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1.
Indian J Med Microbiol ; 38(3 & 4): 261-264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154233

RESUMO

Although children with novel coronavirus infection (COVID-19) typically present with fever and respiratory symptoms, some children have reported gastrointestinal (GI) symptoms including vomiting and diarrhoea during the course of the disease. The continuous positive detection of the viral RNA from faeces in children even after nasopharyngeal swabs turned negative suggests that the GI tract may shed virus and a tentative faecal-oral transmission. The presence of angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2, which are the key proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry process, in the GI tract can explain the digestive symptoms in COVID-19. COVID-19 has implications for the management of children with chronic luminal diseases. There is increasing concern regarding the risk that children with inflammatory bowel disease being infected with SARS-CoV-2.


Assuntos
Infecções por Coronavirus/patologia , Gastroenteropatias/diagnóstico , Gastroenteropatias/patologia , Trato Gastrointestinal/patologia , Pneumonia Viral/patologia , Betacoronavirus , Criança , Infecções por Coronavirus/diagnóstico , Fezes/virologia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Humanos , Doenças Inflamatórias Intestinais/patologia , Pandemias , Pneumonia Viral/diagnóstico , RNA Viral/isolamento & purificação
2.
J Immunol Res ; 2020: 2847316, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062719

RESUMO

Objectives: The COVID-19 epidemic triggered by coronavirus SARS-CoV-2 is rapidly spreading around the globe. This study is aimed at finding out the suspected or confirmed SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD) in Hubei province, China. We also investigated symptoms, medications, life quality, and psychological issues of IBD patients under the ongoing pandemic. Methods: We conducted a self-reported questionnaire survey via an online survey platform. SARS-CoV-2 infection-related data was collected from IBD patients. The status quo of medications and symptoms of the subjects were investigated. Life quality, depression, and anxiety were measured by clinical questionnaires and rated on scoring systems. Results: A total of 204 IBD patients from Hubei province were included in this study. No suspected or confirmed SARS-CoV-2 infection case was found in this study. As a result of city shutdown, two-thirds of the patients (138/204) in our series reported difficulty in accessing medicines and nearly half of them (73/138) had to discontinue medications. Apart from gastrointestinal symptoms, systemic symptoms were common while respiratory symptoms were rare in the cohort. Though their quality of life was not significantly lowered, depression and anxiety were problems that seriously affected them during the COVID-19 epidemic. Conclusions: Inaccessibility to medications is a serious problem for IBD patients after city shutdown. Efforts have to be made to address the problems of drug withdrawal and psychological issues that IBD patients suffer from during the COVID-19 outbreak.


Assuntos
Infecções por Coronavirus/epidemiologia , Acesso aos Serviços de Saúde , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Ansiedade/psicologia , Betacoronavirus/efeitos dos fármacos , China/epidemiologia , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Pandemias , Qualidade de Vida/psicologia , Inquéritos e Questionários
3.
Anticancer Res ; 40(10): 5411-5416, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988861

RESUMO

BACKGROUND: Patients with inflammatory bowel disease have markedly increased risk for developing colitis-associated colorectal adenocarcinoma (CAC). There is no established prognostic biomarker for CAC. MATERIALS AND METHODS: A retrospective study was performed on a cohort of 57 CACs. Expression of caudal type homeobox transcription factor 2 (CDX2) and YES-associated protein 1 (YAP1) expression was correlated with clinicodemographic and histopathological features. RESULTS: Neither YAP1 nor CDX2 expression alone was significantly associated with tumor invasion beyond the muscularis propria or lymph node status. However, a subgroup of CAC with double negativity for expression of YAP1 and CDX2 was more frequently found in younger patients, and more frequently associated with higher pathological tumor stage and nodal metastasis. Furthermore, a positive correlation between CDX2 and YAP1 expression was identified in CAC and sporadic colorectal adenocarcinoma. CONCLUSION: Our study demonstrates that double negativity for expression of YAP1 and CDX2 defines a subgroup of CAC with early onset and aggressive clinical features.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Fator de Transcrição CDX2/genética , Colite/genética , Neoplasias Colorretais/genética , Fatores de Transcrição/genética , Adenocarcinoma/complicações , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Biomarcadores Tumorais/genética , Colite/complicações , Colite/patologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
4.
Z Gastroenterol ; 58(9): 868-871, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32947632

