Renato Borges Fagundes

Prevalência da infecção por Helicobacter pylori e das lesões precusoras do câncer gástrico em pacientes dispéticos

BACKGROUND: Helicobacter pylori infection has been considered to play significant role in gastric carcinogenesis, but only a minority of people who harbor this organism will develop gastric cancer. H. pylori infection first causes chronic non atrophic gastritis. Chronic non atrophic gastritis may evolve to atrophic gastritis and intestinal metaplasia and finally to dysplasia and adenocarcinoma. AIMS: To estimate the prevalence of H. pylori infection and the precancerous gastric lesions and their relationship, in patients with dyspeptic symptoms who underwent upper gastrointestinal endoscopy at a reference center in the central region of Rio Grande do Sul state, Brazil. METHODS: We analyzed gastric biopsies taken from corpus and antrum of patients who underwent upper gastrointestinal endoscopy for H. pylori detection, between 1994 and 2003. According to Sydney system, chronic non atrophic gastritis, atrophic gastritis and intestinal metaplasia were diagnosed by histological examination (H-E stain). The histological diagnoses were related to H. pylori infection status. RESULTS: Biopsies from 2,019 patients were included in the study. Patients mean age was 52 (±15) and 59% were female. Seventy six percent had H. pylori infection. Normal mucosa, chronic non atrophic gastritis, atrophic gastritis and intestinal metaplasia were diagnosed in 5%, 77%, 3% and 15%, respectively. The OR for any degree of gastric mucosa lesion in infected patients was 10 (CI95% 6.50 - 17%). The OR for infected patients had chronic non atrophic gastritis was 3 (CI95% 2,2 - 3,4). The OR for infected patients had atrophic gastritis or intestinal metaplasia was less than 1. CONCLUSIONS: The prevalence of H. pylori infection in this population was high (76%) and infected individuals had the probability 10 folds greater than non infected individuals to have any lesion of gastric mucosa. The prevalence of precancerous lesions was 77% for non atrophic chronic gastritis, 3% for atrophic gastritis and 15% for intestinal metaplasia. Infected patients had risk 3 folds greater than non-infected for the occurrence of non atrophic chronic gastritis. H. pylori infection did not show risk for occurrence of atrophic gastritis and intestinal metaplasia, suggesting that other risk factors should be involved in the carcinogenesis process.

P53 and Ki-67 overexpression in gastroesophageal reflux disease – Barrett's esophagus and adenocarcinoma sequence

Gastroesophageal reflux disease (GERD) is a major risk factor for the development of esophageal adenocarcinoma (ACE). Many molecular alterations occur in esophageal carcinogenesis, yet the exact mechanism of ACE development remains unknown. This study aims to determine p53 protein and Ki-67 expression in esophageal mucosa of patients with GERD and study the correlation between these markers and the progression from normal squamous epithelium to esophagitis, columnar epithelium with or without intestinal metaplasia and ACE. We analyzed p53 protein and Ki-67 expression in biopsies of 200 patients with GERD and 35 patients with ACE. Those biopsies were classified into five groups: (i) G1 normal squamous epithelium (58); (ii) G2 esophagitis (80); (iii) G3 columnar epitheliums without intestinal metaplasia (30); (iv) G4, columnar epitheliums with intestinal metaplasia (32); and (v) G5 ACEs (35). p53 protein overexpression was found in 7% (4) of G1, 37.5% (30) of G2, 30% (9) of G3, 62.5% (20) of G4, and 71.4% (25) of G5 (p < 0.001). Ki-67 index increased according to the severity of histopathological diagnoses. Ki67 index was 21.3 +/- 19.5% in G1, 38.8 +/- 24.9% in G2, 37.7 +/- 26.3% in G3, 52.8 +/- 24.6% in G4, and 57.1 +/- 25.1% in G5 (P < 0.001). Linear correlation between p53/Ki67 expression and the multistep progression from squamous epithelium to ACE was observed (P < 0.001 and P < 0.05). Our results indicate that overexpression of p53 and increased Ki-67 could be associated with the development and progression to ACE in patients with GERD.

Significant variation in the concentration of carcinogenic polycyclic aromatic hydrocarbons in yerba mate samples by brand, batch, and processing method.

Drinking maté, common in southern South America, may increase the risk of esophageal squamous cell carcinoma (ESCC). In 2006, we found high but variable polycyclic aromatic hydrocarbon (PAH) content in commercial yerba maté samples from eight Brazilian brands. The PAH content of new samples from the same brands, purchased in 2008, and four brands from a single manufacturer processed in different ways, obtained in 2010, were quantified to determine whether PAH concentration was still high, whether PAH content variation was brand specific, and whether processing method affects PAH content of commercial yerba maté. Concentrations of individual PAHs were quantified using gas chromatography/mass spectrometry with deuterated PAHs as internal standards. Median total PAH concentration was 1500 ng/g (range: 625-3710 ng/g) and 1090 ng/g (621-1990 ng/g) in 2008 and 2010 samples, respectively. Comparing 2006 and 2008 samples, some brands had high PAH concentrations in both years, while PAH concentration changed considerably in others. Benzo[a]pyrene concentrations ranged from 11.9 to 99.3 ng/g and 5.11 to 21.0 ng/g in 2008 and 2010 samples, respectively. The 2010 sample processed without touching smoke had the lowest benzo[a]pyrene content. These results support previous findings of very high total and carcinogenic PAH concentrations in yerba maté, perhaps contributing to the high incidence of ESCC in southern South America. The large PAH content variation by brand, batch, and processing method suggests it may be possible to reduce the content of carcinogenic PAHs in commercial yerba maté, making it a healthier beverage.

Gastric adenocarcinoma trends in the central region of Rio Grande do Sul (Southern Brazil): what has changed in 25 years?

CONTEXTnGastric cancer is the fourth most common malignancy in the world. Its incidence varies greatly by geographic region. The highest rate is in Eastern Asia, mainly in Japan and China. In Brazil, gastric cancer is the third most common cancer in males and the fifth most common cancer in females. Rio Grande do Sul state, in Southern Brazil, has similar figures. The main histological type of gastric cancer is adenocarcinoma.nnnOBJECTIVEnTo assess the trends of this cancer over 25 years in a reference center in central Rio Grande do Sul.nnnMETHODSnWe reviewed the records of upper gastrointestinal endoscopies performed at the University Hospital of Santa Maria, RS, between 1986 and 2010. We evaluated the incidence, age and gender distribution, anatomical subsite and histological subtype of gastric cancer throughout this 25-year period.nnnRESULTSnWe identified histologically confirmed primary gastric adenocarcinoma in 335 (1.6%) of the 20,521 patients who underwent upper gastrointestinal endoscopy during the study period. The mean age of patients was 62.4 (± 13.0) years, and 67.8% were male (a male: female ratio of 2.0:1). Cardia cancer accounted for 14.3% of the cases, and non-cardia cancer accounted for 85.7%. According to Laurens classification, 48.1% were intestinal subtype and 40.9% were diffuse subtype. There were no differences in mean age or gender distribution by anatomical location or histological subtype. There was also no difference in the proportions of histological subtypes by anatomical location. Over the 25-year period, there was no change in the anatomical distribution of tumors, but there was a significant decrease in the intestinal subtype and a steady increase in the diffuse subtype (P = 0.02). The subset of 39 patients (11.6%) who presented at < 45 years of age was more likely to be female and to have tumors of the diffuse subtype than was the total series of patients.nnnCONCLUSIONSnOver this 25-year period, there were no significant trends in age, gender distribution, or the proportions of cardia and non-cardia gastric adenocarcinomas in this series of patients from Southern Brazil. There was a significant decrease in the intestinal subtype and a steady increase in the diffuse subtype of this malignancy. In patients under 45 years old, gastric cancer was more frequent in women, and the diffuse subtype predominated.

IMMUNOHISTOCHEMICAL EXPRESSION OF HER2 IN ADENOCARCINOMA OF THE STOMACH

BACKGROUNDnWorldwide, gastric cancer is the fourth cancer in incidence and the second most common cause of cancer death. Gastric cancer is asymptomatic in the early stages and very often diagnosed at advanced stages, determining a dismal prognosis. Expression of the HER2 gene has been identified in about 20% of gastric cancer cases, and its hyper-expression is associated with poor prognosis.nnnOBJECTIVEnTo investigate HER2 immunohistochemical expression in gastric adenocarcinoma and its relationship to the histological type and anatomic location.nnnMETHODSnA cross-sectional retrospective study analyzed the immunohistochemical expression of HER2 in a sample of 48 specimens of gastric cancer. Immunohistochemical analysis were performed using avidin-biotin-peroxidase method with C-erb B2 (clone EP1045Y), as a primary antibody (Biocare Medical, USA). Standardized gastric adenocarcinomas HER2 expression criteria has been used in the analysis of samples.nnnRESULTSnThere were seven cases with reactivity for HER2. Five were of intestinal-type while two cases were of mixed-type in which the expression occurred in the intestinal component. It was identified a significant association of HER2 expression in the intestinal subtype of gastric adenocarcinoma (P=0.003). Regarding the anatomical site, HER2 was positive in only one (16.6%) of the six proximal cases and six (14.28%) of the 42 distal cases (P=0.88).nnnCONCLUSIONnHER2 immunoexpression was identified in 14.6% of the samples, and the expression was significantly associated to Laurens intestinal subtype.

Percutaneous endoscopic gastrostomy and peristomal infection: an avoidable complication with the use of a minimum skin incision.

Background Percutaneous endoscopic gastrostomy (PEG) is a fast and simple method. Although considered safe, PEG is associated with many potential complications. Peristomal infection is the complication most frequently reported. Objective To analyze patients who underwent PEG and the association of peristomal infection with the extent of skin incision (SI) and usage of prophylactic antibiotics (PA). Methods A retrospective review of the records of 120 patients who underwent PEG was carried out. Patients were divided into 3 subgroups: (1) Patients with SI 10 mm/without PA, (2) Patients with SI up to 5 mm/without PA, and (3) Patients with SI up to 5 mm/with PA. Results Peristomal infection occurred in 12.8% of patients from subgroup 1, and in 2.2% of patients from subgroup 2. There was no infection in subgroup 3. Peristomal infection was associated with the SI extent (P=0.01) and there was no association with PA (P=0.3). SI >5 mm presented an odds ratio of 10.5 (95% confidence interval, 1.58-68.42) for the occurrence of peristomal infection. Conclusions The use of PA did not seem to reduce peristomal infection rates. However, minimal SI was significantly associated with reduction of this complication.

PEPTIC ULCER FREQUENCY DIFFERENCES RELATED TO H. PYLORI OR AINES

BACKGROUNDnPeptic ulcer etiology has been changing because of H. pylori decline.nnnOBJECTIVESnTo estimate peptic ulcer prevalence in 10 years-interval and compare the association with H. pylori and use of non-steroidal anti-inflammatory drugs. Methods Records assessment in two periods: A (1997-2000) and B (2007-2010), searching for peptic ulcer, H. pylori infection and non-steroidal anti-inflammatory drugs use.nnnRESULTSnPeptic ulcer occurred in 30.35% in A and in 20.19% in B. H. pylori infection occurred in 73.3% cases in A and in 46.4% in B. Non-steroidal anti-inflammatory drugs use was 3.5% in A and 13.3% in B. Neither condition occurred in 10.4% and 20.5% in A and B respectively. Comparing both periods, we observed reduction of peptic ulcer associated to H. pylori (P=0.000), increase of peptic ulcer related to non-steroidal anti-inflammatory drugs (P=0.000) and idiopathic peptic ulcer (P=0.002). The concurrent association of H. pylori and non-steroidal anti-inflammatory drugs was also higher in B (P=0.002). Rates of gastric ulcer were higher and duodenal ulcer lower in the second period.nnnCONCLUSIONSnAfter 10 years, the prevalence of peptic ulcer decreased, as well as ulcers related to H. pylori whereas ulcers associated to non-steroidal anti-inflammatory drugs increased. There was an inversion in the pattern of gastric and duodenal ulcer and a rise of idiopathic peptic ulcer.

