Validation of a novel integral disease index for evaluating the grade of activity in Mexican patients with ulcerative colitis: A prospective cohort study. / Validación de un nuevo índice integral de enfermedad para evaluar el grado de actividad en pacientes mexicanos con colitis ulcerosa: un estudio de cohorte prospectivo.

INTRODUCTION AND AIM: Ulcerative colitis is a chronic condition characterized by inflammation affecting the colon. To objectively and integrally measure disease activity in patients with ulcerative colitis and thus optimize pharmacologic treatment, a novel integral disease index was created that includes the clinical, biochemical, endoscopic, and histologic characteristics necessary for achieving that task. The aim of the present study was to validate the novel integral disease index in patients with ulcerative colitis. MATERIALS AND METHODS: A cohort study on a total of 222 patients with histologic confirmations of ulcerative colitis diagnosis was conducted. The variables included in the disease index were: number of bowel movements per day; values for hemoglobin, high-sensitivity C-reactive protein, and serum albumin; and endoscopic and histologic findings measured through the subscales of the Mayo and Riley scores, respectively. The data analysis was performed utilizing the STATA SE 11.1 statistics program. RESULTS: The correlation of the novel disease index was very good (r=0.817, p <.001 with the Truelove and Witts criteria and r=0.957, p <.0001 with the Mayo score, respectively). Good internal consistency was found with a Cronbach's alpha coefficient of 0.78 and an acceptable mean inter-item correlation (r=0.47, p <.05). The total efficacy of the novel index was 87.2% correctly classified patients, with an AUC according to the three scenarios described of 0.93, 0.92, and 0.96, respectively. CONCLUSIONS: The novel integral disease index (Yamamoto-Furusho Index) provides an integral view of disease activity in patients with ulcerative colitis and is useful for optimizing pharmacologic treatment.

Factors related to gastric neuroendocrine tumors. / Factores relacionados a tumores neuroendocrinos gástricos.

INTRODUCTION AND AIMS: An association between long-term use of proton pump inhibitors and the development of gastric neuroendocrine tumors has been reported, but it is still a subject of debate. The aims of the present study were to determine the presence of this association in a Mexican population and to identify the risk factors for developing gastric neuroendocrine tumors. MATERIALS AND METHODS: A case-control study was conducted, in which the cases were patients with a histopathologic diagnosis of gastric neuroendocrine tumor and the controls were patients evaluated through upper endoscopy. The controls were paired by age, sex, and endoscopic examination indication. Proton pump inhibitor use was considered prolonged when consumption was longer than 5 years. RESULTS: Thirty-three patients with gastric neuroendocrine tumor and 66 controls were included in the study. Eighteen (54.5%) patients in the case group were women, as were 39 (59%) of the patients in the control group. The median age of the patients in the case group was 55 years (minimum-maximum range: 24-82) and it was 54 years (minimum-maximum range:18-85) in the control group. A greater number of patients in the gastric neuroendocrine tumor group presented with gastric atrophy (p<0.0001) and autoimmune atrophic gastritis (p=0.0002), compared with the control group. No association between gastric neuroendocrine tumor and prolonged proton pump inhibitor use, sex, smoking, gastroesophageal reflux disease, Helicobacter pylori infection, diabetes mellitus, or autoimmune diseases was found in the univariate analysis. CONCLUSIONS: The results of our study showed no association between proton pump inhibitor use for more than 5 years and the development of gastric neuroendocrine tumor. The presence of gastric atrophy and autoimmune atrophic gastritis was associated with gastric neuroendocrine tumor development.

Barrett's esophagus: Ten years of experience at a tertiary care hospital center in Mexico. / Esófago de Barrett: experiencia de 10 años en un centro de tercer nivel en México.