RESUMO

BACKGROUND: Concurrent cytomegalovirus (CMV) in inflammatory bowel disease (IBD)-related colitis is an important scenario associated with high rates of colectomy and other morbidity. Due to the low incidence of CMV, testing of all patients is associated with an unacceptably high consumption of resources and delay in treatment. Therefore, several predictive scores have been developed to identify patients at risk for a CMV infection. METHODS: We performed a retrospective single center study in a German University hospital including all IBD patients with available data on CMV-PCR analysis in whole blood between 2010 and 2018 and evaluated 2 prognostic scores for CMV infection for their diagnostic accuracy. RESULTS: In the study, 907 patients with IBD and CMV-PCR were identified. Of them, 21 patients (2.3 %) had a positive CMV-PCR (≥ 1000 copies/mL), 14 of them in ulcerative colitis and 7 in Crohn's disease. The Berlin Score identified 667 patients (73.1 %) as potentially CMV-positive, resulting in a positive predictive value of 2.5 % and a negative predictive value of 98.3 %. In contrast, the Münster Score identified 60 patients as potentially CMV-positive, resulting in a PPV of 20 % and an NPV of 99.4 %. CONCLUSIONS: Scoring systems can help to identify patients at risk for a CMV infection and minimize resource consumption and delay in treatment. Due to low incidence, a 2-step-algorithm, consisting of the Münster Score followed by a CMV-PCR if the score indicates a CMV infection, is preferable.


Assuntos
Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Doenças Inflamatórias Intestinais/complicações , Infecções Oportunistas/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa , Citomegalovirus/genética , Infecções por Citomegalovirus/sangue , DNA Viral/análise , Feminino , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/sangue , Infecções Oportunistas/patologia , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
5.
Inflamm Res ; 69(12): 1163-1172, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32886145

RESUMO

Gut homeostasis is a process that requires a prudent balance of host responses to the beneficial enteric microbial community and the pathogenic stimuli that can arise. The lack of this balance in the intestine can result in inflammatory bowel diseases, where the immune system dysfunctions leading to exacerbated inflammatory responses. In this process, macrophages are considered to play a pivotal role. In this review, we describe the important role of macrophages in maintaining intestinal homeostasis and we discuss how altered macrophage function may lead to inflammatory bowel diseases. The plasticity of macrophages during the gut inflammatory response shows the broad role of these cells in orchestrating not only the onset of inflammation but also its termination as well as healing and repair. Indeed, the state of macrophage polarization can be the key factor in defining the resolution or the progression of inflammation and disease. Here, we discuss the different populations of macrophages and their implication in development, propagation, control and resolution of inflammatory bowel diseases.


Assuntos
Enterite/patologia , Homeostase , Intestinos/patologia , Intestinos/fisiologia , Macrófagos/patologia , Macrófagos/fisiologia , Animais , Polaridade Celular , Humanos , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/fisiopatologia , Ativação de Macrófagos
6.
Cell Prolif ; 53(10): e12900, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32914514

RESUMO

Colorectal cancer (CRC) has become a concern because of its high recurrence rate and metastasis rate, low early diagnosis rate and poor therapeutic effect. At present, various studies have shown that autophagy is closely connected with the occurrence and progression of CRC. Autophagy is a highly cytosolic catabolic process involved in lysosomes in biological evolution. Cells degrade proteins and damaged organelles by autophagy to achieve material circulation and maintain cell homeostasis. Moreover, microRNAs are key regulators of autophagy, and their mediated regulation of transcriptional and post-transcriptional levels plays an important role in autophagy in CRC cells. This review focuses on the recent research advances of how autophagy and related microRNAs are involved in affecting occurrence and progression of CRC and provides a new perspective for the study of CRC treatment strategies.


