Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 89
Filtrar
1.
Digestion ; : 1-12, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34518458

RESUMO

INTRODUCTION: The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins. METHODS: A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence. RESULTS: The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data. CONCLUSIONS: None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.

2.
J Crohns Colitis ; 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34272945

RESUMO

BACKGROUND: While the exact aetiology of microscopic colitis (MC) remains unknown, a dysregulated immune response to luminal factors or medications is the most accepted pathogenesis hypothesis. OBJECTIVE: Systematic review of the pathogenesis of MC. METHODS: We applied the Joanna Briggs Institute methodologies and the PRISMA statement for the reporting of systematic reviews (PROSPERO Trial Identifier: CRD42020145008). Populations, Exposure of interest and Outcome (PEO) questions were used to explore the following topics in MC: 1) intestinal luminal factors, 2) autoimmunity, 3) innate and 4) adaptive immunity, 5) extracellular matrix, 6) genetic risk factors and the 7) mechanism of diarrhoea. A search was done in PubMed, Embase and Web of Science for up to February 2020. A narrative description was performed explaining the findings for each aspect of MC etiopathogenesis. RESULTS: Thirty-eight documents provided evidence for PEO1, 100 for PEO2, 72 for PEO3 and 4, 38 for PEO5, 20 for PEO6 and 23 for PEO7. The majority of documents were cohorts, case reports and case series, with a few case-control and some experimental studies. Consistency among data provided by different studies was considered to support pathogenic hypotheses. MC is a multifactorial disease believed to involve innate and adaptive immune responses to luminal factors, genetic risk, autoimmunity, and extracellular matrix alterations, all contributing to watery diarrhoea by varied mechanisms. CONCLUSION: This is the first systematic review on the aetiology of MC supporting the notion that MC is a multifactorial disease. However, high-profile studies are lacking, and most evidence derive from small heterogeneous studies.

3.
Int J Mol Sci ; 22(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34298894

RESUMO

(1) The high-fat diet (HFD) of western countries has dramatic effect on the health of several organs, including the digestive tract, leading to the accumulation of fats that can also trigger a chronic inflammatory process, such as that which occurs in non-alcohol steatohepatitis. The effects of a HFD on the small intestine, the organ involved in the absorption of this class of nutrients, are still poorly investigated. (2) To address this aspect, we administered a combined HFD with sucrose (HFD w/Suc, fat: 58% Kcal) regimen (18 months) to mice and investigated the morphological and molecular changes that occurred in the wall of proximal tract of the small intestine compared to the intestine of mice fed with a standard diet (SD) (fat: 18% Kcal). (3) We found an accumulation of lipid droplets in the mucosa of HFD w/Suc-fed mice that led to a disarrangement of mucosa architecture. Furthermore, we assessed the expression of several key players involved in lipid metabolism and inflammation, such as perilipin, leptin, leptin receptor, PI3K, p-mTOR, p-Akt, and TNF-α. All these molecules were increased in HFD mice compared to the SD group. We also evaluated anti-inflammatory molecules like adiponectin, adiponectin receptor, and PPAR-γ, and observed their significant reduction in the HFD w/Suc group compared to the control. Our data are in line with the knowledge that improper eating habits present a primary harmful assault on the bowel and the entire body's health. (4) These results represent a promising starting point for future studies, helping to better understand the complex and not fully elucidated spectrum of intestinal alterations induced by the overconsumption of fat.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/administração & dosagem , Sacarose na Dieta/efeitos adversos , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Adiponectina/metabolismo , Animais , Comportamento Alimentar/fisiologia , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/patologia , PPAR gama/metabolismo , Receptores para Leptina/metabolismo
4.
Pol J Pathol ; 72(1): 87-88, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34060292