INTRODUCTION: The prevalence of Barrett's esophagus has been calculated at between 1.3 and 1.6%. There is little information with respect to this in Mexico. AIM: To determine the frequency and characteristics of Barrett's esophagus in patients that underwent endoscopy at a national referral center, within a 10-year time frame. MATERIAL AND METHODS: The databases of the pathology and gastrointestinal endoscopy departments of the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" were analyzed, covering the period of January 2002 to December 2012. Patients with a histologic diagnosis of Barrett's esophagus were included. The variables of age, sex, the presence of dysplasia/esophageal adenocarcinoma, Barrett's esophagus length, and follow-up were analyzed. RESULTS: Of 43,639 upper gastrointestinal endoscopies performed, 420 revealed Barrett's esophagus, corresponding to a frequency of 9.6 patients for every 1,000 endoscopies. Of those patients, 66.9% (n=281) were men, mean patient age±SD was 57.2±15.3 years, 223 patients (53%) presented with long-segment Barrett's esophagus, and 197 (47%) with short-segment Barrett's esophagus. Dysplasia was not present in 339 patients (80.7%). Eighty-one (19.3%) patients had some grade of dysplasia or cancer: 48/420 (11.42%) presented with low-grade dysplasia, 20/420 (4.76%) with high-grade dysplasia, and 13/420 (3.1%) were diagnosed with esophageal cancer arising from Barrett's esophagus. Mean follow-up time was 5.6 years. CONCLUSIONS: The frequency of Barrett's esophagus was 9.6 cases for every 1,000 upper gastrointestinal endoscopies performed. Dysplasia was not documented in the majority of the patients with Barrett's esophagus and they had no histopathologic changes during follow-up. A total of 19.3% of the patients presented with dysplasia or cancer.

Inflammatory fibroid polyp of the gastrointestinal tract: 10 years of experience at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. / Pólipo fibroideo inflamatorio del tracto gastrointestinal: 10 años de experiencia del Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.

BACKGROUND: Inflammatory fibroid polyp (lFP) is a rare, benign, and solitary neoplasm predominantly located in the gastric antrum and small bowel. Its clinical symptoms are heterogeneous and essentially depend on the location and size of the tumor. Definitive diagnosis is made through histopathology and this pathology has excellent long-term prognosis. AIM: To identify the cases of IFP seen at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán over a 10-year period. METHODS: A retrospective, cross-sectional, descriptive, and observational study was conducted that included patients with histopathologic diagnosis of IFP within the time frame of January 2001 and December 2011. RESULTS: Six cases were found and 5/6 (83.3%) of them were women. The median age was 41 years (minimum-maximum range of 19-56 years). The most frequent symptoms were weight loss (n=3), fever (n=2), nausea (n=2), and vomiting (n=2). Three patients presented with iron deficiency anemia and 2 cases with intussusception. The IFPs were located at the following sites: esophagus (n=1), stomach (n=2), small bowel (n=2), and colon (n=1). Treatment was surgical in 5/6 (83.3%) of the patients. CONCLUSIONS: IFPs are extremely rare in our population. They usually present with weight loss and iron deficiency anemia and are more frequently located in the stomach and small bowel. This is the largest reported IFP case series in a Mexican population.

[Intelukin-10 expression with immunorreglatory function in the mucosa of patients with ulcerative colitis]. / Expresión de la interleucina (IL-10) con función inmunorreguladora en mucosa de pacientes con colitis ulcerosa crónica idiopática.

BACKGROUND: Interleukin-10 (IL-10) is an important immunoregulatory cytokine that acts on antigen presenting cells by the inhibiting both the synthesis of cytokines, co-stimulatory and HLA class II molecules. OBJECTIVE: To study the gene and protein expression of IL-10 in the mucosa from patients with ulcerative colitis (UC). METHODS: We studied 40 patients with UC and 18 controls without endoscopic evidence of intestinal inflammation. From rectal biopsies was determined the gene expression of IL- 10 by real time polymerase chain reaction (PCR). The detection of the protein in tissue was performed by immunohistochemistry. RESULTS: patients with UC in remission had significantly higher expression of il-10 gene in mucosa compared to the group of patients with active UC (p = 0.01) and the control group (p = 0.05). All patients with active UC had pancolitis, while patients in remission from distal inflammation, 16 had extra-intestinal manifestations and 23 had mild to moderate inflammation with less than one relapse within a year. Patients with UC in remission had significantly higher expression of IL-10 gene in mucosa compared with the group of patients with active UC (p = 0.01) or the control group (p = 0.05). CONCLUSIONS: The expression of IL-10 gene is increased in colonic mucosa from patients with UC in remission, confirming that it is an immunoregulatory cytokine that promotes remission in patients with UC.

Risk of hyperamylasemia and acute pancreatitis after double-balloon enteroscopy: a prospective study.

