Journal of Pathology and Translational Medicine

Review

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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Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition
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Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef

Case Study

Diffuse Involvement of Primary Colorectal Lymphoma Simulating Ulcerative Colitis: Ji-Ye Kim, Sun Hee Chang, Han Seong Kim, Mee Joo; J Pathol Transl Med. 2019;53(5):332-336. Published online August 2, 2019; DOI: https://doi.org/10.4132/jptm.2019.07.12

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Abstract PDF: Diffuse involvement of colorectal lymphoma masquerading as colitis is a very rare presentation of primary colorectal lymphoma. Detecting occult lymphoma is difficult in the setting of diffuse colonic involvement with no definite mass and inflammatory mucosal changes. We encountered a case of diffuse-type primary colorectal lymphoma simulating ulcerative colitis in a previously healthy 31-year-old woman. Despite multiple mucosal biopsies, the biopsy diagnosis was not made due to unawareness of atypical lymphocytes admixed with dense lymphoplasmacytic infiltration. The present case emphasizes the importance of being aware of this rare presentation of primary colorectal lymphoma in order to avoid misdiagnosis.

Case Report

Mycophenolate Mofetil-Related Colitis: A Case Report.: Kyungeun Kim, Jerad M Gardner, Mary Schwartz, Matthew L Tompson, Jae Y Ro; Korean J Pathol. 2010;44(3):333-337.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.333

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Abstract PDF

Mycophenolate mofetil (MMF)-related colitis is one of the common causes of afebrile diarrhea in transplant patients. Pathologic diagnosis of MMF-related colitis is difficult because microscopic findings of MMF effects resemble those of graft-versus-host disease, inflammatory bowel disease and ischemic colitis. However, if diagnosed, MMF-induced colitis can be markedly improved by discontinuing the drug. A 70-year-old man having a history of transplantation presented with a one month history of afebrile diarrhea. Colonoscopy revealed patchy erosions. The colonoscopic biopsy specimen showed not only crypt disarray with degenerated crypts and scattered epithelial cell apoptosis, but also stromal inflammatory cell infiltration. A review of his medical records showed that he had been taking immunosuppressive drugs including MMF since his heart transplantation 6 years prior. The histologic findings of colonic mucosa were consistent with MMF-related colitis. After discontinuing MMF, the diarrhea quickly resolved and has not recurred for 10 months.

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Colitis eosinofílica inducida por micofenolato: reporte de caso
Mario Alberto Caviedes-Cleves, Ariel Antonio Arteta-Cueto
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Mycophenolate Mofetil-Induced Colonic Injury Manifesting Endoscopically As Ischemic Colitis
Clive J Miranda, Murad H Ali, Muddasir Ayaz, Raheel M Khan, Mayada Ismail
Cureus.2023;[Epub] CrossRef
Transformation of the Amino Acid Pool in the Rat Brain under Conditions of Experimental Immunodeficiency
N. I. Filina, M. N. Kurbat
Neurochemical Journal.2022; 16(2): 174. CrossRef
A Case Series of De Novo Inflammatory Bowel Disease After Kidney Transplantation
P. Azevedo, C. Freitas, P. Aguiar, H. Silva, T. Santos, P. Farrajota, M. Almeida, S. Pedroso, L.S. Martins, L. Dias, R. Vizcaíno, A. Castro Henriques, A. Cabrita
Transplantation Proceedings.2013; 45(3): 1084. CrossRef

Original Articles

Microscopic Colitis: The Pathologic Features of 24 Korean Patients.: Sun Ah Lee, Min Jung Kang, Sung Ae Jung, Heasoo Koo; Korean J Pathol. 2009;43(2):133-138.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.133

