Maria Manuel Donato

Helicobacter pylori antimicrobial resistance rates in the central region of Portugal

Helicobacter pylori resistance to antimicrobial agents is steadily increasing. It is extremely important to be aware of the local prevalence of antibiotic resistance so as to adjust treatment strategies. During this single-centre, prospective study, we aimed to determine primary and secondary resistance rates of H. pylori to antibiotics as well as host and bacterial factors associated with this problem. Overall, 180 patients (131 female; mean age 43.4±13.5 years; primary resistance 103; secondary resistance 77) with positive (13) C-urea breath test were submitted to upper endoscopy with gastric biopsies. Helicobacter pylori was cultured and antimicrobial susceptibility was determined by Etest and molecular methods. Clinical and microbiological characteristics associated with resistance were evaluated by logistic regression analysis. Among the 180 isolates 50% were resistant to clarithromycin (primary 21.4%; secondary 88.3%), 34.4% to metronidazole (primary 29.1%; secondary 41.6%), 33.9% to levofloxacin (primary 26.2%; secondary 44.2%), 0.6% to tetracycline and 0.6% to amoxicillin. Being female was an independent predictor of resistance to clarithromycin and metronidazole. Previous, failed, eradication treatments were also associated with a decrease in susceptibility to clarithromycin. History of frequent infections, first-degree relatives with gastric carcinoma and low education levels determined increased resistance to levofloxacin. Mutations in the 23S rRNA and gyrA genes were frequently found in isolates with resistance to clarithromycin and levofloxacin, respectively. This study revealed that resistance rates to clarithromycin, metronidazole and levofloxacin are very high and may compromise H. pylori eradication with first-line and second-line empiric triple treatments in Portugal.

Triple Therapy with High-Dose Proton-Pump Inhibitor, Amoxicillin, and Doxycycline Is Useless for Helicobacter pylori Eradication: A Proof-of-Concept Study

Helicobacter pylori resistance to antibiotics is steadily increasing and multidrug‐resistant strains are common and difficult to eliminate, mainly in countries where bismuth, tetracycline, furazolidone, and rifabutin are unavailable.

Surveillance in ulcerative colitis: is chromoendoscopy-guided endomicroscopy always better than conventional colonoscopy? A randomized trial.

Background:Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer. Chromoendoscopy showed superiority to conventional colonoscopy (CC) in surveillance studies including high-risk patients. We aimed to compare chromoendoscopy-guided endomicroscopy (CGE) with CC for intraepithelial neoplasia (IN) detection in patients with longstanding UC without primary sclerosing cholangitis and/or history of IN. Methods:One hundred sixty-two patients with longstanding (≥8 yr) distal/extensive UC and without primary sclerosing cholangitis and/or history of IN were prospectively randomized to undergo CGE (group A) or CC (group B). Seventeen patients were excluded. In group A (n = 72), circumscribed lesions highlighted by pan-chromoendoscopy were evaluated by endomicroscopy, and targeted biopsy/polypectomy was performed. In group B (n = 73), 4 random biopsies every 10 cm and targeted biopsy/polypectomy of detected lesions were performed. Results:Thirteen IN, all low grade, were detected: 7 IN in group A and 6 in group B (P > 0.05), distributed, respectively, by 6 and 4 patients (P > 0.05). Significantly, more biopsies were performed in group B (4.7 ± 4.9 versus 36.0 ± 6.2, P < 0.001), and the per-biopsy yield of IN was higher in group A (1/48 versus 1/438, P < 0.001). Examination time was 61.5 ± 15.6 minutes in group A and 40.7 ± 8.7 minutes in group B (P < 0.001). The IN detection by endomicroscopy revealed: sensitivity = 85.7%, specificity = 97.9%, positive predictive value = 75.0%, and negative predictive value = 98.9%. Conclusions:CGE does not improve the detection of IN in the endoscopic screening of patients with longstanding UC without primary sclerosing cholangitis and/or history of IN. CGE takes longer than CC, but it decreases the number of biopsies performed and significantly increases the per-biopsy yield of IN. Endomicroscopy is an accurate tool for IN detection.