BACKGROUND AND STUDY AIMS: There have been reports, mainly retrospective, of pancreatitis and hyperamylasemia after anterograde double-balloon enteroscopy (DBE). Our aim was to report the incidence of pancreatitis and hyperamylasemia after DBE and investigate possible risk factors associated with its occurrence. PATIENTS AND METHODS: In this single-center prospective cohort study, serum samples were taken for amylase and lipase before and 3 hours after anterograde DBE in consecutive patients. Multiple variables were recorded, including total procedure time, insertion depth, and number of passes. Patients were evaluated to 24 hours later for signs of pancreatitis. The main outcome measures were the occurrence of hyperamylasemia and pancreatitis. RESULTS: 92 patients were included in the analysis (58 women, 34 men; mean age 54 years, range 18-89). The mean total procedure time was 62 minutes (range 30-120). The mean post-procedure amylase and lipase levels were significantly higher in comparison with the baseline levels (165 U/L vs. 69 U/L and 144 U/L vs. 28 U/L respectively, P<.05); 36 patients (39%) showed hyperamylasemia after the procedure and three patients developed acute mild pancreatitis. Hyperamylasemia was associated more frequently with procedure duration greater than 60 minutes ( P<.001) and insertion depth greater than 25 cm ( P<.013). CONCLUSIONS: The incidence of hyperamylasemia after anterograde DBE is common and particularly associated with longer procedure time and insertion depth. The cumulative incidence of pancreatitis was 3%. We recommend the avoidance of both unnecessarily lengthy procedures and deep insertion distances in patients who undergo anterograde DBE.

[IL-6 and TNF-α gene expression in the rectal mucosal of patients with chronic idiopathic ulcerative colitis and controls]. / Expresion del gen de IL-6 y TNF-α en la mucosa rectal de pacientes con colitis ulcerosa crónica idiopática y controles.

BACKGROUND: It has been reported that pro-inflammatory cytokines levels like IL-6 and TNF-α can determine the degree of inflammation of ulcerative colitis (UC). AIMS: To measure the gene expression of IL-6 and TNF-á in patients with UC and controls and to correlate with histological activity. PATIENTS AND METHODS: We studied 36 patients with UC, 13 healthy controls and 11 with inflammation. After total ribonucleic acid (RNA) extraction, complementary deoxyribonucleic acid (DNA) was synthesized by polymerase chain reaction (PCR) and relative expression was determined through real-time PCR for IL-6 and TNF-á. Statistical analysis was performed using the Kruskal-Wallis test and Spearman correlation. RESULTS: The expression of IL-6 increases in patients with active UC compared to controls (p = 0.004) as well as UC patients in remission (p = 0.014). There was no significant difference between patients with active UC and controls with inflammation. (p = 0.446). Gene expression of TNF-α was higher in biopsies from patients with UC activity compred with control subjects (p = 0.004), as well as those in remission (p = 0.001). The expression of IL-6 correlated significantly (p = 0.02) with histological activity. CONCLUSIONS: The gene expression of IL-6 and TNF-α is increased in active UC. Interleukin 6 is better marker of bowel inflammation because its expression correlates with histological activity.

Diagnostic yield, therapeutic impact, and complications of double-balloon enteroscopy in patients with small-bowel pathology.

BACKGROUND AND AIMS: Until recently the study of small bowel was limited to the radiographic approach. This paper describes experience with the first 86 procedures evaluated and treated with the new technique of double-balloon enteroscopy (DBE). PATIENTS AND METHODS: Between August 2005 and September 2006, DBE was conducted in consecutive patients. The characteristics of the patients, indications for the procedures, procedural parameters, and diagnostic yield are described here. All conventional treatment options were available. All the patients had previously undergone esophagogastroduodenoscopy and colonoscopy. RESULTS: Eighty-six procedures in sixty-eight patients were carried out (41 women, 27 men; mean age 48.5 years, range 20-82). The most common indications were gastrointestinal bleeding (n = 40) and iron deficiency anemia (n = 7). The mean duration of the procedure was 63 (range 20-194) mins and 80 (range 20-150) minutes for the oral and anal routes, respectively. The mean depth of small-bowel insertion was 250 and 200 cm for the oral and anal routes, respectively. Impact in diagnosis and/or treatment was obtained in 50 patients (73.5%). The commonest findings in the 68 patients were angiodysplasia (n = 11), polyps (n = 8), nodular lymphoid hyperplasia (n = 5) and normal (n = 20). No major complications were observed. CONCLUSION: DBE is a useful tool for the diagnosis and treatment of patients with small-bowel pathology in whom traditional methods have not been effective. In almost two-thirds of patients DBE was clinically useful for diagnosis and treatment. The complication rate with the procedure was very low.

Misconceptions on early gastric cancer in Japan.

