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Objective. Celiac disease (CD) has strongly been established as associated with some site-specific gastrointestinal malignancies. On the contrary, according to the few reports available, the risk of colon carcinoma in CD patients has been described similar to that of general population. In this cohort study, we describe the risk of colon carcinoma in a group of Italian celiac patients. Materials and methods. The study population included all CD patients diagnosed at the Collaborating Centers of the Italian Registry of CD between 1st January 1982 and 31st December 2006. Upon diagnosis of CD and upon at every subsequent clinical control, the Collaborating Centers filled in a validated form for each CD patient reporting information about demographic data, possible occurrence of a neoplasm and adherence to a gluten-free diet. Results. Out of 1757 celiac patients enrolled, 6 developed a colon carcinoma during the follow-up period (mean: 18.1 years). The standardized incidence ratio (SIR) resulted 0.29 (95% CI = 0.07–0.45). Stratifying the risk for the dietary gluten intake, the SIR dropped to 0.07 (95% CI = 0.009–0.27) for CD patients with a strict adherence to a gluten-free diet. Conclusion. We confirm the previous finding that there is low risk to develop a colon cancer in celiac patients.

Analysis of integration distribution of gamma-retroviral vectors in gene therapy treated patients is crucial in order to assess the accessibility to insertion events in human genome as well as the influence of vector on host genome and clonal selection of transduced cells. To address these issues we compared through 454-pyrosequencing the distribution of MLV-vector integrations in two different gene therapy (GT) trials for ADA-SCID based on repeated infusions of transduced mature lymphocytes (PBL) or a single infusion of hematopoietic stem/progenitor cells (HSC) combined with nonmyeloablative conditioning. In the PBL-GT group we isolated a total of 2509 unique integrations derived from in vitro transduced PBL or ex vivo blood samples in 4 patients (5 to 7 years after last infusion). In the HSC-GT group we retrieved 1064 integrations from in vitro transduced CD34+ cells and ex vivo purified blood cells in 3 patients (2 to 5 years after GT). In both groups MLV vector displays the classical non-random distribution favoring gene-dense regions and TSSs. However, integrations from PBL-GT displayed a significant preference for genes highly expressed in T cells and involved in T cell specific functions (proliferation, differentiation and development) and signaling pathways (IL-2, IL-15, TCR) as compared with insertions from HSC-GT (IPA software). The T-cell specific pattern was observed both in in vitro and ex vivo integrations, and did not result in clonal selection or in vivo skewing. On the other hand, in T cells derived from patients treated with HSC-GT, these genes were not represented and hit genes were involved in a wider range of functional categories reflecting the stemness of the transduced precursors from which they derived. CIS were also specifically different between the two groups of patients. For example, LMO2 was an hotspot both before and after infusion in HSC-GT patients while we did not detect any integration in this locus in PBL-GT patients. Comparison of the expression profile of hit genes profile by Affymetrix analysis revealed that these differences could be partly related to their expression state at the time of transduction in transduced PBL vs CD34+cells. In addition, we found a preferential distribution of PBL-GT integrations in regions with a higher density of T cells hypersensitive sites as compared to HSC-GT, suggesting a possible link with T-cell specific accessibility of genome. Overall our data show in ADA-SCID patients treated with GT clues of a cell-specific integration profile with no particular in vivo biases before infusion and following in vivo selections years after GT.

Patients with celiac disease have an increased rate of enteropathy-associated T-cell lymphoma, but conflicting data are available about the protective role of a gluten-free diet with regard to the development of this malignancy. We followed 1,757 celiac patients for a total period of 31,801 person-years, collecting data about the frequency of gluten intake and the incidence of the enteropathy-associated T-cell lymphoma. Out of the nine celiac patients who developed an intestinal lymphoma [standard morbidity ratio of 6.42 (95% CI = 2.9-12.2; P < 0.001)], only two kept a strict gluten-free diet after the diagnosis of celiac disease and developed the malignancy after the peridiagnosis period of 3 years, dropping therefore the standard morbidity ratio to 0.22 (95%CI = 0.02-0.88; P < 0.001). The risk of developing an intestinal lymphoma for the celiac patients that used to have dietary gluten was significant (X(2 )= 4.8 P = 0.01). These results show that a strict gluten-free diet is protective towards the development of enteropathy-associated T-cell lymphoma.