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Abstract PDF

BACKGROUND
The clinical presentation of microscopic colitis (MC) consists of chronic non-bloody watery diarrhea for weeks or months at a time, abdominal pain, and changes in bowel habits with a normal mucosal appearance upon performing colonoscopy. MC includes two relatively well established histopathologic entities: collagenous colitis (CC) and lymphocytic colitis (LC) as well as atypical forms. The recognition of the microscopic findings of this heterogeneous entity is very important for making the correct diagnosis and providing proper treatment.
METHODS
We studied the colonoscopic biopsy specimens that were obtained from 26 patients who had clinical findings that were suggestive of MC.
RESULTS
Fifteen patients (M:F=9:6) and 9 patients (M:F=5:4) showed the microscopic features of LC and MC, not otherwise specified, respectively.
CONCLUSIONS
The clinicopathologic findings (the incidence of the subtypes, the patients' ages and the male/female ratio) of the 24 cases of MC in this study showed differences from the previously reported findings from other countries. Further studies with a sufficient number of patients from multi-centers would be necessary to confirm the regional or ethnic influence.

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A Case of Methicillin-Resistant Staphylococcal Enterocolitis with Subsequent Development of Lymphocytic Colitis
Joong Ho Bae, Dong Soo Han, Hye Sun Park, Yil Sik Hyun, Tae Yeob Kim, Chang Soo Eun, Yong Cheol Jeon, Joo Hyun Sohn
Intestinal Research.2011; 9(2): 139. CrossRef

Clinicopathologic Characteristics of Ulcerative Colitis Diagnosed by Endoscopic Biopsy Specimen: An analysis of discrepancy between clinical and pathologic diagnosis.: Jong Yup Bae, Ho Guen Kim; Korean J Pathol. 1996;30(12):1091-1098.

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Abstract PDF: Chronic ulcerative colitis is a systemic inflammatory disease with uncertain etiology primarily involving the colonic mucosa. The mucosal biopsy interpretation is important for an evaluation of the disease state and further medical or surgical treatment. However, few clinical and pathological studies of the endoscopic diagnosis of this disease are available in Korea. Therefore, we evaluated the clinical and pathological characteristics of it diagnosed by endoscopic biopsy and analysed the reasons for the discrepancy between clinical and pathologic diagnosis for a more accurate endoscopic mucosal biopsy diagnosis in the future. A total of 702 cases of colonic mucosal biopsy specimens during Feb. 1994 and Jan. 1995 at Severance hospital, Yonsei University College of Medicine were reevaluated for the study. A clinical diagnosis of ulcerative colitis, after endoscopic examination, was made in 61(8.7%) cases. A pathological diagnosis was made when there is an increased inflammatory cell infiltration in the mucosa with evidences of a chronic crypt injury in the biopsy specimens. Using this criteria, a diagnosis was made in 32(52.3%) cases. In 29 cases the diagnosis was made in the first biopsy specimen and in the remaining 3 cases the diagnosis was made in the second or third biopsy specimens. No pathologic diagnosis of ulcerative colitis was made in the cases that clinical diagnosis was not. In the 32 cases diagnosed as ulcerative colitis, 14 cases were involved the rectum and sigmoid colon, 9 cases were involved up to the descending colon, 1 case was involved up to the transverse colon and 8 cases showed pancolonic involvement. In 29 cases, which ulcerative colitis was suspected clinically but was not consistent with it pathologically, 8 cases were proved to be ischemic colitis, 5 cases were acute infectious colitis and one case was Crohn's disease by repeat examination and follow up. Ten cases were histologically within normal range and lesions subsided spontaneously with no recurrence. A conclusive diagnosis could not be made in 5 cases during this study period. From these results, we conclude that ulcerative colitis can be diagnosed accurately by endoscopic biopsy, and clinical follow up and repeat examination are valuable in the differential diagnosis of this disease.

Obstructive Colitis: A Clinicopathologic Analysis of 7 Cases.: Jung Sun Kim, Yong Il Kim; Korean J Pathol. 1996;30(12):1116-1122.

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Abstract PDF: Obstructive colitis is an ulceroinflammatory lesion of the large intestine at a distance proximal to the obstructing or potentially obstructing lesion of any etiology. It has been suggested that a rise in the intraluminal pressure related to the obstruction results in a fall in the intramural blood flow with subsequent ischemic necrosis. We examined 7 cases of surgically resected obstructive colitis associated with distal constrictive adenocarcinoma of the large intestine. Two cases of the obstructive colitis were radiologically suspected prior to surgery either as a separate tumor mass or diverticulosis, and another case was suggested to be a tumor seeding by colonoscopy. Grossly, five cases presented with single or multiple, shallow, well-demarcated ulcerative lesions, and the remaining two were featured with a segmental ulcerative lesion the with pseudopolypoid area. The ulceroinflammatory lesions were separated from the distal obstructive carcinoma by a skipped zone of relatively normal mucosa measuring 4-43 cm. The proximal colon to the obstructive lesions were obviously dilated except in one case. Microscopically, mucosa and submucosa were replaced by granulation tissue, and showed inflammatory cell infiltration and fibrin exudates. Muscle coat often accompanied ischemic contraction. Fissuring was noted in one case. The recognition of these lesions prior to or during surgery is stressed based on the morphological features corresponding to an ischemic change in the proximal mucosa to the primary obstructive lesion.

Antibiotics-associated Pseudomembranous Colitis: A Clinico-Pathologic Analysis with Special Reference to Non-pseudomembranous Mucosal Change.: Jin Haeng Chung, Yong Il Kim; Korean J Pathol. 1997;31(4):308-313.

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Abstract PDF: The presence of volcano-shaped pseudomembrane(PM) formations above the inflamed mucosa has been referred to as the unique biopsy criterion of the pseudomembranous colitis, but PM might be lost during the bowel preparation, and such loss leads pathologists to erroneous interpretations of the endoscopic biopsy specimens. The purpose of this paper is to identify the additional diagnostic clue other than PM among various histologic features in pseudomembranous colitis. We reviewed sigmoidoscopic biopsy specimens from 13 cases of antibiotics-associated pseudomembranous colitis which was confirmed to reveal characteristic PM by endoscopy aside from the clinical history of antibiotics administration. The cases were divided into two groups: the presence of PM (n=7) and its absence (n=6). Both groups showed basically identical histology, which included features of glandular distension, epithelial necrosis, crypt abscess, regenerative glands and mucous plug within the necrotic/dilated glands. Mucous plugs within the necrotic/ dilated glands were found in all cases and seemed to be the most characteristic microscopic feature. Ten cases of resected chronic ulcerative colitis in the active stage were compared for a differential diagnosis of crypt abscess-associated mucosal change. None of them revealed necrotic gland with mucous plugs, although crypt abscess formation was common in both conditions. We conclude that presence of mucous plugs in the dilated/necrotic glands is a useful diagnostic clue even though the biopsy specimens fail to demonstrate PM.

Case Report

Crohn's Disease Involving Small Intestine and Colon: 2 cases report.: Shi Nae Lee, Sun Hee Chang, Hee Soo Yoon, Hea Soo Koo, Ok Kyung Kim, Ryung Ah Lee, Eung Beum Park; Korean J Pathol. 1997;31(4):379-382.

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Abstract PDF: Crohn's disease was originally described as a small bowel disorder and has been known to involve the large bowel in approximately 40% of all cases with or without concomitant ileal component. We describe two cases of Crohn's diseas of small intestine and colon with a summary of differential diagnosis with ulcerative colitis. Both cases were originally diagnosed and treated as ileal tuberculosis. Grossly, there were skip lesions in both cases with prominent pseudopolyps and ulcerations in colon. Also noted were typical serpentine lesions in ileum as well as in colon. Microscopically, transmural inflammation was confirmed and one case showed scattered noncaseating granulomas in the wall. Submucosal edema and fibrosis with thickening of the wall was not prominent in colon. Polymerase chain reaction performed on paraffin block for the demonstration of Mycobacterium tuberculosis in one case showed negative reaction.

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.

Histopathological Features of Endoscopic Biopsies in Ischemic Colitis.: Young Lyun Oh, Cheol Keun Park; Korean J Pathol. 1999;33(7):490-496.