RESUMO

We read with great interest the review article "Lymphocytic gastritis" by Puderecki et al., which was recently published in your journal [1]. The article describes the features of lymphocytic gastritis (LG), a rare form of gastritis with unclear pathogenesis. The diagnosis of LG is based on histology which reveals intraepithelial lymphocytosis (> 25 intraepithelial lymphocytes per 100 gastric surface and foveolar epithelial cells). The endoscopic appearance of LG can vary from normal mucosa to aphthous erosions, nodularity, local spots, polyps, and ulcers. The most common locations of the lesions are the body and the antrum. With regard to etiology, Celiac disease (CD) is the main reported cause of LG, followed by Helicobacter pylori infection. After a careful review of the argument, Puderecki et al. conclude that there is no one exact cause of LG, and rather than being a separate disease, LG is more likely a sign of the disease with which it is associated [1]. We wrote to remark on the strong connection between LG and CD. Such a connection may allow some etiopathogenetic and clinical speculations.


Assuntos
Doença Celíaca , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Mucosa Gástrica , Infecções por Helicobacter/complicações , Humanos
5.
Virchows Arch ; 479(4): 667-678, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33963925

RESUMO

Most Crohn's disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Histologic patterns and phenotypic markers potentially predictive of CrD-SBC histogenesis and prognosis were analysed. Cytokeratin 7 or MUC5AC-positive metaplastic changes were found in about half of investigated CrD-SBCs, significantly more frequently than in CrD-unrelated SBCs. They correlated with metaplastic changes of their associated mucosa, while being absent in normal ileal mucosa. Histologic patterns suggestive for progression of some cytokeratin 7 and/or MUC5AC-positive metaplastic lesions into cancer of the same phenotype were also observed. Patient survival analyses showed that tumour cytokeratin 7 or MUC5AC expression and non-cohesive histotype were adverse prognostic factors at univariable analysis, while cytokeratin 7 and non-cohesive histotype were also found to predict worse survival in stage- and age-inclusive multivariable analyses. Besides conventional dysplasia, hyperplasia-like non-conventional lesions were observed in CrD-SBC-associated mucosa, with patterns suggestive for a histogenetic link with adjacent cancer. In conclusion the cytokeratin 7 and/or MUC5AC-positive metaplastic foci and the non-conventional growths may have a role in cancer histogenesis, while tumour cytokeratin 7 and non-cohesive histotype may also predict poor patient survival. Present findings are worth being considered in future prospective histogenetic and clinical studies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34034270

RESUMO

BACKGROUND AND AIM: Serum transglutaminase antibodies (tTGs) are used for celiac disease screening and to monitor celiac disease patients on a gluten-free diet (GFD). The need for histology of duodenal biopsies to assess mucosal healing after a GFD is still a matter of debate. We evaluated whether tTGs are adequate to detect the persistence of histological lesions of duodenal mucosa in celiac patients after a GFD. METHODS: In total 253 patients with histological diagnosis of celiac disease according to Marsh criteria, both at the time of diagnosis (T0) and 18-24 months after starting a GFD (T2), were included. tTGs were evaluated both at T0 and T2; endomysial antibodies (EMAs) only at T0. RESULTS: At T0, 9.2% of patients had both tTG and EMA negative values, despite the evidence of duodenal lesions: 33.3% of Marsh 1, 14.3% of Marsh 2 and 5.2% of Marsh 3. At T2, tTGs were negative in 77.6% of patients: 82.2% of Marsh 0, 79.8% of Marsh 1, 70.0% of Marsh 2 and 59.1% of Marsh 3. At T2, approximately 60% of patients with the persistence of mucosal atrophy had negative tTGs. At T0, tTG median values were lower in patients with Marsh 1 and Marsh 2 than patients with Marsh 3 (P < 0.001), whereas no difference was found at T2 regardless of Marsh's grade (P = 0.4). CONCLUSIONS: The results of our study highlight how histologic evaluation of duodenal biopsies remains the gold standard for both celiac disease diagnosis and the evaluation of mucosal recovery after 18-24 months of a GFD.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33619914

RESUMO

INTRODUCTION: Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, nonbloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. METHODS: Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. RESULTS: These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. CONCLUSION: These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.

