Persistent Villous Atrophy in De Novo Adult Patients With Celiac Disease and Strict Control of Gluten-Free Diet Adherence: A Multicenter Prospective Study (CADER Study).

INTRODUCTION: A substantial proportion of adult patients with celiac disease on a gluten-free diet exhibit persistent villous atrophy, and inadvertent gluten exposure may be one of the causes. The aim of the present study was to evaluate villous atrophy persistence after 2 years on a gluten-free diet in de novo adult patients with celiac disease with strict control of gluten exposure. METHODS: Symptomatic de novo adult patients with celiac disease were prospectively included. Clinical visits and dietary surveillance were scheduled every 6 months during a 2-year follow-up period. At each visit, fecal samples were collected and stored at -20 °C until analysis for gluten immunogenic peptides (f-GIPs). A follow-up duodenal biopsy was performed at 2 years. We evaluated the variables associated with persistent villous atrophy. RESULTS: Seventy-six patients completed the study (36.5 ± 1.6 years, 73% women); persistent villous atrophy was observed in 40 (53%), whereas 72.5% were asymptomatic and 75% had negative serology. Detectable f-GIP >0.08 µg/g in at least 1 fecal sample was seen in 69% of patients. There were no significant differences in the median f-GIP at each visit and median area under the curve over the serial measurements between patients with persistent villous atrophy and those who recovered. On multivariate analysis, only older age was associated with persistent villous atrophy (32% for 16-30 years; 67% for >30 years; P = 0.016). DISCUSSION: The rate of persistent villous atrophy after 2 years was high in adult patients with celiac disease on an intentionally strict gluten-free diet. Low-level ongoing inadvertent gluten exposure could be a contributing factor to persistent villous atrophy.

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.

[Non-celiac gluten sensitivity: a critical review of current evidence]. / Sensibilidad al gluten no celiaca: una revisión crítica de la evidencia actual.

Non-celiac gluten sensitivity (NCGS) is an emerging disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food in non-celiac patients. Its prevalence has been estimated to be six to ten-times higher than that of celiac disease (CD). A gluten-free diet is the most widely recommended therapy, but the causative agent remains unknown and there are no consensus diagnostic criteria. Recent studies on NCGS have included patients with possibly overlooked minor CD and diarrhea-predominant irritable bowel syndrome without self-reported gluten intolerance, but showing a response to a gluten-free diet. Furthermore, FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) have recently been postulated as the culprit component for NCGS in wheat, instead of gluten. This review updates evidence on the pathophysiology of NCGS and the efficacy of different dietary interventions in its treatment, stressing the need for proper screening for CD before a diagnosis of NCGS is made.

[Lymphocytic duodenosis: etiological study and clinical presentations]. / Duodenosis linfocítica: estudio etiológico y formas de presentación clínica.

INTRODUCTION: Lymphocytic duodenosis (LD) is a characteristic lesion in the initial phases of celiac disease (CD) but can be associated with many other entities. The aim of this study was to evaluate the prevalence of distinct causes of LD and possible differences in clinical presentation according to etiology. METHODS: A retrospective study was performed that included 194 patients diagnosed with LD (more than 25 intraepithelial lymphocytes per 100 epithelial cells). A preestablished strategy to evaluate the cause of the disease was followed that included celiac serology (antitransglutaminase antibodies), HLA-DQ2/DQ8 genotypes, diagnosis of Helicobacter pylori and small intestinal bacterial overgrowth (SIBO). Diagnosis of CD was established on the basis of clinical and histological response to a gluten-free diet in patients with positive serology or compatible findings on HLA-DQ2 (at least one of the alleles) or -DQ8 (both alleles) study. RESULTS: The most frequent cause of LD was CD (39%), followed by SBBO (22%), H.pylori (14%), CD and SIBO (12%), and other causes (13%). Most of the patients (83%) had a compatible HLA-DQ2 or -DQ8 genotype. In these patients, the most frequent diagnosis was CD (46%), while in the absence of HLA-DQ2/DQ8, the most frequent diagnoses were SIBO (44%) and H. pylori (22%). CD was the most frequent diagnosis in patients referred for dyspepsia, diarrhea and anemia, while H. pylori was the most frequent diagnosis in patients with abdominal pain. CONCLUSIONS: The most common causes of LD in our environment are CD, followed by SIBO and H. pylori infection.

