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.
INTRODUÇÃODescrito em 1769 pela primeira vez pelo cirurgião inglês Ludlow19 e posteriormente pelos patologistas alemães Zenker e von Ziemssen 30 , o divertículo faringoesofágico -consagrado como divertículo de Zenker (DZ) -, é na realidade pseudodivertículo, uma vez que consiste apenas das camadas mucosa e submucosa da parede posterior da hipofaringe. Origina-se a partir do músculo constritor inferior da faringe, entre as fibras do constritor faríngeo posterior e o músculo cricofaríngeo (esfíncter esofágico superior).A incidência desta doença aumenta com a idade, sendo predominantemente encontrada em homens com mais de 60 anos. Inicialmente o divertículo determina abaulamento progressivo na região posterior do esôfago, tornando-se perpendicular a ele. Com a entrada de alimentos e o aumento de pressão, o divertículo vai adquirindo posição vertical até atingir posição paralela ao esôfago. Clinicamente, manifesta-se principalmente por disfagia, regurgitação de alimentos não digeridos, murmúrios no pescoço após alimentação, halitose e emagrecimento. Sintomas compressivos e complicações respiratórias ocasionais, como broncoaspiração e pneumonia, podem ocorrer. Como o principal sintoma é disfagia e o acometimento é predominante em pacientes com mais de 60 anos, outras afecções esofágicas devem ser investigadas no diagnóstico diferencial: neoplasias, hérnia hiatal, megaesôfago, estenose esofágica péptica ou química e doença do refluxo gastroesofágico. O exame contrastado da faringe-esôfago-estômago é o principal método diagnóstico. A endoscopia digestiva alta e a manometria auxiliam no diagnóstico diferencial, porém esses exames devem ser realizados com cautela para evitar perfuração do esôfago 10 . Dois fatores parecem ser essenciais na sua patogênese: o aumento da pressão na hipofaringe durante a deglutição e a diminuição da resistência da sua parede posterior ao nível do triângulo de Killian 10 . Controvérsias persistem sobre a importância de cada um destes fatores na formação do DZ. Cook et al. 5 , através de estudo videofluoroscópico e manométrico simultâneos, avaliaram a fisiopatologia da obstrução ao fluxo dos alimentos durante a deglutição. Os autores concluíram que o DZ é desordem relacionada à diminuição da abertura do esfíncter esofágico superior (EES), a qual não seria causada por incoordenação motora anos. Sintomas pré-operatórios principais: disfagia (91%) e regurgitação (46%). Todos foram investigados com estudo radiográfico contrastado de faringe-esôfago-estômago e 58% dos casos com endoscopia digestiva alta. Não houve diferença significativa entre os Grupos 1 e 2 em relação ao tempo operatório (96 x 99 min), tempo de internação (5,5 x 5 dias), início da alimentação via oral (7,5 x 4 dias), ocorrência de fístulas esôfago-cutâneas (35 x 22%), recidiva da disfagia (6 x 11%), complicações pós-operatórias em geral (41 x 33%) e tempo de seguimento (7,5 x 9 meses). A mortalidade foi nula. Conclusão -O tratamento cirúrgico do divertículo de Zenker é método terapêutico relativamente seguro, com morbidade aceitá...
p53 overexpression and the Ki-67 (MIB-1) index were correlated with histologic findings of inflammation in the esophageal mucosa, particularly in the moderate and severe forms of chronic esophagitis.
GERD patients showed lower levels of EGFR expression than patients with Barrett's esophagus or patients with adenocarcinoma of the esophagus, suggesting a direct relationship between EGFR expression and disease progression.
No abstract
BackgroundCancer is a public health problem, especially in developing countries. In order to establish effective measures for the cancer control, there is a need for quality information, thus enabling a better understanding of the disease and its determinants, formulation of causal hypotheses, evaluation of the technological advances applied to prevention and treatment as well as the effectiveness of health care. The objective of the study was to investigate the prevalence of solid neoplasms diagnosed between the years 2011 to 2016 and treated at the Oncology Department of the University Hospital of Santa Maria and the existing oncological context.MethodsThis is an observational cross-sectional study. The target population was comprised of adult patients (18 years of age or older) and elderly people (60 years of age or older) diagnosed with solid cancer by anatomico-pathological examination between 2011 and 2016, who started oncological treatment, according to high complexity procedure authorization (APAC)/Oncology.ResultsA total of 2,757 patients were selected, of which 1,493 patients were female (54.2%) and 1,264 male (45.8%). The mean age at the time of initiation of treatment was 59.94 years for both sexes, with the 95% confidence interval (59.44 - 60.44). The majority of patients were aged 61 - 70 years, totaling 747 patients, followed by 718 patients between 51 - 60 years. In all 31 primary sites identified the most prevalent one of neoplasms are breast, prostate, colorectal and lung; and most cases were stage IV (1,039 cases). A percentage of the number of cases of breast and esophageal cancer was higher than expected, and in contrast to a low percentage of hepatocarcinoma, kidney cancer and central nervous system tumors. The patients came from the entire area of the fourth Health Coordinating Area, where 100% of the municipalities referred to the institution, as well as other nine locations belonging to other coordinators.ConclusionMost of the data obtained are consistent with the Brazilian reality, not identifying any peculiar characteristic of this region of the study worthy of note, except for the difference in the prevalence of some types of cancer, a fact that deserves further studies. There were also no discrepancies in a regional analysis. Along with this work, it was possible to demonstrate the cancer situation and the profile of oncology patients attended at a reference center for 41 municipalities, mainly in the central region of Rio Grande do Sul state, which may be useful in the elaboration of public policies to modify the profile identified, and serve as the basis for further studies in this region.
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