Journal of Pathology and Translational Medicine

Reviews

Inflammatory bowel disease–associated intestinal fibrosis: Ji Min Park, Jeongseok Kim, Yoo Jin Lee, Sung Uk Bae, Hye Won Lee; J Pathol Transl Med. 2023;57(1):60-66. Published online January 10, 2023; DOI: https://doi.org/10.4132/jptm.2022.11.02

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Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn’s disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end.

Citations

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M. Seco-Cervera, D. Ortiz-Masiá, D.C. Macias-Ceja, S. Coll, L. Gisbert-Ferrándiz, J. Cosín-Roger, C. Bauset, M. Ortega, B. Heras-Morán, F. Navarro-Vicente, M. Millán, J.V. Esplugues, S. Calatayud, M.D. Barrachina
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Food additives impair gut microbiota from healthy individuals and IBD patients in a colonic in vitro fermentation model
Irma Gonza, Elizabeth Goya-Jorge, Caroline Douny, Samiha Boutaleb, Bernard Taminiau, Georges Daube, Marie–Louise Scippo, Edouard Louis, Véronique Delcenserie
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Epigenetic Regulation of EMP/EMT-Dependent Fibrosis
Margherita Sisto, Sabrina Lisi
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Disease clearance in ulcerative colitis: A new therapeutic target for the future
Syed Adeel Hassan, Neeraj Kapur, Fahad Sheikh, Anam Fahad, Somia Jamal
World Journal of Gastroenterology.2024; 30(13): 1801. CrossRef
Pathways Affected by Falcarinol-Type Polyacetylenes and Implications for Their Anti-Inflammatory Function and Potential in Cancer Chemoprevention
Ruyuf Alfurayhi, Lei Huang, Kirsten Brandt
Foods.2023; 12(6): 1192. CrossRef
Time to eRAASe chronic inflammation: current advances and future perspectives on renin-angiotensin-aldosterone-system and chronic intestinal inflammation in dogs and humans
Romy M. Heilmann, Georg Csukovich, Iwan A. Burgener, Franziska Dengler
Frontiers in Veterinary Science.2023;[Epub] CrossRef
Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition
Dulce C. Macias-Ceja, M. Teresa Mendoza-Ballesteros, María Ortega-Albiach, M. Dolores Barrachina, Dolores Ortiz-Masià
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef

Non-conventional dysplastic subtypes in inflammatory bowel disease: a review of their diagnostic characteristics and potential clinical implications: Won-Tak Choi; J Pathol Transl Med. 2021;55(2):83-93. Published online March 9, 2021; DOI: https://doi.org/10.4132/jptm.2021.02.17

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Abstract PDF

The early detection and grading of dysplasia is the current standard of care to minimize mortality from colorectal cancer (CRC) in patients with inflammatory bowel disease. With the development of advanced endoscopic resection techniques, colectomy is now reserved for patients with invisible/flat dysplasia (either high-grade [HGD] or multifocal low-grade dysplasia) or endoscopically unresectable lesions. Although most pathologists are familiar with the morphologic criteria of conventional (intestinal type) dysplasia, the most well-recognized form of dysplasia, an increasing number of diagnostic material has led to the recognition of several different morphologic patterns of epithelial dysplasia. The term “non-conventional” dysplasia has been coined to describe these changes, but to date, the recognition and full appreciation of these novel forms of dysplasia by practicing pathologists is uneven. The recognition of these non-conventional subtypes is becoming increasingly important, as some of them appear to have a higher risk of developing HGD or CRC than conventional dysplasia or sporadic adenomas. This review describes the morphologic characteristics of all seven non-conventional subtypes that have been reported to date as well as our current understanding of their clinicopathologic and molecular features that distinguish them from conventional dysplasia or sporadic adenomas.