Background The association between coeliac disease (CD) and neoplasms has been long established, but few data are available about the risk factors. The aim of this paper is to estimate the risk of developing a neoplasm among non diagnosed coeliac patients and to evaluate if this risk correlates with the age of patients at diagnosis of coeliac disease. Methods The study population consists of patients (n = 1968) diagnosed with CD at 20 Italian gastroenterology referral Centers between 1st January 1982 and 31st March 2005. Results The SIR for all cancers resulted to be 1.3; 95% CI = 1.0–1.7 p < 0.001. The specific SIRs for non Hodgkin lymphoma was 4.7; 95% CI = 2.9–7.3 p < 0.001, for the small bowel carcinoma 25; 95% CI = 8.5–51.4 p < 0.001, for non Hodgkin lymphoma 10; 95% CI = 2.7–25 p = 0.01, finally for the stomach carcinoma 3; 95% CI = 1.3–4.9 p < 0.08. The mean age at diagnosis of CD of patients that developed sooner or later a neoplasm was 47,6 ± 10.2 years versus 28.6 ± 18.2 years of patients who did not. Conclusion Coeliac patients have an increased risk of developing cancer in relation to the age of diagnosis of CD. This risk results higher for malignancies of the gastro-intestinal sites. An accurate screening for tumors should be performed in patients diagnosed with CD in adulthood and in advancing age.

Escherichia coli has been recognized as the principal indicator of fecal contamination of water. Indeed, E. coli is the only species in the coliform group found in relationship with gastrointestinal tract of human and warm-blooded animals and subsequently excreted in large numbers in the human feces. To obtain a complete picture of water quality and therefore, a better protection of public health, different techniques for water analysis have been proposed. In this article, we describe an alternative method that uses SYBR green real time-polymerase chain reaction (RT-PCR) technology to identify and quantify all E. coli biotypes in a group of wastewater samples collected from a wastewater depurator located in South of Italy. This new RT-PCR protocol is accurate in measuring the concentration of chromosomal E. coli DNA using the amplification of three new specific fragments of the following bacteria genes: CadC, HNS, and Allan whose sequence is specific for E. coli family and conserved in all E. coli subtypes. This method allowed us to detect the presence of all E. coli biotypes directly in wastewater samples and estimated the correspondence between colony forming units and bacterial DNA concentrations. The availability of a rapid and sensitive method may be useful to monitor the persistence of E. coli in water, to evaluate the efficiency of wastewater purification treatments and the possible recycle for agricultural use. Furthermore, the development of a simple and routine method to monitor water quality with RT-PCR analysis can encourage the testing of a higher number of samples. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 1106–1113, 2012

The association between celiac disease (CD) and several liver disorders has long been documented. About 40% of adult celiac patients have been reported to have mild to moderate hypertransaminasemia (up to five times the upper limit of normal) at the time of diagnosis of CD [1, 2]. In addition, CD has been found in roughly 10% of patients with unexplained hypertransaminasemia, and the majority of them have had their liver enzyme levels normalized after one year of following a strict gluten-free diet [3, 4]. In addition, an increased prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis among CD patients has been reported [5, 6]. CD might also be linked to very severe liver conditions such as end-stage liver failure and hepatocellular carcinoma [7]. There is also evidence, even contrasting reports, about the association of CD with nonalcoholic steatohepatitis and fatty liver disease [8]. In contrast, no definitive evidence is available about the association between chronic hepatitis C (hepatitis C virus [HCV]) and CD. Fine et al. described a three-fold increase of CD prevalence among HCV patients compared to noninfected celiac individuals [9]. It has also been reported the activation of silent CD during the antiviral treatment for HCV with interferon-α and ribavirin, both alone and in combination [10]. Consequently, a routine serological screening for CD has been proposed in HCV patients before starting antiviral therapy. In case of HCV positivity, the achievement of the histological normalization of the intestinal mucosa after following a gluten-free diet has been advised before starting the therapy [10]. On the contrary, some recent prospective studies have not shown increased prevalence of CD among HCV patients and reported that the link between these two conditions is biased by the route of transmission [11, 12]. Among the 3,725 celiac patients included in the Italian Registry of the Complication of Celiac Disease, we identified 34 individuals (0.91%) that had an HCV chronic hepatitis at the time of diagnosis of CD. For the diagnosis of HCV, we considered the serological positivity of antiHCV antibodies. Some of the patients had the diagnosis made in the early 1980s, when the molecular tests for the detection of the viral antigens were not yet available. The demographic and clinical features of the patients with both CD and HCV with respect to those of patients with CD only are listed in Table 1. The prevalence of HCV among our celiac series is lower than the overall prevalence of HCV among the general population in Italy, matched for age and gender, which is estimated to be around 2% [13]. This finding does not support the hypothesis of a potential correlation between these two disorders. It has been assumed that antiviral therapy with INF-α and ribavirin may precipitate the onset of CD in susceptible individuals, promoting a Th1-specific response in the small intestine [14]. However, in our series, only 12 of the 34 celiac patients with HCV had antiviral therapy before CD diagnosis. Looking at our series, it seems more likely that an overall increased risk of CD in HCV patients exists, due to the predisposition for autoimmune diseases related to Eur J Clin Microbiol Infect Dis (2009) 28:1267–1269 DOI 10.1007/s10096-009-0769-6