[Barrett's esophagus: histochemical difference between goblet cells and blue cells]. / Esófago de Barrett: diferencia histoquímica entre células caliciformes y células azules.

Background: Barrett's esophagus (BE) is the replacement of the usual esophageal mucosa by a simple columnar epithelium with the presence of goblet cells (GC) of intestinal type. It has been related to different risk factors such as gastroesophageal reflux disease (GERD), inappropriate consumption of irritating foods, smoking and overweight. There are CC mimic cells, known as blue cells (BC), which make the diagnosis of BE difficult, due to the lack of a precise definition of the nature and location of the gastroesophageal junction and the microscopic variations in this area. Objective: To identify morphologically and with histochemical techniques Alcian blue (AA) and periodic acid-Schiff (PAS) between GC and BC. Material and methods: Retrolective cross-sectional analytical study where 45 samples of patients diagnosed with BE were included. Results: The morphological characteristics are similar in both cell varieties. PAS staining was 100%, unlike AA staining, with only 16 cases with staining, corresponding to 35.55%. Conclusions: PAS staining has a high sensitivity and specificity for the identification of GC, this being a fundamental pillar for the correct diagnosis of BE. The presence of BC detected by AA does not exclude the diagnosis of BE, since both cell types can coexist.

Introducción: el esófago de Barrett (EB) es el recambio de la mucosa habitual esofágica por un epitelio cilíndrico simple con presencia de células caliciformes (CC) de tipo intestinal. Se ha relacionado con factores de riesgo como la enfermedad por reflujo gastroesofágico (ERGE), consumo inapropiado de alimentos irritantes, tabaquismo o sobrepeso. Hay células imitadoras de las CC, las células azules (CA), que dificultan el diagnóstico del EB y es debido a falta de una definición precisa sobre la naturaleza y ubicación de la unión gastroesofágica y las variaciones microscópicas en esta zona. Objetivo: identificar morfológicamente y con las técnicas de histoquímica azul alciano (AA) y ácido peryódico de Schiff (PAS) las CC y las CA. Material y métodos: estudio transversal retrolectivo analítico; se incluyeron 45 muestras de pacientes diagnosticados con EB. Resultados: las características morfológicas son similares en ambas variedades celulares. La tinción de PAS fue del 100%, a diferencia de la tinción de AA, con solo 16 casos con tinción, correspondiente al 35.55%. Conclusiones: la tinción de PAS tiene una alta sensibilidad y especificidad para la identificación de CC, lo cual es fundamental para el correcto diagnóstico de la EB. La presencia de CA detectadas mediante AA no excluye el diagnóstico de EB, ya que ambos tipos celulares pueden coexistir.

Lipid droplet biogenesis and COX-2 pathway activation are triggered by Barrett's esophagus and adenocarcinoma, but not esophageal squamous cell carcinoma risk factors.

Esophageal cancer (EC) is an aggressive disease, presenting two main histological subtypes: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). The two EC subtypes widely differ concerning virtually all factors. ESCC development is mainly associated with tobacco and alcohol abuse, whereas obesity and chronic gastroesophageal reflux disease (GERD) are important risk factors not only for EAC, but also for for Barrett's esophagus (BE), an intestinal metaplasia that precedes EAC. Obesity triggers ectopic lipid droplets (LD) accumulation in non-adipose tissues. LD are organelles involved in cell metabolism, signaling, proliferation and production of inflammatory mediators. Therefore, the aim of this work was to investigate LD occurrence and role in EC. This study shows progressive LD levels increase along EAC development, in esophageal samples from non-obese through obese individuals, as well as BE, and EAC patients, whereas no significant changes were observed in ESCC samples, when compared to non-tumor samples. Additionally, in order to mimic BE and EAC risk factors exposure, a non-tumor esophageal cell line was incubated with oleic acid (OA) and acidified medium and/or deoxycholic acid (DCA), revealing a significant increment in LD amount as well as in COX-2 and CXCL-8 expression, and in IL-8 secretion. Further, COX-2 expression and LD amount presented a significant positive correlation and were detected co-localized in EAC, but not in ESCC, suggesting that LD may be the site for eicosanoid production in EAC. In conclusion, this study shows that obesity, and BE- and EAC-associated inflammatory stimuli result in a gradual increase of LD, that may be responsible for orchestrating inflammatory mediators' production and/or action, thus contributing to BE and EAC genesis and progression.

Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma.

BACKGROUND: Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, 'a disintegrin and metalloproteinases'. METHODS: We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry. RESULTS: EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett's dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA. CONCLUSIONS: ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies.

Increase of epidermal growth factor receptor expression in progression of GERD, Barrett, and adenocarcinoma of esophagus.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a pathology with a wide range of clinical and endoscopic manifestations. Epidermal growth factor receptor (EGFR), found in the epithelium of the digestive tract, plays an important role in epithelial repair and shows increased expression in different neoplasms, including esophageal tumors. OBJECTIVES: The purpose of this study was to evaluate EGFR expression using immunohistochemistry in esophageal biopsies obtained from patients with GERD, Barrett's esophagus, and adenocarcinoma of the esophagus. METHODS: EGFR expression was immunohistochemically determined in biopsies from 194 patients with symptoms suggestive of GERD or adenocarcinoma of the esophagus, seen at two Brazilian university hospitals between January 2003 and December 2008. Based on histopathological analysis, patients were divided into three groups: GERD, Barrett's esophagus and adenocarcinoma of the esophagus. EGFR expression was considered positive when staining was detected in the membrane. RESULTS: Mean age was 55.25 years (range 30-90). Patients with GERD (n = 127) accounted for 65.5% of the sample, compared with 12.4% (n = 24) of patients with Barrett's esophagus and 22.2% (n = 43) of patients with esophageal adenocarcinoma. Immunohistochemical analysis was positive for EGFR in 19.1% of the patients (37/194), divided as follows: 8.7% (11/127) in the GERD group, 25% (6/24) in the Barrett's esophagus group, and 46.5% (20/43) in the esophageal adenocarcinoma group. Statistical analysis revealed significant differences between the three groups (p = 0.0001). CONCLUSIONS: 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.

Detection of the risk of adenocarcinoma in Barrett's esophagus by means of tumor markers (p53 and Ki67).

The rising incidence of adenocarcinoma in Barrett's esophagus has intensified the research into methods of early recognition of cancer risk, detecting cytological and architectural changes (dysplasia) or using biomarkers as predictive tests. The aim of this paper is to evaluate the involvement of two tumor markers: p53 (tumor suppressor gene) and Ki67 (proliferation marker), by means of immunohistochemical analysis with monoclonal antibodies designed for the specific localization of p53 and Ki67 antigens, in esophageal biopsies with columnar metaplasia of patients with and without dysplasia and adenocarcinoma, and to anticipate which ones are liable to suffer it in the future. Both markers were positive in all intestinal metaplasia patients with high-grade dysplasia and adenocarcinoma, and even in some cases with low grade or without dysplasia. In contrast, in those who have gastric metaplasia, tumor markers were negative. Expression of biomarkers next to dysplasia reduces interobserver variation. Patients with these abnormalities have to be included into a surveillance protocol.

Immunoreactivity of cytokeratins 7 and 20 in goblet cells and columnar blue cells in patients with endoscopic evidence of Barrett's esophagus.

CONTEXT: Barrett's 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 Barrett's 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. OBJECTIVE: To compare the expression of cytokeratin 7 and 20 in goblet cells and columnar blue cells in patients with endoscopic evidence of Barrett's esophagus. METHODS: Biopsies from 86 patients with endoscopic evidence of Barrett's esophagus were evaluated. The biopsies were stained for cytokeratin 7 and 20. RESULTS: Goblet 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%. CONCLUSION: Goblet cells and columnar blue cells have similar immunohistochemical staining patterns for cytokeratins 7 and 20 in patients with endoscopic evidence of Barrett's esophagus.

Immunoreactivity of cytokeratins 7 and 20 in goblet cells and columnar blue cells in patients with endoscopic evidence of Barrett's esophagus / Imunoreatividade das citoqueratinas 7 e 20 nas células caliciformes e células colunares azuis em pacientes com evidência endoscópica de esôfago de Barrett

CONTEXT: Barrett's 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 Barrett's 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. OBJECTIVE: To compare the expression of cytokeratin 7 and 20 in goblet cells and columnar blue cells in patients with endoscopic evidence of Barrett's esophagus. METHODS: Biopsies from 86 patients with endoscopic evidence of Barrett's esophagus were evaluated. The biopsies were stained for cytokeratin 7 and 20. RESULTS: Goblet 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 percent of the cases, and cytokeratin 20 staining was the same in 77 percent. CONCLUSION: Goblet cells and columnar blue cells have similar immunohistochemical staining patterns for cytokeratins 7 and 20 in patients with endoscopic evidence of Barrett's esophagus.

