1,721,037 research outputs found
MICRO-RNAs TISSUTALI COME BIOMARCATORI DI DIAGNOSI PRECOCE E MONITORAGGIO IN PAZIENTI CON CANCRO DEL COLONRETTO ASSOCIATO A MALATTIA INFIAMMATORIA CRONICA INTESTINALE
No full textINTRODUZIONE: Sebbene i tassi di CRC correlati all'IBD stiano diminuendo nel tempo, probabilmente grazie al miglioramento delle terapie mediche, dello screening e della sorveglianza colonscopica, il CRC è ancora una delle principali cause di morte e motivo di colectomia nei pazienti con IBD. Tra i diversi biomarcatori del cancro, i microRNAs ricercati in tessuti e nei biofluidi sono considerati validi strumenti non invasivi per la diagnosi, il monitoraggio e la prognosi dei pazienti con IBD. Pertanto, il nostro progetto si è posto l’obiettivo di studiare il ruolo dei miRNA nello sviluppo e nel corso naturale del CRC correlato all'IBD, al fine di identificare potenziali biomarcatori precoci per lo screening e la progressione del CRC correlato all'IBD.
MATERIALI E METODI: I casi considerati nel presente progetto sono stati raccolti retrospettivamente dagli archivi dell'Unità di Patologia Chirurgica e Citopatologia dell'Università di Padova. Abbiamo analizzato nove miRs in biopsie coliche di pazienti con IBD con adenoma (gruppo A) o displasia (gruppo B), con CRC correlato all'IBD (gruppo C), oltre a due gruppi di controllo di pazienti con CRC sporadico (sCRC WT_MSI e WT_MSS, gruppo D e gruppo E, rispettivamente) e di soggetti sani (gruppo F). Inoltre, abbiamo incluso nel progetto campioni di biopsie coliche provenenti da una colonscopia che i pazienti con IBD con adenoma o displasia hanno eseguito alcuni anni prima della diagnosi delle lesioni (da 2 a 5 anni prima) senza evidenza di adenoma (gruppo A2) o displasia (gruppo B2). I risultati sono stati analizzati con il software ThermoFisher ConnectedTM (Applied BiosystemsTM) e un valore p <0,05 è stato considerato significativo.
RISULTATI: Rispetto ai controlli sani, tutti e nove i miRs analizzati erano significativamente sovraespressi nei pazienti con sCRC, con CRC correlato all'IBD e nei pazienti con IBD con adenoma. Mentre, solo 3 miR (miR-135b, mir-21, miR-224) erano significativamente sovraespressi nei pazienti IBD con displasia (e nei loro controlli, gruppo B2) rispetto ai controlli sani (p <0,0001). In particolare, non sono state riscontrate differenze nei livelli di espressione di miR nei pazienti con CRC correlato a IBD rispetto a quelli riscontrati nei pazienti con sCRC. Inoltre, tra tutti i miR analizzati, solo miR-135b e miR-21 sono risultati significativamente sovraespressi nei pazienti con IBD. In particolare, considerando i livelli di miR-135b nelle biopsie coliche dei pazienti con IBD, abbiamo osservato un evidente trend crescente passando da campioni senza lesioni a quelli con adenoma o displasia e poi a quelli con lesioni neoplastiche. Infine, il miR-21 è stato significativamente sovraespresso nei pazienti con CRC correlato a IBD rispetto a entrambi i pazienti con IBD con adenoma e ai propri controlli (gruppo A2) provenienti da una precedente colonscopia negativa per lesioni (p = 0.003 e p = 0.006, rispettivamente). Allo stesso modo, è stata osservata una differenza statisticamente significativa nei livelli di miR-21 tra i pazienti con CRC correlato a IBD e quelli con displasia (p=0.02).
