<p>Supplementary Material and Methods, Results, 1 figure, and 1 table</p>

Knowledge on the role of Helicobacter pylori (HP) infection is continually evolving, and treatment is becoming more challenging due to increasing bacterial resistance. Since the management of HP infection is changing, an update of the national Italian guidelines delivered in 2007 was needed. In the III Working Group Consensus Report 2015, a panel of 17 experts from several Italian regions reviewed current evidence on different topics relating to HP infection. Four working groups examined the following topics: (1) "open questions" on HP diagnosis and treatment (focusing on dyspepsia, gastro-oesophageal reflux disease, non-steroidal anti-inflammatory drugs or aspirin use and extra-gastric diseases); (2) non-invasive and invasive diagnostic tests; (3) treatment of HP infection; (4) role of HP in the prevention of gastric cancer. Statements and recommendations were discussed and a consensus reached in a final plenary session held in February 2015 in Bologna. Recommendations are based on the best current evidence to help physicians manage HP infection in Italy. The guidelines have been endorsed by the Italian Society of Gastroenterology and the Italian Society of Digestive Endoscopy.

AIMTo investigate the clinical response of gastro-esophageal reflux disease (GERD) symptoms to exclusion diets based on food intolerance tests.METHODSA double blind, randomized, controlled pilot trial was performed in 38 GERD patients partially or completely non-responders to proton pump inhibitors (PPI) treatment. Fasting blood samples from each patients were obtained; leukocytotoxic test was performed by incubating the blood with a panel of 60 food items to be tested. The reaction of leukocytes (rounding, vacuolization, lack of movement, flattening, fragmentation or disintegration of cell wall) was then evaluated by optical microscopy and rated as follows: level 0 = negative, level 1 = slightly positive, level 2 = moderately positive, and level 3 = highly positive. A "true" diet excluding food items inducing moderate-severe reactions, and a "control" diet including them was developed for each patient. Then, twenty patients received the "true" diet and 18 the "control" diet; after one month (T1) symptoms severity was scored by the GERD impact scale (GIS). Hence, patients in the "control" group were switched to the "true" diet, and symptom severity was re-assessed after three months (T2).RESULTSAt baseline (T0) the mean GIS global score was 6.68 (range: 5-12) with no difference between "true" and control group (6.6 ± 1.19 vs 6.7 ± 1.7). All patients reacted moderately/severely to at least 1 food (range: 5-19), with a significantly greater number of food substances inducing reaction in controls compared with the "true" diet group (11.6 vs 7.0, P < 0.001). Food items more frequently involved were milk, lettuce, brewer's yeast, pork, coffee, rice, sole asparagus, and tuna, followed by eggs, tomato, grain, shrimps, and chemical yeast. At T1 both groups displayed a reduction of GIS score ("true" group 3.3 ± 1.7, -50%, P = 0.001; control group 4.9 ± 2.8, -26.9%, P = 0.02), although the GIS score was significantly lower in "true" vs "control" group (P = 0.04). At T2, after the diet switch, the "control" group showed a further reduction in GIS score (2.7 ± 1.9, -44.9%, P = 0.01), while the "true" group did not (2.6 ± 1.8, -21.3%, P = 0.19), so that the GIS scores didn't differ between the two groups.CONCLUSIONOur results suggest that food intolerance may play a role in GERD symptoms development, and leucocytotoxic test-based exclusion diets may be a possible therapeutic approach when PPI are not effective or indicated.

