Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 268
Filtrar
Mais filtros










Intervalo de ano de publicação
2.
Mod Pathol ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066859

RESUMO

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1+ immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1+ cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1+ microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.

3.
Transl Oncol ; 13(3): 100740, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32105990

RESUMO

BACKGROUND: In search of novel biomarkers of response to bevacizumab in metastatic colorectal cancer (mCRC), we analyzed the expression and prognostic role of several proteins related to angiogenesis. METHODS: A retrospective, multicenter study on 80 surgical samples from mCRC patients treated in first line with bevacizumab plus chemotherapy was accomplished. The following proteins were analyzed by immunohistochemistry: hERG1 potassium channel, ß1-integrin, pAKT, NFkB, HIF-1α, HIF-2α, p53, VEGF-A, GLUT-1, and CA-IX. Data were analyzed in conjunction with the clinicopathological characteristics of the patients, KRAS status, response to bevacizumab, and follow-up. RESULTS: (1) All the proteins were expressed in the samples, with statistically significant associations between HIF-1α and gender, HIF-2α and left colon, hERG1 and VEGF-A, ß1-integrin and HIF-2α, GLUT-1 and both HIF-1α and HIF-2α, and CA-IX and VEGF-A. (2) At the univariate analysis, positivity for hERG1, VEGF-A, and the active form of HIF-2α (aHIF-2α), and the G3 histological grade showed a positive impact on progression-free survival (PFS). (3) hERG1 and aHIF-2α maintained their positive impact on PFS at the multivariate analysis. (4) hERG1 behaved as a protective factor for PFS independently on KRAS status. CONCLUSIONS: hERG1 and aHIF-2α might help to identify patients who would benefit from bevacizumab treatment.

5.
EBioMedicine ; 51: 102567, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31901853

RESUMO

BACKGROUND: Intestinal coeliac auto-antibodies are the marker of coeliac disease (CD). Since the determination of these antibodies is still not widely available, we used immunoassays to identify the most suitable technology for revealing intestinal auto-antibodies in the wide clinical spectrum of CD. METHODS: Intestinal auto-antibodies have been prospectively investigated in CD suspected children using two immunoassays: intestinal-deposits of IgA anti-tissue transglutaminase antibodies (anti-tTG) and biopsy-culture IgA anti-endomysium (AEA). Intestinal IgM antibodies have been determined in IgA-deficient subjects. FINDINGS: Two-hundred and twenty-one suspected CD patients were enrolled. Intestinal antibodies were tested positive for both assays in classical CD patients (n = 178) with villous atrophy and positive serum-CD antibodies, potential CD patients (n = 16) with normal intestinal mucosa and positive serum-CD antibodies, and pre-potential CD patients (n = 14) with normal intestinal mucosa and negative serum-CD antibodies. In 13/221 with normal intestinal mucosa, negative CD-serum antibodies and negative intestinal antibodies CD has been excluded. All classical, 14/16 potential and 11/14 pre-potential CD patients on gluten-free diet (GFD) improved their symptoms. In 9/11 pre-potential patients intestinal antibodies disappeared on GFD. Both assays were negative in 69/71 control subjects. The two assays showed high diagnostic sensitivity (100%) and specificity (99%). INTERPRETATION: Intestinal CD-antibodies make prompt diagnosis in the wide clinical spectrum of CD reducing the delay in diagnosis and treatment, especially in pre-potential CD patients. The easy handling biopsy culture assay is an effective diagnostic tool which should be carried out by any gastroenterology unit to recognize all CD clinical manifestations. FUNDING: Interreg Central-Europe, IRCCS "Burlo Garofolo".

7.
Dig Liver Dis ; 52(3): 262-267, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31884010

RESUMO

Diagnosis of the inflammatory bowel diseases ulcerative colitis (UC) and Crohn's disease (CD) relies mainly on the histopathological examination of endoscopic biopsies of the gastrointestinal tract. To facilitate the accurate diagnosis of these two conditions, this paper addresses key issues on the: (A) gastrointestinal biopsy procedure, (B) histomorphological characteristics of UC and CD, and (C) diagnosis of dysplasia. The 13 statements presented here represent the consensus of two groups of Italian pathologists (IG-IBD and GIPAD).

