Histopathologic Evaluation and Single-cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients With Inflammatory Bowel DiseaseSummary
Background & Aims: Total abdominal colectomy (TAC) with a staged ileal pouch-anal anastomosis (IPAA) is a common surgical treatment for ulcerative colitis (UC). However, a significant percentage of patients experience pouch failure, leading to morbidity. This retrospective case-control study...
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Elsevier
2025-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X25001043 |
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| author | Andrea D. Olivas Paul Chak Mou Ngai Emily Schahrer Junjie Xing Mobarakeh Ghadiri Kinga S. Olortegui John F. Cursio Shintaro Akiyama Eugene B. Chang Le Shen Konstantin Umanskiy David T. Rubin David Zemmour Christopher R. Weber |
| author_facet | Andrea D. Olivas Paul Chak Mou Ngai Emily Schahrer Junjie Xing Mobarakeh Ghadiri Kinga S. Olortegui John F. Cursio Shintaro Akiyama Eugene B. Chang Le Shen Konstantin Umanskiy David T. Rubin David Zemmour Christopher R. Weber |
| author_sort | Andrea D. Olivas |
| collection | DOAJ |
| description | Background & Aims: Total abdominal colectomy (TAC) with a staged ileal pouch-anal anastomosis (IPAA) is a common surgical treatment for ulcerative colitis (UC). However, a significant percentage of patients experience pouch failure, leading to morbidity. This retrospective case-control study identified histopathologic features of the TAC specimen associated with pouch failure and investigated the molecular mechanisms of this susceptibility using single-cell spatial transcriptomics. Methods: We analyzed a cohort of 417 patients who underwent IPAA between 2000 and 2010 at the University of Chicago Medical Center for up to 18 years. Histologic examination of TAC specimens focused on disease activity, depth of inflammation, and specific features, including granulomas and deep ulcers. A subset of patients was profiled using single-cell spatial transcriptomics to map gene expression and immune cell interactions in relation to the risk of pouch failure. Results: The 18-year pouch failure risk was 23%, with post-procedure clinical features of Crohn’s disease as a major risk factor (hazard ratio [HR], 4.3; 95% confidence interval [CI], 2.3–8.1) as well as high-risk histologic features, including deep chronic inflammation (HR, 21; 95% CI, 11–41) and severe disease activity (HR, 14; 95% CI, 5.7–32) in TAC specimens. Spatial transcriptomics showed immune infiltration of T and myeloid cells, reduced myocyte-glial interactions, and cytokine signaling pathways such as interleukin (IL)-10, IL-1β, and type I/II interferons, associated with an increased risk of pouch failure. CD68 immunohistochemistry confirmed that deep CD68+ macrophage infiltration is associated with increased risk of future pouch failure. Conclusion: Histologic features including CD68 immunohistochemisty and spatial molecular profiling are predictive of IPAA failure. These findings support the use of histologic evaluation and targeted molecular analysis of the TAC specimen to identify high-risk patients and improve IPAA outcomes. |
| format | Article |
| id | doaj-art-84eabd0556b548fda04872f824fd3e87 |
| institution | Kabale University |
| issn | 2352-345X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj-art-84eabd0556b548fda04872f824fd3e872025-08-20T04:01:03ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2025-01-01191010156310.1016/j.jcmgh.2025.101563Histopathologic Evaluation and Single-cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients With Inflammatory Bowel DiseaseSummaryAndrea D. Olivas0Paul Chak Mou Ngai1Emily Schahrer2Junjie Xing3Mobarakeh Ghadiri4Kinga S. Olortegui5John F. Cursio6Shintaro Akiyama7Eugene B. Chang8Le Shen9Konstantin Umanskiy10David T. Rubin11David Zemmour12Christopher R. Weber13Department of Pathology, University of Chicago Medical Center, Chicago, IllinoisDepartment of Pathology, University of Chicago Medical Center, Chicago, Illinois; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IllinoisDepartment of Pathology, University of Chicago Medical Center, Chicago, Illinois; Committee on Cancer Biology, University of Chicago, Chicago, IllinoisDepartment of Pathology, University of Chicago Medical Center, Chicago, IllinoisDepartment of Pathology, University of Chicago Medical Center, Chicago, IllinoisDepartment of Surgery, University of Chicago Medical Center, Chicago, IllinoisDepartment of Public Health Sciences, University of Chicago, Chicago, IllinoisDepartment of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, JapanSection of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IllinoisDepartment of Surgery, University