Underwater cap-suction pseudopolyp formation for endoscopic mucosal resection: a simple technique for treating flat, appendiceal orifice or ileocecal valve colorectal lesions.

BACKGROUND: We aimed to evaluate the safety and technical success of an easy-to-use technique that applies underwater cap suction pseudopolyp formation to facilitate the resection of flat lesions or those at the appendiceal orifice or ileocecal valve. METHODS: We retrospectively analyzed a register of consecutive cap suction underwater endoscopic mucosal resection (CAP-UEMR) procedures performed at two centers between September 2020 and December 2021. Procedures were performed using a cone-shaped cap, extending 7 mm from the endoscope tip, to suction the lesion while submerged underwater, followed by underwater snare resection. Our primary end point was technical success, defined as macroscopic complete resection. RESULTS: We treated 83 lesions (median size 20 mm; interquartile range [IQR] 15-30 mm) with CAP-UEMR: 64 depressed or flat lesions (18 previously manipulated, 9 with difficult access), 11 from the appendix, and 8 from the ileocecal valve. Technical success was 100 %. There were seven intraprocedural bleedings and two delayed bleedings, all managed endoscopically. No perforations or other complications occurred. Among the 64 lesions with follow-up colonoscopy, only one recurrence was detected, which was treated endoscopically. CONCLUSIONS: CAP-UEMR was a safe and effective technique for removing nonpolypoid colorectal lesions, including those arising from the appendiceal orifice or ileocecal valve.

The Answer to "When to Clip" After Colorectal Endoscopic Mucosal Resection Based on a Cost-Effectiveness Analysis.

INTRODUCTION: Delayed bleeding (DB) is the most common major complication of endoscopic mucosal resection (EMR). Two randomized clinical trials recently demonstrated that clip closure after EMR of large nonpedunculated colorectal polyps (LNPCPs) reduces the risk of DB. We analyzed the cost-effectiveness of this prophylactic measure. METHODS: EMRs of LNCPCPs were consecutively registered in the ongoing prospective multicenter database of the Spanish EMR Group from May 2013 until July 2017. Patients were classified according to the Spanish Endoscopy Society EMR group (GSEED-RE2) DB risk score. Cost-effectiveness analysis was performed for both Spanish and US economic contexts. The average incremental cost-effectiveness ratio (ICER) thresholds were set at 54,000 € or $100,000 per quality-adjusted life year, respectively. RESULTS: We registered 2,263 EMRs in 2,130 patients. Applying their respective DB relative risk reductions after clip closure (51% and 59%), the DB rate decreased from 4.5% to 2.2% in the total cohort and from 13.7% to 5.7% in the high risk of the DB GSEED-RE2 subgroup. The ICERs for the universal clipping strategy in Spain and the United States, 469,706 € and $1,258,641, respectively, were not cost effective. By contrast, selective clipping in the high-risk of DB GSEED-RE2 subgroup was cost saving, with a negative ICER of -2,194 € in the Spanish context and cost effective with an ICER of $87,796 in the United States. DISCUSSION: Clip closure after EMR of large colorectal lesions is cost effective in patients with a high risk of bleeding. The GSEED-RE2 DB risk score may be a useful tool to identify that high-risk population.

Clinical validation of risk scoring systems to predict risk of delayed bleeding after EMR of large colorectal lesions.

BACKGROUND AND AIMS: The Endoscopic Resection Group of the Spanish Society of Endoscopy (GSEED-RE) model and the Australian Colonic Endoscopic Resection (ACER) model were proposed to predict delayed bleeding (DB) after EMR of large superficial colorectal lesions, but neither has been validated. We validated and updated these models. METHODS: A multicenter cohort study was performed in patients with nonpedunculated lesions ≥20 mm removed by EMR. We assessed the discrimination and calibration of the GSEED-RE and ACER models. Difficulty performing EMR was subjectively categorized as low, medium, or high. We created a new model, including factors associated with DB in 3 cohort studies. RESULTS: DB occurred in 45 of 1034 EMRs (4.5%); it was associated with proximal location (odds ratio [OR], 2.84; 95% confidence interval [CI], 1.31-6.16), antiplatelet agents (OR, 2.51; 95% CI, .99-6.34) or anticoagulants (OR, 4.54; 95% CI, 2.14-9.63), difficulty of EMR (OR, 3.23; 95% CI, 1.41-7.40), and comorbidity (OR, 2.11; 95% CI, .99-4.47). The GSEED-RE and ACER models did not accurately predict DB. Re-estimation and recalibration yielded acceptable results (GSEED-RE area under the curve [AUC], .64 [95% CI, .54-.74]; ACER AUC, .65 [95% CI, .57-.73]). We used lesion size, proximal location, comorbidity, and antiplatelet or anticoagulant therapy to generate a new model, the GSEED-RE2, which achieved higher AUC values (.69-.73; 95% CI, .59-.80) and exhibited lower susceptibility to changes among datasets. CONCLUSIONS: The updated GSEED-RE and ACER models achieved acceptable prediction levels of DB. The GSEED-RE2 model may achieve better prediction results and could be used to guide the management of patients after validation by other external groups. (Clinical trial registration number: NCT03050333.).