8.
Virchows Arch ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31696360

RESUMO

Celiac disease (CD) is a risk factor for developing small-bowel carcinoma with a 14-fold higher risk compared with general population. As small-bowel carcinomas associated with CD (CD-SBCs) are extremely rare, very few molecular data are available about their pathogenesis, and information about their transcriptomic profiling is lacking. We generated RNA-seq data on 13 CD-SBCs, taken from the largest well-characterized series published so far, collected by the Small Bowel Cancer Italian Consortium, and compared the tumor transcriptional signatures with the four Consensus Molecular Subtypes (CMS) of colorectal carcinoma by applying the "CMS classifier." CpG Island Methylator Phenotype (CIMP) was evaluated using methylation-sensitive multiple ligation-dependent probe amplification. Up to 12 of 13 cancers fell within the two main subtypes exhibiting high immune and inflammatory signatures, i.e., subtypes 1 and 4. The first and predominant subset was commonly microsatellite unstable, and exhibited CIMP and high CD3+ and CD8+ T cell infiltration. Moreover, it showed increased expression of genes associated with T helper 1 and natural killer cell infiltration, as well as upregulation of apoptosis, cell cycle progression, and proteasome pathways. By contrast, cancers falling in subtype 4 showed prominent transforming growth factor-ß activation and were characterized by complement-associated inflammation, matrix remodeling, cancer-associated stroma production, and angiogenesis. Parallel histologic and histochemical analysis confirmed such tumor subtyping. In conclusion, two molecular subtypes have been consistently identified in our series of CD-SBCs, a microsatellite instability-immune and a mesenchymal subtype, the former likely associated with an indolent and the latter with a worse tumor behavior.

9.
Int J Mol Sci ; 20(21)2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31652976

RESUMO

BACKGROUND: The long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) seems to be involved in the regulation of mediators of tissue injury, in particular matrix metalloproteinases (MMPs), implicated in the pathogenesis of inflammatory bowel disease (IBD). We investigated the role of GAS5 in regulating MMP2 and MMP9 expression in pediatric patients with IBD and in vitro. METHODS: In total, 25 IBD patients were enrolled: For each patient paired inflamed and non-inflamed biopsies were collected. RNA was extracted and GAS5, MMP2, and MMP9 were quantified by TaqMan assay. The expression of GAS5 and MMPs was also determined in the human monocytic THP1 cells differentiated into macrophages and stimulated with lipopolysaccharide (LPS). The function of GAS5 was assessed by overexpressing the lncRNA and evaluating the MMPs levels. RESULTS: Real-time PCR results demonstrated a downregulation of GAS5 and an upregulation of both MMPs in inflamed tissues. In vitro data confirmed the trend observed in patients for the three genes: The stimulation with LPS promoted a downregulation of GAS5 while an increase of MMPs was observed. Overexpression experiments showed that higher levels of GAS5 lead to a decrease of both enzymes. CONCLUSION: These results provide new information about the role of GAS5 in IBD: The lncRNA could mediate tissue damage by modulating the expression of MMPs.

10.
J Crohns Colitis ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31418007

RESUMO

BACKGROUND AND AIMS: Crohn's disease-associated small bowel carcinoma is a rare event, usually reported to have a severe prognosis. However, in previous investigations we have found a minority of cases displaying a relatively favorable behavior, thus outlining the need to improve the histopathologic prediction of Crohn's disease-associated small bowel carcinoma prognosis. METHODS: As in recent studies on colorectal cancer a substantial improvement in prognostic evaluations has been provided by the histologic analysis of the tumor invasive front, we therefore systematically analyzed the tumor budding and poorly differentiated clusters in the invasive front of 47 Crohn's disease-associated small bowel carcinomas collected through the Small Bowel Cancer Italian Consortium. RESULTS: Both tumor budding and poorly differentiated cluster analyses proved highly effective in prognostic evaluation of Crohn's disease-associated small bowel carcinomas. In addition, they retained prognostic value when combined with two other parameters, i.e. glandular histology and stage I/II, both known to predict a relatively favorable small bowel carcinoma behavior. In particular, association of tumor budding and poorly differentiated clusters in a combined invasive front score allowed to identify a minor subset of cancers (12/47, 25%), characterized by combined invasive front-low grade coupled with a glandular histology and a low stage (I or II) and showing no cancer-related death during a median follow-up of 73.5 months. CONCLUSIONS: The improved distinction of lower from higher grade Crohn's disease-associated small bowel carcinomas provided by invasive front analysis should be of potential help in choosing appropriate therapy for these rare and frequently ominous neoplasms.