To the Editor: In our previous report, we documented a different expression of soluble HLA (human leukocyte antigen)-G molecules between ulcerative colitis (UC) and Crohn’s disease (CD) patients, confirming the presence of different biological characteristics. We observed a spontaneous secretion in peripheral blood mononuclear cell (PBMC) cultures of CD patients but not in those of UC patients. Moreover, a lack of sHLA-G antigens has been reported in UC patient cultures after lipopolysaccharide (LPS) activation. HLA-G molecules are nonclassical HLA Ib antigens characterized by a lower allelic polymorphism and a restricted tissue distribution in comparison with other HLA-Ia molecules. Furthermore, the mRNA alternative splicing generates different membranebound (HLA-G1, G2, G3, and G4) and soluble isoforms (HLA-G5, G6, and G7). HLA-G molecules, in both membrane-bound (mHLA-G) and soluble (sHLA-G) isoforms, are mediators of immunosuppressive functions against innate and adaptive immune responses inducing apoptosis in CD8þ T cells, inhibiting natural killer cell activity, and allo-specific CD4þ T-cell proliferation, enhancing the production of regulatory CD4þ T cells and suppressing the differentiation of dendritic cells. Detectable levels of sHLA-G molecules have been reported in a percentage of plasma samples from healthy subjects and significant variations in the concentrations have been evidenced in different pathological conditions. In our previous study we analyzed the production of sHLA-G molecules in 20 UC (9 females, 8 males; median age 54 years) and 17 CD (11 females, 9 males; median age 51 years) patients without immunosuppressant therapy. Since different molecules are able to induce HLA-G production as cytokines (interleukin10), hormones (progesterone), and immunosuppressant drugs (methotrexate), we evaluated 27 UC (17 females, 10 males; median age 50 years) and 22 CD (12 females, 10 males; median age 55 years) patients attending the Gastroenterology and Digestive Endoscopy Unit of the Ferrara Sant’Anna Hospital for their production of sHLA-G molecules during treatment with multiple drugs (azathioprine, corticosteroids, mesalazine). We analyzed sHLA-G levels in ‘‘in vitro’’ cultures of PBMCs with or without LPS-activation and compared them with the values obtained in the previous untreated cohort. PBMCs were extracted by Ficoll centrifugation (Cederlane, Hornby, Ontario, Canada) from whole peripheral blood and activated by 10 ng/mL of LPS (Calbiochem, La Jolla, CA) for 48 hours. The culture supernatants and the plasma samples were analyzed in triplicate by enzymelinked immunosorbent assay (ELISA) for sHLA-G quantification following the Essen Workshop protocol. Informed consent for blood drawing was obtained from each subject. We compared the sHLA-G levels in PBMC cultures with or without LPS activation from untreated and treated patients. The levels of HLA-G secretion remained higher in nonactivated PBMC cultures from CD patients versus UC patients, even in the treated cohort (Fig. 1A,B) (P 1⁄4 0.011, Wilcoxon test). UC treated patients presented an increased HLA-G secretion in both nonactivated (P 1⁄4 0.057 Mann–Whitney U-test) and LPS-activated PBMC cultures (P 1⁄4 0.004 Mann–Whitney U-test) in comparison with the previous cohort of untreated UC patients (Fig. 1A,B). On the contrary, LPS-activated PBMC cultures from treated CD and UC patients released similar amounts of HLA-G (P 1⁄4 0.075; Wilcoxon test). These data suggest that therapy is able to control the hyperactivation of CD PBMCs and the unbalanced microenvironment of UC patients in the presence of an inflammatory stimulus such as LPS. Age, gender, activity, localization, or duration of the disease and previous surgery did not influence the sHLA-G levels (P 1⁄4 NS; Wilcoxon test). We also analyzed sHLA-G levels in plasma samples from treated CD and UC patients and compared the results with the HLA-G secretion by the corresponding nonactivated PBMC cultures. There was a strict correlation between in vitro and plasmatic levels of sHLAG in both CD (r 1⁄4 0.693; P 1⁄4 0.003; Spearman Correlation test) (Fig. 1C) and UC (r 1⁄4 0.911; P 1⁄4 0.0002; Spearman Correlation test) (Fig. 1D) patients, suggesting the possible use of plasma samples to screen the follow-up of immunosuppressant therapy. Our results suggest that the therapy is able to normalize the production of HLA-G molecules in both CD and UC patients but in a different way: immunosuppressant therapy decreases the hyperproduction of HLA-G in CD patients, while it starts the release of HLA-G in UC patients. These data confirm the diversity in the behavior of these two pathologies and propose the analysis of sHLA-G levels in CD and UC patients during therapeutic follow-up with the goal of distinguishing between UC and CD patients and to monitor therapy. If these results are confirmed in a prospective study, HLA-G could be considered a plasmatic biomarker to establish an individualized treatment to control inflammation, to reduce symptoms, Supported by a grant from AMICI (Associazione per le Malattie Infiammatorie Croniche dell’Intestino). Copyright VC 2011 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.21756 Published online 20May 2011 inWiley Online Library (wileyonlinelibrary.com).

We report on the first screening round in the District of Ferrara, a region of Emilia-Romagna, carried out between March 2005 and March 2007 to illustrate the effort of colorectal cancer (CRC) screening from administration and information to therapy and follow-up. After invitation of 38 344 persons aged 50-69 years (28.5%), 19 480 (50.8%) accepted the immunological faecal occult blood test, with 1 149 (6%) resulting positive. One thousand and one individuals (88.2%) who tested positive for immunological faecal occult blood test accepted examination by either colonoscopy (99.5%) or barium enema (0.5%). Out of 996 screenees having a colonoscopy, 231 had low-risk adenomas (23.2%) and 239 had high-risk adenomas (24%), and were treated endoscopically (96%) or surgically (4%). Ninety-one cancers were diagnosed in 9.1% of colonoscopies (Dukes stadia: A, 58.2%; B, 19.8%; C, 18.7%; D, 3.3%). Fourteen cancers (all in polyps) were treated endoscopically, and the remaining 77 were treated by surgery. One Dukes B patient and 13 of 17 Dukes C patients received adjuvant chemotherapy. Three Dukes D patients had chemotherapy only. During the 2-year study period, 87 screenees had a follow-up colonoscopy: no neoplasia was found in 35 patients initially diagnosed with cancer; low-risk adenomas were found in 31 of 52 patients with initial high-risk adenomas. In conclusion, the first CRC screening round in Ferrara was easy to organize, had a high acceptance, and detected 91 cancers (78% of which were in Dukes stages A and B, compared with only 40% in sporadic CRC in the same background population). Chemotherapy was necessary in 17 cases. This report may motivate other health authorities to initiate CRC screening campaigns.

INTRODUCTION:Recent data suggest that mucosal abnormalities can occur even in the duodenum, jejunum, and distal ileum of cirrhosis patients. We present a case of portal hypertensive enteropathy in a cirrhosis patient shown by capsule endoscopy and the effect of transjugular intrahepatic portosystemic shunt on the ileal pictures.CASE PRESENTATION:An 83-year-old Caucasian woman was admitted to our hospital for anemia and a positive fecal occult blood test. An upper gastrointestinal endoscopy revealed small varices without bleeding signs and hypertensive gastropathy. Colonoscopy was negative. To rule out any other cause of bleeding, capsule endoscopy was performed; capsule endoscopy revealed severe hyperemia of the jejunum-ileal mucosa with active bleeding. Because of the persistence of anemia and the frequent blood transfusions, not responding to β-blocker drugs or octreotide infusion, a transjugular intrahepatic portosystemic shunt was performed. Anemia improved quickly after the transjugular intrahepatic portosystemic shunt, and no further blood transfusion was necessary in the follow-up. The patient developed portal encephalopathy two months later and was readmitted to our department. We repeated the capsule endoscopy that showed a significant improvement of the gastric and ileal mucosa without any signs of bleeding.CONCLUSION:Hypertensive enteropathy is a rare condition, but it seems more common with the introduction of capsule endoscopy in clinical practice. This case shows that the jejunum can be a source of bleeding in cirrhosis patients, and this is the first demonstration of its resolution after transjugular intrahepatic portosystemic shunt placement.

INTRODUCTION:Capsule endoscopy has, over the last few years, become a first-line test to visualize the mucosa of the small intestine. This technique is generally considered safe and does not cause discomfort for patients. However, although patients may have difficulty in swallowing the capsule, bronchial aspiration of a capsule endoscope is a very rare complication. We report the case of an 82-year-old man who experienced prolonged bronchial aspiration of a capsule endoscope without relevant symptoms, followed by a spontaneous return of the capsule to the gastrointestinal tract.CASE PRESENTATION:An 82-year-old Caucasian man was referred to our unit from another local hospital to undergo capsule endoscopy. He swallowed the capsule without any apparent difficulties and did not show any overt symptoms. The following day, when we reviewed the capsule endoscopy images, we realized that the capsule was in the bronchial system and remained there for the duration of the study. An urgent X-ray of the chest confirmed the presence of the capsule in the left side of the bronchopulmonary tree. Two days later a repeat chest X-ray showed the capsule in the right bronchus. After two days the capsule was retrieved in the feces. Our patient remained asymptomatic during the entire admission period.CONCLUSIONS:Aspiration of a capsule endoscope is a rare complication; to the best of our knowledge this is the first reported case in which a capsule endoscope remained for six days in the bronchial system of a patient without causing airway compromise or pneumonitis and spontaneously returned to the gastrointestinal tract.