Clip Closure After Resection of Large Colorectal Lesions With Substantial Risk of Bleeding.

BACKGROUND & AIMS: It is not clear whether closure of mucosal defects with clips after colonic endoscopic mucosal resection (EMR) prevents delayed bleeding, although it seems to have no protective effects when risk is low. We performed a randomized trial to evaluate the efficacy of complete clip closure of large (≥2 cm) nonpedunculated colorectal lesions after EMR in patients with an estimated average or high risk of delayed bleeding. METHODS: We performed a single-blind trial at 11 hospitals in Spain from May 2016 through June 2018, including 235 consecutive patients who underwent EMR for large nonpedunculated colorectal lesions with an average or high risk of delayed bleeding (based on Spanish Endoscopy Society Endoscopic Resection Group score). Participants were randomly assigned to groups that received closure of the scar with 11-mm through-the-scope clips (treated, n = 119) or no clip (control, n = 116). The primary outcome was proportion of patients in each group with delayed bleeding, defined as evident hematochezia that required medical intervention within 15 days after colonoscopy. RESULTS: In the clip group, complete closure was achieved in 68 (57%) cases, with partial closure in 33 (28%) cases and failure to close in 18 (15%) cases. Delayed bleeding occurred in 14 (12.1%) patients in the control group and in 6 (5%) patients in the clip group (absolute risk difference, reduction of 7% in the clip group; 95% confidence interval, -14.7% to 0.3%). After completion of the clip closure, there was only 1 (1.5%) case of delayed bleeding (absolute risk difference, reduction of 10.6%; 95% confidence interval, -4.3% to 17.9%). CONCLUSIONS: In a randomized trial of patients with large nonpedunculated colorectal lesions undergoing EMR, we found that clip closure of mucosal defects in patients with a risk of bleeding can be a challenge, but also reduces delayed bleeding. Prevention of delayed bleeding required complete clip closure. ClinicalTrials.gov ID: NCT02765022.

Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype.

Variations in DNA repair genes have been reported as key factors in gastric cancer (GC) susceptibility but results among studies are inconsistent. We aimed to assess the relevance of DNA repair gene polymorphisms and environmental factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA from 603 patients with primary GC and 603 healthy controls was typed for 123 single nucleotide polymorphisms in DNA repair genes using the Illumina platform. Helicobacter pylori infection with CagA strains (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.55-2.54), tobacco smoking (OR: 1.77; 95% CI: 1.22-2.57), and family history of GC (OR: 2.87; 95% CI: 1.85-4.45) were identified as independent risk factors for GC. By contrast, the TP53 rs9894946A (OR: 0.73; 95% CI: 0.56-0.96), TP53 rs1042522C (OR: 0.76; 95% CI: 0.56-0.96), and BRIP1 rs4986764T (OR: 0.55; 95% CI: 0.38-0.78) variants were associated with lower GC risk. Significant associations with specific anatomopathological GC subtypes were also observed, most notably in the ERCC4 gene with the rs1799801C, rs2238463G, and rs3136038T variants being inversely associated with cardia GC risk. Moreover, the XRCC3 rs861528 allele A was significantly increased in the patient subgroup with diffuse GC (OR: 1.75; 95% CI: 1.30-2.37). Our data show that specific TP53, BRIP1, ERCC4, and XRCC3 polymorphisms are relevant in susceptibility to GC risk and specific subtypes in Caucasians.

Grado de adecuación de las indicaciones de la colonoscopia en una unidad de acceso abierto / Inappropriateness rate for colonoscopy indications in an open access unit

INTRODUCCIÓN Y OBJETIVO: La adecuación de las indicaciones de la colonoscopia a las recomendaciones vigentes es importante para optimizar los recursos disponibles. El objetivo fue valorar el grado de adecuación de las indicaciones de colonoscopia en una unidad de endoscopia de acceso abierto utilizando los criterios EPAGE II. MÉTODOS: Se incluyeron de forma retrospectiva las colonoscopias realizadas entre el 1 de octubre y el 30 de noviembre de 2011. La adecuación de la colonoscopia se estableció de acuerdo con los criterios EPAGE II. Se registraron datos demográficos, médicos solicitantes, indicaciones y hallazgos relevantes de estas exploraciones. RESULTADOS: Se incluyeron 440 colonoscopias (54% mujeres; edad, 60,8 ± 16,3 años). La indicación fue apropiada en 75,4% (IC: 71-79,3%), incierta en 13,1% (IC: 10,2-16,6%) e inapropiada en 11,4% (IC: 8,7-14,8%). En el análisis univariante la presencia de hallazgos relevantes se asoció a la edad, el sexo, la indicación y EPAGE II. En el análisis de regresión logística la edad ≥ 50 años (OR: 1,84), el sexo masculino (OR: 2,7) y 2 indicaciones, control EII y vigilancia pospolipectomía (p < 0,03), se asociaron de forma independiente con la presencia de hallazgos relevantes. El rendimiento diagnóstico de los criterios EPAGE II fue 37,3% para las exploraciones consideradas apropiadas y 28,3% para las inadecuadas (p = 0,09). CONCLUSIONES: El grado de inadecuación de la colonoscopia es elevado, sobre todo en pacientes jóvenes (< 50 años) y en algunas indicaciones. La edad (≥ 50 años) y el sexo masculino se asocian de forma independiente con la presencia de hallazgos relevantes. El rendimiento diagnóstico de los criterios EPAGE II no fue diferente entre exploraciones adecuadas e inadecuadas

INTRODUCTION AND OBJECTIVE: The suitability of indications for colonoscopy is important to optimize the available resources. The aim of this study was to assess the appropriateness of colonoscopy indications in an open access endoscopy unit using the EPAGE II criteria. METHODS: Colonoscopies performed between October 1 and November 30, 2011 were retrospectively included. The appropriateness of the colonoscopy was established according to the EPAGE II criteria. Demographics, medical applicants, indications and relevant findings from these examinations were recorded. RESULTS: We included 440 colonoscopies (60.8 ± 016.3 years, 54% women). The indication was appropriate in 75.4% (CI, 71-79.3%), uncertain in 13.1% (CI, 10.2-16.6%) and inappropriate in 11.4% (CI, 8.7-14.8%). In the univariate analysis, the relevant findings in the colonoscopy were associated with age, sex, colonoscopy indications and EPAGE II. In the logistic regression analysis, factors independently associated with the presence of relevant findings were age (≥ 50 years) (OR, 1.84), male sex (OR, 2.7) and two indications, inflammatory bowel disease and post-polypectomy surveillance (P < .03). The diagnostic yield of EPAGE II criteria was 37.3% for appropriate colonoscopies and 28.3% for inappropriate colonoscopies (P = .09). CONCLUSIONS: The rate of unnecessary colonoscopy is high, especially in young patients (< 50 years) and some colonoscopy indications. Age (≥ 50 years) and male sex are independently associated with the presence of relevant findings in colonoscopy. The diagnostic yield of EPAGE II criteria does not differ between appropriate and inappropriate examinations

[Inappropriateness rate for colonoscopy indications in an open access unit]. / Grado de adecuación de las indicaciones de la colonoscopia en una unidad de acceso abierto.

INTRODUCTION AND OBJECTIVE: The suitability of indications for colonoscopy is important to optimize the available resources. The aim of this study was to assess the appropriateness of colonoscopy indications in an open access endoscopy unit using the EPAGE II criteria. METHODS: Colonoscopies performed between October 1 and November 30, 2011 were retrospectively included. The appropriateness of the colonoscopy was established according to the EPAGE II criteria. Demographics, medical applicants, indications and relevant findings from these examinations were recorded. RESULTS: We included 440 colonoscopies (60.8 ± 016.3 years, 54% women). The indication was appropriate in 75.4% (CI, 71-79.3%), uncertain in 13.1% (CI, 10.2-16.6%) and inappropriate in 11.4% (CI, 8.7-14.8%). In the univariate analysis, the relevant findings in the colonoscopy were associated with age, sex, colonoscopy indications and EPAGE II. In the logistic regression analysis, factors independently associated with the presence of relevant findings were age (≥ 50 years) (OR, 1.84), male sex (OR, 2.7) and two indications, inflammatory bowel disease and post-polypectomy surveillance (P < .03). The diagnostic yield of EPAGE II criteria was 37.3% for appropriate colonoscopies and 28.3% for inappropriate colonoscopies (P = .09). CONCLUSIONS: The rate of unnecessary colonoscopy is high, especially in young patients (<50 years) and some colonoscopy indications. Age (≥ 50 years) and male sex are independently associated with the presence of relevant findings in colonoscopy. The diagnostic yield of EPAGE II criteria does not differ between appropriate and inappropriate examinations.

Association of PSCA rs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease.

Two recent genome-wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection-related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated. Genomic DNA from 603 Spanish patients with primary GC, 139 with DU and 675 healthy controls was typed for the PSCA rs2294008C>T polymorphism by PCR-TaqMan assays. H. pylori infection [odds ratio (OR): 8.27; 95% confidence interval (CI): 3.45-15.33] and nonsteroidal anti-inflammatory drugs (OR: 6.54; 95% CI: 3.19-12.43) were identified as independent risk factors for DU whereas the rs2294008T allele was associated with reduced risk of developing the disease (OR: 0.52; 95% CI: 0.33-0.82). Infection with CagA strains (OR: 2.10; 95% CI: 1.63-2.34), smoking (OR: 1.93; 95% CI: 1.54-2.61), family history of GC (OR: 2.83; 95% CI: 2.01-3.83), and the rs2294008T allele (OR: 1.46; 95% CI: 1.07-1.99) were associated with increased risk of GC. Interestingly, the association with the rs2294008T allele was restricted to noncardia GC (OR: 1.43; 95% CI: 1.12-1.82), particularly of the diffuse histotype (OR: 1.59; 95% CI: 1.16-1.92). Finally, Cox regression analysis identified the rs2294008T variant as a prognosis factor associated with worse overall survival in patients with diffuse-type GC (hazard ratio: 1.85; 95% CI: 1.12-3.06). From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse-type of GC in Caucasians.

Tumores carcinoides gástricos: análisis de 24 casos / Gastric carcinoid tumors: an analysis of 24 cases

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Helicobacter pylori infection as a cause of iron deficiency anaemia of unknown origin.

AIM: To assess the aetiological role of Helicobacter pylori (H. pylori) infection in adult patients with iron-refractory or iron-dependent anaemia of previously unknown origin. METHODS: Consecutive patients with chronic iron-deficient anaemia (IDA) with H. pylori infection and a negative standard work-up were prospectively evaluated. All of them had either iron refractoriness or iron dependency. Response to H. pylori eradication was assessed at 6 and 12 mo from follow-up. H. pylori infection was considered to be the cause of the anaemia when a complete anaemia resolution without iron supplements was observed after eradication. RESULTS: H. pylori was eradicated in 88 of the 89 patients. In the non-eradicated patient the four eradicating regimens failed. There were violations of protocol in 4 patients, for whom it was not possible to ascertain the cause of the anaemia. Thus, 84 H. pylori eradicated patients (10 men; 74 women) were available to assess the effect of eradication on IDA. H. pylori infection was considered to be the aetiology of IDA in 32 patients (38.1%; 95%CI: 28.4%-48.8%). This was more frequent in men/postmenopausal women than in premenopausal women (75% vs 23.3%; P < 0.0001) with an OR of 9.8 (95%CI: 3.3-29.6). In these patients, anaemia resolution occurred in the first follow-up visit at 6 mo, and no anaemia or iron deficiency relapse was observed after a mean follow-up of 21 ± 2 mo. CONCLUSION: Gastric H. pylori infection is a frequent cause of iron-refractory or iron-dependent anaemia of previously unknown origin in adult patients.

Prognostic role of host cyclooxygenase and cytokine genotypes in a Caucasian cohort of patients with gastric adenocarcinoma.

BACKGROUND: Genetic factors influencing the prognosis of gastric adenocarcinoma (GAC) are not well known. Given the relevance of cytokines and other pro-inflammatory mediators in cancer progression and invasiveness, we aimed to assess the prognostic role of several functional cytokine and cyclooxygenase gene polymorphisms in patients with GAC. METHODOLOGY: Genomic DNA from 380 Spanish Caucasian patients with primary GAC was genotyped for 23 polymorphisms in pro-inflammatory (IL1B, TNFA, LTA, IL6, IL12p40), anti-inflammatory (IL4, IL1RN, IL10, TGFB1) cytokine, and cyclooxygenase (PTGS1 and PTGS2) genes by PCR, RFLP and TaqMan assays. Clinical and histological information was collected prospectively. Survival curves were estimated by the Kaplan-Meier method and compared using the log rank test. Outcome was determined by analysis of Cox proportional hazards, adjusting for confounding factors. RESULTS: The median follow-up period and median overall survival (OS) time were 9.9 months (range 0.4-120.3) and 10.9 months (95% CI: 8.9-14.1), respectively. Multivariate analysis identified tumor stages III (HR, 3.23; 95% CI:2-5.22) and IV (HR, 5.5; 95% CI: 3.51-8.63) as independent factors associated with a significantly reduced OS, whereas surgical treatment (HR: 0.44; 95%CI: 0.3-0.6) was related to a better prognosis of the disease. Concerning genetic factors, none of the 23 polymorphisms evaluated in the current study did influence survival. Moreover, no gene-environment interactions on GAC prognosis were observed. CONCLUSIONS: Our results show that, in our population, the panel of selected pro- and anti-inflammatory cytokine, and cyclooxygenase gene polymorphisms are not relevant in determining the prognosis of gastric adenocarcinoma.

Relevance of GSTM1, GSTT1, and GSTP1 gene polymorphisms to gastric cancer susceptibility and phenotype.

Human glutathione S-transferases (GSTs) are phase II metabolizing enzymes that play a key role in protecting against cancer by detoxifying numerous potentially cytotoxic/genotoxic compounds. The genes encoding the human GST isoenzymes GSTM(mu)1, GSTT(theta)1 and GSTP(pi)1 harbour polymorphisms, which have been considered important modifiers of the individual risk for environmentally induced cancers such as gastric cancer (GC). However, results are inconsistent among studies from different geographic areas and ethnic groups. Our goal was to perform a nationwide, case-control study in Spain to evaluate the relevance of several functional GST gene polymorphisms and environmental factors to GC risk and phenotype. DNA from 557 GC patients and 557 sex- and age-matched healthy controls (HC) was typed for two deletions in the GSTM1 and GSTT1 genes and two SNPs in the GSTP1 gene (rs1695 and rs1138272) using polymerase chain reaction-restriction fragment length polymorphism methods. Logistic regression analysis identified Helicobacter pylori infection with CagA strains [odds ratio (OR): 2.36; 95% confidence interval (CI): 1.78-3.15], smoking habit (OR: 2.10; 95% CI: 1.48-2.97) and family history of GC (OR: 3.2; 95% CI: 2.02-5.16) as independent risk factors for GC. No differences in the frequencies of GSTM1 or GSTT1 null genotypes were observed between cases and controls (GSTM1: 50.8% vs. 48%; GSTT1: 21.5% vs. 21%). Moreover, simultaneous carriage of both, the GSTM1 and the GSTT1 null genotypes, was almost identical in both groups (10.7% in GC vs. 10.6% in HC). In addition, no significant differences in GSTP1 Ile105Val (rs1695) and GSTP1 Val114Ala (rs1138272) genotype distribution were observed between GC patients and controls. Subgroup analysis for age, gender, Helicobacter pylori status, smoking habits, family history of GC, anatomic location and histological subtype revealed no significant association between GST variants and GC risk. Our results show that the GST polymorphisms evaluated in this study are not relevant when determining the individual susceptibility to GC or phenotype in a South-European population.

Lymphocytic duodenosis: aetiology and long-term response to specific treatment.

BACKGROUND: The clinical significance of lymphocytic duodenosis remains unclear. AIM: To prospectively assess the aetiology of lymphocytic duodenosis and the patterns of clinical presentation. METHODS: Ninety consecutive patients with lymphocytic duodenosis and clinical symptoms of the coeliac disease spectrum were prospectively included. All subjects underwent serological testing and HLA genotyping for coeliac disease, assessment of Helicobacter pylori infection, and parasite stool examination. Intake of non-steroidal anti-inflammatory drugs was also recorded. The final aetiology of lymphocytic duodenosis was evaluated on the basis of the long-term response to specific therapy. RESULTS: More than one initial potential aetiology was observed in 44% of patients. The final diagnosis was gluten-sensitive enteropathy alone or associated with Helicobacter pylori infection in 43.3%, Helicobacter pylori infection (without gluten-sensitive enteropathy) in 24.4%, non-steroidal anti-inflammatory drugs intake in 5.5%, autoimmune disease in 3.3%, and parasitic infection in 2.2%. Among first degree relatives and patients with chronic diarrhoea, the most common final diagnosis was gluten-sensitive enteropathy. In contrast, in the group presenting with chronic dyspepsia the most common diagnosis was Helicobacter pylori infection ('Diarrhoea' vs 'Dyspepsia' groups, p=0.008). CONCLUSIONS: Lymphocytic duodenosis is often associated with more than one potential initial aetiology. Clinical presentation may be useful to decide the initial therapeutic approach with these patients.

Apoptosis resistance of mucosal lymphocytes and IL-10 deficiency in patients with steroid-refractory Crohn's disease.

BACKGROUND: Apoptosis resistance of T-cells is considered an abnormality of immune pathways in Crohn's disease (CD). It has been previously shown that corticosteroids induce apoptosis of cells involved in inflammation. Thus, our aim was to assess the apoptosis of mononuclear cells and pro/antiinflammatory cytokines in the intestinal mucosa of patients with active CD, related to steroid response, and identify cellular and molecular factors that may predict this response to therapy. METHODS: Patients with CD (n = 26), ulcerative colitis (UC) (n = 32), and controls (n = 10) were prospectively studied with mucosal biopsies before and 7-10 days after corticosteroid treatment. Immunophenotype and apoptosis of T and B lymphocytes, plasma cells, and macrophages were assessed by flow cytometry, immunohistochemistry, and immunofluorescence. The cytokine expression pattern was evaluated by quantitative polymerase chain reaction (PCR). RESULTS: Apoptosis resistance of T and B lymphocytes was observed only in steroid-refractory and -dependent CD patients as compared to responsive patients (P = 0.032; P = 0.004, respectively), being evident after steroid treatment. Interleukin (IL)-10 was markedly increased at baseline in steroid-responsive patients compared to the nonresponders (P = 0.006; sensitivity: 88.8%; specificity: 66.6% to predict steroid response). CONCLUSIONS: Apoptosis resistance of mucosal T and B cells in steroid-refractory and -dependent CD patients appears during the evolution of the acute phase, limiting its clinical application as a predictor marker. In contrast, increased expression of IL-10 at an early stage of active steroid-sensitive CD patients supports its usefulness at predicting a good steroid response. Steroid-dependent and -refractory CD patients share similar molecular and cellular pathophysiological mechanisms.

Mild enteropathy as a cause of iron-deficiency anaemia of previously unknown origin.

BACKGROUND AND AIMS: We assessed whether mild enteropathy with negative coeliac serology may be gluten-dependent, and a cause of iron-deficiency anaemia. In cases not responding to gluten-free diet, the role of Helicobacter pylori infection was evaluated. METHODS: 55 consecutive unexplained iron-deficiency anaemia patients were included. In all of them we performed: HLA-DQ2/DQ8 coeliac genetic study, distal duodenum biopsies, and tests to assess H. pylori infection. A gluten-free diet or H. pylori eradication was used as indicated. Final diagnosis was established based on response to specific therapy after a 12-month follow-up period. RESULTS: Histological findings were: (1) group A (positive genetics): 21 Marsh I, 2 Marsh IIIA, 12 normal; (2) group B (negative genetics): 16 Marsh I, 4 normal. Final diagnosis of anaemia in patients with enteropathy were: group A, gluten-sensitive enteropathy, 45%; H. pylori infection, 20%; gluten-sensitive enteropathy plus H. pylori, 10%; other, 10%; unknown, 15%; group B, gluten-sensitive enteropathy, 10%; H. pylori infection, 0% (1 non-eradicated case, 10%); non-steroidal anti-inflammatory drug intake, 20%; other, 20%; unknown, 40% (p=0.033). CONCLUSIONS: Mild enteropathy is frequent in patients with unexplained iron-deficiency anaemia and negative coeliac serology. Most cases are secondary to either gluten-sensitive enteropathy or H. pylori infection, or both; however, there is also a substantial number of patients without a definitive diagnosis.