CONCLUSIONI: I miRNAs stanno attirando un crescente interesse nella comunità scientifica alla luce del loro ruolo centrale nell'eziologia di diverse patologie. Abbiamo dimostrato che miR-21 e miR-135b sono coinvolti nel processo di carcinogenesi dei pazienti con IBD. Considerando il loro ruolo nel processo di carcinogenesi e, considerando che possono essere rilevati rapidamente ed efficacemente nei tessuti, potrebbero essere potenziali biomarcatori per la stratificazione diagnostica, prognostica e predittiva dei pazienti con IBD. Inoltre, la possibilità di controllare la sovraespressione di questi miRs potrebbe portare a una svolta nella prevenzione del CRC correlato all'IBD, interferendo potenzialmente con la tumorigenesi. Sebbene siano necessari ulteriori studi più ampi e prospettici.BACKGROUND: Although the rates of IBD related-CRCs are decreasing over time, probably due to improved medical therapies and colonoscopic screening and surveillance, CRC is still a leading cause of mortality and reason for colectomy in patients with IBD. Among the different cancer biomarkers, miRs have emerged as noninvasive tools for diagnosis, monitoring and prognosis in tissues and biofluids of patients with IBD. Therefore, with our project, we aimed to investigate the role of miRNAs in the development and natural course of IBD-related CRC, in order to identify potential early biomarkers for IBD-related CRC screening and progression.
MATERIALS AND METHODS: The cases considered in the present project were retrospectively collected from the archives of the Surgical Pathology and Cytopathology Unit at the University of Padua. We analysed nine miRs in colonic tissue specimens of patients with IBD with adenoma (group A) or dysplasia (group B), with IBD related-CRC (group C), other than two control groups of patients with sporadic CRC (sCRC WT_MSI and WT_MSS, group D and group E, respectively) and of healthy subjects (group F). In addition, we included tissue samples from a colonoscopy that patients with IBD with adenoma or dysplasia underwent some years before the development of mucosal lesions (from 2 to 5 years before) without evidence of adenoma (group A2) or dysplasia (group B2). Results were analyzed with ThermoFisher ConnectedTM Software (Applied BiosystemsTM) and a p-value < 0.05 was considered significant.
RESULTS: We found that, compared to healthy controls, all nine analysed miRs were significantly up-regulated in patients with sCRC, with IBD-related CRC and in IBD patients with adenoma. While, only 3 miRs (miR-135b, mir-21, miR-224) were significantly up-regulated in IBD patients with dysplasia (and in their own controls) compared to healthy controls (p<0.0001). Notably, no differences in miRs expression levels were found in patients with IBD-related CRC compared to those found in patients with sCRC. Moreover, among all miRs analyzed, only miR-135b and miR-21 resulted significantly up-regulated in patients with IBD. Particularly, considering the levels of miR-135b in the tissue samples of IBD patients, we observed an evident increasing trend going from tissue specimens without lesions to those with adenoma or dysplasia and then to those with neoplastic lesions. Finally, miR-21 was significantly up-regulated in patients with IBD-related CRC compared to both IBD pa-tients with adenoma and their own control samples from a previous negative colonoscopy (p=0.003 and p=0.006, respectively). Likewise, a statistically significant difference in miR-21 levels was observed between patients with IBD-related CRC and those with dysplasia (p=0.02).
CONCLUSIONS: MiRNAs are attracting a growing interest in the scientific community due to their central role in the etiology of several diseases. We demonstrated that miR-21 and miR-135b are involved in the carcinogenesis process of patients with IBD. Considering their role in cancer development and that they can be detected rapidly and efficiently in tissues, they could be potential candidate biomarkers for diagnostic purpose, prognostic and predictive stratification of patients. In addition, the possibility of controlling upregulation of these miRs could lead to a breakthrough in the prevention of IBD-related CRC, potentially interfering with tumorigenesis. Although further larger and prospective studies are needed, developments in this field could open new therapeutic perspectives in the management of our patients, preventing neoplastic progression toward colon carcinoma
The Adherence to Infusible Biologic Therapies in Inflammatory Bowel Disease Patients during the COVID-19 Pandemic: Is It Really a Problem?