Screening for colorectal cancer (CRC) has become established to varying degrees in several Western countries for the past 30 years. Because of its effectiveness, screening has been adopted or is planned in a number of other countries. In most countries, the screening method (e.g., fecal occult blood test [FOBT], sigmoidoscopy) is followed by colonoscopy, for verification. In other countries (e.g., United States, Germany), colonoscopy is the preferred first-line investigation method. However, because colonoscopy is considered to be invasive, might be poorly tolerated, and can be associated with complications, the idea of adopting colonoscopy as the primary screening method suffers. Negative effects of screening methods can reduce participation in programs and thereby negate the desired effect on individual and societal health. At present, there is no generally accepted method either to assess the perception and satisfaction of patients screened or the outcome of the screening procedures in CRC. In this review, we discuss the past development and present availability of instruments to measure health-related quality of life (HRQoL), the scarce studies in which such instruments have been used in screening campaigns, and the findings. We suggest the creation of a specific instrument for the assessment of HRQoL in CRC screening.

BACKGROUND AND AIM:Few studies have specifically addressed interobserver agreement in describing lesions identified during capsule endoscopy. The aim of our study is to evaluate interobserver agreement in the description of capsule endoscopy findings. MATERIALS AND METHODS:Consecutive short segments of capsule endoscopy were prospectively observed by 8 investigators. Seventy-five videos were prepared by an external investigator (gold standard). The description of the findings was reported by the investigators using the same validated and standardized capsule endoscopy structured terminology. The agreement was assessed using Cohen's kappa statistic. RESULTS:As concerns the ability to detect a lesion, the agreement with the gold standard was moderate (kappa 0.48), as well as the agreement relating to the final diagnosis (κ 0.45). The best agreement was observed in identifying the presence of active bleeding (κ 0.72), whereas the poorest agreement concerned the lesion size (κ 0.32). The agreement with the GS was significantly better in endoscopists with higher case/volume of capsule endoscopy per year. Diagnostic concordance was better in the presence of angiectasia than in the presence of polyps or ulcers/erosions. CONCLUSIONS:Correct lesion identification and diagnosis seem more likely to occur in presence of angiectasia, and for readers with more experience in capsule endoscopy reading.

Prevention of colorectal tumors has become a priority in Italian health policy only in recent times. In 2004, Emilia Romagna became the first Italian region with a colorectal screening program (CSP) covering the resident target population in its entirety. Each local health agency (AUSL) operating in the region's nine provinces was left free to choose the organizational model for its CSP.As no study on the matter had been carried out in the region before, an in-depth survey on cost, effectiveness and efficiency of CSPs in Emilia Romagna was commissioned by the Italian Health Ministry in 2008, to act as a basis for possible future systematic analysis of the investigated aspects, as well as a support for improving the regional and national policy of prevention of colorectal tumors.

OBJECTIVES:Efficacy of symbiotics in patients with irritable bowel syndrome (IBS) remains unknown.METHODS:Patients were randomized to a prebiotic (n=135), or a symbiotic formulation containing Lactobacillus paracasei B21060 (Flortec, n=132). Primary efficacy was the responder rate for pain and global relief of symptoms in the overall population and in patients with predominant diarrhea (n=47). Post hoc time-trend analyses for changes within each treatment were carried out.RESULTS:Patients with absent/mild pain amounted to 54.7% in the symbiotic group and to 57.4% in the prebiotic group at treatment week 4, and to 53.9% and 53.4% at the end of treatment. Patients with amelioration of well-being were, respectively, 60.7% versus 61.7% at treatment week 4, and 63.3% versus 60.9% at the end of treatment. Within each treatment group, patients with absent/mild pain increased in the Flortec and the prebiotic group, but time trend analyses were significant only for Flortec (P=0.019). In IBS-predominant diarrhea, Flortec significantly reduced bowel movements, pain, and IBS scores.CONCLUSIONS:To improve pain and well-being, Flortec is encouraging in patients with diarrhea predominant IBS. To establish its efficacy for the majority of IBS patients, Flortec has to be compared with an inert placebo in future work.