A coupled convection-diffusion level set model for tracking epithelial cells in colonic crypts

Abstract Colorectal cancer is initiated in colonic crypts as a consequence of alterations leading to the disruption of the normal colonic cellular process. We propose a model, which couples a convection-diffusion type equation with a level set equation, for tracking the time evolution of an epithelial cell set, inside a colonic crypt, until it reaches the top of the crypt. The convection-diffusion equation describes the evolution of the density of the cells in the epithelial cell set. The parameters of this equation regulate the geometric and temporal cellular mechanism, and different parameter choices lead to distinct cell behavior. The level set equation tracks the location and shape of the epithelial cell set, inside the crypt, as well as its interface, separating the cell set from the others cells, which reside within the crypt. The interfacial velocity of the epithelial cell set is obtained from the convection-diffusion type equation. Some in silico experiments are described. They are performed in a relative small time, with respect to the real biological evolution.

Predictive value of rectal aberrant crypt foci for intraepithelial neoplasia in ulcerative colitis - a cross-sectional study.

Abstract Background. Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). Aberrant crypt foci (ACF) are important biomarkers of sporadic CRC risk. Their correlation with the risk of intraepithelial neoplasia (IN) in UC remains unclear. Aims. To assess whether ACF are a risk factor for IN in long-standing UC and to investigate any correlation between the clinico-epidemiological characteristics and prevalence/number of ACF in these patients. Methods. Seventy-six patients with long-standing UC were prospectively screened by colonoscopy with chromoendoscopy-guided endomicroscopy. ACF were sought in the lower rectum. Results. Eight INs were detected in seven (9.2%) patients. The ACF prevalence and mean number were 60.5% and 2.4 ± 2.8, respectively. The number of ACF was independently associated with the risk of having IN (odds ratio = 1.338; 95% confidence interval 1.030–1.738). ACF number revealed a good calibration (area under the receiver operating characteristic curve = 0.829) and discriminative ability (p = 0.205, Hosmer–Lemeshow test) for the prediction of synchronous IN. Patients with ≥3 ACF have a significantly higher prevalence of IN than patients with <3 ACF (22.6% vs. 0%, p = 0.001). Using this cut-off value, the performance of ACF in predicting the presence of IN was as follows: sensitivity = 100%, specificity = 65.2%, positive predictive value = 22.6%, and negative predictive value = 100%. Age >40 years, family history of CRC, and increased body mass index (BMI) were associated with a significantly higher number of ACF. Conclusion. Long-standing UC patients with ≥3 ACF have a significantly higher likelihood of having IN. Age >40 years, family history of CRC, and increased BMI have significant positive associations with the number of ACF.

Card15 mutations and gastric cancer in a Portuguese population.

Abstract Background. CARD15 is involved in the innate immune response and mutations of this gene have been linked with increased risk of Crohns disease and colorectal cancer. The relation between CARD15 mutations and gastric cancer (GC) remains controversial. Aims. To assess whether CARD15 mutations are risk factors for GC in Portugal and whether there are genotype–phenotype correlations in these patients. Methods. The 3 main CARD15 mutations (3020insC, R702W and G908R) were searched in 150 patients with GC and in 202 healthy controls. Results. Overall, CARD15 mutations were found in 28 patients (18.7%) and in 27 controls (13.4%) (p = 0.176). Individually, the incidence of 3020insC was significantly higher in patients than in controls (6.0% vs. 1.0%, p = 0.021). This polymorphism was linked with an increased risk for the intestinal-type of GC (p = 0.002), while no association was found with the diffuse and/or mixed types. Genotype frequencies for R702W (10.0% vs. 7.9%) and G908R (4.0% vs. 4.0%) were not statistically different between the two groups. Similarly, no significant associations were detected between these two polymorphisms and the different histological GC types. No correlations were observed between CARD15 mutations and family history, mean age at diagnosis or GC stage. Conclusions. The CARD15 3020insC variant is a risk factor for intestinal GC in Portugal. CARD15 variants are not correlated with age of diagnosis or family aggregation of the disease neither with the GC stage.