Submucosal Fibrosis and Basic-Fibroblast Growth Factor-Positive Neutrophils Correlate with Colonic Stenosis in Cases of Ulcerative Colitis

Yamagata, Masaru; Mikami, Taisei; Tsuruta, Tomoko; Yokoyama, Keitaro; Sada, Miwa; Kobayashi, Kiyonori; Katsumata, Tomoe; Koizumi, Wasaburou; Saigenji, Katsunori; Okayasu, Isao

doi:10.1159/000320773

Cited by 62 publications

(51 citation statements)

References 34 publications

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“…For a long time, it was assumed that UC-related strictures were caused by muscular hypertrophy and thickening of the muscularis mucosae and muscularis propria rather than from fibrosis. However, recent studies have suggested that the cause of colonic stenosis in longstanding UC is fibrosis, possibly induced by inflammatory neutrophils producing b-FGF [25].…”

Section: Discussionmentioning

confidence: 99%

Ulcerative Colitis: Are We Neglecting Its Progressive Character

Massinha

Portela

Campos

et al. 2017

GE Port J Gastroenterol

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"lead pipe," 16% with pseudopolyps, and 3% with stenosis and fibrous bridges. Reference to functional anorectal disorders was identified in 49%, mostly previous and self-limited episodes of incontinence, but including persistent incontinence in 10% (CCIS 8 ± 4.8). There was an increased incidence of structural damage and anorectal dysfunction in patients who needed corticosteroid therapy (p = 0.001), immunosuppressants (p < 0.001), and anti-TNFs (p = 0.002) and an association of structural damage with anorectal dysfunction (p < 0.001). There was no association between age and anorectal dysfunction, including incontinence episodes. Conclusions: UC is a disease with structural and functional consequences in a significant subset of patients. This should be incorporated when defining the therapeutic strategy. AbstractIntroduction: Ulcerative colitis (UC) is a chronic disease but its progressive character, with structural damage, is insufficiently studied. Objectives: To analyze a group of patients without referral bias, regarding its clinical course, the morphological damage, and functional status. Methods: We evaluated UC patients diagnosed between January 1, 2000 and December 31, 2004, living in the direct referral area of the hospital and determined the medication use, colectomy rate, structural damage ("lead pipe," stenosis, pseudopolyps, fibrous bridges), and anorectal function (prospective evaluation with the Cleveland Clinic Incontinence Score [CCIS] and the Fecal Incontinence Quality of Life Scale). Results: We identified 104 patients, 47% female, with a mean age at diagnosis of 38 ± 17 years, 24% with proctitis, 57% with left colitis, and 19% with pancolitis. In 3 patients, it was not possible to obtain follow-up data. Of the studied patients, 56% needed corticosteroid therapy, 38% immunosuppressants, and 16% anti-tumor necrosis factors (anti-TNFs). After a mean follow-up of 13 ± 2 years, we found structural damage in 25 patients (24%): 5% with proctocolectomy, 15% with ResumoIntrodução: A colite ulcerosa (CU) é uma doença crónica mas o seu carácter progressivo, com danos estruturais, encontra-se insuficientemente estudado. Objetivos: Analisar um grupo de doentes, sem viés de referenciação, quanto ao percurso clínico, aos danos morfológicos e ao estado funcional. Métodos: Avaliaram-se os doentes com diagnóstico de CU estabelecido entre 01-01-2000 e 31-12-2004, com residência na área de referenciação directa do hospital, tendo-se determinado a medicação usada, a taxa de colectomia, os danos estruturais ("cano de chumbo", estenoses, pseudopolipos, pontes fibrosas) ou funcionais ano-rectais (avaliação prospectiva com Cleaveland Clinic Incontinence Score, CCIS e Fecal Incontinence Quality of Life, FIQL). Resultados: Identificaram-se 104 doentes, 47% do sexo feminino, idade média no diagnós-tico de 38 ± 17 anos, proctite 24%, colite esquerda 57%, pancolite 19%. Em 3 doentes não foi possível obter dados de seguimento. Dos doentes estudados 56% tiveram necessidade de corticoterapia, 38% de imunossupressores e ...