Assuntos
Autofagia , Neoplasias Colorretais/patologia , MicroRNAs/metabolismo , Antineoplásicos/uso terapêutico , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Pontos de Checagem do Ciclo Celular/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
9.
Lancet Gastroenterol Hepatol ; 5(11): 986-995, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32818437

RESUMO

BACKGROUND: Use of antibiotics in early life has been linked with childhood inflammatory bowel disease (IBD), but data for adults are mixed, and based on smaller investigations that did not compare risk among siblings with shared genetic or environmental risk factors. We aimed to investigate the association between antibiotic therapy and IBD in a large, population-based study. METHODS: In this prospective case-control study, we identified people living in Sweden aged 16 years or older, with a diagnosis of IBD based on histology and at least one diagnosis code for IBD or its subtypes (ulcerative colitis and Crohn's disease). We identified consecutive patients with incident IBD from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, cross-referenced with the Swedish Patient Register and the Prescribed Drug Register. We accrued data for cumulative antibiotic dispensations until 1 year before time of matching for patients and up to five general population controls per patient (matched on the basis of age, sex, county, and calendar year). We also included unaffected full siblings as a secondary control group. Conditional logistic regression was used to estimate multivariable-adjusted odds ratios (aORs) and 95% CIs for diagnosis of incident IBD. FINDINGS: We identified 23 982 new patients with IBD (15 951 ulcerative colitis, 7898 Crohn's disease, 133 unclassified IBD) diagnosed between Jan 1, 2007, and Dec 31, 2016. 117 827 matched controls and 28 732 siblings were also identified. After adjusting for several risk factors, aOR in patients who had used antibiotics versus those who had never used antibiotics was 1·88 (95% CI 1·79-1·98) for diagnosis of incident IBD, 1·74 (1·64-1·85) for ulcerative colitis, and 2·27 (2·06-2·49) for Crohn's disease. aOR was higher in patients who had received one antibiotic dispensation (1·11, 1·07-1·15), two antibiotic dispensations (1·38, 1·32-1·44), and three or more antibiotic dispensations (1·55, 1·49-1·61) than patients who had none. Increased risk was noted for ulcerative colitis (aOR with three or more antibiotic dispensations 1·47, 95% CI 1·40-1·54) and Crohn's disease (1·64, 1·53-1·76) with higher estimates corresponding to broad-spectrum antibiotics. Similar but attenuated results were observed when siblings were used as the reference group, with an aOR of 1·35 (95% CI 1·28-1·43) for patients who had received three or more dispensations, compared with general population controls. INTERPRETATION: Higher cumulative exposure to systemic antibiotic therapy, particularly treatments with greater spectrum of microbial coverage, may be associated with a greater risk of new-onset IBD and its subtypes. The association between antimicrobial treatment and IBD did not appear to differ when predisposed siblings were used as the reference controls. Our findings, if substantiated by longer-term prospective studies in humans or mechanistic preclinical investigations, suggest the need to further emphasise antibiotic stewardship to prevent the rise in dysbiosis-related chronic diseases, including IBD. FUNDING: National Institutes of Health. Crohn's and Colitis Foundation.


Assuntos
Antibacterianos , Disbiose , Doenças Inflamatórias Intestinais , Adolescente , Adulto , Idade de Início , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Biópsia/estatística & dados numéricos , Estudos de Casos e Controles , Sistemas de Informação em Farmácia Clínica/estatística & dados numéricos , Disbiose/induzido quimicamente , Disbiose/prevenção & controle , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/patologia , Masculino , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco , Irmãos , Suécia/epidemiologia
10.
Nat Rev Gastroenterol Hepatol ; 17(9): 543-556, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32651553

RESUMO

The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. As the transit-amplifying progenitors of the intestinal epithelium generate ~300 cells per crypt every day, regulated cell death and sloughing at the apical surface keeps the overall cell number in check. An aberrant increase in the rate of intestinal epithelial cell (IEC) death underlies instances of extensive epithelial erosion, which is characteristic of several intestinal diseases such as inflammatory bowel disease and infectious colitis. Emerging evidence points to a crucial role of necroptosis, autophagy and pyroptosis as important modes of programmed cell death in the intestine in addition to apoptosis. The mode of cell death affects tissue restitution responses and ultimately the long-term risks of intestinal fibrosis and colorectal cancer. A vicious cycle of intestinal barrier breach, misregulated cell death and subsequent inflammation is at the heart of chronic inflammatory and infectious gastrointestinal diseases. This Review discusses the underlying molecular and cellular underpinnings that control programmed cell death in IECs, which emerge during intestinal diseases. Translational aspects of cell death modulation for the development of novel therapeutic alternatives for inflammatory bowel diseases and colorectal cancer are also discussed.


Assuntos
Morte Celular/fisiologia , Células Epiteliais/patologia , Doenças Inflamatórias Intestinais/etiologia , Mucosa Intestinal/patologia , Humanos , Inflamação , Doenças Inflamatórias Intestinais/patologia
11.
Postepy Biochem ; 66(2): 143-150, 2020 06 27.
Artigo em Polonês | MEDLINE | ID: mdl-32700508

RESUMO

Inflammatory bowel diseases are a group of chronic diseases of the digestive tract of unknown origin. The etiology of IBD is multifactorial and involves interaction between genetic, environmental and immunological factors with oxidative stress being an inherent part of any one of them. Therefore, the redox equilibrium is crucial to maintain cell homeostasis in the gastrointestinal (GI) tract, which is constantly exposed to large numbers of commensal and pathological bacteria. Distortion of this homeostasis and increase in oxidative stress leads to the propagation of inflammation, mucosal injury in the GI tract and is associated with the development and exacerbation of IBD.


Assuntos
Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/metabolismo , Estresse Oxidativo , Homeostase , Humanos , Inflamação , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Oxirredução
12.
Adv Clin Exp Med ; 29(5): 547-556, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32424999

RESUMO

BACKGROUND: The effect of bowel inflammation and cancer on the expression of the most prevalent internal controls: ACTB, GAPDH and B2M in whole blood is unknown, although at least GAPDH occurred to be tightly regulated and suspected of supporting cancer growth, challenging its suitability as a reference. OBJECTIVES: To evaluate the effect of colorectal cancer (CRC) and active inflammatory bowel disease (IBD) on the stability of ACTB, B2M, GAPDH, HPRT1, SDHA, and TBP leukocyte expression. MATERIAL AND METHODS: Gene expression in controls and CRC and IBD patients (n = 21/18/25) was evaluated in real-time quantitative polymerase chain reaction (RT-qPCR) using NormFinder, geNorm, BestKeeper, and comparative ΔCt method, and validated by comparison with absolute quantification of interleukin 1ß (IL-1ß) and CCL4. RESULTS: HPRT1, SDHA and TBP were superior normalizers in CRC and IBD. The highest expression variability was noted in active IBD. B2M was significantly lower in CRC but higher in IBD. GAPDH was higher in CRC and IBD. ACTB and GAPDH corresponded with CRC advancement (ρ = 0.52 and ρ = 0.53) and with clinical activity in Crohn's disease (ρ = 0.44 and ρ = 0.57) and ulcerative colitis (GAPDH: ρ = 0.72). ACTB, B2M and GAPDH correlated with circulating inflammatory/angiogenic indices, differently in IBD and CRC. CONCLUSIONS: Leukocyte GAPDH, ACTB, and B2M expression is affected by bowel inflammation and cancer, rendering them unsuitable as a reference in CRC and IBD.


Assuntos
Actinas/sangue , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Perfilação da Expressão Gênica/métodos , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/sangue , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Microglobulina beta-2/sangue , Actinas/metabolismo , Indutores da Angiogênese/sangue , Quimiocina CCL4 , Neoplasias Colorretais/metabolismo , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Interleucina-1beta , Fragmentos de Peptídeos , Padrões de Referência , Microglobulina beta-2/metabolismo
13.
Hum Pathol ; 100: 24-37, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32387105

RESUMO

Distinct histomorphologic features of colitis-associated dysplasia (CAD) or neoplastic precursors in inflammatory bowel disease (IBD) have never been clearly identified. In this study, we tried to further explore the differentiating morphologic features of CAD by retrospectively reviewing the lesions that were clearly associated with carcinomas (carcinoma-related lesions) and by comparing between endoscopically nonpolypoid (non-adenoma-like) lesions and polypoid (adenoma-like) lesions and sporadic conventional adenomas found in the noncolitic mucosa and in patients without IBD. Our study results have revealed that (1) precursor lesions related to IBD-associated colorectal carcinomas were almost always nonpolypoid in macroscopic/endoscopic appearance; (2) nearly half of the carcinoma-related lesions and nonpolypoid lesions were similarly nonadenomatous (nonconventional) lesions, largely serrated type, with no or only mild/focal adenomatous dysplasia, and commonly had mixed adenomatous and nonadenomatous features; (3) carcinoma-related and nonpolypoid adenomatous dysplastic lesions frequently showed some peculiar histocytologic features that we observed and described for the first time, including mixed features of inflammatory pseudopolyps or granulation tissue, pleomorphic and disarrayed nuclei, micropapillary or hobnailing surface epithelial cells, and microvesicular or bubbling cytoplasm of dysplastic cells; and (4) polypoid lesions in the colitic mucosa were identical to sporadic adenomas in the noninflamed mucosa and in patients without IBD, and they lacked the aforementioned features. The seemingly distinctive morphologic characteristics that we proposed here, although still not absolutely specific or unique, can be used as the features of inclusion for identifying CAD on endoscopic biopsies when the endoscopy images are not readily available to pathologists and thus to alert clinicians for a closer follow-up.


Assuntos
Pólipos Adenomatosos/patologia , Colo/patologia , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
PLoS Pathog ; 16(5): e1008553, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32453761

RESUMO

IRGM and its mouse orthologue Irgm1 are dynamin-like proteins that regulate vesicular remodeling, intracellular microbial killing, and pathogen immunity. IRGM dysfunction is linked to inflammatory bowel disease (IBD), and while it is thought that defective intracellular killing of microbes underscores IBD susceptibility, studies have yet to address how IRGM/Irgm1 regulates immunity to microbes relevant to intestinal inflammation. Here we find that loss of Irgm1 confers marked susceptibility to Citrobacter rodentium, a noninvasive intestinal pathogen that models inflammatory responses to intestinal bacteria. Irgm1-deficient mice fail to control C. rodentium outgrowth in the intestine, leading to systemic pathogen spread and host mortality. Surprisingly, susceptibility due to loss of Irgm1 function was not linked to defective intracellular killing of C. rodentium or exaggerated inflammation, but was instead linked to failure to remodel specific colon lamina propria (C-LP) myeloid cells that expand in response to C. rodentium infection and are essential for C. rodentium immunity. Defective immune remodeling was most striking in C-LP monocytes, which were successfully recruited to the infected C-LP, but subsequently underwent apoptosis. Apoptotic susceptibility was induced by C. rodentium infection and was specific to this setting of pathogen infection, and was not apparent in other settings of intestinal inflammation. These studies reveal a novel role for Irgm1 in host defense and suggest that deficiencies in survival and remodeling of C-LP myeloid cells that control inflammatory intestinal bacteria may underpin IBD pathogenesis linked to IRGM dysfunction.


Assuntos
Citrobacter rodentium/imunologia , Colo/imunologia , Infecções por Enterobacteriaceae/imunologia , Proteínas de Ligação ao GTP/deficiência , Doenças Inflamatórias Intestinais/imunologia , Monócitos/imunologia , Animais , Colo/microbiologia , Colo/patologia , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/patologia , Proteínas de Ligação ao GTP/imunologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Camundongos , Camundongos Knockout , Monócitos/microbiologia , Monócitos/patologia , Membrana Mucosa/imunologia , Membrana Mucosa/microbiologia , Membrana Mucosa/patologia
15.
Aliment Pharmacol Ther ; 52(1): 5-19, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32432797

RESUMO

INTRODUCTION: The prognosis of dysplasia in patients with IBD is largely determined from observational studies from the pre-videoendoscopic era (pre-1990s) that does not reflect recent advances in endoscopic imaging and resection. AIMS: To better understand the risk of synchronous colorectal cancer and metachronous advanced neoplasia (ie high-grade dysplasia or cancer) associated with dysplasia diagnosed in the videoendoscopic era, and to stratify risk according to a lesion's morphology, endoscopic resection status or whether it was incidentally detected on biopsy of macroscopically normal colonic mucosa (ie invisible). METHODS: A systematic search of original articles published between 1990 and February 2020 was performed. Eligible studies reported on incidence of advanced neoplasia at follow-up colectomy or colonoscopy for IBD-dysplasia patients. Quantitative and qualitative analyses were performed. RESULTS: Thirty-three studies were eligible for qualitative analysis (five for the meta-analysis). Pooled estimated proportions of incidental synchronous cancers found at colectomy performed for a pre-operative diagnosis of visible high-grade dysplasia, invisible high-grade dysplasia, visible low-grade dysplasia and invisible low-grade dysplasia were 13.7% (95% CI 0.0-54.1), 11.4% (95% CI 4.6-20.3), 2.7% (95% CI 0.0-7.1) and 2.4% (95% CI 0.0-8.5) respectively. The lowest incidences of metachronous advanced neoplasia, for dysplasia not managed with immediate colectomy but followed up with surveillance, tended to be reported by the studies where high definition imaging and/or chromoendoscopy was used and endoscopic resection of visible dysplasia was histologically confirmed. CONCLUSIONS: The prognosis of IBD-dysplasia diagnosed in the videoendoscopic era appears to have been improved but the quality of evidence remains low. Larger, prospective studies are needed to guide management. PROSPERO registration no: CRD42019105736.


Assuntos
Colo/diagnóstico por imagem , Colonoscopia/métodos , Doenças Inflamatórias Intestinais/complicações , Mucosa Intestinal/diagnóstico por imagem , Colo/patologia , Humanos , Hiperplasia/diagnóstico por imagem , Hiperplasia/etiologia , Hiperplasia/patologia , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Adv Exp Med Biol ; 1238: 11-22, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32323177

RESUMO

The gastrointestinal (GI) tract is inhabited by a diverse array of microbes, which play crucial roles in health and disease. Dysbiosis of microbiota has been tightly linked to gastrointestinal inflammatory and malignant diseases. Here we highlight the role of Helicobacter pylori alongside gastric microbiota associated with gastric inflammation and cancer. We summarize the taxonomic and functional aspects of intestinal microbiota linked to inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and colorectal cancer in clinical investigations. We also discuss microbiome-related animal models. Nevertheless, there are tremendous opportunities to reveal the causality of microbiota in health and disease and detailed microbe-host interaction mechanisms by which how dysbiosis is causally linked to inflammatory disease and cancer, in turn, potentializing clinical interventions with a personalized high efficacy.


Assuntos
Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Disbiose/microbiologia , Disbiose/patologia , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Animais , Helicobacter pylori/patogenicidade , Humanos , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/patologia
17.
Am J Surg Pathol ; 44(7): 955-961, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32235151

RESUMO

Surveillance colonoscopies focused to detect dysplasia are recommended to prevent colorectal cancer in patients with long-standing colonic inflammatory bowel disease (IBD). To date, histologic diagnosis and gradation of IBD-related dysplasia has been challenged by a high variability among pathologists. We aimed to analyze the observer characteristics that are correlated with concordance deviations in this diagnosis. Eight pathologists evaluated a set of 125 endoscopic biopsy samples with a representative distribution of nondysplastic and dysplastic lesions from long-standing IBD patients. Two rounds of diagnosis were carried out during a period of 18 months. The κ test was applied to analyze concordance. Pathologists were grouped on the basis of their experience. A subanalysis was performed by eliminating the highly prevalent nondysplastic samples, as well as an analysis after observers' grouping. Overall interobserver agreement was good (κ=0.73), with an even higher pairwise value (κ=0.86) as well as the intraobserver agreement values (best κ=0.85). After eliminating the highly prevalent nondysplastic samples, the interobserver agreement was still moderate to good (best overall κ=0.50; best paired κ=0.72). Notable differences were seen between the pathologists with a high-volume and low-volume practice (best overall κ=0.61 and 0.41, respectively). The agreement in the diagnosis of dysplasia in IBD endoscopic biopsies may have been undervalued over time. This is the first study evaluating pathologists' diagnostic robustness in this field. The results suggest that examining a large volume of samples is the key factor to increase the consistency in the diagnosis and gradation of IBD-related dysplasia.


