Progression of low-grade dysplasia to advanced neoplasia based on the location and morphology of dysplasia in ulcerative colitis patients with extensive colitis under colonoscopic surveillance

Navaneethan, Udayakumar; Jegadeesan, Ramprasad; Gutierrez, Norma G.; Venkatesh, Preethi G.K.; Hammel, Jeffrey; Shen, Bo; Kiran, Ravi P.

doi:10.1016/j.crohns.2013.06.006

Cited by 70 publications

(50 citation statements)

References 20 publications

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“…Fusobacterium nucleatum numbers are significantly correlated with tumor size, and shortened survival times in a population of human Japanese patients with later stage CRC compared to earlier stages 53. These findings, as well as additional observations in rodent models and humans with CRC suggest that chronic inflammatory disease of the GI tract is a potential risk factor for the development of additional channels for amplified inflammatory processes, aneuploidy, high‐grade dysplasia, metaplasia and loss of cellular proliferative checkpoints, all of which are processes that can be appreciated in malignancy 13, 19, 54, 58, 59. The increased numbers of mucosal Fusobacterium spp.…”

Section: Discussionmentioning

confidence: 82%

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Garraway

Johannes

Bryan

et al. 2018

Veterinary Internal Medicne

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BackgroundThe gastrointestinal (GI) microbiota in healthy cats is altered in IBD. Little research has been performed to identify whether specific bacterial groups are associated with small cell GI lymphoma (LSA).HypothesisMucosal bacteria, including Enterobacteriaceae and Fusobacterium spp., are abundant in intestinal biopsies of cats with small cell GI LSA compared to cats with IBD.AnimalsFourteen cats with IBD and 14 cats with small cell GI LSA.MethodsRetrospective case control study. A search of the medical records was performed to identify cats diagnosed with IBD and with GI LSA. Bacterial groups identified by FISH in GI biopsies were compared between cohorts and correlated to CD11b+ and NF‐κB expression.Results Fusobacterium spp. (median; IQR bacteria/region) were higher in cats with small cell GI LSA in ileal (527; 455.5 – 661.5; P = .046) and colonic (404.5; 328.8 – 455.5; P = .016) adherent mucus, and combined colonic compartments (free mucus, adherent mucus, attaching to epithelium) (8; 0 – 336; P = .017) compared to cats with IBD (ileum: 67; 31.5 – 259; colon: 142.5; 82.3 – 434.5; combined: 3; 0 – 34). Bacteroides spp. were higher in ileal adherent mucus (P = .036) and 3 combined ileal compartments (P = .034) of cats with small cell GI LSA. There were significant correlations between Fusobacterium spp. totals and CD11b+ cell (P = .009; rs .476) and NF‐κB expression (P = .004; rs .523).ConclusionsThe bacterial alterations appreciated might be influential in development of small cell GI LSA, and should drive further studies to elucidate the effects of microbial‐mediated inflammation on GI cancer progression.

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Section: Discussionmentioning

confidence: 82%

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Garraway

Johannes

Bryan

et al. 2018

Veterinary Internal Medicne

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“…Associated factors with progression from LGD to advanced neoplasia were available in six studies. 7,18-20,23,25 The quality of the included studies is shown in Supplementary Table 1. There was no high-quality study; four studies were classified as low-quality.…”

Section: Resultsmentioning

confidence: 99%

“…Five studies reported rates of progression to advanced neoplasia in patients with non-visible (‘flat’) LGD and endoscopically visible dysplasia (DALM/ALM lesions), separately. 19,20,21,23,24 On meta-analysis, pooled IR of advanced neoplasia in patients with non-visible LGD was 6.1 per 100-patient year follow-up (95% CI, 0.9-11.4), and with endoscopically visible dysplasia was 1.0 per 100-patient year follow-up (95% CI, 0-2.1).…”

Section: Resultsmentioning

confidence: 99%

“…7,18-20,23,25 Where ≥2 studies reported on same risk factor, meta-analysis was performed and is summarized in Table 2. Concomitant PSC (OR, 3.4; 95% CI, 1.5-7.8), invisible dysplasia (vs. visible dysplasia) (OR, 1.9; 95% CI, 1.0-3.4), distal dysplasia location (vs. proximal to splenic flexure) (OR, 2.0; 95% CI, 1.1-3.7) and multifocal dysplasia (vs. unifocal dysplasia) (OR, 3.5; 95% CI, 1.5-8.5) were significantly associated with progression to advanced neoplasia.…”

Section: Resultsmentioning

confidence: 99%

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Incidence, Risk Factors, and Outcomes of Colorectal Cancer in Patients With Ulcerative Colitis With Low-Grade Dysplasia: A Systematic Review and Meta-analysis

Fuméry

Dulai

Gupta

et al. 2017

Clinical Gastroenterology and Hepatology

130

111

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Background & Aims Little is known about outcomes of patients with ulcerative colitis with low-grade dysplasia (UC-LGD). We estimated the incidence of and risk factors for progression to colorectal cancer (CRC) in cohorts of patients with UC-LGD who underwent surveillance (surveillance cohort), and the prevalence of dysplasia-related findings among patients who underwent colectomy for UC-LGD (surgical cohort). Methods We performed a systematic literature review through June 1, 2016 to identify cohort studies of adults with UC-LGD. We estimated pooled incidence rates of CRC and risk factors associated with dysplasia progression in surveillance cohorts, and prevalence of synchronous advanced neoplasia (CRC and/or high-grade dysplasia) in surgical cohorts. Results In 14 surveillance cohort studies of 671 patients with UC-LGD (52 developed CRC), the pooled annual incidence of CRC was 0.8% (95% CI, 0.4–1.3); the pooled annual incidence of advanced neoplasia was 1.8% (95% CI, 0.9–2.7). Risk of CRC was higher when LGD was diagnosed by expert gastrointestinal pathologist (1.5%) than by community pathologists (0.2%). Factors significantly associated with dysplasia progression were concomitant primary sclerosing cholangitis (OR, 3.4; 95% CI, 1.5–7.8), invisible dysplasia (vs visible dysplasia; OR, 1.9; 95% CI, 1.0–3.4), distal location (vs proximal location; OR, 2.0; 95% CI, 1.1–3.7) and multifocal dysplasia (vs unifocal dysplasia; OR, 3.5; 95% CI, 1.5– 8.5). In 12 surgical cohort studies of 450 patients who underwent colectomy for UC-LGD, 34 patients had synchronous CRC (pooled prevalence, 17%; 95% CI, 8–33). Conclusion In a systematic review of the literature, we found that among patients with UC-LGD under surveillance, the annual incidence of progression to CRC was 0.8%; differences in rates of LGD diagnosis varied with pathologists' level of expertise. Concomitant primary sclerosing cholangitis, invisible dysplasia, distal location, and multifocal LGD are high-risk features associated with dysplasia progression.

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“…Colorectal cancer is the cancer of lower digestive system which has been implicated in patients with a history of chronic ulcerative colitis (UC), an inflammatory bowel disease (IBD) (Eaden et al , 2001; Xie and Itzkowitz, 2008; Navaneethan et al , 2013). It is the cancer of western world but has recently been reported with increasing frequencies in several South Asian countries, including India (Sung et al , 2005; Ray, 2011).…”

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confidence: 99%

Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia

et al. 2017

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Background:Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma.Methods:Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia. Findings from the study are also compared with previously published genome wide and exome sequencing data in inflammatory bowel disease-associated and sporadic colorectal carcinoma.Results:Next-generation sequencing analysis identified 1107 mutations in 275 genes in UCHR subjects. In addition to TP53 (17%) and KRAS (22%) mutations, recurrent mutations in APC (33%), ACVR2A (61%), ARID1A (44%), RAF1 (39%) and MTOR (61%) were observed in UCHR subjects. In addition, APC, FGFR3, FGFR2 and PIK3CA driver mutations were identified in UCHR subjects. Recurrent mutations in ARID1A (44%), SMARCA4 (17%), MLL2 (44%), MLL3 (67%), SETD2 (17%) and TET2 (50%) genes involved in histone modification and chromatin remodelling were identified in UCHR subjects.Conclusions:Our study identifies new oncogenic driver mutations which may be involved in the transition of non-dysplastic cells to dysplastic phenotype in the subjects with long-standing UC with high risk of progression into colorectal neoplasia.

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Progression of low-grade dysplasia to advanced neoplasia based on the location and morphology of dysplasia in ulcerative colitis patients with extensive colitis under colonoscopic surveillance

Abstract: The frequency of progression of LGD to AN is low. Flat dysplasia located in the distal colon is associated with a greater risk of progression to AN.

Cited by 70 publications

References 20 publications

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Incidence, Risk Factors, and Outcomes of Colorectal Cancer in Patients With Ulcerative Colitis With Low-Grade Dysplasia: A Systematic Review and Meta-analysis

Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia

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