8.
Nutrients ; 13(2)2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33499406

RESUMO

The main role of vitamin D is calcium homeostasis and bone metabolism, although its activity as an immuno-modulator and its anti-inflammatory effect is well-known. Low blood vitamin D levels are common among patients with inflammatory bowel disease (IBD). Whether low vitamin D levels could affect the disease activity or it is an effect of a worse condition of the disease is still unclear. This study aimed to investigate the role of blood vitamin D levels to identify the clinical, endoscopic, and histological activity in a cohort of patients with ulcerative colitis (UC) or Crohn's disease (CD) on therapy with biological drugs. In this retrospective cohort study, 50 IBD patients (24 UC and 26 CD) that underwent colonoscopy from January 2017 to January 2020 with a concomitant serological evaluation of vitamin D were included. Patients with clinical, endoscopic, and histological activity and those who lost their clinical response to the biological drug had lower vitamin D levels compared to patients in remission or patients that did not change therapeutic regimens. A receiver operating characteristic (ROC) analysis and Youden's Index were performed to assess the optimal vitamin D levels to identify patients with the active disease. The ROC analysis showed an area under the curve (AUC) of 0.709 (p = 0.005; confidence interval (CI): 0.564-0.829), 0.769 (p < 0.001; CI: 0.628-0.876), and 0.810 (p < 0.001; CI: 0.670-0.910) for the clinical, endoscopic, and histological outcomes, respectively. The optimal vitamin D cut-off was ≤25 ng/mL. The vitamin D level is an additional useful tool in the evaluation of IBD patients with good accuracy to predict their endoscopic and histological activity and clinical response to biologics.


Assuntos
Produtos Biológicos/uso terapêutico , Colite Ulcerativa/sangue , Doença de Crohn/sangue , Vitamina D/sangue , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
9.
Int J Med Sci ; 18(3): 593-603, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33437194

RESUMO

Sleep disturbances often result from inappropriate lifestyles, incorrect dietary habits, and/or digestive diseases. This clinical condition, however, has not been sufficiently explored in this area. Several studies have linked the circadian timing system to the physiology of metabolism control mechanisms, energy balance regulation, and nutrition. Sleep disturbances supposedly trigger digestive disorders or conversely represent specific clinical manifestation of gastrointestinal (GI) diseases. Poor sleep may worsen the symptoms of GI disorders, affecting the quality of life. Conversely, short sleep may influence dietary choices, as well as meal timing, and the circadian system drives temporal changes in metabolic patterns. Emerging evidence suggests that patients with inappropriate dietary habits and chronic digestive disorders often sleep less and show lower sleep efficiency, compared with healthy individuals. Sleep disturbances may thus represent a primary symptom of digestive diseases. Further controlled trials are needed to fully understand the relationship between sleep disturbances, dietary habits, and GI disorders. It may be also anticipated that the evaluation of sleep quality may prove useful to drive positive interventions and improve the quality of life in a proportion of patients. This review summarizes data linking sleep disorders with diet and a series of disease including gastro-esophageal reflux disease, peptic disease, functional gastrointestinal disorders, inflammatory bowel diseases, gut microbiota alterations, liver and pancreatic diseases, and obesity. The evidence supporting the complex interplay between sleep dysfunction, nutrition, and digestive diseases is discussed.


Assuntos
Gastroenteropatias/complicações , Doenças Negligenciadas/complicações , Transtornos Nutricionais/complicações , Transtornos do Sono-Vigília/complicações , Ritmo Circadiano/fisiologia , Digestão/fisiologia , Gastroenteropatias/fisiopatologia , Humanos , Doenças Negligenciadas/fisiopatologia , Transtornos Nutricionais/fisiopatologia , Qualidade de Vida , Sono/fisiologia , Transtornos do Sono-Vigília/fisiopatologia
10.
Int J Mol Sci ; 22(3)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498177

RESUMO

The pathophysiological processes of inflammatory bowel diseases (IBDs), i.e., Crohn's disease (CD) and ulcerative colitis (UC), are still not completely understood. The exact etiology remains unknown, but it is well established that the pathogenesis of the inflammatory lesions is due to a dysregulation of the gut immune system resulting in over-production of pro-inflammatory cytokines. Increasing evidence underlines the involvement of both environmental and genetic factors. Regarding the environment, the microbiota seems to play a crucial role. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that exert pleiotropic effects on glucose homeostasis, lipid metabolism, inflammatory/immune processes, cell proliferation, and fibrosis. Furthermore, PPARs modulate interactions with several environmental factors, including microbiota. A significantly impaired PPARγ expression was observed in UC patients' colonic epithelial cells, suggesting that the disruption of PPARγ signaling may represent a critical step of the IBD pathogenesis. This paper will focus on the role of PPARγ in the interaction between environmental factors and IBD, and it will analyze the most suitable in vitro and in vivo models available to better study these relationships.