Unchanging pattern of prevalence of esophageal cancer, overall and by histological subtype, in the endoscopy service of the main referral hospital in the central region of Rio Grande do Sul State, in Southern Brazil.

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the two main histological types of esophageal cancer. Southern Brazil has the highest rates of esophageal cancer in South America, and the most prevalent subtype of esophageal cancer has been SCC. This study assessed the trend changes in the histological types of esophageal cancer, in a 20-year period, in the central region of Rio Grande do Sul State, Brazil. We searched all cases of esophageal cancer from 1993 to 2012 by their histological diagnosis, grouping the patients in 4-year time periods to evaluate time trends. Among 18u2009441 upper gastrointestinal endoscopies we identified 686 cases of esophageal cancer. Histological study confirmed the diagnosis of SCC in 640 (93.3%) patients and ADC in 46 (6.7%). Overall, 522 men were diagnosed with esophageal carcinoma; from these, 489 (93.6%) presented SCC, and 33 (6.3%) ADC. Among women, 164 had the diagnosis of esophageal cancer, 151 (92%) SCC, and 13 (7.9%) ADC. The proportion found among men and women was 3.1:1, respectively. The prevalence rate of esophageal cancer, along a 20 year-period, remained stable, as well as the rates of SCC and ADC. SCC was the most common type of esophageal cancer, and ADC presented very low prevalence.

Pyoderma gangrenosum as a initial manifestation of ulcerative proctocolitis

pyoderma gangrenosum is a rare inflammatory skin condition characterized by progressive and recurrent skin ulceration of destructive course. It is usually associated with rheumatoid arthritis, paraproteinemia, myeloproliferative diseases and inflammatory bowel diseases, especially non-specific ulcerative proctocolitis. In these situations, skin lesions are described as concurrent with the intestinal condition. However, reports on pyoderma gangrenosum preceding intestinal findings are less frequent. The authors describe a case of a woman with febrile condition associated with skin lesions diagnosed by biopsy as pyoderma gangrenosum. Two weeks later, she developed diarrhea, arthralgia and sepsis, being diagnosed as ulcerative proctocolitis. After the administration of the treatment for ulcerative proctocolitis, she showed improvements in sepsis care, remission of diarrhea and regression of skin lesions. This case highlights the importance of considering pyoderma gangrenosum as a manifestation associated with inflammatory bowel disease, regardless of its timing in relation to intestinal symptoms.

IMMUNOREACTIVITY OF CYTOKERATINS 7 AND 20 IN GOBLET CELLS AND COLUMNAR BLUE CELLS IN PATIENTS WITH ENDOSCOPIC EVIDENCE OF BARRETT'S ESOPHAGUS

CONTEXTnBarretts esophagus is characterized by the presence of goblet cells. However, when alcian-blue is utilized, another type of cells, called columnar blue cells, is frequently present in the distal esophagus of patients with endoscopic evidence of Barretts esophagus. Cytokeratin 7 and 20 immunoreactivity has been previously studied in areas of intestinal metaplasia at the esophagogastric junction. However, the expression of these cytokeratins in columnar blue cells has not been characterized.nnnOBJECTIVEnTo compare the expression of cytokeratin 7 and 20 in goblet cells and columnar blue cells in patients with endoscopic evidence of Barretts esophagus.nnnMETHODSnBiopsies from 86 patients with endoscopic evidence of Barretts esophagus were evaluated. The biopsies were stained for cytokeratin 7 and 20.nnnRESULTSnGoblet cells were present in 75 cases and columnar blue cells in 50 cases. Overall, cytokeratin 7 expression was similar in goblet cells and columnar blue cells (P = 0.25), while cytokeratin 20 was more common in goblet cells (P <0.001). In individuals with both cell types, however, cytokeratin 7 staining was the same in goblet and columnar blue cells in 95% of the cases, and cytokeratin 20 staining was the same in 77%.nnnCONCLUSIONnGoblet cells and columnar blue cells have similar immunohistochemical staining patterns for cytokeratins 7 and 20 in patients with endoscopic evidence of Barretts esophagus.