Assuntos
Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Lesões Pré-Cancerosas/patologia , Biópsia , Colo/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Consenso , Humanos , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Mucosa Intestinal/diagnóstico por imagem , Variações Dependentes do Observador , Patologistas , Lesões Pré-Cancerosas/diagnóstico por imagem , Estudos Prospectivos
18.
Nature ; 580(7803): 386-390, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32296174

RESUMO

The aetiology of inflammatory bowel disease (IBD) is a multifactorial interplay between heredity and environment1,2. Here we report that deficiency in SETDB1, a histone methyltransferase that mediates the trimethylation of histone H3 at lysine 9, participates in the pathogenesis of IBD. We found that levels of SETDB1 are decreased in patients with IBD, and that mice with reduced SETDB1 in intestinal stem cells developed spontaneous terminal ileitis and colitis. SETDB1 safeguards genome stability3, and the loss of SETDB1 in intestinal stem cells released repression of endogenous retroviruses (retrovirus-like elements with long repeats that, in humans, comprise approximately 8% of the genome). Excessive viral mimicry generated by motivated endogenous retroviruses triggered Z-DNA-binding protein 1 (ZBP1)-dependent necroptosis, which irreversibly disrupted homeostasis of the epithelial barrier and promoted bowel inflammation. Genome instability, reactive endogenous retroviruses, upregulation of ZBP1 and necroptosis were all seen in patients with IBD. Pharmaceutical inhibition of RIP3 showed a curative effect in SETDB1-deficient mice, which suggests that targeting necroptosis of intestinal stem cells may represent an approach for the treatment of severe IBD.


Assuntos
Instabilidade Genômica , Histona-Lisina N-Metiltransferase/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Necroptose , Células-Tronco/metabolismo , Animais , Histona-Lisina N-Metiltransferase/genética , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Camundongos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Células-Tronco/citologia
19.
Phytother Res ; 34(10): 2649-2664, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32281697

RESUMO

Inflammatory bowel disease (IBD) is a chronic autoimmune disease associated with various risk factors. Pycnoporus sanguineus (L.) Murrill is a saprotrophic fungus used worldwide for its industrial and medical purposes. Here, polysaccharide from P. sanguineus (PPS) was explored for its antiinflammatory potential in a murine colitis model of IBD induced by dextran sulfate sodium (DSS). PPS ameliorated the colitis as manifested by the lowered disease activity index (DAI), prolonged colon, and reduced serum lipopolysaccharide (LPS). PPS recovered the histological lesion by upregulating the expressions of Zonula occludens-1 (ZO-1), E-cadherin, and proliferating cell nuclear antigen (PCNA). PPS inhibited the helper T cells (Th)-mediated immune response by decreasing the proportions of Th cells (including Th2 cells, Th17 cells, and regulatory T cells), which was accompanied with reductions on myeloperoxidase (MPO) activity and releases of several interleukins and chemokines within the colon. Moreover, PPS exhibited an evident inhibition on autophagy, in which the ratio of light chain 3 (LC3) II/I was declined, while the expression of p62 and Beclin-1 was increased. The present study highlighted important clinical implications for the treatment application of PPS against IBD, which relies on the regulation of Th cells repertoire and autophagy suppression to restore epithelium barrier.


Assuntos
Autofagia/efeitos dos fármacos , Colite/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Doenças Inflamatórias Intestinais/induzido quimicamente , Polissacarídeos/metabolismo , Pycnoporus/química , Linfócitos T Reguladores/metabolismo , Animais , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
20.
Sci Rep ; 10(1): 6346, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286352

RESUMO

To investigate the diagnostic value of texture analysis (TA) for differentiating between colorectal cancer (CRC), colonic lesions caused by inflammatory bowel disease (IBD), and normal thickened colon wall (NTC) on computed tomography (CT) and assess which scanning phase has the highest differential diagnostic value. In all, 107 patients with CRC, 113 IBD patients with colonic lesions, and 96 participants with NTC were retrospectively enrolled. All subjects underwent multiphase CT examination, including pre-contrast phase (PCP), arterial phase (AP), and portal venous phase (PVP) scans. Based on these images, classification by TA and visual classification by radiologists were performed to discriminate among the three tissue types. The performance of TA and visual classification was compared. Precise TA classification results (error, 2.03-12.48%) were acquired by nonlinear discriminant analysis for CRC, IBD and NTC, regardless of phase or feature selection. PVP images showed a better ability to discriminate the three tissues by comprising the three scanning phases. TA showed significantly better performance in discriminating CRC, IBD and NTC than visual classification for residents, but there was no significant difference in classification between TA and experienced radiologists. TA could provide useful quantitative information for the differentiation of CRC, IBD and NTC on CT, particularly in PVP images.


Assuntos
Colo/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Diagnóstico Diferencial , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Idoso , Colo/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
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