Spectrum of gluten-sensitive enteropathy in patients with dysmotility-like dyspepsia.

BACKGROUND: Dysmotility-like dyspepsia symptoms are frequent in patients with gluten-sensitive enteropathy (GSE). Current data suggest that patients with mild enteropathy may be present with gluten-sensitive symptoms and complications. AIM: To investigate the prevalence of GSE, including mild enteropathy, in patients with dysmotility-like dyspepsia symptoms. METHODS: We retrospectively studied 142 patients who presented dysmotility-like dyspepsia symptoms and normal upper gastrointestinal endoscopy. Endoscopic duodenal biopsies were taken and processed using hematoxylin-eosin staining and CD3 immunophenotyping. In patients with enteropathy (number of intraepithelial lymphocytes greater than 25 per 100 enterocytes) we also performed coeliac serology (anti-tissue transglutaminase IgA) and HLA-DQ2/DQ8 genotyping. A gluten-free diet was offered if one of these markers was positive. The final GSE diagnosis was established based on clinical and histopathological response to the gluten-free diet after 18 months of follow-up. RESULTS: Fifty-one patients (35.9%) had enteropathy; 4 (2.8%) Marsh type 3b, 24 (16.9%) Marsh type 3a, 3 (2.1%) Marsh type 2, and 20 (14.1%) Marsh type 1. A positive serology result was extremely low (6.7%) in mild enteropathy (Marsh type 1-3a) in contrast with Marsh type 3b patients (50%). Most patients with enteropathy had positive HLA DQ2 or -DQ8 genotyping (84.1%). Out of the 37 patients who started a gluten-free diet, 34 (91.9%) improved their symptoms, and 28 of 32 (87.5%) had a histopathological or serological response. A final GSE diagnosis was established in 28 of the 142 patients (19.7%). CONCLUSION: Gluten-sensitive enteropathy can be a frequent and unsuspected cause of dysmotility-like dyspepsia.

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.

Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).

BACKGROUND: There is a lack of prospective studies evaluating the natural history of colonic ischaemia (CI). We performed such a study to evaluate the clinical presentation, outcome, and mortality as well as clinical variables associated with poor prognosis. METHODS: An open, prospective, and multicentre study was conducted in 24 Spanish hospitals serving a population of 3.5 million people. The study included only patients who met criteria for definitive or probable CI. A website (www.colitisisquemica.org) provided logistical support. RESULTS: A total of 364 patients met criteria for inclusion. CI was suspected clinically in only 24.2% of cases. The distribution of clinical patterns was as follows: reversible colopathy (26.1%), transient colitis (43.7%), gangrenous colitis (9.9%), fulminant pancolitis (2.5%), and chronic segmental colitis (17.9%). A total of 47 patients (12.9%) had an unfavorable outcome as defined by mortality and/or the need for surgery. Multivariate analysis identified the following signs as independent risk factors for an unfavorable outcome: abdominal pain without rectal bleeding [odds ratio (OR) 3.9; 95% confidence interval (CI) = 1.6-9.3], non-bloody diarrhoea (OR 10; 95% CI = 3.7-27.4), and peritoneal signs (OR 7.3; 95% CI = 2.7-19.6). Unfavorable outcomes also were more frequent in isolated right colon ischaemia (IRCI) compared with non-IRCI (40.9 vs. 10.3%, respectively; p < 0.0001). The overall mortality rate was 7.7%. CONCLUSIONS: The clinical presentation of CI is very heterogeneous, perhaps explaining why clinical suspicion of this disease is so low. The presence of IRCI, and occurrence of peritoneal signs or onset of CI as severe abdominal pain without bleeding, should alert the physician to a potentially unfavorable course.

Antral localization worsens the efficacy of enteral stents in malignant digestive tumors.