Assuntos
Meio Ambiente , Doenças Inflamatórias Intestinais/metabolismo , PPAR gama/metabolismo , Animais , Microbioma Gastrointestinal , Homeostase , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/microbiologia , PPAR gama/genética
11.
Medicina (Kaunas) ; 57(2)2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33504050

RESUMO

Background and Objectives: Conflicting evidence is reported regarding any association between colonic diverticula with colorectal adenomas or cancer. The present study aimed to evaluate, in a cohort of Caucasian patients, the association between colonic diverticula and colorectal polyps and cancer. Materials and Methods: All consecutive patients undergoing colonoscopy at our institution were included in the study. The presence and location of diverticula, polyps, and cancers were recorded. Histologically, polyps were classified as adenoma (with low or high dysplasia), hyperplastic, or inflammatory. The relative risk of the association of polyps and cancer with diverticula was assessed. Multiple logistic regression analyses, including age, sex, family history for colorectal cancer (CRC), and family history for diverticula, were carried out. Results: During the study period, 1490 patients were enrolled; 37.2% (n = 555) showed colonic diverticula or polyps or CRC (308 males, mean age 66 years). Particularly, 12.3% (n = 183) patients presented only diverticula, 13.7% (n = 204) only polyps or cancer, 11.3% (n = 168) both diseases, and 62.7% (n = 935) neither diverticula nor polyps and cancer. A total of 38 patients presented colorectal cancer, 17 of which had also diverticula. A significant increase in relative risk (RR 2.81, 95% CI 2.27-3.47, p < 0.0001) of colorectal adenoma and cancer in patients with colonic diverticula was found. At multivariate analysis, only diverticula resulted to be significantly associated with colorectal adenomas and cancer (Odds Ratio, OR 3.86, 95% CI 2.90-5.14, p < 0.0001). Conclusions: A significant association of colonic diverticula with colorectal adenoma or cancer was found. This implies that patients with colonic diverticula require a vigilant follow-up procedure for the prevention of colorectal cancer from those applicable to the general population.


Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Divertículo do Colo , Adenoma/complicações , Adenoma/epidemiologia , Idoso , Pólipos do Colo/complicações , Pólipos do Colo/epidemiologia , Colonoscopia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Divertículo do Colo/complicações , Divertículo do Colo/epidemiologia , Humanos , Masculino
12.
Nutrients ; 13(1)2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33401525

RESUMO

The development of colorectal cancer, responsible for 9% of cancer-related deaths, is favored by a combination of genetic and environmental factors. The modification of diet and lifestyle may modify the risk of colorectal cancer (CRC) and prevent neoplasia in up to 50% of cases. The Western diet, characterized by a high intake of fat, red meat and processed meat has emerged as an important contributor. Conversely, a high intake of dietary fiber partially counteracts the unfavorable effects of meat through multiple mechanisms, including reduced intestinal transit time and dilution of carcinogenic compounds. Providing antioxidants (e.g., vitamins C and E) and leading to increased intraluminal production of protective fermentation products, like butyrate, represent other beneficial and useful effects of a fiber-rich diet. Protective effects on the risk of developing colorectal cancer have been also advocated for some specific micronutrients like vitamin D, selenium, and calcium. Diet-induced modifications of the gut microbiota modulate colonic epithelial cell homeostasis and carcinogenesis. This can have, under different conditions, opposite effects on the risk of CRC, through the production of mutagenic and carcinogenic agents or, conversely, of protective compounds. The aim of this review is to summarize the most recent evidence on the role of diet as a potential risk factor for the development of colorectal malignancies, as well as providing possible prevention dietary strategies.