Background: nasal route for upper endoscopy was first considered by Shaker (Gastrointest Endosc, 1994) and proposed as routinely diagnostic and selected therapeutic procedure by Barberani (It.J.Gastroent.Hepat. 1998) with his innovative technique. Aim: 1) to evaluate safety, feasibility and satisfaction rate of T-EGD from both medical and patient points of view, focusing by a multivariate analysis on final judgement influencing criteria 2) to evaluate effect of aromatized lubrification gel (eucalyptus, lemon or rose Sapimed-Italy) on pts satisfaction rate. Methods: 1006 pts (576M,430F;range 16-99) underwent T-EGD performed. Pts were divided in three groups in relation to previous experience of T-EGD (C), oral-EGD (B) or no previous endoscopy (A). Medical satisfaction rate was evaluated analyzing pts collaboration during T-EGD and technical difficulties in nasal insertion;safety was evaluated by complication incidence, monitoring cardiac frequency and O2 saturation; pts satisfaction was evaluated considering nasal discomfort, vomiting, burping and choking by means analogical scale (1-10). Aromatized gel effect was evaluated monitoring satisfaction rate of group C-patients (previous T-EGD with neutral gel). T-EGD were performed by means of Fuji-Olympus-Pentax 6 mm video-endoscope. Statistical analysis were performed by χ2 test for proportion and one way analysis variants for continuous data (R. Marmo MD, Italy); p < 0.05 was considered statistically significant. Results: Pts collaboration was bad(8,5%), good (47,6%) excellent (43,9%). No problems in nasal insertion in 81,4%, mild in 11%, high in 7,6% without differences between sex. Pts discomfort at the insertion was none (17,3%) mild (63,5%) high (19,2%). No pO2 variation before, during and after examination while cardiac frequency increased 9% during T-EGD(p < 0,0005). Complications rate was 0,3% (1 vertigo,2 epistaxis spontaneously recovered). Mild tearing in 50% and sneeze 10%. Vomiting was present in only 9,1%, burping in 10,8%, choking in 2,5%. In 6,1% of the pts was evident. ENT pathology Final judgement of pts about T-EGD was positive in 92%. 90% of pts appreciated aromatized gel and eucalyptus was favourite; T-EGD was more comfortable than previous with neutral gel in 91% of C group pts. The correlation between collaboration, nasal discomfort, symptoms, difficulty of nasal insertion, emphasize 10% of pts with negative judgment about T-EGD related to nasal and pharyngeal high sensitivity. Conclusions: T-EGD high satisfaction and safety were confirmed by both medical and patient point of view and are emphasized by using aromatized gel; nasal and pharyngeal high sensitivity could explain 10% of unsatisfacted pts that need sedation.

The aim of this study was three-fold: (a) to present a surveillance plan for colorectal cancer prevention with colonoscopy, focused on first-degree relatives of colorectal cancer patients in the province of Ferrara (Italy); (b) to analyse the cost of colonoscopy at the University Hospital of Ferrara; and (c) to analyse the cost of the surveillance plan in our province. In January 2000, in the province of Ferrara, following a campaign of public sensitization, a plan of surveillance with colonoscopy was started, addressing the population at an increased risk for colorectal cancer (i.e. over 45-year-old first-degree relatives of patients with either colorectal cancer or adenomatous polyps revealed before 60 years of age). In addition, we estimated the cost of colonoscopy both at the University Hospital of Ferrara and of the surveillance plan. Between January 2000 and October 2003, 585 individuals at increased risk were interviewed. Five hundred and forty-four (94%) accepted to undergo a colonoscopy. By October 2003, 439 (81%) colonoscopies had been performed. Colonoscopy was normal in 330 individuals (75%). In 109 individuals (25%), 144 lesions were found: 35 patients (32%) had hyperplastic polyps, 66 (61%) had adenomas, and eight (7%) adenocarcinomas (six Dukes A, one Dukes B, and one Dukes C stage). Out of a total of 101 adenomas, 68 were tubular adenomas (67%), 24 tubulo-villous adenomas (24%), and nine adenomas with high-grade dysplasia (9%). The cost of colonoscopy at our hospital and the costs of the surveillance plan amounted to euro 130.84 (euro 169.57 with single biopsy) and euro 43,103.66 (euro 42 310.34/year), respectively. These data show (a) the efficacy of colonoscopy in the early diagnosis of colorectal cancer and premalignant lesions in first-degree relatives of colorectal cancer patients; (b) the low cost of colonoscopy at the centre performing the surveillance; and (c) the feasibility of screening and surveillance programmes for colorectal cancer prevention.