BACKGROUND AND AIMS: Malignant gastric outlet obstruction can be treated by means of enteral stenting or surgical gastrojejunalanatomosis. We evaluated in a prospective and multicentre study the efficacy of the enteral stent on food intake, the quality of life impact, and the relationship between efficacy and determined clinical and technical parameters. PATIENTS AND METHODS: Seventy one patients affected by symptoms arising from gastroduodenal obstruction due to malignant tumors, with criteria of irresecability, metastatic disease or very high surgical risk, were treated by means of self expanding metal stents. We used the GOOSS index to evaluate efficacy, and the Euro Qol-5D index to evaluate quality of life. RESULTS: Before stenting patients with GOOSS 0 and 1 were 68 (98.5%). After stenting patients with GOOSS 2 and 3 (semisolid and solid food) were 58 (84,1%) (P<.0001). The Euro Qol-5D index measured before and a month after stenting were 10.17 and 10.04 respectively (P=.6). The median survival was 91 days (9-552). The enteral stents for localised tumors in the duodenum and the gastrojejunalanastomosis were effective in 26 patients (70.2%) and 13 patients respectively (86.6%), while the enteral stents of tumors in the antrum were effective in only 5 patients (29.4%). CONCLUSIONS: The palliative treatment of malignant gastric outlet obstruction with a uncovered metal stent produces a significant improvement of oral food intake and maintains the overall quality of life index. The antral localization is associated with a lower efficacy of the procedure.

Rate of adverse events of gastroduodenal snare polypectomy for non-flat polyp is low: A prospective and multicenter study.

AIM: To evaluate the rate of adverse events (AEs) during consecutive gastric and duodenal polypectomies in several Spanish centers. METHODS: Polypectomies of protruded gastric or duodenal polyps ≥ 5 mm using hot snare were prospectively included. Prophylactic measures of hemorrhage were allowed in predefined cases. AEs were defined and graded according to the lexicon recommended by the American Society for Gastrointestinal Endoscopy. Patients were followed for 48 h, one week and 1 mo after the procedure. RESULTS: 308 patients were included and a single polypectomy was performed in 205. Only 36 (11.7%) were on prior anticoagulant therapy. Mean polyp size was 15 ± 8.9 mm (5-60) and in 294 cases (95.4%) were located in the stomach. Hemorrhage prophylaxis was performed in 219 (71.1%) patients. Nine patients presented AEs (2.9%), and 6 of them were bleeding (n = 6, 1.9%) (in 5 out of 6 AE, different types of endoscopic treatment were performed). Other 24 hemorrhagic episodes could be managed without any change in the outcome of the endoscopy and, consequently, were considered incidents. We did not find any independent risk factor of bleeding. CONCLUSION: Gastroduodenal polypectomy using prophylactic measures has a rate of AEs small enough to consider this procedure a safe and effective method for polyp resection independently of the polyp size and location.

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.

Lack of association of IL-12 p40 gene polymorphism with peptic ulcer disease.

Interleukin 12 (IL-12) is a proinflammatory cytokine composed by two chains, p40 and p35, that plays a key role in the promotion of a Th1 immune response in the gastrointestinal mucosa. An enhanced expression of IL-12 mRNA in gastric mucosa has been reported in individuals infected by Helicobacter pylori. The aim of our study was to assess whether a functional polymorphism located at position 1188 (A-->C) of the IL-12 p40 (IL12B) gene is associated with the susceptibility and clinical features of peptic ulcer disease. Genotyping of 184 unrelated white Spanish patients with peptic ulcer and 107 healthy controls was performed by polymerase chain reaction and restriction fragment length polymorphism. Helicobacter pylori status and nonsteroidal antiinflammatory drugs use were studied in patients and controls. There were no significant differences in carriage, genotype, and allele frequencies of the IL-12 p40 gene polymorphism between patients with peptic ulcer and controls. Moreover, no differences were found with respect to the localization of the ulcer, Helicobacter pylori status, nonsteroidal antiinflammatory drug use, age, sex, bleeding episodes, and family history of peptic ulcer. Our data reveal that the IL12B 1188 (A-->C) gene polymorphism is not involved in defining the genetic basis of the susceptibility to and final outcome of peptic ulcer disease.

[Helicobacter pylori resistance to metronidazole and clarythromicin: descriptive analysis 1997-2000]. / Resistencia de Helicobacter pylori al metronidazol y a la claritromicina: análisis descriptivo entre 1997 y 2000.