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Recently described types of dysplasia associated with IBD: tips and clues for the practising pathologist
Zahra Alipour, Kristen Stashek
Journal of Clinical Pathology.2024; 77(2): 77. CrossRef
Nonconventional Dysplasia is Frequently Associated With Goblet Cell Deficient and Serrated Variants of Colonic Adenocarcinoma in Inflammatory Bowel Disease
Andrew Xiao, Masato Yozu, Bence P. Kővári, Lindsay Yassan, Xiaoyan Liao, Marcela Salomao, Maria Westerhoff, Anita Sejben, Gregory Y. Lauwers, Won-Tak Choi
American Journal of Surgical Pathology.2024;[Epub] CrossRef
DNA content abnormality frequently develops in the right/proximal colon in patients with primary sclerosing cholangitis and inflammatory bowel disease and is highly predictive of subsequent detection of dysplasia
Ruth Zhang, Peter S. Rabinovitch, Aras N. Mattis, Gregory Y. Lauwers, Won‐Tak Choi
Histopathology.2023; 83(1): 116. CrossRef
Non‐conventional dysplasia is frequently associated with low‐grade tubuloglandular and mucinous adenocarcinomas in inflammatory bowel disease
Fahire Goknur Akarca, Masato Yozu, Lindsay Alpert, Bence P Kővári, Lei Zhao, Marcela Salomao, Xiaoyan Liao, Maria Westerhoff, Gregory Y Lauwers, Won‐Tak Choi
Histopathology.2023; 83(2): 276. CrossRef
The yield of dysplasia and serrated lesions in a single-centre tertiary inflammatory bowel disease cohort
Fiona Yeaman, Lena Thin
Therapeutic Advances in Gastroenterology.2023; 16: 175628482311672. CrossRef
MYC overexpression in inflammatory bowel disease-associated conventional dysplasia and association of subsequent low-grade dysplasia in follow-up biopsies
Yuanxin Liang, Yansheng Hao, Yiqin Xiong, Minghao Zhong, Dhanpat Jain
Pathology - Research and Practice.2023; 248: 154642. CrossRef
Characteristics, Reporting, and Potential Clinical Significance of Nonconventional Dysplasia in Inflammatory Bowel Disease
Won-Tak Choi
Surgical Pathology Clinics.2023; 16(4): 687. CrossRef
Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
Vladislava Stojic, Natasa Zdravkovic, Tamara Nikolic-Turnic, Nebojsa Zdravkovic, Jelena Dimitrijevic, Aleksandra Misic, Kristijan Jovanovic, Stefan Milojevic, Jelena Zivic
Open Medicine.2023;[Epub] CrossRef
Morphological subtypes of colorectal low-grade intraepithelial neoplasia: diagnostic reproducibility, frequency and clinical impact
Corinna Lang-Schwarz, Maike Büttner-Herold, Stephan Burian, Ramona Erber, Arndt Hartmann, Moritz Jesinghaus, Kateřina Kamarádová, Carlos A Rubio, Gerhard Seitz, William Sterlacci, Michael Vieth, Simone Bertz
Journal of Clinical Pathology.2023; : jcp-2023-209206. CrossRef
And the story goes on: non-conventional dysplasia of the colorectum
Lavisha S. Punjabi, Yi Neng Lai, Anjula Thomas
Journal of Pathology and Translational Medicine.2022; 56(2): 109. CrossRef
Clinicopathologic features of undetected dysplasia found in total colectomy or proctocolectomy specimens of patients with inflammatory bowel disease
Dorukhan Bahceci, Gregory Y Lauwers, Won‐Tak Choi
Histopathology.2022; 81(2): 183. CrossRef
Increased Risk of Non-conventional and Invisible Dysplasias in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease
Ruth Zhang, Gregory Y Lauwers, Won-Tak Choi
Journal of Crohn's and Colitis.2022; 16(12): 1825. CrossRef
Increased histologic inflammation is an independent risk factor for nonconventional dysplasia in ulcerative colitis
Eric D. Nguyen, Dongliang Wang, Gregory Y. Lauwers, Won‐Tak Choi
Histopathology.2022; 81(5): 644. CrossRef

Advances in the Endoscopic Assessment of Inflammatory Bowel Diseases: Cooperation between Endoscopic and Pathologic Evaluations: Jae Hee Cheon; J Pathol Transl Med. 2015;49(3):209-217. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.04.09

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Abstract PDF

Endoscopic assessment has a crucial role in the management of inflammatory bowel disease (IBD). It is particularly useful for the assessment of IBD disease extension, severity, and neoplasia surveillance. Recent advances in endoscopic imaging techniques have been revolutionized over the past decades, progressing from conventional white light endoscopy to novel endoscopic techniques using molecular probes or electronic filter technologies. These new technologies allow for visualization of the mucosa in detail and monitor for inflammation/dysplasia at the cellular or sub-cellular level. These techniques may enable us to alter the IBD surveillance paradigm from four quadrant random biopsy to targeted biopsy and diagnosis. High definition endoscopy and dye-based chromoendoscopy can improve the detection rate of dysplasia and evaluate inflammatory changes with better visualization. Dye-less chromoendoscopy, including narrow band imaging, iScan, and autofluorescence imaging can also enhance surveillance in comparison to white light endoscopy with optical or electronic filter technologies. Moreover, confocal laser endomicroscopy or endocytoscopy have can achieve real-time histology evaluation in vivo and have greater accuracy in comparison with histology. These new technologies could be combined with standard endoscopy or further histologic confirmation in patients with IBD. This review offers an evidence-based overview of new endoscopic techniques in patients with IBD.

