Small bowel adenocarcinoma associated with celiac disease: clinical, histological and immunological features.

L’adenocarcinoma dell’intestino tenue (SBA) è una neoplasia estremamente rara nella popolazione generale. La letteratura suggerisce che la malattia celiaca (MC) sia associata ad un aumentato rischio di sviluppare un SBA, ma non ci siano dati sulle caratteristiche di questa variante associata a MC. Lo scopo dello studio è consistito nel chiarire la prevalenza del SBA in una coorte soggetti con MC, definendo le loro caratteristiche cliniche, istologiche ed immunologiche. Sono stati studiati retrospettivamente (1995-2014) tutti i casi di SBA trovati in associazione a MC. Le biopsie dei casi identificati sono state valutate attraverso indagini immunoistochimiche impiegando anticorpi monoclonali che riconoscono markers epiteliali intestinali (e.g. MUC2, CDX2 e CD10) e gastrici (e.g. MUC5AC e MUC6). Sono inoltre state ricercate eventuali mutazioni di KRAS, NRAS e BRAF. Sono stati identificati 5 SBA su 779 pazienti con MC (0,65%), tutte di sesso femminile età media 53. La tipizzazione dell'HLA ha mostrato un DQ2+ in tutti i casi. Al momento della diagnosi di SBA il quadro clinico di questi pazienti era caratterizzato da diarrea in 3 casi e da episodi subocclusivi negli altri due casi. La più frequente localizzazione anatomica dell’SBA era il digiuno. In nessuno dei 5 casi lo SBA è stato preceduto da una malattia celiaca refrattaria. L’esame istologico eseguito mostrava la presenza in tre casi di un carcinoma di alto grado, scarsamente differenziato (grado III-IV). La sopravvivenza a 5 anni è risultata molto migliore rispetto al SBA sporadico. KRAS è stato trovato mutato in 2/5 casi. L’ SBA associato a MC sembra avere caratteristiche cliniche, istologiche e fenotipiche differenti rispetto al SBA sporadico. In particolare: a) il più frequente coinvolgimento del sesso femminile; b) l’età di esordio più giovane; c) la localizzazione digiunale; d) una migliore prognosi associata a positività per CDX2; e) presenza di neoplasie con KRAS mutato.The small bowel adenocarcinoma (SBA) is a very rare neoplasia in the general population. Previous studies suggest that celiac disease (CD) is associated with an increased risk in developing a SBA. Unfortunatly, there are no information about the features of this cancer when associated with CD. The aims of the present study were to shed light on the prevalence of SBA in a CD patients cohort and to define its clinical, histological and immunological features. We retrospectively investigated all the cases of SBAs in a cohort of CD patients during a 19 years period (1995-2014). Biopsies from selected cases were analyzed by immunohistochemestry, looking for intestinal and gastric markers, using monoclonal antibodies against MUC2, CDX2, CD10, MUC5AC, MUC6. Moreover, we checked the presence of KRAS, NRAS and BRAF mutations. We identified 5 cases of SBA in a population of 779 CD patients (0,65%). All the SBA found were in female patients with a mean age of 53 years. The HLA genotyping revealed a positivity for the DQ2+ in all cases. At onset SBA showed a clinical picture characterized by diarrhoea in 3 cases and subocclusion in 2 cases. Refractory CD never preceded the onset of a SBA. Th histologica evaluation revealed a high grade, poorly differentiated neoplasia in 3 cases (G3-G4). Overall survival at 5 years was extremely better than that of the sporadic SBA. A mutation of KRAS was found in 2/5 cases. In conclusion, the SBA associated with CD showed different features in comparison to the sporadic one, in particular: a) a female gender predominace, b) a lower median age at diagnosis, c) a preferred jejunal localization, d) a better prognosis (in particular when associated witha CDX2 positivity) and e) for the finding of KRAS mutations

Distribution of α-transducin and α-gustducin immunoreactive cells in the chicken (Gallus domesticus) gastrointestinal tract

The expression and distribution patterns of the taste signaling molecules, α-gustducin (Gαgust) and α-transducin (Gαtran) G-protein subunits, were studied in the gastrointestinal tract of the chicken (Gallus domesticus) using the immunohistochemical method. Gαgust and Gαtran immunoreactive (-IR) cells were observed in the mucosal layer of all examined segments, except the esophagus, crop, and the saccus cranialis of the gizzard. The highest numbers of Gαgust and Gαtran-IR cells were found in the proventriculus glands and along the villi of the pyloric, duodenum, and rectal mucosa. Gαgust and Gαtran-IR cells located in the villi of the jejunum, ileum, and cloaca were much less numerous, while only a few Gαgust and Gαtran-IR cells were detected in the mucosa of the proventriculus and cecum. In the crypts, IR cells were observed in the small and large intestine as well as in the cloaca. Gαgust and Gαtran-IR cells displayed elongated ("bottle-" or "pear-like") or rounded shape. The demonstration of Gαgust and Gαtran expression provides evidence for taste receptor mediated mucosal chemosensitivity in the chicken gastrointestinal tract