BACKGROUND AND OBJECTIVE: We aimed to assess the resistance of H. pylori to clarithromycin and metronidazole, in patients with and without previous eradication treatment, in a geographic area from the north of Spain. We also analyzed the evolution of resistance rates and its relationships with annual antibiotic consumption. PATIENTS AND METHOD: Retrospective study including all patients with H. pylori infection and positive culture from January 1997 to December 2000. Minimal inhibitory concentrations (MIC) determined by the E test were used to report the clarithromycin (MIC > 2 mg/l) and metronidazole (MIC > 32 mg/l) resistance. RESULTS: A total of 537 clinical H. pylori isolates from patients without (n = 389) and with previous eradication treatment (n = 148) were studied. H. pylori resistance to clarithromycin and metronidazole was found in 8.7% (95% CI, 6.1-12) and 13.8% (95% CI, 10.4-17.3) patients without previous eradication treatment and in 39.2% (95% CI, 31.3-47.1) and 37.8% (95% CI, 30-45.7) patients with previous eradication treatment (p < 0.001), respectively. Clarithromycin resistance remained stable (1997: 9.7%; 1998: 5.7%; 1999: 11.8%; 2000: 6.2%) whereas metronidazole resistance decreased over the 4 years study period (1997: 38.7%; 1998: 15.1%; 1999: 9%; 2000: 6.9%). We did not observe any clear relationship between resistance's evolution and antibiotic annual consumption. CONCLUSIONS: In our geographic area, primary resistance rates for clarithromycin remained stable whereas resistance for metronidazole decreased over the 4 years period.

Accuracy of GastroPanel for the diagnosis of atrophic gastritis.

BACKGROUND: It has been suggested that GastroPanel might be a useful tool for the diagnosis of chronic atrophic gastritis (CAG) measuring four biomarkers in blood: basal gastrin-17 (G17), pepsinogen I and II (PGI and PGII), and Helicobacter pylori antibodies. AIM: To determine the accuracy of GastroPanel for the diagnosis of CAG. METHODS: This was a prospective, blinded, multicenter study that included dyspeptic patients. G17, PGI, and PGII were determined by enzyme immunoassays. Three antrum and two corpus biopsies were obtained for standard histological analysis and rapid urease test. Biopsies were analyzed by a single blinded expert pathologist. RESULTS: Ninety-one patients were included (77% women, mean age 44 years, 51% H. pylori positive, 17% with CAG). G17 was reduced in patients with antrum CAG (5.4 vs. 13.4 pmol/l; P<0.01) and increased in patients with corpus CAG (11 vs. 24 pmol/l; P<0.05), but its accuracy was only acceptable in the case of corpus localization [area under the receiver operating characteristic curve (AUC), 74%]; PGII difference was almost statistically significant only when testing for corpus atrophy (33 vs. 21 µg/l; P=0.05; AUC=72%). The PGI and PGI/PGII ratio showed no significant differences (AUCs were all unacceptably low). Helicobacter pylori antibody levels were higher in H. pylori-infected patients (251 vs. 109 EIU, P=0.01; AUC=70). The accuracy of GastroPanel for the diagnosis of CAG was as follows: sensitivity 50%; specificity 80%; positive 25% and negative 92% predictive values; and positive 2.4 and negative 0.6 likelihood ratios. CONCLUSION: GastroPanel is not accurate enough for the diagnosis of CAG; thus, its systematic use in clinical practice cannot be recommended.

Prognosis and follow-up of 135 patients with ischemic colitis over a five-year period.

AIM: To study the prognosis (recurrence and mortality) of patients with ischemic colitis (IC). METHODS: This study was conducted in four Spanish hospitals, participants in the Ischemic Colitis in Spain study We analyzed prospectively 135 consecutive patients who met criteria for definitive or probable IC according to Brandt criteria, and follow up these patients during the next five years, retrospectively. Long-term results (recurrence and mortality) were evaluated retrospectively after a median interval of 62 mo (range 54-75 mo). RESULTS: Estimated IC recurrence rates were 2.9%, 5.1%, 8.1% and 9.7% at years 1, 2, 3 and 5 years, respectively. Five-year survival was 69% (93 of 135) and 24% (10 of 42 patients) died for causes related to the IC. Among these 10 patients, 8 died in their first episode at hospital (4 had gangrenous colitis and 4 fulminant colitis) and 2 due to recurrence. CONCLUSION: The five-year recurrence rate of IC was low. On the other hand, mortality during follow-up was high and was not associated with ischemic colitis.

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.

Eradication of Helicobacter pylori for the prevention of peptic ulcer rebleeding.