BACKGROUND:HLA-G antigens are nonclassical major histocompatibility complex (MHC) class I molecules characterized by tolerogenic and antiinflammatory properties. Recently, a different expression of HLA-G antigens has been observed between intestinal biopsies of ulcerative colitis (UC) and Crohn's disease (CD) patients. These data suggested a functional role for HLA-G molecules in the diseases and proposed the HLA-G modulation as a marker for the diagnosis of UC and CD. The soluble HLA-G antigens (sHLA-G) are circulating molecules mainly produced by activated peripheral blood CD14+ monocytes.METHODS:We tested, by specific enzyme-linked immunosorbent assay (ELISA), the sHLA-G molecule levels in the supernatants of unstimulated and bacterial lipopolysaccharide (LPS)-stimulated cultures of peripheral blood mononuclear cells (PBMC) from 30 healthy subjects, 10 CD, and 18 UC patients. The data were not influenced by treatment or disease activity.RESULTS:The results confirmed a different sHLA-G expression between the diseases, with a spontaneous secretion of sHLA-G in CD patients but not in UC and healthy subjects. Moreover, a lack of sHLA-G antigens has been reported in UC patient cultures after LPS activation but not in healthy subjects and CD patients. The defective sHLA-G production was related to an impaired IL-10 secretion in UC but not in CD.CONCLUSIONS:Overall, these results confirm the presence of a different biological characteristic between CD and UC patients and suggest sHLA-G production by PBMC as a noninvasive diagnostic tool in the early phases of the diseases.

Colorectal cancer represents the second leading cause of cancer deaths in western countries with elevated costs for health service. It's very important to develop screening and surveillance programs for cancer prevention with "cost-effective" means. We present a surveillance program with colonoscopy focused on first degree relatives of CRC patients. Colonoscopy is a "cost-effective" mean of screening for high risk subjects.

AIM:The fears and concerns are associated with gastroscopy (EGD) decrease patient compliance. Conscious sedation (CS) and non-pharmacological interventions have been proposed to reduce anxiety and allow better execution of EGD. The aim of this study was to assess whether CS, supplementary information with a videotape, or presence of a relative during the examination could improve the tolerance to EGD.METHODS:Two hundred and twenty-six outpatients (pts), scheduled for a first-time non-emergency EGD were randomly assigned to 4 groups: Co-group (62 pts): throat anaesthesia only; Mi-group (52 pts): CS with i.v. midazolam; Re-group (58 pts): presence of a relative throughout the procedure; Vi-group (54 pts): additional information with a videotape. Anxiety was measured using the "Spielberger State and Trait Anxiety Scales". The patients assessed the overall discomfort during the procedure on an 100-mm visual analogue scale, and their tolerance to EGD answering a questionnaire. The endoscopist evaluated the technical difficulty of the examination and the tolerance of the patients on an 100-mm visual analogue scale and answering a questionnaire.RESULTS:Pre-endoscopy anxiety levels were higher in the Mi-group than in the other groups (P<0.001). On the basis of the patients' evaluation, EGD was well tolerated by 80.7% of patients in Mi-group, 43.5% in Co-group, 58.6% in Re-group, and 50% in Vi-group (P<0.01). The discomfort caused by EGD, evaluated by either the endoscopist or the patients, was lower in Mi-group than in the other groups. The discomfort was correlated with "age" (P<0.001) and "groups of patients" (P<0.05) in the patients' evaluation, and with "gender" (females tolerated better than males, P<0.001) and "groups of patients" (P<0.05) in the endoscopist's evaluation.CONCLUSION:Conscious sedation can improve the tolerance to EGD. Male gender and young age are predictive factors of bad tolerance to the procedure.

Background: Gene promoter methylation is a mechanism for tumor suppressor gene silencing and inactivation. The development of highly sensitive methods for revealing aberrant cancer-associated DNA methylation allows the identification of tumor markers not only in tumor samples, but also in body fluid, an approach that can be useful in the early detection of neoplasms. Methods: We analyzed the methylation status at 16 loci in tumor samples of the gastrointestinal tract and in early or pre-neoplastic lesions of the colon. Results: Tumor samples revealed that methylation at the transmembrane protein containing epidermal growth factor and follistatin domains (TPEF) locus had the best ratio of discrimination between tumor samples versus normal tissues (83 versus 0%). Its combination with hypermethylated in cancer 1 (HIC1) , death-associated protein kinase (DAPK) and O -6-methylguanine DNA methyltransferase (MGMT) , allowed the detection of aberrant methylation in 98% of colorectal carcinomas and 100% of gastric carcinomas. The same alterations were also detected in colon adenomas and tissues surrounding the adenomas, indicating that hypermethylation at these loci occurred early in tumor progression. Analysis of DNA from peripheral blood revealed that TPEF methylation was detectable in colorectal tumor patients and patients with early or pre-neoplastic lesions, but not in healthy volunteers. Conclusions: Our results identify TPEF as a tumor marker that could be useful in the follow-up of gastrointestinal cancer patients or the screening of individuals at risk of developing gastrointestinal neoplasms.