CONTEXTO: Esôfago de Barrett é caracterizado pela presença de células caliciformes. Entretanto, quando "alcian blue" é utilizado, outro tipo de células, chamadas células colunares azuis, estão frequentemente presentes no esôfago distal de pacientes com evidência endoscópica de esôfago de Barrett. A imunoreatividade das citoqueratinas 7 e 20 tem sido estudada previamente em áreas de metaplasia intestinal na junção esôfago-gástrica. Entretanto, a expressão destas citoqueratinas nas células colunares azuis não foi caracterizada. OBJETIVO: Comparar a expressão das citoqueratinas 7 e 20 nas células caliciformes e células colunares azuis em pacientes com evidência endoscópica de esôfago de Barrett. MÉTODOS: Biopsias de 86 pacientes com evidência endoscópica de esôfago de Barrett foram avaliadas. Estas foram coradas com citoqueratinas 7 e 20. RESULTADOS: Células caliciformes estavam presentes em 75 casos e células colunares azuis em 50 casos. Ao todo, a expressão da citoqueratina 7 foi similar nas células caliciformes e células colunares azuis (P = 0,25), enquanto que a da citoqueratina 20 foi mais comum nas células caliciformes (P<0,001). Por outro lado, em indivíduos apresentando ambos os tipos de células, a coloração da citoqueratina 7 foi a mesma nas células caliciformes e células colunares azuis em 95 por cento dos casos, e a coloração da citoqueratina 20 foi a mesma em 77 por cento. CONCLUSÃO: As células caliciformes e as células colunares azuis têm padrões similares de coloração imunoistoquímica para citoqueratina 7 e 20 em pacientes com evidência endoscópica de esôfago de Barrett.

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.

c-Myc overexpression is strongly associated with metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.

We aim to determine the expression of the proto-oncogene c-Myc in patients with Barrett's esophagus (BE) and esophageal adenocarcinoma, and to evaluate the prevalence of such expression in relation to the metaplasia-dysplasia-adenocarcinoma sequence. BE develops as a result of a severe esophageal mucosa injury from gastroesophageal reflux. BE is a premalignant lesion and plays an important role in the development of esophageal adenocarcinoma. Several genetic alterations have been identified in the process that transforms a normal cell into a tumorous one. In the development of human tumors, one of the most important genes is the proto-oncogene c-Myc. The c-Myc protein expression was determined by immunohistochemical analysis in four different groups: 31 patients with normal tissue, 43 patients with BE without dysplasia, 11 patients with dysplasia in BE and 37 patients with esophageal adenocarcinoma. The material was obtained from esophageal biopsies or the dissection of patient esophagectomy specimens. Demographic and endoscopic data (sex, age, race and intestinal metaplasia extension), and morphologic and histopathologic tumor characteristics (deep tumor invasion, lymph node status, and tumor differentiation) were analyzed. The c-Myc expression was assessed using the Immunoreactive Scoring System (IRS). Overexpression of c-Myc was found in only 9.6% of normal tissue specimens, 37.2% of Barrett's esophagus, 45.5% of BE patients with dysplasia and 73% of adenocarcinoma samples, with significant statistical difference among these groups. No correlation was identified when the c-Myc expression was compared with morphologic and histologic tumor features or endoscopic data. However, linear correlation of c-Myc overexpression along the metaplasia-dysplasia-adenocarcinoma sequence was observed. This study demonstrates a significant increase in the expression of c-Myc in Barrett's esophagus, dysplasia and adenocarcinoma in relation to the control group, as well as a linear progression of this gene expression in this sequence. These results point out the importance of this marker in the development of esophageal adenocarcinoma from BE.

Expression of mucin-2 and correlation with PAS-alcian blue stain in Barrett's esophagus.