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Section: Discussionmentioning

confidence: 99%

Ulcerative Colitis: Are We Neglecting Its Progressive Character

Massinha

Portela

Campos

et al. 2017

GE Port J Gastroenterol

View full text Add to dashboard Cite

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“…They also confirmed the overexpression of bFGF in the epithelium of patients with colitis (23). Yamagata et al reported the variability of concentration of bFGF in a single patient with colitic cancer and showed a higher bFGF-positive cell count in stenotic sites than that in non-stenotic sites (25). These reports imply that bFGF and its pathway play key roles in activated inflammation induced by immune dysfunction.…”

Section: Discussionmentioning

confidence: 98%

Colitic Cancer Develops Through Mutational Alteration Distinct from that in Sporadic Colorectal Cancer: A Comparative Analysis of Mutational Rates at Each Step

Tanaka

Kobunai

Yamamoto

et al. 2017

CGP

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Abstract. Background: Patients with ulcerative colitis (UC)are at risk of UC-associated Colorectal carcinogenesis is considered to develop through multistep genetic or epigenetic alteration along with the pathological change called the adenoma-carcinoma sequence (1-5). Further accumulation of genetic changes confers invasiveness or metastatic potential on the tumor (6, 7), and to date, several indicators have been identified to predict outcomes (7,8). In contrast, colitic cancer, which develops through inflammation-prone carcinogenesis in patients with ulcerative colitis (UC), has a somewhat different etiology (9). UC is characterized by chronic inflammation of the colonic mucosa, and the underlying causes of inflammation are the disturbance or disorganization of the epithelial barrier, alteration of colonic microflora, and abnormal immune response caused by the dysregulation of the mucosal immune system (10). During the progression of colitis, genetic alterations associated with mucosal permeability [e.g. those in extracellular matrix protein 1 (ECM1), cadherin 1 (CDH1), and hepatocyte nuclear factor 4 alpha (HNF4A)] have been observed and considered to confer the risk of severe UC (11,12). The pathogenesis of colitic cancer originates from longstanding and severe bowel inflammation and differs from that of sporadic CRC in several aspects. For instance, colitic cancer often occurs multifocally and is widespread; therefore, performing total coloproctectomy is recommended if any dysplastic or cancerous lesions are identified in patients with UC. Moreover, the behavior and morphology of colitic cancer differ from those of sporadic CRC in that colitic cancer often invades to deeper layers of the bowel wall at an earlier stage of progression; this feature makes it difficult to identify dysplastic lesions when the tumor elevation and size is not large. These distinctive characteristics of colitic cancer are likely to be caused by its genetic etiology, which is different from that of sporadic cancer. However, to date, little information is available in this regard.In this study, we compared the mutation of oncogenes in colitic cancer to those in sporadic cancer. In addition, we examined the non-neoplastic mucosa of patients with colitic cancer, so as to identify the step in UC carcinogenesis in 341

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“…Colorectal strictures may occur in both Crohn's disease (CD) and ulcerative colitis (UC) (3,4,5). Old referral centers studies, most of them published before the 90's, reported a prevalence of colonic stricture in UC ranging from 1.5% to 11% (6,7,8,9,10,11) and from 10 to 14% in CD (12,13). The occurrence of colonic strictures raises concerns about the risk of dysplasia/cancer in IBD patients.…”

Section: Methodsmentioning

confidence: 99%

“…Characteristics of the study population are listed in Table 1 [1][2][3][4][5][6][7][8][9][10][11][12] years in UC and 8 [3][4][5][6][7][8][9][10][11][12][13][14] years in CD.…”

Section: Study Populationmentioning

confidence: 99%