Assuntos
Neoplasias do Colo/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Dieta , Dieta Hiperlipídica/efeitos adversos , Dieta Ocidental , Fibras na Dieta , Ingestão de Alimentos , Epigenômica , Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Humanos , Minerais , Carne Vermelha , Vitaminas
13.
Ann Surg Oncol ; 28(2): 1167-1177, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32761330

RESUMO

BACKGROUND: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer. PATIENTS AND METHODS: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability. RESULTS: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status. CONCLUSIONS: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.


Assuntos
Adenocarcinoma , Neoplasias Colorretais , Adenocarcinoma/genética , Reparo de Erro de Pareamento de DNA/genética , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Prognóstico
14.
Rev Esp Enferm Dig ; 113(2): 154-155, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33207902

RESUMO

We read with great interest the article "Effectiveness and safety of adalimumab biosimilar ABP 501 in Crohn's disease: an observational study" by Ribaldone et al., which was recently published in your journal. The authors report the first real-life study of the adalimumab biosimilar ABP 501 in Crohn's disease (CD). The study investigated the short-term effectiveness and safety of ABP 501 in 87 patients with CD, 25 patients naïve to adalimumab and 62 switched from the adalimumab originator. A meaningful proportion of CD patients treated with ABP 501 showed clinical benefit with a satisfactory safety profile until the end of follow-up.


Assuntos
Medicamentos Biossimilares , Doença de Crohn , Adalimumab/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Doença de Crohn/tratamento farmacológico , Humanos
15.
Cancers (Basel) ; 12(11)2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33228145

RESUMO

Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small SBA series, often including a very limited number of Crohn's disease-associated SBAs (CrD-SBAs) and celiac disease-associated SBAs (CD-SBA), have been investigated for SATB2 expression. We evaluated the expression of SATB2 and other GI phenotypic markers (cytokeratin (CK) 7 and CK20, caudal type homeobox 2 (CDX2) and alpha-methylacyl-CoA racemase (AMACR)), as well as mismatch repair (MMR) proteins, in 100 SBAs, encompassing 34 CrD-SBAs, 28 CD-SBAs and 38 sporadic cases (Spo-SBAs). Any mutual association and correlation with other clinico-pathologic features, including patient prognosis, were searched. Twenty (20%) SATB2-positive SBAs (4 CrD-SBAs, 7 CD-SBAs and 9 Spo-SBAs) were identified. The prevalence of SATB2 positivity was lower in CrD-SBA (12%) in comparison with both CD-SBAs (25%) and Spo-SBAs (24%). Interestingly, six SBAs (two CD-SBAs and four Spo-SBAs) displayed a full colorectal carcinoma (CRC)-like immunoprofile (CK7-/CK20+/CDX2+/AMACR+/SATB2+); none of them was a CrD-SBA. No association between SATB2 expression and MMR status was observed. Although SATB2-positive SBA patients showed a more favorable outcome in comparison with SATB2-negative ones, the difference did not reach statistical significance. When cancers were stratified according to CK7/CK20 expression patterns, we found that CK7-/CK20- SBAs were enriched with MMR-deficient cases (71%) and patients with CK7-/CK20- or CK7-/CK20+ SBAs had a significantly better survival rate compared to those with CK7+/CK20- or CK7+/CK20+ cancers (p = 0.002). To conclude, we identified a small (6%) subset of SBAs featuring a full CRC-like immunoprofile, representing a potential diagnostic pitfall in attempts to identify the site of origin of neoplasms of unknown primary site. In contrast with data on colorectal carcinoma, SATB2 expression is not associated with MMR status in SBAs. CK patterns influence patient survival, as CK7-/CK20- cancers show better prognosis, a behavior possibly due to the high rate of MMR-deficient SBAs within this subgroup.

16.
United European Gastroenterol J ; : 2050640620951905, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32819215

RESUMO

INTRODUCTION: Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, non-bloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. METHODS: Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. RESULTS: These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. CONCLUSION: These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.