BACKGROUND/AIMS: Hematoxylin-eosin stain may fail to show intestinal metaplasia in Barrett's esophagus, and PAS-alcian blue may present difficulties of interpretation due to its more heterogeneous staining. We investigated whether Mucin-2 is a good substitute for PAS-alcian blue in the detection of goblet cells. METHODOLOGY: Biopsy specimens from 47 Barrett's esophagus patients were stained with hematoxylineosin and PAS-alcian blue. Mucin-2 expression was evaluated with monoclonal antibody. The intra- and interobserver agreements about the expression of Mucin-2 and PAS-alcian blue stain were determined by kappa statistics. RESULTS: PAS-alcian blue and Mucin-2 were positive in all cases. Mucin expression was positive in goblet cells and few columnar cells. PAS-alcian blue showed heterogeneous staining. The columnar epithelium and the submucosal glands were also stained. Intra- and interobserver agreement in the identification of intestinal metaplasia was 100%. CONCLUSIONS: Mucin-2 agreed fully with PAS-alcian blue. The intra- and interobserver agreement was perfect, justifying its use in the diagnosis of Barrett's esophagus.

O critério de positividade para a análise imunoistoquímica da p53 na confirmação da displasia do esôfago de Barrett faz diferença? / Does positive criterium for p53 immunohistochemical analysis in the confirmation of Barrett's dysplasia make difference?

RACIONAL: O esôfago de Barrett é uma complicação da doença do refluxo gastroesofágico com importante potencial de malignização. Relata-se que a expressão do marcador tumoral p53 se acentua com a progressão displasia-adenocarcinoma. OBJETIVO: Avaliar a expressão da p53 no epitélio de Barrett com presença ou não de displasia conforme dois critérios de positividade. MATERIAL E MÉTODOS: O material foi constituído por biopsias endoscópicas de 42 doentes com esôfago de Barrett. Cortes histológicos foram corados pela hematoxilina-eosina, pelo PAS-alcian blue e avaliados quanto à expressão imunoistoquímica da p53. O diagnóstico de displasia foi firmado pela concordância entre três patologistas. Foram utilizados dois critérios de positividade para a p53: 1. a coloração de, pelo menos, metade dos núcleos e 2. o encontro de qualquer núcleo corado. RESULTADOS: O número total de fragmentos foi de 229, com média de 5,4 por paciente. A displasia foi detectada em seis (14,3 por cento) casos. Para diferentes critérios de positividade, a p53 foi detectada, respectivamente, em 5 (13,9 por cento) e 14 (38,9 por cento) com epitélio metaplásico não-displásico. Especificamente nos seis casos displásicos, a p53 foi detectada, conforme o critério de positividade, em um (16,7 por cento) e quatro (66,7 por cento) casos, respectivamente. CONCLUSÕES: Nesta pequena série, a expressão imunoistoquímica da p53, independente do critério de positividade, não foi de auxílio para a confirmação de alterações displásicas no esôfago de Barrett.

p53 immunohistochemical expression in Barrett's esophagus before and after endoscopic ablation by argon plasma coagulation.

OBJECTIVE: Few studies have evaluated p53 accumulation in the squamous mucosa contiguous (SMC) to Barrett's esophagus (BE) and in the new squamous epithelium after endoscopic ablation. We evaluated the p53 expression in BE, in the SMC, and in the new squamous mucosa generated after ablation by argon plasma coagulation (APC). MATERIAL AND METHODS: Endoscopic biopsy specimens from 37 BE patients, before and after ablation by APC, were analyzed. The p53 immunostaining criterion used was the staining of at least half of the nuclei. RESULTS: p53 was detected in BE in 5 (13.5%) cases. In all these cases, SMC was p53(+). In addition, SMC was p53(-) in all cases of p53(-) BE (p <0.001). In the 5 cases with p53(+) BE and SMC, the new squamous mucosa continued to be p53(+). However, in the 32 cases with p53(-) SMC, the new squamous mucosa was also p53(-) (p <0.001). No case with p53(+) SMC turned out to be p53(-) after ablation. Similarly, no case with p53(-) BE and SMC before eradication became p53(+) after ablation (p < 0.001). CONCLUSIONS: p53 was highly prevalent in the contiguous squamous mucosa when it is present in BE. After ablation, none of the cases lost p53 expression, and none of the negative cases turned out to be positive.

Origin of adenocarcinoma in Barrett's esophagus: p53 and Ki67 expression and histopathologic background.