No full text
Systematic Review: esophageal motility patterns in patients with eosinophilic esophagitis
No full textEosinophilic esophagitis (EoE) is a chronic disorder of the esophagus characterized by an eosinophil-predominant inflammation and symptoms of esophageal dysfunction. Eosinophils can influence esophageal motility, leading to dysphagia worsening. The spectrum of esophageal motility in EoE is uncertain
Primary sclerosing cholangitis and inflammatory bowel disease: a complicated yet unique relationship
No full textPrimary sclerosing cholangitis (PSC) is a rare liver disorder characterized by biliary ducts inflammation, fibrosis and consequently chronic cholestasis, which progressively lead to liver cirrhosis. The main feature of PSC is the frequent association with inflammatory bowel disease (IBD), with an estimated prevalence of around 70% of the cases. This strong relationship seems due to the presence of shared pathogenetic mechanisms, which seem to involve the intestinal barrier function, the human gut microbiota and the immune innated and adaptative response to antigens derived from the bowel. Of relevance, PSC-IBD have specific clinical and pathological features that differ from PSC and IBD as separate entities, explaining the diversity in outcomes among these categories, and therefore the distinct clinical management that is required. The aim of this review is to present recent data regarding the epidemiology, pathobiology and clinical features of PSC-IBD
Advancements in the use of 24-hour impedance-pH monitoring for GERD diagnosis
No full textGastro-esophageal reflux disease (GERD) occurs in about 25% of the general population. The complexity of the disease and the multiplicity of its clinical manifestations impair the availability of a singular diagnostic test. The majority of GERD patients do not have any endoscopically visible lesions, the so-called non erosive reflux disease (NERD). This latter population consists of several subgroups characterized by: 1. excess of acid; 2. normal acid, but hypersensitivity to acid or weakly acidic reflux; 3. normal acid, but lack of any relationship between symptoms and reflux episodes. At present, 24-h impedance-pH monitoring represents the best diagnostic tool to detect abnormal reflux and to correlate symptoms to reflux episodes. Moreover, the recent adoption of novel impedance metrics, such as mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index, seem to be able to improve the diagnostic yield of 24-h impedance-pH monitoring, making this test the most accurate in diagnosis of GERD
Fecal microbiota transplantation for norovirus infection: a clinical and microbiological success.
Full text linkIncidence comparison of adverse events in patients with inflammatory bowel disease receiving different biologic agents: retrospective long-term evaluation
Full text linkCurrent literature is lacking in studies comparing the incidence of adverse events (AEs) in patients with inflammatory bowel diseases (IBD) treated with adalimumab (ADA) or vedolizumab (VDZ) in a real-life scenario. Therefore, our primary aim was to compare the AEs occurring in patients taking ADA to those of patients taking VDZ
REAL LIFE COMPARISON OF DIFFERENT ANTI-TNF BIOLOGIC THERAPIES FOR ULCERATIVE COLITIS TREATMENT: A RETROSPECTIVE COHORT STUDY
No full textBACKGROUND: Head-to-head comparison studies evaluating the effectiveness and tolerability of anti-TNF drugs in IBD patients are lacking.AIMS: to compare the effectiveness and tolerability of anti-TNF-alpha drugs used in clinical practice in a cohort of patients with moderate to severe UC.METHODS: Retrospectively, 122 UC patients treated with Infliximab (IFX) Originator and Biosimilar, Adalimumab (ADA) and Golimumab (GOL) were included. We performed an ITT analysis to evaluate clinical response and remission, steroid-free clinical remission and endoscopy response according to the different time-points of the follow-up. Baseline and post-induction predictor factors of these outcomes were evaluated using multivariate logistic regressions models. Moreover, a propensity score-based weighting analysis was performed. Data were analyzed using R and STATA11 software.RESULTS: Overall clinical response was 77% after induction, 81.4% at 30 weeks, 76.9% at 52 weeks, while the steroid-free clinical remission was 39.7%, 46%, 54.6%, respectively. After induction, a higher rate of treatment failure was observed in GOL group. At the end of follow-up, lower rates of steroid-free clinical remission and clinical response were obtained by GOL. At week 52, endoscopic response was achieved by 46.5% of the population.CONCLUSIONS: Among the different anti-TNF treatment, moderate-to-severe UC seems to respond better to IFX and ADA, whereas GOL seems to be less effective, despite a similar good safety profile
- …