17.
Medicina (Kaunas) ; 56(8)2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32751480

RESUMO

Background and objectives: Electrocardiograph abnormalities (i.e., QT interval prolongation) have been described in inflammatory bowel diseases (IBD). We aimed to measure the QT interval in a cohort of patients with IBD and to analyze its relationship with clinical and inflammatory activity. Materials and Methods: We performed a cross-sectional study that included 38 IBD outpatients and 38 "age- and sex-matched" healthy controls. Nine patients had active IBD, and 29 were in clinical remission. Among the latter, 10 patients had sustained (lasting >1 year) and 19 had short-term remission (≤1 year). Corrected QT (QTc) interval was measured on standard 12-lead electrocardiograph. A systematic review of the literature on studies investigating the QT interval in patients with IBD was also performed. Results: QTc interval values were similar between IBD patients and healthy controls (417.58 ± 22.05 ms vs. 409.13 ± 19.61 ms, respectively; p: 0.479). Patients with active IBD had significantly higher QTc values (435.11 ± 27.31 ms) than both controls (409.13 ± 19.61 ms) and patients in remission (412.14 ± 17.33 ms) (p: 0.031). Post hoc analysis showed that the difference in QTc values between active IBD and remission was attributable to the group of patients with sustained remission (p < 0.05). Lastly, a significant correlation between QTc interval and C-reactive protein (CRP) values was observed (Spearman test: r = 0.563; p: 0.0005). Conclusions: Our study demonstrates an association between QTc duration and both clinical and inflammatory activity in patients with IBD. The higher the CRP value, the longer is the QTc duration. For practical purposes, all patients with active IBD should undergo a standard ECG. Prescription of drugs able to modify the QT interval should be avoided in patients with active IBD. The systematic review of the literature indicated that this is the first published study demonstrating an association between the QTc duration and CRP values in patients with IBD.


Assuntos
Proteína C-Reativa/análise , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/fisiopatologia , Síndrome do QT Longo/etiologia , Adulto , Estudos Transversais , Eletrocardiografia/métodos , Feminino , Humanos , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade
18.
Nutrients ; 12(8)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32708019

RESUMO

Celiac disease (CD) is an autoimmune disorder characterized by intolerance to dietary gluten in genetically predisposed subjects. Iron deficiency anemia (IDA) is a common sign in CD, being the only abnormality in approximately 40% of celiac patients. A multifactorial etiology leads to IDA in CD. The two main causes are the villous atrophy of the mucosa at the site of iron absorption (the duodenum) and the resulting inflammation, which triggers the mechanism that leads to the anemia of chronic disease. Until now, it has been unclear why some patients with CD continue to have IDA despite a careful gluten-free diet (GFD) and the normalization of villous atrophy. Furthermore, some celiac patients are refractory to oral iron supplementation despite the healing of the mucosa, and they thus require periodic intravenous iron administration. The Marsh classification evaluates the degree of inflammation and villous atrophy, but it does not assess the possible persistence of ultrastructural and molecular alterations in enterocytes. The latter was found in CD in remission after adopting a GFD and could be responsible for the persistently reduced absorption of iron and IDA. Even in non-celiac gluten sensitivity, anemia is present in 18.5-22% of patients and appears to be related to ultrastructural and molecular alterations in intestinal microvilli. It is possible that a genetic component may also play a role in IDA. In this review, we evaluate and discuss the main mechanisms of IDA in CD and the possible causes of its persistence after adopting a GFD, as well as their therapeutic implications.


Assuntos
Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Doença Celíaca/sangue , Dieta Livre de Glúten , Administração Intravenosa , Administração Oral , Doença Celíaca/dietoterapia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Ferro/administração & dosagem , Ferro/sangue , Ferro/farmacocinética , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Cells ; 9(8)2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32717828

RESUMO

Fibrogenesis is a physiological process of tissue repair triggered by acute inflammation, but in chronic inflammation it may become a progressive and independent process leading to fibrosis [...].


Assuntos
Fibroblastos , Piridonas , Proliferação de Células , Fibrose , Humanos , Piridonas/farmacologia , Piridonas/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...