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Abstract PDF: Ischemic colitis still remains largely underdiagnosed despite the fact that it is one of the most common disorders of the large bowel. The aims of the present study were to evaluate the variable histologic findings of ischemic colitis and to find out helpful histopathological features in diagnosis. Retrospective review of the clinical symptoms, underlying diseases, endoscopic findings of 23 patients, and the histologic features of 37 biopsies was done. We analyzed the significant pathologic features in the histologically diagnosed ischemic colitis group and compared the biopsy time between the histologically diagnosed ischemic colitis group and the non-diagnosed group. Comparison of the endoscopic biopsy time between the group that showed significant histologic features and the group that showed no significant histologic features was also done. The age of the patients ranged from 27 to 87 years. Most patients had abdominal pain, hematemesis, and melena. Endoscopic differential diagnoses included ischemic colitis, ulcerative colitis, infectious colitis, tuberculous colitis, Crohn's disease, and pseudomembranous colitis. Histologic features and diagnoses were also variable. The coagulative necrosis of mucosa and the epithelial desquamation were frequently detected in the group pathologically diagnosed as ischemic colitis. The most pathognomonic finding was coagulative necrosis of the mucosa that was almost always detected within seven days after the onset of clinical symptoms. Recognition of variable patterns of ischemic colitis in a biopsy specimen will direct the clinician to evaluate the vascular system. Early endoscopic biopsy is essential for the precise diagnosis of ischemic colitis.

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.

Case Report

Localized Pseudopolyposis of the Ascending Colon Associated with Granulomatous Colitis: A case report.: Jeong Ja Kwak, Kye Hyun Kwon, So Young Jin, Dong Wha Lee; Korean J Pathol. 1994;28(1):82-85.

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Abstract PDF: Pseudopolyps represent discrete areas of mucosal inflammation and regeneration that are seen in a variety of inflammatory bowel disease including ulcerative colitis and Crohn's disease. These polyps are typically short, measuring less than 1.5 cm in height. Rarely, localized giant pseudopolyposis can occur, i.e., a collection of larger inflammatory pseudopolyps giving rise to a mass lesion within the colon. The most serious problem concerned with pseudopolyposis is a confusion with carcinoma. We experienced a case of localized giant pseudopolyposis causing partial large bowel obstruction. Right hemicolectomy was done for a preoperative diagnosis of ascending colon carcinoma. The resected specimen contained a circumferential lesion, which was composed of numerous interconnecting cylindrical villi, measuring 12 cm in length and 3 cm in height. Microscopically, these polypoid lesions were inflammatory pseudopolyps. Several deep fissure-like ulcerations were noted with multifocal microabscess, lymphoid hyperplasia and an area of noncaseating granuloma.

Original Article

Neonatal Necrotizing Enterocolitis: Pathologic analysis of 14 cases.: Yeon Lim Suh, Je G Chi; Korean J Pathol. 1993;27(2):115-124.

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Abstract PDF: We reviewed surgical or autopsy specimens of the gastrointestinal tract from 14 patients with necrotizing enterocolitis(NEC) to define the specific pathologic findings and the pathologic changes of the bowel in the premature and fullterm infants, and then to see how these findings are related each other and to clinical features. In two-thirds of patients two or more continuous segments of the gastrointestinal tract were affected, and the ileum and colon were by far the most common sites of involvement. Pathologically, coagulation necrosis, inflammatory reaction, ulceration, microthrombi, overgrowth of microorganism, and perforation were the leading changes of NEC. On the basis of these histopathologic findings of the involving intestine, we could classify the pathology of NEC into two different histologic types. Type 1 and II are thought to represent pathologic changes of the intestine in acute and chronic stages of disease process. The symptom duration of the patients was significantly different between two types. The pathologic changes of the involved bowel were similar in both premature and fullterm infants, although the premature tended to have type 1 and the fullterm babies had more cases of type II. These pathologic changes could be associated with various clinical manifestation of NEC.

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