Marianna Salemme

Gastrointestinal motility disorders in inflammatory bowel diseases

The relationship between motility and inflammatory gastrointestinal disorders is at the same time complex and intriguing since these conditions might share some genetic, environmental, immunological and microbial predisposing factors. In addition, significant symptom overlapping may occur, muddling the waters within the clinical context. Although on one hand this represents a challenge for the clinician for a potential under- or over-treatment and diagnostic delay, on the other hand it possibly represents an opportunity for the researcher to better disclose the intimate relationship between chronic (often low-grade) inflammation, motor disorders and deranged sensory function. The best example is probably represented by Crohns disease and ulcerative colitis. In fact, a number of gastrointestinal motor disorders have been described in association with these diseases, disorders which span from the esophagus to the anorectum, and which will be extensively covered in this review. It is conceivable that at least part of this derangement is strictly related to inflammatory cytokine trafficking and neuromuscular changes; however, given the high prevalence of functional gastrointestinal disorders in the general population, this overlap might also be serendipitous. However, it is worth noting that literature data on this topic are relatively scarce, sometimes quite outdated, and mostly focused on the interplay between irritable bowel syndrome and inflammatory bowel disease. Nevertheless, both researchers and clinicians must be aware that symptoms related to gastrointestinal motility disorders may be highly prevalent in both active and inactive inflammatory bowel disease, correlate with greater psychological comorbidity and poorer quality of life, and may negatively influence the therapeutic approaches.

Pseudomembranous collagenous colitis with superimposed drug damage.

Pseudomembranous collagenous colitis is a rare pathological condition, not related to infectious agents, and characterized by thickening of the subepithelial collagen and formation of pseudomembranes. We report one such case, which responded to budesonide treatment after failures of previous approaches given, being unaware of the correct diagnosis.

Intestinal, Systemic, and Oral Gluten-related Alterations in Patients With Nonceliac Gluten Sensitivity

Background: Nonceliac gluten sensitivity (NCGS) is an emergent condition, the framework of which is yet unclear, whereas the diagnosis is suggested only by gluten-dependent symptoms after excluding wheat allergy and celiac disease (CD). Our goal was to highlight intestinal, systemic, and oral alterations to clarify the NCGS pathogenesis and identify new diagnostic tools. Study: A total of 60 NCGS patients, 20 untreated CD, 20 treated CD, and 20 healthy volunteers were recruited. The differential diagnosis among gluten-related disorders was performed by serological, allergy, and histologic tools. NCGS patients were also subjected to antigliadin antibody (AGA) detection and HLA typing. All participants underwent an oral mucosa patch test for gluten (GOMPT), whereas an oral provocation test (OPT) for gluten was performed in 26 NCGS patients. Results: About 6/60 (10%) NCGS patients showed IgG AGA-positive results, whereas 45/60 (75%) patients carried HLA-DQ2 and/or HLA-DQ8 genes. GOMPT showed positive results in 45/60 (75%) NCGS patients, 3/20 (15%) untreated CD patients, 5/20 (25%) treated CD patients, and in no healthy volunteers. No significant difference was found between the severity of symptoms reported by NCGS patients subjected to OPT with gluten-containing croissants and those who underwent OPT with gluten-free croissants. Conclusions: GOMPT seems to be a specific tool for NCGS diagnosis, although further investigations are needed to overcome limits due to the small population studied and to contextualize GOMPT false-positive results.

Incidental 11C-choline PET/CT uptake due to esophageal carcinoma in a patient studied for prostate cancer.

A 75-years-old patient with a history of prostate cancer, previously treated with radical prostatectomy, underwent C-choline PET/CT for restaging due to a rise in the prostate-specific antigen level. The study revealed a focal uptake of C-choline in the esophagus. A subsequent endoscopic examination showed the presence of an esophageal lesion, and after surgery, the histologic diagnosis was mildly differentiated squamous cell carcinoma. In our case, the incidental esophageal uptake revealed by C-choline PET/CT allowed the early diagnosis of an unsuspected esophageal carcinoma.

Adenocarcinoma at the gastroesophageal junction

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the clinical differences between carcinomas arising slightly above, slightly below, and within the gastroesophageal junction (GEJ); information provided by biopsies; information provided by resection specimens following neoadjuvant therapy; histologic differences existing between carcinomas arising slightly above, slightly below, and within the GEJ; differences provided by immunohistochemistry in these tumors; information given by endoscopic mucosal resection specimens; the role of esophageal pyloric gland adenomas as precursors of adenocarcinomas in the region of the cardia; the role of pancreatic metaplasia; Her2 immunoreactivity to make distinctions in the site of origin; and intestinal metaplasia limited to the cardia as a precursor of adenocarcinoma.

Intestinal metaplasia in Barrett's oesophagus: An essential factor to predict the risk of dysplasia and cancer development

BACKGROUND To date, there is still uncertainty on the role of specialized intestinal metaplasia in the carcinogenic process of Barretts oesophagus (BE); this fact seems of importance for planning adequate surveillance programs. AIMS To predict the risk of progression towards dysplasia/cancer based on typical morphological features by evaluating the importance of intestinal metaplasia in BE patients. METHODS 647 cases with a histological diagnosis of BE, referred to the Endoscopy Unit of a tertiary centre between 2000 and 2012 were retrospectively identified, and divided into two groups according to the presence/absence of intestinal metaplasia. For each patient, all histological reports performed during a follow-up of 4-8 years were analyzed. RESULTS Overall, 537 cases (83%) with intestinal metaplasia and 110 cases (17%) without intestinal metaplasia were included. During the follow-up period, none of the patients without intestinal metaplasia developed dysplasia/cancer nor progressed to metaplasia, whereas 72 patients with intestinal metaplasia (13.4%) showed histological progression of the disease. CONCLUSION The histological identification of intestinal metaplasia seems to be an essential factor for the progression towards dysplasia and cancer in BE patients.

