Browsing by Author "Carneiro, Fatima"
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- Comparing the continuous geboes score with the Robarts Histopathology Index: definitions of histological remission and response and their relation to faecal calprotectin levelsPublication . Magro, Fernando; Lopes, Joanne; Borralho, Paula; Lopes, Susana; Coelho, Rosa; Cotter, Jose; de Castro, Francisca Dias; Sousa, Helena Tavares; Salgado, Marta; Andrade, Patricia; Vieira, Ana Isabel; Figueiredo, Pedro; Caldeira, Paulo; Sousa, A.; Duarte, Maria A.; Avila, Filipa; Silva, Joao; Moleiro, Joana; Mendes, Sofia; Giestas, Silvia; Ministro, Paula; Sousa, Paula; Goncalves, Raquel; Goncalves, Bruno; Oliveira, Ana; Chagas, Cristina; Cravo, Marilia; Dias, Claudia Camila; Afonso, Joana; Portela, Francisco; Santiago, Mafalda; Geboes, Karel; Carneiro, FatimaBackground and Aims: The histological status of ulcerative colitis [UC] patients in clinical and endoscopic remission has gained space as an important prognostic marker and a key component of disease monitoring. Our main aims were to compare two histological indexes-the continuous Geboes score [GS] and the Robarts Histopathology index [RHI]-regarding their definitions of histological remission and response, and the ability of faecal calprotectin [FC] levels to discriminate between these statuses. Methods: This was an analysis of three prospective cohorts including 422 patients previously enrolled in other studies. Results: The two continuous scores [GS and RHI] were shown to be significantly correlated [correlation coefficient of 0.806, p < 0.001] and particularly close regarding their definition of histological response: 95% and 88% of all patients classified as having/not having [respectively] histological response according to RHI also did so according to GS. Moreover, median FC levels in patients with histological response were lower than those in patients without histological response [GS: 73.00 vs 525.00, p < 0.001; RHI: 73.50 vs 510.00, p < 0.001]; a similar trend was observed when FC levels of patients in histological remission were compared to those of patients with histological activity [GS: 76.00 vs 228.00, p < 0.001; RHI: 73.50 vs 467.00, p < 0.001]. FC levels allowed us to exclude the absence of histological remission [according to RHI] and absence of histological response [according to RHI and GS], with negative predictive values varying from 82% to 96%. However, optimization of the FC cut-off to exclude the absence of histological remission, as for the continuous GS, falls within values that resemble those of the healthy population. Conclusion: The continuous GS and RHI histological scores are strongly correlated in their definitions of histological response. An absence of histological remission could only be excluded at physiological levels of FC.
- Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levelsPublication . Magro, Fernando; Lopes, Joanne; Borralho, Paula; Lopes, Susana; Coelho, Rosa; Cotter, Jose; de Castro, Francisca Dias; Sousa, Helena Tavares; Salgado, Marta; Andrade, Patricia; Vieira, Ana Isabel; Figueiredo, Pedro; Caldeira, Paulo; Sousa, A.; Duarte, Maria A.; Avila, Filipa; Silva, Joao; Moleiro, Joana; Mendes, Sofia; Giestas, Silvia; Ministro, Paula; Sousa, Paula; Goncalves, Raquel; Goncalves, Bruno; Oliveira, Ana; Rosa, Isadora; Rodrigues, Marta; Chagas, Cristina; Dias, Claudia Camila; Afonso, Joana; Geboes, Karel; Carneiro, FatimaObjective Histological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems-Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels. Design Biopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients' Mayo Endoscopic Score and FC levels. Result GS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa. Conclusions GS, NI and RHI histopathological scoring systems are comparable in what concerns patients' stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.
- Methylation patterns in dysplasia in inflammatory bowel disease patientsPublication . Rosa, Isadora; Silva, Patricia; da Mata, Sara; Magro, Fernando; Carneiro, Fatima; Peixoto, Armando; Silva, Marco; Sousa, Helena Tavares; Roseira, Joana; Parra, Jose; Barosa, Rita; Vieira, Ana; Brito, Maria Jos; Lago, Paula; Coelho, Andre; Moleiro, Joana; da Silva, Joao Pereira; Fonseca, Ricardo; Albuquerque, Cristina; Dias Pereira, A.Background and aims:Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis. Methods:Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification. Results:Mean age at IBD diagnosis: 42 +/- 16 years;at dysplasia diagnosis: 56 +/- 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation ofIGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation ofMSH6, TIMP3was significantly associated to IBD-related dysplasia/cancer. Promoter methylation ofMSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1,BCL2genes was significantly associated to active IBD. Conclusions:Methylation analysis, namely ofMSH6, may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies.
- Transmural histological scoring systems in Crohn's Disease: A systematic review With assessment of methodological quality and operating propertiesPublication . Sousa, Helena Tavares; Estevinho, Maria Manuela; Peyrin-Biroulet, Laurent; Danese, Silvio; Dias, Claudia Camila; Carneiro, Fatima; Magro, FernandoBackground: The relative proportion of inflammation and fibrosis in a stricture is highly relevant in defining the clinical approach for Crohn's disease [CD] patients. Whereas transmural inflammation in CD can be accurately estimated by cross-sectional imaging, evaluating the extent and severity of fibrosis still requires surgical pathology of intestinal resection specimens.This study systematically reviewed all existing transmural histopathological scoring systems developed for the assessment of inflammation and/or fibrosis in CD. Methods: A systematic review of histopathological scoring systems for the assessment of transmural inflammation and/or fibrosis in CD, focusing on originally developed scoring systems. Risk of bias, methodological quality, and operating or psychometric properties [validity, reliability, responsiveness, and feasibility] of each histological scoring system were analysed. Results: A total of 29 original scoring systems were included in this review. Three scoring systems were highlighted as the most widely reproduced, one aimed at assessing inflammation only and two aimed at assessing inflammation and fibrosis. These scores were more widely reproduced probably due to their ease of application in clinical studies. Two highly comprehensive scores were identified, showing good operating properties and high methodological quality, as well as the lowest risk of bias; these should, therefore, be further validated in clinical research studies. Conclusions: This study reviewed all existing transmural histopathological scoring systems for the assessment of inflammation and/or fibrosis in CD and identified the most reliable and accurate scores for clinical research and clinical practice settings.