of Chicago Medical Center, Chicago, IllinoisDepartment of Surgery, University of Chicago Medical Center, Chicago, IllinoisDepartment of Pathology, University of Chicago Medical Center, Chicago, Illinois; Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IllinoisDepartment of Pathology, University of Chicago Medical Center, Chicago, Illinois; Committee on Cancer Biology, University of Chicago, Chicago, Illinois; Committee on Immunology, University of Chicago, Chicago, Illinois; Correspondence Address correspondence to: David Zemmour, MD, PhD, 927 East 57th Street, Room R214, Chicago, Illinois, 60637.Department of Pathology, University of Chicago Medical Center, Chicago, Illinois; Christopher R. Weber, MD, PhD, 5841 South Maryland Avenue, Room AMBS319, Chicago, Illinois 60637.Background & Aims: Total abdominal colectomy (TAC) with a staged ileal pouch-anal anastomosis (IPAA) is a common surgical treatment for ulcerative colitis (UC). However, a significant percentage of patients experience pouch failure, leading to morbidity. This retrospective case-control study identified histopathologic features of the TAC specimen associated with pouch failure and investigated the molecular mechanisms of this susceptibility using single-cell spatial transcriptomics. Methods: We analyzed a cohort of 417 patients who underwent IPAA between 2000 and 2010 at the University of Chicago Medical Center for up to 18 years. Histologic examination of TAC specimens focused on disease activity, depth of inflammation, and specific features, including granulomas and deep ulcers. A subset of patients was profiled using single-cell spatial transcriptomics to map gene expression and immune cell interactions in relation to the risk of pouch failure. Results: The 18-year pouch failure risk was 23%, with post-procedure clinical features of Crohn’s disease as a major risk factor (hazard ratio [HR], 4.3; 95% confidence interval [CI], 2.3–8.1) as well as high-risk histologic features, including deep chronic inflammation (HR, 21; 95% CI, 11–41) and severe disease activity (HR, 14; 95% CI, 5.7–32) in TAC specimens. Spatial transcriptomics showed immune infiltration of T and myeloid cells, reduced myocyte-glial interactions, and cytokine signaling pathways such as interleukin (IL)-10, IL-1β, and type I/II interferons, associated with an increased risk of pouch failure. CD68 immunohistochemistry confirmed that deep CD68+ macrophage infiltration is associated with increased risk of future pouch failure. Conclusion: Histologic features including CD68 immunohistochemisty and spatial molecular profiling are predictive of IPAA failure. These findings support the use of histologic evaluation and targeted molecular analysis of the TAC specimen to identify high-risk patients and improve IPAA outcomes.http://www.sciencedirect.com/science/article/pii/S2352345X25001043Histopathologic FeaturesIL-1βIL-10Ileal Pouch-Anal Anastomosis (IPAA)ImmunologyInflammatory Bowel Disease |
| spellingShingle | Andrea D. Olivas Paul Chak Mou Ngai Emily Schahrer Junjie Xing Mobarakeh Ghadiri Kinga S. Olortegui John F. Cursio Shintaro Akiyama Eugene B. Chang Le Shen Konstantin Umanskiy David T. Rubin David Zemmour Christopher R. Weber Histopathologic Evaluation and Single-cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients With Inflammatory Bowel DiseaseSummary Cellular and Molecular Gastroenterology and Hepatology Histopathologic Features IL-1β IL-10 Ileal Pouch-Anal Anastomosis (IPAA) Immunology Inflammatory Bowel Disease |
| title | Histopathologic Evaluation and Single-cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients With Inflammatory Bowel DiseaseSummary |
| title_full | Histopathologic Evaluation and Single-cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients With Inflammatory Bowel DiseaseSummary |
| title_fullStr | Histopathologic Evaluation and Single-cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients With Inflammatory Bowel DiseaseSummary |
| title_full_unstemmed | Histopathologic Evaluation and Single-cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients With Inflammatory Bowel DiseaseSummary |
| title_short | Histopathologic Evaluation and Single-cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients With Inflammatory Bowel DiseaseSummary |
| title_sort | histopathologic evaluation and single cell spatial transcriptomics of the colon reveal cellular and molecular abnormalities linked to j pouch failure in patients with inflammatory bowel diseasesummary |
| topic | Histopathologic Features IL-1β IL-10 Ileal Pouch-Anal Anastomosis (IPAA) Immunology Inflammatory Bowel Disease |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X25001043 |
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