Linee guida per la diagnosi di laboratorio e istologica della malattia celiaca. Revisione 2015

RiassuntoIl Gruppo di Studio in Autoimmunologia della SIPMeL ha riveduto e aggiornato le linee guida già proposte nel 2005 alla luce delle evidenze scientifiche comparse negli ultimi 10 anni per l’inquadramento diagnostico e il monitoraggio del paziente celiaco. L’identificazione della nonceliac gluten sensitivity come entità nosologica a se stante ha reso inoltre necessari alcuni chiarimenti su aspetti diagnostici e classificativi. L’attuale versione ripropone sotto forma di raccomandazioni le indicazioni per un appropriato utilizzo dei test sierologici oggi disponibili, dei test genetici in grado di definire l’appartenenza ai gruppi a rischio e dei diversi quadri istologici, definendo gli step diagnostici e interpretativi in maniera diversificata a seconda della motivazione della richiesta (diagnosi, monitoraggio, gruppi a rischio) e dell’età dei pazienti. Le raccomandazioni sono il risultato delle più recenti evidenze disponibili in letteratura, del consenso tra i componenti del gruppo di studio e del lavoro interdisciplinare tra patologi clinici, immunologi e anatomo-patologi e ha l’obiettivo di supportare il lavoro del medico nell’approccio quotidiano alla diagnosi delle patologie glutine-associate.SummaryIn light of scientific evidence that has appeared over the last 10 years, the Study Group on Autoimmune Diseases of the Italian Society of Clinical Pathology and Laboratory Medicine has revised and updated the guidelines—first issued in 2005—on the correct and appropriate procedures for the diagnosis of celiac disease. The identification of non-celiac gluten sensitivity as a disease in itself also needed some clarification as to diagnosis and classification. The current version of the diagnostic guidelines takes the form of recommendations for proper use of available serological and genetic tests, and description of the different histological features, both to diagnose the disease and to define at risk subjects. Diagnostic and interpretative steps are formulated according to the purpose of the request (diagnosis, monitoring, screening) and the age of patients. The recommendations are the result of the latest available evidence in the literature, a consensus among the members of the study group and interdisciplinary work among clinical pathologists, immunologists and pathologists. They are designed to support the work of physicians in the everyday approach to the diagnosis of gluten-associated disorders.

Progression of esophageal dysplasia to cancer.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the evolution of low‐grade squamous and glandular dysplasia to invasive carcinoma; the mutational spectra of Barretts esophagus and adenocarcinoma; the risk of p53‐immunoreactive glandular dysplasia compared to non‐immunoreactive mucosa for progression to cancer; the role of lectins in progression to adenocarcinoma; and the role of racemase immunoreactivity in the prediction of risk of adenocarcinoma.

hERG1 behaves as biomarker of progression to adenocarcinoma in Barrett’s esophagus and can be exploited for a novel endoscopic surveillance

Barretts esophagus (BE) is the only well-known precursor lesion of esophageal adenocarcinoma (EA). The exact estimates of the annual progression rate from BE to EA vary from 0.07% to 3.6%. The identification of BE patients at higher risk to progress to EA is hence mandatory, although difficult to accomplish. In search of novel BE biomarkers we analyzed the efficacy of hERG1 potassium channels in predicting BE progression to EA. Once tested by immunohistochemistry (IHC) on bioptic samples, hERG1 was expressed in BE, and its expression levels increased during progression from BE to esophageal dysplasia (ED) and EA. hERG1 was also over-expressed in the metaplastic cells arising in BE lesions obtained in different BE mouse models, induced either surgically or chemically. Furthermore, transgenic mice which over express hERG1 in the whole gastrointestinal tract, developed BE lesions after an esophago-jejunal anastomosis more frequently, compared to controls. A case-control study was performed on 104 bioptic samples from newly diagnosed BE patients further followed up for at least 10 years. It emerged a statistically significant association between hERG1 expression status and risk of progression to EA. Finally, a novel fluorophore- conjugated recombinant single chain variable fragment antibody (scFv-hERG1-Alexa488) was tested on freshly collected live BE biopsies: it could recognize hERG1 positive samples, perfectly matching IHC data. Overall, hERG1 can be considered a novel BE biomarker to be exploited for a novel endoscopic surveillance protocol, either in biopsies or through endoscopy, to identify those BE patients with higher risk to progress to EA.

Persistent Intraepithelial Lymphocytosis in Celiac Patients Adhering to Gluten-Free Diet Is Not Abolished Despite a Gluten Contamination Elimination Diet.

The gluten-free diet (GFD) is the only validated treatment for celiac disease (CD), but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED) or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12–18 months of GFD (early control) were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control) and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control). Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCRγδ+ (T-Cell Receptor gamma delta) T cell and eosinophils significantly decreased at GCED control (Cohort A) and at late control (Cohort B), compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696]