Citations

Citations to this article as recorded by

Colorectal cancer in inflammatory bowel disease: review of the evidence
D. S. Keller, A. Windsor, R. Cohen, M. Chand
Techniques in Coloproctology.2019; 23(1): 3. CrossRef
Probe-based confocal laser endomicroscopy in the differential diagnosis of inflammatory bowel diseases: a case series
Jung Won Park, Tae Il Kim, Jae Hee Cheon
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How to Assess and Document Endoscopies in IBD Patients by Including Standard Scoring Systems
Anna M. Buchner, Gary R. Lichtenstein
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Nodular lymphoid hyperplasia: A marker of low-grade inflammation in irritable bowel syndrome?
Anna Chiara Piscaglia, Lucrezia Laterza, Valentina Cesario, Viviana Gerardi, Rosario Landi, Loris Riccardo Lopetuso, Giovanni Calò, Giovanna Fabbretti, Massimo Brisigotti, Maria Loredana Stefanelli, Antonio Gasbarrini
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Original Articles

Cytomegalovirus Infection in Idiopathic Inflammatory Bowel Disease: Clinicopathologic Analysis of 6 Cases.: Won Ae Lee, Hye Sung Hahn, Woo Ho Kim, Yong Il Kim; Korean J Pathol. 1998;32(2):125-130.

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Abstract PDF: Cytomegalovirus (CMV) infection is an uncommon association with idiopathic inflammatory bowel disease (IBD) often leading to a variety of serious complications. A total of 41 resected cases of IBD were examined to elucidate the pathologic features of intestinal CMV infection which was assessed by histologic examination and confirmed by immunohistochemistry with CMV antibody. Six cases were positve for CMV antibody; five cases in 19 ulcerative colitis (UC, 26.3%) and one case in 22 Crohn's disease (CD, 4.5%). Of 7 cases of the steroid-treated UC group, five cases were superinfected with CMV (71.4%) but none in 12 cases of the steroid-untreated UC group. All of the five CMV-positive cases in UC showed deep ulceration and transmural inflammation, while none of 10 UC cases without above features were CMV positive. Fibrinoid necrosis and thrombi were found in 83.3% of the CMV infected group, while none in the CMV-negative group of UC cases (p=0.01). We conclude that IBD, particularly UC, is susceptible to the CMV infection when steroid hormone is administered, and that deep colonic ulceration, transmural inflammation and fibrinoid necrosis of vasculature may suggest superinfection of CMV in UC patients. It seems that deep colonic ulceration may be the consequence of an ischemic change following vascular luminal occlusion or vasculitis by CMV infection.

Effect of Atorvastatin, a HMG-CoA Reductase Inhibitor, in Experimental Colitis in Mice.: Hyo Jin Park, Tae Woon Kim, Jae Nam Seo, Kwon Ik Oh, Eun Young Choi, Hyung Sik Shin, Young Euy Park; Korean J Pathol. 2004;38(6):401-407.

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Abstract PDF: BACKGROUND
The statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are approved for cholesterol reduction, and may also be beneficial in the treatment of inflammatory disease. In this study, atorvastatin was tested in experimental colitis, a disease model of inflammatory bowel disease.
METHODS
To induce colitis, dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS) were administrated to C57BL/6 or BALB/c mice. Mice were monitored daily for loss of body weight and survival for indicated days. Colon length and histology were examined after sacrifice.
RESULTS
The administration of DSS induced marked colonic inflammation and shortening, and resulted in a loss of body weight. DSSinduced colitis was not affected by atorvastatin treatment, but in contrast, the administration of atorvastatin relieved TNBS-induced colitis with a resultant rapid recovery of weight loss and a reduction in colonic length shortening. Histologically, inflammatory cell infiltration in the colonic wall, mucosal ulceration and crypt disruption were also suppressed in atorvastatin treated mice.
CONCLUSION
These results suggest that atorvastatin preserves intestinal integrity in colitis, probably via the modulation of Th cell-mediated immune response, in a manner independent of innate immunity.

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