11.
Clin Gastroenterol Hepatol ; 17(10): 2141-2142, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31445746
12.
Clin Immunol ; 207: 10-17, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31279857

RESUMO

Autoimmune enteropathy (AIE) is a rare condition that may affect pediatric and adult patients, frequently associated with primary immunodeficiencies. We performed a retrospective study on clinical and histological findings from 40 AIE patients. Histological presentation showed a prevalent celiac disease pattern (50%), followed by the mixed pattern (35%), independently of age, chronic active duodenitis (10%), and GVHD-like pattern (5%). Patients with primary immunodeficiencies (24/40) presented mainly with the celiac disease pattern (72.2% versus 22.2%; p < .0001), while patients without primary immunodeficiencies presented with a mixed histological pattern (61.1% versus 13.6%; p < .0001). Our study shows that the prevalent histological presentation is the celiac disease-like pattern, independently of age, and, for the first time, that the histological presentation of AIE differs significantly between patients with and without primary immunodeficiencies. These findings may be helpful for more precise and timely diagnosis and management of this rare disorder.

13.
Ital J Pediatr ; 45(1): 69, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171002

RESUMO

BACKGROUND: Eosinophilic gastrointestinal disorders (EGID) are characterized by eosinophilic inflammation and are subclassified according to the affected site(s) as eosinophilic esophagitis, eosinophilic gastritis, eosinophilic enteritis and eosinophilic colitis. Clinical presentation includes dyspeptic symptoms, vomiting, abdominal pain, diarrhoea and gastrointestinal bleeding. Peripheral eosinophilia is usually found but is not required for the diagnosis. The treatment is based on dietary elimination therapy, consisting of removal of common food triggers, most frequently cow's milk in infants. Corticosteroids are used as first line drug therapy in EG if dietary therapy fails to achieve an adequate clinical response or is impractical. CASE PRESENTATION: A four month old infant was admitted for an episode of melena and hematemesis. An esophagogastroduodenoscopy showed haemorrhagic gastritis with ulcerative lesions and fibrin. A significant gastric bleeding was noted after the procedure. The gastric mucosa biopsies showed an eosinophilic infiltration. CONCLUSIONS: A clinically relevant anaemia is a quite rare complication in infants with eosinophilic gastritis and a biopsy may worsen bleeding, to a potentially severe level of low haemoglobin. In infants with low haemoglobin levels and suspect eosinophilic gastritis a watchful follow up after the biopsy should be considered, as well as the possibility of postponing the biopsy to reduce the bleeding risk.


Assuntos
Anemia/etiologia , Biópsia/efeitos adversos , Enterite/diagnóstico , Eosinofilia/diagnóstico , Gastrite/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Lactente
14.
Pediatr Rep ; 11(2): 7848, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31214299

RESUMO

A limited number of sclerosing Angiomatoid Nodular Transformation (SANT) have been reported in pediatric age. We describe the first case of SANT occurring in a nine-week-old female infant that was admitted to our unit for severe abdominal distension and rectal bleeding. Enlarged spleen was detected on physical examination. Laboratory investigations revealed severe anemia and coagulation abnormalities. Abdominal ultrasound and computed tomography revealed ascites and splenomegaly with a large mass at the lower medial splenic pole. A diagnosis of intraabdominal hemorrhage was presumed and an exploratory laparotomy was performed. A complete transformation of the giant splenomegaly to bossellated masses and multiple bleeding capsular ruptures without subcapsular hematoma were found and an urgent splenectomy was performed. At histology, a SANT was diagnosed (CD34, CD31, CD8 positivity). The postoperative follow up was uneventful. SANT may also occur in infancy with a potentially lifethreatening presentation. Splenectomy may represent the only treatment in severe cases.

15.
Ann Diagn Pathol ; 41: 8-13, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31112900

RESUMO

Serrated polyps evaluation represents a challenge for pathologists for lacking of univocal criteria that leads to different inter -individual interpretation. The aim of our review is to offer an alternative simpler histologic and endoscopic approach to these lesions for a more correct relationship between endoscopists and pathologists.


Assuntos
Pólipos do Colo/classificação , Pólipos do Colo/patologia , Lesões Pré-Cancerosas/classificação , Lesões Pré-Cancerosas/patologia , Humanos
16.
J Clin Immunol ; 39(5): 470-475, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129864

RESUMO

PURPOSE: Selective IgA deficiency (SIgAD) is the most common humoral primary immunodeficiency. Long-term follow-up data in large cohort of pediatric patients are scarce. METHODS: We report on a single-center cohort of 184 pediatric patients affected with selective IgA deficiency and describe the characteristics at diagnosis and during follow-up. RESULTS: Respiratory infections were the most common clinical finding leading to the initial diagnosis (62%). Positive family history for antibody deficiencies (selective IgA deficiency, common variable immunodeficiency) led to SIgAD diagnosis in 16% of cases. During follow-up, while the incidence of respiratory infections was not particularly high, gastrointestinal symptoms were reported in 27% of patients. Allergic manifestations were found in 23% at diagnosis and an additional 16% of patients during follow-up, leading to a prevalence of atopy of 39% among SIgAD patients. Autoimmune manifestations, excluding celiac disease, were found in 9% of affected patients during follow-up. Celiac disease was found in a high prevalence (14%). Increase of serum IgA levels to partial deficiency (9%) and normal serum levels for age (4%) was observed during follow-up. A small percentage of patients (2%) progressed to common variable immunodeficiency (CVID). CONCLUSIONS: In conclusion, this is the first study to describe a large single-center pediatric cohort of patients affected with SIgAD, revealing that overall most patients do well with regard to infections. Many develop CD, at a rate much higher than the general population. A few normalize their IgA levels. A few progress to CVID. Thus, careful follow-up is suggested to diagnose and treat potential complications earlier for avoiding potential morbidities.