Non-coeliac gluten/wheat sensitivity: advances in knowledge and relevant questions

Introduction: Non-coeliac gluten/wheat sensitivity (NCG/WS) is a syndrome characterized by intestinal and extra-intestinal symptoms occurring a few hours or days after the ingestion of gluten and wheat proteins in patients testing negative for coeliac disease and wheat allergy. Areas covered: The present review deals with recent scientific acquisitions of this gluten-related syndrome, including pathogenetic mechanisms, clinical picture, symptom score, biomarkers and double-blind placebo-controlled trial for diagnosis, and treatment. The methodology used was a literature search on NCG/WS using Medline and Premedline from 1970 to August 2016. Expert commentary: We discussed the pathogenesis of symptom generation and altered gut physiology in NCG/WS. Possible mechanisms include innate and adaptive immune activation, impaired intestinal epithelial barrier and changes in gut microbiome. These interlinked factors may be exploited for their clinical relevance as possible biomarkers. A systemic immune response to microbial and wheat antigens, together with intestinal cell damage, occurs in patients with NCG/WS. Due to the lack of established biomarkers, it is mandatory to validate the diagnosis of the syndrome by means of a well-defined work-up involving dietary challenge. Finally, dietary and other therapeutic indications have been thoroughly reviewed

Old and new serological tests for celiac disease screening

Evaluation of: Lewis NR, Scott BB. Meta-analysis: deamidated gliadin peptide (DGP) antibody and tissue transglutaminase (tTG) antibody compared as screening test for celiac disease. Aliment. Pharmacol. Ther. 31(1), 73-81 (2010). In celiac disease (CD), deamidation of gliadin peptides, induced by tissue transglutaminase (tTG), generates novel antigenic epitopes evoking a specific immune response. Serological tests based on the detection of antibodies to deamidated gliadin peptides (DGP) have been developed with very promising results in terms of sensitivity and specificity for CD screening. In the present study, a meta-analysis of studies published from 1998 to 2008 was designed to compare the performance of DGP antibodies with that of tTG antibodies, the validated and routinely employed test for CD screening. The authors have limited their analysis to IgA class antibodies underlining that most of the considered studies had methodological imperfections, especially ascertainment bias. The results of this meta-analysis indicated that the pooled sensitivities for DGP and tTG antibodies were 87.8% (95% CI: 85.6-89.9) and 93% (95% CI: 91.2-94.5), respectively, and the pooled specificities were 94.1% (95%CI: 92.5-95.5) and 96.5% (95% CI: 95.2-97.5), respectively. In summary, although both tests represent a very good tool for identifying celiac patients, tTG antibodies display a higher predictive value than DGP antibodies, and must still be considered the best serological test for CD screening

Fibromyalgia and coeliac disease: a media hype or an emerging clinical problem?

OBJECTIVES: Fibromyalgia (FM) association with autoimmune diseases has been widely reported in literature. Coeliac disease (CD) is a small intestine immune-mediated disorder triggered by gluten ingestion in genetically predisposed patients. In recent years, the Internet and the non-medical press have reported a correlation between gluten-related disorders and fibromyalgia-like symptoms. The aim of our study was to verify a possible association between FM and CD, by assessing the prevalence of CD in a cohort of FM patients and vice versa. METHODS: 90 consecutive subjects from our Rheumatologic outpatient clinic who had been diagnosed with FM were serologically tested for CD and positive patients underwent esophagogastroduodenoscopy to obtain duodenal biopsies. A second group of 114 consecutive subjects from our Coeliac Disease outpatient clinic were investigated for the presence of FM-like symptoms through a questionnaire. Patients reporting chronic widespread pain were addressed to a rheumatologist for further evaluation. RESULTS: The overall prevalence of CD in our FM patients was identical to that expected in general population (around 1%). In our CD group 17 patients (14.9%) reported chronic widespread pain at the questionnaire and 13 (11.4%) satisfied ACR 1990 criteria for FM. Their symptoms had not been modified by GFD. CONCLUSIONS: A serological screening for CD is not recommended in FM patients but rather a case-finding strategy should be performed. At the same time, proposals of GFD in FM patients, in absence of a well-established diagnosis of CD, should be rigorously avoided

Features and Progression of Potential Celiac Disease in Adults

Background & Aims: Individuals with potential celiac disease have serologic and genetic markers of the disease with little or no damage to the small intestinal mucosa. We performed a prospective study to learn more about disease progression in these people. Methods: We collected data from 77 adults (59 female; median age, 33 years) diagnosed with potential celiac disease (on the basis of serology and HLA type) at Bologna University in Italy from 2004 through 2013. The subjects had normal or slight inflammation of the small intestinal mucosa. Clinical, laboratory, and histologic parameters were evaluated at diagnosis and during a 3-year follow-up period. Results: Sixty-one patients (46 female; median age, 36 years) showed intestinal and extraintestinal symptoms, whereas the remaining 16 (13 female; median age, 21 years) were completely asymptomatic at diagnosis. All subjects tested positive for immunoglobulin A endomysial antibody and tissue transglutaminase antibody, except for 1 patient with immunoglobulin A deficiency; 95% of patients were carriers of HLA-DQ2. Duodenal biopsies from 26% patients had a Marsh score of 0, and 74% had a Marsh score of 1. A higher proportion of symptomatic patients had autoimmune disorders (36%) and antinuclear antibodies (41%) than asymptomatic patients (5% and 12.5%, respectively), and symptomatic patients were of older age at diagnosis (P <.05). Gluten withdrawal led to significant clinical improvement in all 61 symptomatic patients. The 16 asymptomatic patients continued on gluten-containing diets, and only 1 developed mucosal flattening; levels of anti-endomysial and tissue transglutaminase antibodies fluctuated in 5 of these patients or became undetectable. Conclusions: In a 3-year study of adults with potential celiac disease, we found most to have symptoms, but these improved on gluten withdrawal. Conversely, we do not recommend a gluten-free diet for asymptomatic adults with potential celiac disease because they do not tend to develop villous atrophy

Guidelines of the Italian societies of gastroenterology on the diagnosis and management of coeliac disease and dermatitis herpetiformis

Introduction: Coeliac disease and dermatitis herpetiformis are immune-mediated diseases triggered by the consumption of gluten in genetically predisposed individuals. These guidelines were developed to provide general practitioners, paediatricians, gastroenterologists, and other clinicians with an overview on the diagnosis, management and follow-up of coeliac patients and those with dermatitis herpetiformis.Methods: Guidelines were developed by the Italian Societies of Gastroenterology. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodol-ogy was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists and a paediatrician with expertise in this field.Results: These guidelines provide a practical guidance for the diagnosis, management and follow-up of coeliac patients and dermatitis herpetiformis in children and adults, both in primary care and in specialist settings. We developed four sections on diagnosis, gluten-free diet, follow-up and risk of complications in adults, one section focused on diagnosis and follow-up in children and one on the diagnosis and man-agement of dermatitis herpetiformis.Conclusions: These guidelines may support clinicians to improve the diagnosis and management of pa-tients with coeliac disease.(c) 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Durable viral suppression in an HIV-infected patient in the absence of antiretroviral therapy

We describe the case of a young woman with an acute HIV infection characterized at onset by neurological features. The patient spontaneously controlled her HIV infection and recovered in a short period of time. The patient's clinical and virological history showed a peculiar evolution of HIV infection, with an MDR HIV-1 in CSF and a wild HIV strain in PBMCs. The patient's PBMC showed a rapid shift from a wild type to an MDR strain in few days

Wheat ATIs : Characteristics and Role in Human Disease

Amylase/trypsin-inhibitors (ATIs) comprise about 2-4% of the total wheat grain proteins and may contribute to natural defense against pests and pathogens. However, they are currently among the most widely studied wheat components because of their proposed role in adverse reactions to wheat consumption in humans. ATIs have long been known to contribute to IgE-mediated allergy (notably Bakers' asthma), but interest has increased since 2012 when they were shown to be able to trigger the innate immune system, with attention focused on their role in coeliac disease which affects about 1% of the population and, more recently, in non-coeliac wheat sensitivity which may affect up to 10% of the population. This has led to studies of their structure, inhibitory properties, genetics, control of expression, behavior during processing, effects on human adverse reactions to wheat and, most recently, strategies to modify their expression in the plant using gene editing. We therefore present an integrated account of this range of research, identifying inconsistencies, and gaps in our knowledge and identifying future research needs. Note This paper is the outcome of an invited international ATI expert meeting held in Amsterdam, February 3-5 2020Peer reviewe

Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: TheGI-COVID-19 is a prospective,multicenter, controlled study. Patientswith and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID1and 296 COVID2) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P &lt; 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels. DISCUSSION: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection