., Atkins, Dan, Biedermann, Luc, Blanchard, Carine, Cianferoni, Antonella, Ciriza de los Rios, Constanza, Clayton, Frederic, Davis, Carla M., de Bortoli, Nicola, Dias, Jorge A., Falk, Gary W., Genta, Robert M., Ghaffari, Gisoo, Gonsalves, Nirmala, Greuter, Thomas, Hopp, Russell, Hsu Blatman, Karen S., Jensen, Elizabeth T., Johnston, Doug, Kagalwalla, Amir F., Larsson, Helen M., Leung, John, Louis, Hubert, Masterson, Joanne C., Menard-Katcher, Calies, Menard-Katcher, Paul A., Moawad, Fouad J., Muir, Amanda B., Mukkada, Vincent A., Penagini, Roberto, Pesek, Robert D., Peterson, Kathryn, Putnam, Philip E., Ravelli, Alberto, Savarino, Edoardo V., Schlag, Christoph, Schreiner, Philipp, Simon, Dagmar, Smyrk, Thomas C., Spergel, Jonathan M., Taft, Tiffany H., Terreehorst, Ingrid, Vanuytsel, Tim, Venter, Carina, Vieira, Mario C., Vieth, Michael, Vlieg-Boerstra, Berber, von Arnim, Ulrike, Walker, Marjorie M., Wechsler, Joshua B., Woodland, Philip, Woosley, John T., Yang, Guang-Yu, Zevit, Noam, and Safroneeva, Ekaterina

Published
2022
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20. RE.GA.IN.:the Real-world Gastritis Initiative-updating the updates

Author

Rugge, Massimo, Genta, Robert M., Malfertheiner, Peter, Dinis-Ribeiro, Mario, El-Serag, Hashem, Graham, David Y., Kuipers, Ernst J., Leung, Wai Keung, Park, Jin Young, Rokkas, Theodore, Schulz, Christian, El-Omar, Emad M., Rugge, Massimo, Genta, Robert M., Malfertheiner, Peter, Dinis-Ribeiro, Mario, El-Serag, Hashem, Graham, David Y., Kuipers, Ernst J., Leung, Wai Keung, Park, Jin Young, Rokkas, Theodore, Schulz, Christian, and El-Omar, Emad M.

Abstract

At the end of the last century, a far-sighted ' working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle. The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.

Published
2024

23. RE.GA.IN.: the Real-world Gastritis Initiative–updating the updates

Author

Rugge, Massimo, primary, Genta, Robert M, additional, Malfertheiner, Peter, additional, Dinis-Ribeiro, Mario, additional, El-Serag, Hashem, additional, Graham, David Y, additional, Kuipers, Ernst J, additional, Leung, Wai Keung, additional, Park, Jin Young, additional, Rokkas, Theodore, additional, Schulz, Christian, additional, and El-Omar, Emad M, additional

Published
2024
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25. Mast Cell Esophagitis: A Novel Entity in Patients with Unexplained Esophageal Symptoms.

Author

Ocampo, Adolfo A., Genta, Robert M., and Dellon, Evan S.

Abstract

It is not known whether esophageal mast cells may be a cause of unexplained esophageal symptoms. We aimed to determine the prevalence of esophageal mastocytosis in patients without other underlying causes of symptoms and assess the relationship between symptoms and mast cells. In this retrospective study, we identified adults with esophageal symptoms, a normal endoscopy, normal esophageal biopsies, and no definitive diagnosis during clinical evaluation. We quantified mast cell density (mast cells/mm2) in archived esophageal biopsies using tryptase immunohistochemistry, and compared mast cell levels by clinical features and physiologic testing. In the 87 patients identified (mean age 37, 72% female, 63% white, 92% non-Hispanic), common symptoms were dysphagia (76%), heartburn (71%), and chest pain (25%). Overall, the mean esophageal epithelial mast cell count was 83.0 ± 51.8 mast cells/mm2; 60% of patients had ≥ 60 mast/mm2, and 17% had ≥ 120 masts/mm2. There were no differences in mast cell counts by type of esophageal testing. Mast cell levels did not differ significantly by type of symptoms, atopic status, medications, smoking status, or alcohol use. There were also no major differences in clinical characteristics by mast cell quartiles or thresholds. In conclusion, esophageal mast cell infiltration was common in patients with symptoms unexplained by prior testing, and levels were higher than previously published values for patients with no underlying esophageal condition. Mast cell esophagitis could be a novel cause of unexplained esophageal symptoms in a subset of patients, though it reamins to be determined if such patients benefit from mast cell-targeted treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Gastric Cancer as Preventable Disease

Author

Rugge, Massimo, Genta, Robert M., Di Mario, Francesco, El-Omar, Emad M., El-Serag, Hashem B., Fassan, Matteo, Hunt, Richard H., Kuipers, Ernst J., Malfertheiner, Peter, Sugano, Kentaro, and Graham, David Y.

Published
2017
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42. A Summary of the 2016 James W. Freston Conference of the American Gastroenterological Association: Intestinal Metaplasia in the Esophagus and Stomach: Origins, Differences, Similarities and Significance

Author

Spechler, Stuart J., Merchant, Juanita L., Wang, Timothy C., Chandrasoma, Parakrama, Fox, James G., Genta, Robert M., Goldenring, James R., Hayakawa, Yoku, Kuipers, Ernst J., Lund, Pauline K., McKeon, Frank, Mills, Jason C., Odze, Robert D., Peek, Richard M., Jr., Pham, Thai, Que, Jianwen, Rustgi, Anil K., Shaheen, Nicholas J., Shivdasani, Ramesh A., Souza, Rhonda F., Storz, Peter, Todisco, Andrea, Wang, David H., and Wright, Nicholas A.

Published
2017
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43. Autoimmune gastritis

Author

Lenti, Marco Vincenzo, Rugge, Massimo, Lahner, Edith, Miceli, Emanuela, Toh, Ban-Hock, Genta, Robert M., De Block, Christophe, Hershko, Chaim, and Di Sabatino, Antonio

Published
2020
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48. Data from Chemoprevention of Intestinal Polyps in ApcMin/+ Mice Fed with Western or Balanced Diets by Drinking Annurca Apple Polyphenol Extract

Author

Fini, Lucia, primary, Piazzi, Giulia, primary, Daoud, Yahya, primary, Selgrad, Michael, primary, Maegawa, Shinji, primary, Garcia, Melissa, primary, Fogliano, Vincenzo, primary, Romano, Marco, primary, Graziani, Giulia, primary, Vitaglione, Paola, primary, Carmack, Susanne W., primary, Gasbarrini, Antonio, primary, Genta, Robert M., primary, Issa, Jean-Pierre, primary, Boland, C. Richard, primary, and Ricciardiello, Luigi, primary

Published
2023
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49. Supplementary Materials from Chemoprevention of Intestinal Polyps in ApcMin/+ Mice Fed with Western or Balanced Diets by Drinking Annurca Apple Polyphenol Extract

Author

Fini, Lucia, primary, Piazzi, Giulia, primary, Daoud, Yahya, primary, Selgrad, Michael, primary, Maegawa, Shinji, primary, Garcia, Melissa, primary, Fogliano, Vincenzo, primary, Romano, Marco, primary, Graziani, Giulia, primary, Vitaglione, Paola, primary, Carmack, Susanne W., primary, Gasbarrini, Antonio, primary, Genta, Robert M., primary, Issa, Jean-Pierre, primary, Boland, C. Richard, primary, and Ricciardiello, Luigi, primary

Published
2023
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50. Macroscopy predicts tumor progression in gastric cancer: A retrospective patho-historical analysis based on Napoleon Bonaparte's autopsy report

Author

Dawson, Heather, Novotny, Alexander, Becker, Karen, Reim, Daniel, Langer, Rupert, Gullo, Irene, Svrcek, Magali, Niess, Jan H., Tutuian, Radu, Truninger, Kaspar, Diamantis, Ioannis, Blank, Annika, Zlobec, Inti, Riddell, Robert H., Carneiro, Fatima, Fléjou, Jean-François, Genta, Robert M., and Lugli, Alessandro

Published
2016
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