In Japan, gastric cancer is still the leading cause of death, although the mortality rate has recently been decreasing and early gastric cancer comprised half of all resected cancers. Recently, some interesting problems of early gastric cancer have been raised in Western literature. However, they seem to be different from Japanese experience or to include misconceptions of early gastric cancer in Japan. The purpose of this article is to mainly provide Western readers with the Japanese experience in early gastric cancer which may assist them in understanding its diversity.

[Importance of Helicobacter pylori in the pathogenesis of gastric cancer. Experimental models in rodents]. / Importancia del Helicobacter pylori en la patogénesis del cáncer gástrico. Modelos experimentales en roedores.

UNLABELLED: We found that the seroprevalence in Cancer Institute of H. pylori infection was significantly more frequent in gastric cancer than in age- and gender-matched controls. This study suggested an epidemiological link between H. pylori infection and gastric cancer. H. pylori exhibits a complex system of enzymes which serve a range of functions. Toxic effects are produced by urease (UR), phospholipase (PL) and alcohol dehydrogenase (ADH). We embarked on an exploration of the enzyme activities of H. pylori infected patients using a TLC-autoradioluminography. This method has a wide dynamic range and could offer an analytical technique for studying a radioactive compound and its enzymes in H. pylori infected mucosa. Biopsies samples taken from 21 gastric cancer patients and 95 controls were studied. Although high activity of UR indicates well the presence of H. pylori impairment, activities of ADH and PL reflects more the chronicity of mucosal damage in both groups. Clearly, the enzyme profile showed in our study reflects the "physiological" adaptations behind chronic injured mucosal changes but its relation to gastric cancer and H. pylori needs further study. There is an urgent need to understand the carcinogenesis process using animal models. We performed previous study for to explore the effect of H. pylori infection on N- methyl-N-nitrosourea-induced (MNU) gastric carcinogenesis in mice C57BL/6 mice were administered broth culture of H. pylori and given MNU in drinking water. In terms of the incidence of neoplasms development was increase in the MNU group pre-infected with H. pylori. That findings showed that C57BL/6 mice-infected model is well suited for investigating the bacteria promoter effect in the gastric carcinogenesis. Finally another rodent model study (still in process) showed rapid development of hyperplastic gastritis with gastric erosions in H. pylori-infected MTH1 knockout mice. We sought to further evaluate MTH1 knockout mice as potential test animal for carcinogenesis. CONCLUSION: It is suggested that H. pylori infection is an important risk factor for the development of gastric cancer. The possibility that this organism acts etiologically, exerting its effect over long period of time, is biologically plausible. However, the role of H. pylori per se in that process is still a matter of discussion. The various enzymes of H. pylori discussed in this paper support colonization, and are perhaps important for epithelial damage, they could contribute to the stimulation and modulation of the chronic inflammatory response, but its relation to gastric cancer and H. pylori needs further study. Finally H. pylori in C57BL/6 and knockout mice showed excellent colonization at two months and six months after infection there was adenomatous, hyperplastic and ulcerative changes. Those findings showed that both mice-infected models are well suited for investigating the bacteria promoter effect in the gastric carcinogenesis.

Significance of Helicobacter pylori infection as a risk factor in gastric cancer: serological and histological studies.

We conducted a case-control study to examine the association of Helicobacter pylori infection as a risk factor in gastric cancer in the Japanese population. Serum IgG antibodies for Helicobacter pylori were determined in 55 consecutive patients with gastric cancer and in 75 age- and sex-matched mass survey subjects and 57 age- and sex-matched cancer-free patients with conditions considered at a high risk for development of gastric cancer (precancerous condition). We examined the histology in all subjects and particular focus was placed on the extent of Helicobacter pylori-associated gastritis. The seroprevalence of Helicobacter pylori in gastric cancer patients (82%) and those with a precancerous condition (89%) was significantly higher (P < 0.005) than that in the mass survey subjects (60%). Positive relative risk associations were found for patients with gastric cancer (odds ratio, 3, with 95% confidence intervals of 1.69-5.33) and those with a precancerous condition (odds ratio, 5.66, with 95% confidence intervals 2.66-12.03). Significant differences were found when comparisons were made among the case-control groups who were H. pylori-positive and had inflammatory cell infiltration (P = 0.0127). The characteristics of Helicobacter pylori in histologically examined gastric mucosa showed differences between Helicobacter pylori-infected and uninfected persons in all groups. However, for none of these groups was there a significant differences between background mucosa for Helicobacter pylori-infected persons with or without gastric cancer. Helicobacter pylori seroprevalence is strongly associated with an increased risk of gastric cancer and with a precancerous condition; histological investigation did not define additional factors that might be associated with increased cancer risk.