UNLABELLED: Barrett's esophagus is the substitution of squamous epithelium of the distal esophagus by columnar epithelium. Intestinal metaplasia in Barrett's esophagus is considered to be the main risk factor for the development of adenocarcinoma. Diffuse adenocarcinoma and Barrett's esophagus without intestinal metaplasia are rare, and reports on the subject are scarce. PURPOSE AND METHOD: To estimate the prevalence of adenocarcinoma in 297 patients with Barrett's esophagus, during the period of 1990 to 2002, and in 13 patients undergoing surgery, to conduct detailed macroscopic and microscopic analysis, with performance of immunohistochemical tests for p53 and Ki67, correlating the type of tumor with its adjacent epithelium. RESULTS: In our patients with Barrett's esophagus, there was a prevalence of 5.7% of adenocarcinoma. The tumors developed only when the Barrett's esophagus segment was long (>3.0 cm). Tumors were located close to the squamous-columnar junction. The histological study revealed 2 patients (15.4%) with Barrett's esophagus adjacent to a tumor with gastric metaplasia without the presence of intestinal metaplasia. Tumors were classified according to Nakamura's classification (23% differentiated pattern, and 77% undifferentiated pattern) and to Lauren's classification (61% intestinal and 39% diffuse). The difference is due to the migration of microtubular and foveolar tumors of undifferentiated (gastric) pattern in Nakamuras classification to the Lauren's intestinal type. The immunohistochemical test for Ki67 was strongly positive in all the patients, thus evidencing intense cell proliferation in both the columnar epithelium and tumor. Expression of p53 was negative in 67% of the adjacent columnar epithelia and 42% of the tumors, without any correlation between the tissue types. CONCLUSION: Adenocarcinoma develops from mixed columnar epithelium, either intestinal or gastric, showing both the gastric and the intestinal patterns; thus, tumors can also grow in columnar epithelium without intestinal metaplasia. Barrett's esophagus should be followed up for the possibility of progression to malignancy, especially when the segment is longer than 3 cm.

Origin of adenocarcinoma in Barrett's esophagus: P53 and Ki67 expression and histopathologic background

O esôfago de Barrett é definido como a substituição do epitélio escamoso do esôfago distal por epitélio colunar. A metaplasia intestinal no esôfago de Barrett é considerada por muitos como o principal fator de risco para o desenvolvimento do adenocarcinoma. Embora já descrito, o adenocarcinoma do tipo difuso e o esôfago de Barrett sem metaplasia intestinal, são raros e pouco estudados. OBJETIVO E MÉTODO: O presente estudo objetivou o cálculo da prevalência do adenocarcinoma no esôfago de Barrett, assim como a análise macroscópica e microscópica detalhada de treze pacientes operados no período de 1990 a 2002, com realização de estudo imunohistoquímico do p53 e Ki67, correlacionando o tipo de tumor com o epitélio adjacente a este. RESULTADOS: Obtivemos uma prevalência de 5,7% de adenocarcinoma em pacientes internados para tratamento cirúrgico de esôfago de Barrett . Encontraram-se tumores relativamente grandes, com média de 4,67 ± 2,28 cm, e sempre em esôfago de Barrett longo, com média de 7,71 ± 1,5 cm. Observou-se tendência de os tumores se localizarem próximos à transição escamo-colunar. O estudo histológico mostrou dois pacientes (15,4%) que apresentavam esôfago de Barrett adjacente ao tumor do tipo juncional sem presença de metaplasia intestinal. Classificaram-se os tumores segundo a classificação japonesa de Nakamura (23% de padrão diferenciado ou intestinal e 77% de padrão indiferenciado ou gástico) e pela classificação de Laurén (61% intestinais e 39% difusos). A diferença decorre da migração dos tumores microtubulares e foveolares do padrão gástrico para o tipo intestinal de Laurén. O estudo do Ki67 foi fortemente positivo em todos os pacientes, mostrando o alto índice de proliferação celular no epitélio colunar e no tumor. O p53 mostrou-se negativo em 66,7% dos pacientes no epitélio colunar e 41,7% no tumor, não mostrando correlação entre os dois materiais. CONCLUSAO: O adenocarcinoma se desenvolve sobre o esôfago de Barrett a partir do epitélio colunar misto, intestinal, bem como do juncional, apresentando padrão tanto gástrico como intestinal; portanto tumores podem se desenvolver em epitélio colunar sem metaplasia intestinal o qual também deve ser seguido, principalmente quando for extenso.

[Does the criterium of positivity for the immunohistochemical analysis of p53 in the confirmation of Barrett's dysplasia make any difference?]. / O critério de positividade para a análise imunoistoquímica da p53 na confirmação da displasia do esôfago de Barrett faz diferença?

BACKGROUND: Barrett's esophagus is the most serious complication of the gastroesophageal reflux disease and presents a malignant potential. The expression of the tumoral marker p53 increases with the dysplasia-adenocarcinoma sequence. AIMS: To evaluate the p53 expression in Barrett's esophagus with or without dysplasia according to the two positive immunostaining criteria. MATERIALS AND METHODS: The material was constituted by endoscopic biopsy specimens from 42 patients with Barrett's esophagus. Section of formalin-fixed and paraffin-embedded biopsies were stained with hematoxylin-eosin, PAS-alcian blue and evaluated the p53 immunohistochemical expression. Two p53 immunostaining criteria were utilized: 1. The staining of, at least, half of the nuclei, and 2. The staining of any nucleus. The diagnosis of dysplasia was confirmed by the agreement between three pathologists. RESULTS: The total number of tissue specimens was 229, with an average of 5.4 specimens per patient. Dysplasia, with agreement for all pathologists examining the same set of slides, was detected in six (14.3%) cases. According to the two different p53 immunostaining criteria, the protein was detected in non-dysplastic Barrett's metaplasia, respectively, in 5 (13.9%) and 14 (38.9%) patients. Specifically in the six dysplastic cases, p53 was detected, according to the immunostaining criteria, in one (16.7%) and four (66.7%) cases, respectively. CONCLUSIONS: In this group, p53 immunohistochemical expression, regardless of positive criteria take into account, was not useful for detecting dysplasia in Barrett's esophagus.

A new physiologic approach for the surgical treatment of patients with Barrett's esophagus: technical considerations and results in 65 patients.

OBJECTIVE: To determine the results of a new surgical procedure for patients with Barrett's esophagus. SUMMARY BACKGROUND DATA: In addition to pathologic acid reflux into the esophagus in patients with severe gastroesophageal reflux and Barrett's esophagus, increased duodenoesophegeal reflux has been implicated. The purpose of this study was to establish the effect of a new bile diversion procedure in these patients. METHODS: Sixty-five patients with Barrett's esophagus were included in this study. A complete clinical, radiologic, endoscopic, and bioptic evaluation was performed before and after surgery. Besides esophageal manometry, 24-hour pH studies and a Bilitec test were performed. After surgery, gastric emptying of solids, gastric acid secretion, and serum gastrin were determined. All patients underwent highly selective vagotomy, antireflux procedure (posterior gastropexy with cardial calibration or fundoplication), and duodenal switch procedure, with a Roux-en-Y anastomosis 60 cm in length. RESULTS: No deaths occurred. Morbidity occurred in 14% of the patients. A significant improvement in symptoms, endoscopic findings, and radiologic evaluation was achieved. Lower esophageal sphincter pressure increased significantly (p < 0.0001), as did abdominal length and total length of the sphincter (p < 0.0001). The presence of an incompetent sphincter decreased from 87.3% to 20.9% (p < 0.0001). Three of seven patients with dysplasia showed disappearance of this dysplasia. Serum gastrin and gastric emptying of solids after surgery remained normal. Basal and peak acid output values were low. Twenty-four hour pH studies showed a mean value of 24.8% before surgery, which decreased to 4.8% after surgery (p < 0.0001). The determination of the percentage time with bilirubin in the esophagus was 23% before surgery; this decreased to 0.7% after surgery (p < 0.0001). Late results showed Visick I and II gradation in 90% of the patients and grade III and IV in 10% of the patients. CONCLUSIONS: This physiologic approach to the surgical treatment of patients with Barrett's esophagus produces a permanent decrease of acid secretion (and avoids anastomotic ulcer), decreases significantly acid reflux into the esophagus, and abolishes duodenoesophageal reflux permanently. Significant clinical improvement occurs, and dysplastic changes at Barrett's epithelium disappear in almost 50% of the patients.