17.
Expert Rev Gastroenterol Hepatol ; 13(6): 541-546, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30987472

RESUMO

INTRODUCTION: Celiac disease (CD) is an immune-mediated disorder associated with gluten exposure in genetically predisposed subjects. Areas covered: Infectious disease is one of the causes of morbidity and mortality in CD patients. Invasive streptococcus pneumoniae (pneumococcus) is a particularly dangerous morbid condition in both the general population and celiac patients. Pneumococcal vaccination is the most effective means for its prevention. Expert opinion: In CD, evaluation of spleen function should be useful to select patients who may benefit from vaccination to reduce the risk of pneumococcal disease. Different strategies could be employed: physicians could search for signs of hyposplenism on peripheral blood smear or abdominal ultrasound. However, the best strategy to identify which patients will benefit from pneumococcal vaccination has not yet been defined.


Assuntos
Doença Celíaca/imunologia , Hospedeiro Imunocomprometido , Infecções Oportunistas/prevenção & controle , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Vacinação , Animais , Doença Celíaca/diagnóstico , Doença Celíaca/genética , Humanos , Hiperesplenismo/diagnóstico , Hiperesplenismo/imunologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/efeitos adversos , Prognóstico , Fatores de Proteção , Fatores de Risco , Baço/imunologia , Baço/patologia
18.
Clin Immunol ; 200: 31-34, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30639166

RESUMO

This study reports on a novel activating p110δ mutation causing adult-onset hypogammaglobulinemia with lymphopenia without the classical presentation of atypical Activated phosphoinositide 3-kinase δ syndrome (ADPS-1), underlining thus the heterogeneous clinical and immunological presentation of p110δ mutated individuals and offers additional data on the role of p110δ in early and late B cell development in humans.


Assuntos
Agamaglobulinemia/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Linfopenia/genética , /genética , Adulto , Agamaglobulinemia/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Classe I de Fosfatidilinositol 3-Quinases/imunologia , Feminino , Mutação com Ganho de Função , Humanos , Linfopenia/imunologia , Linfopoese , /imunologia
19.
Virchows Arch ; 474(5): 639-640, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30643960

Assuntos
Glutens , Humanos
20.
J Clin Gastroenterol ; 53(4): 269-276, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29394176

RESUMO

GOALS: The aim of this study was to analyze the performance of Fuji Intelligent Color Enhancement (FICE) using the classification of Kudo in the differentiation of neoplastic and non-neoplastic raised lesions in ulcerative colitis (UC). BACKGROUND: The Kudo classification of mucosal pit patterns is an aid for the differential diagnosis of colorectal polyps in the general population, but no systematic studies are available for all forms of raised lesions in UC. STUDY: All raised, polypoid and nonpolypoid, lesions found during consecutive surveillance colonoscopies with FICE for long-standing UC were included. In the primary prospective analysis, the Kudo classification was used to predict the histology by FICE. In a post hoc analysis, further endoscopic markers were also explored. RESULTS: Two hundred and five lesions (mean size, 8 mm; range, 2 to 30 mm) from 59 patients (mean age, 56 y; range, 21 to 79 y) were analyzed. Twenty-three neoplastic (11%), 18 hyperplastic (9%), and 164 inflammatory (80%) lesions were found. Thirty-one lesions (15%), none of which were neoplastic, were unclassifiable according to Kudo. After logistic regression, a strong negative association resulted between endoscopic activity and neoplasia, whereas the presence of a fibrin cap was significantly associated with endoscopic activity. Using FICE, the sensitivity, specificity, and positive and negative likelihood ratios of the Kudo classification were 91%, 76%, 3.8, and 0.12, respectively. The corresponding values by adding the fibrin cap as a marker of inflammation were 91%, 93%, 13, and 0.10, respectively. CONCLUSIONS: FICE can help to predict the histology of raised lesions in UC. A new classification of pit patterns, based on inflammatory markers, should be developed in the setting of UC to improve the diagnostic performance.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA