Context: Multiple endocrine neoplasia type 1 (MEN1) patients frequently develop Zollinger-Ellison syndrome (ZES). These patients can develop proliferative changes of gastric enterochromaffin-like (ECL) cells and gastric carcinoids (ECL-cell tumors). ECL-cell changes have been extensively studied in sporadic ZES patients and can be precursor lesions of gastric carcinoids, but little is known about factors influencing their severity or development of carcinoids in MEN1/ZES patients. Objectives: Our objective was to prospectively analyze ECL-cell changes and gastric carcinoids (ECL-cell tumors) in a large series of MEN1/ZES patients to detect risk factors and deduct clinical guidelines. Setting and Patients: Fifty-seven consecutive MEN1/ZES patients participated in this prospective study at two tertiary-care research centers. Interventions and Outcome Measures: Assessment of MEN1, gastric hypersecretion, and gastroscopy with multiple biopsies was done according to a fixed protocol and tumor status. ECL-cell changes and α-human chorionic gonadotropin staining were assessed in each biopsy and correlated with clinical, laboratory, and MEN1 features. Results: ECL-cell proliferative changes were universally present, advanced changes in 53% and carcinoids in 23%. Gastric nodules are common and are frequently associated with carcinoids. Patients with high fasting serum gastrin levels, long disease duration, or a strong α-human chorionic gonadotropin staining in a biopsy are at higher risk for an advanced ECL-cell lesion and/or gastric carcinoid. Conclusions: Gastric carcinoids and/or advanced ECL-cell changes are frequent in MEN1/ZES patients, and therefore, regular surveillance gastroscopy with multiple routine biopsies and biopsies of all mucosal lesions are essential. Clinical/laboratory data and biopsy results can be used to identify a subgroup of MEN1/ZES patients with a significantly increased risk for developing gastric carcinoids, allowing development of better surveillance strategies.

Somatostatin influences motility, secretion, and absorption and often has in vivo a modulating, indirect effect on target cells in the gastrointestinal tract. Knowledge on tissue-specific expression of the five somatostatin receptors (SSTRs), their capacities for internalization and downregulation, their subtype-specific intracellular messengers, and the possibility of forming functionally distinct homodimers or heterodimers, has further complicated the actual in-vivo mechanism of action of somatostatin. This review reports recent in-vivo and in-vitro studies on somatostatin effects on the gastrointestinal tract and pancreas, most of them using a new engineered animal model able to define specific roles of somatostatin and/or its receptor subtypes. SSTR2 knockout mice showed normal circulating gastrin and unchanged acid output, suggesting a high degree of plasticity behind gastric acid secretion. Intestinal inflammation significantly increased somatostatin mRNA in SSTR2 null compared to wild type suggesting that somatostatin mediates inflammation also in SSTR2 null mice. In pancreatic islets of SSTR1-5 null mice no variations of islet size, cellular organization or glucagon or insulin content was shown when compared with null SSTRs and control mice. Although none of the recent findings produced on somatostatin seem ready to be considered for clinical application, recent developments of animal models such as SSTR knockout mice have highlighted promising results to better understand the direct and indirect effects of somatostatin on gastrointestinal tract functions.

The majority of gastroenteropancreatic well-differentiated endocrine carcinomas (WDEC) express somatostatin receptors (SSTR). To correlate the expression of SSTR subtypes by reverse transcriptase-polymerase chain reaction (RT-PCR) with clinicopathological features and survival in a group of WDEC patients, 42 WDEC tissue specimens from 33 patients were analysed. All patients were treated with somatostatin analogues and had a median follow-up period of 45 months (range 6–196). Neither SSTR2 and SSTR5 expression nor Ki-67 level alone correlated with survival. A significantly better survival rate was observed in patients with tumours expressing SSTR2, SSTR5 and Ki-67 <2%, compared to those with SSTR2– and SSTR5–negative tumours and Ki-67 ≥2% (p < 0.038), with 5-year survival rates of 91 vs. 43%, respectively. Expression of SSTR2 and SSTR5 appears to play a positive prognostic role, possibly correlated with the high affinity that the available somatostatin analogues display for these 2 specific SSTR subtypes.

Celiac disease (CD) is an immune-mediated enteropathy caused by gluten ingestion, affecting approximately 1% of the worldwide population. Extraintestinal symptoms may be present as the first signs of CD, years before the CD diagnosis is made. A great variety of extraintestinal manifestations may be associated with CD. Cutaneous manifestations represent the main extraintestinal manifestations, with dermatitis herpetiformis being the most common in patients with CD. In adults, it has been demonstrated that the role of a gluten-free diet is crucial not only for the recovery of signs and symptoms associated with CD but also for cutaneous manifestations, which often improve after gluten avoidance. In children with CD, the association with skin disorders is well documented regarding dermatitis herpetiformis, but studies considering other dermatological conditions, such as psoriasis and atopic dermatitis, are few. The prevalence and manifestations of dermatological disorders in celiac children are often different from those in adults, explaining the gap between these populations. In addition, the therapeutic role of a gluten-free diet in the improvement in skin alterations is not fully understood in children and in adult population except for dermatitis herpetiformis. Therefore, cutaneous CD symptoms need to be known and recognized by physicians despite their specialties to improve early CD diagnosis, which is critical for a better prognosis. This review describes the current scientific evidence on skin manifestations associated with CD in the pediatric population.

Recent studies have indicated that Toll-like receptor polymorphisms or their impaired signalling, specifically TLR-2 and TLR-4, were correlated with a higher risk for allergy. The purpose of this study is to evaluate the associations of TRL-2 and TRL-4 single nucleotide polymorphisms (SNP) and atopic traits in a cohort of 159 Italian allergic children (102 affected by eczema and 57 by IgE-mediated food allergy) and 147 healthy controls recruited in Rome, Italy. DNA was isolated from the peripheral blood and TLR-2 R753Q/TLR-4 D299G polymorphisms were determined by TaqMan MGB probes using Real-Time PCR technique. In the control group, the TLR-2 polymorphism R753Q had a prevalence of 2.5% while the frequency of the TLR-4 D299G was 12%. None of the 159 allergic patients showed the R753Q SNP. By contrast, 7/57 patients with food allergy (12%) and 6/102 subjects with eczema (6%) carried the TLR-4 mutation. In our cohort, no evidence of correlation between TLR-2 or TLR-4 polymorphism and eczema and food allergy incidence and/or severity was found. Further studies are needed to clarify the possible role of TLR-2 and TLR-4 polymorphism in allergic disease, in Italian children.