AIM: To evaluate the effect of Helicobacter pylori eradication on ulcer bleeding recurrence in a prospective, long-term study including more than 400 patients. METHODS: Patients with peptic ulcer bleeding were prospectively included. H. pylori infection was confirmed by rapid urease test, histology or (13)C-urea breath test. Several eradication regimens were used. Ranitidine 150 mg was administered daily until eradication was confirmed by breath test 8 weeks after completing eradication therapy. Patients with therapy failure received a second or third course of therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy, and were controlled yearly with a repeated breath test. RESULTS: Four hundred and twenty-two patients were followed up for at least 12 months, with a total of 906 patient-years of follow up. Mean age was 59 years, and 35% were previous nonsteroidal anti-inflammatory drug (NSAID) users. Sixty-nine percent had duodenal, 24% gastric, and 7% pyloric ulcer. Recurrence of bleeding was demonstrated in two patients at 1 year (incidence: 0.22% per patient-year of follow up), which occurred after NSAID use in both cases. CONCLUSION: Peptic ulcer rebleeding does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved.

Gastric cancer susceptibility is not linked to pro-and anti-inflammatory cytokine gene polymorphisms in whites: a Nationwide Multicenter Study in Spain.

BACKGROUND AND AIMS: Recent studies have reported an association between cytokine gene polymorphisms and GC risk. However, results are inconsistent among studies from different geographic regions and ethnic groups. Our goal was to evaluate the influence of Helicobacter pylori (H. pylori) infection and host genetic factors on GC susceptibility in a population of Spanish white GC patients. METHODS: DNA from 404 unrelated patients with GC and 404 sex- and age-matched healthy controls was typed for several functional polymorphisms in pro- (IL-1B, TNFA, LTA, IL-12p40) and anti-inflammatory (IL-4, IL-1RN, IL-10, TGFB1) genes by PCR, RFLP, and TaqMan assays. H. pylori infection and CagA/VacA antibody status were also determined by western blot serology. RESULTS: Logistic regression analysis identified H. pylori infection with cagA strains (OR 2.54, 95% CI 1.77-3.66), smoking habit (OR 1.91, 95% CI 1.25-2.93), and positive family history of GC (OR 3.67, 95% CI 2.01-6.71) as independent risk factors for GC. None of the cytokine gene polymorphisms analyzed in this study were associated with susceptibility to GC development, whether GC patients were analyzed as a group or categorized according to anatomic location or histological subtype. Some simultaneous combinations of proinflammatory genotypes reportedly associated with greater GC risk yielded no significant differences between patients and controls. CONCLUSIONS: Our results show that, at least in some white populations, the contribution of the cytokine gene polymorphisms evaluated in this study (IL-1B, IL-1RN, IL-12p40, LTA, IL-10, IL-4, and TGF-B1) to GC susceptibility may be less relevant than previously reported.

A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use.

BACKGROUND: The worst outcome of gastrointestinal complications is death. Data regarding those associated with nonsteroidal antiinflammatory drug (NSAID) or aspirin use are scarce. AIM: To determine mortality associated with hospital admission due to major gastrointestinal (GI) events and NSAID/aspirin use. METHODS: The study was based on actual count of deaths from two different data sets from 2001. Study 1 was carried out in 26 general hospitals serving 7,901,198 people. Study 2 used a database from 197 general hospitals, representative of the 269 hospitals in the Spanish National Health System. Information regarding gastrointestinal complications and deaths was obtained throughout the Minimum Basic Data Set (CIE-9-MC) provided by participating hospitals. Deaths attributed to NSAID/aspirin use were estimated on the basis of prospectively collected data from hospitals of study 1. RESULTS: The incidence of hospital admission due to major GI events of the entire (upper and lower) gastrointestinal tract was 121.9 events/100,000 persons/year, but those related to the upper GI tract were six times more frequent. Mortality rate was 5.57% (95% CI = 4.9-6.7), and 5.62% (95% CI = 4.8-6.8) in study 1 and study 2, respectively. Death rate attributed to NSAID/aspirin use was between 21.0 and 24.8 cases/million people, respectively, or 15.3 deaths/100,000 NSAID/aspirin users. Up to one-third of all NSAID/aspirin deaths can be attributed to low-dose aspirin use. CONCLUSION: Mortality rates associated with either major upper or lower GI events are similar but upper GI events were more frequent. Deaths attributed to NSAID/ASA use were high but previous reports may have provided an overestimate and one-third of them can be due to low-dose aspirin use.