CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett’s Esophagus Malignant Progression

Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett's malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett's progression, CYR61 and TAZ. Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that CYR61 and TAZ have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett's samples associated with high-grade dysplasia/adenocarcinoma. In our cohort CYR61 and TAZ up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett's esophagus index samples. Finally, we found that CYR61 and TAZ over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both CYR61 and TAZ genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett's esophagus neoplastic progression.

Lavado peritoneal como método diagnóstico de lesión intraabdominal. Estudio en pacientes politraumatizados con sospecha de trauma abdominal cerrado y con herida penetrante abdominal por arma blanca, en el Hospital Vicente Corral Moscoso, octubre de 1998 a julio de 1999. Cuenca-Ecuador

Analizamos en base a nuestra experiencia apoyados por bibliografía reciente, la importancia, validez, precisión y actualidad del Lavado Peritoneal como método diagnóstico de lesión intraabdominal en pacientes con trauma contuso y penetrante por arma blanca hemodinámicamente estables que cumplían los criterios de inclusión predeterminados para el caso. Durante un período de 10 meses desde Octubre de 1998 a Julio de 1999, tomando como Universo a los pacientes politraumatizados de la sala de emergencia del Hospital Vicente Corral Moscoso de Cuenca - Ecuador, se obtuvo una muestra de 50 casos con sospecha de lesión intraabdominal por trauma abdominal contuso o herida penetrante por objeto corto punzante, en quienes se efectuó un estudio cuasi experimental descriptivo al ser sometido a lavado peritoneal diangóstico para determinar casos positivos, negativos, falsos positivos y falsos negativos. Se utilizó la técnica abierta de Fisher por considerarla la más segura y con menos complicaciones. Se decidió laparotomía de urgencia en los casos positivos registrándose los hallazgos transoperatorios. Se obtuvieron 27 lavados positivos, 20 negativos, un falso positivo que al ser laparotomizado se comprobó que la sangre en cavidad provenía de la pared del abdomen y dos falsos negativos que se desestabilizaron hemodinámicamente, presentaron reacción peritoneal y también fueron intervenidos quirúrgicamente. Por lo tanto, se realizaron 30 laparotomías, justificándose 27, dos resultaron ser los casos falsos negativos y una sola laparotomía fue innecesaria. Las complicaciones por el procedimiento estuvieron ausentes. En este estudio, el Lavado Peritoneal Diagnosticó demostró una sensibilidad del 93.1 por ciento especificidad del 95.2 por ciento, un valor predictivo positivo del 96.4 por ciento, un valor predictivo negativo del 90.9 por ciento; datos que se equiparan con otros estudios. De acuerdo a la experiencia realizada concluimos que el Lavado Peritoneal Diagnóstico constituye una prueba efectiva, precisa, rápida, económica para la manejor evaluación clínica en centros de baja complejidad o faltos de otros métodos complementarios diagnósticos como ultrasonido o T.A.C. y que ante su existencia, el Lavado Peritoneal Diagnóstico es coadyuvante, por tanto, debe formar parte de los protocolos de valoración de traumatismo abdominal en nuestros hospitales

Valor diagnóstico y pronóstico de la medición de la presión intraabdominal transvesical en pacientes con abdomen agudo en el H.V.C.M. Cuenca febrero a septiembre del 2000

A 60 pacientes ingresados en emergencia y cirugía se realizó la medición de la presión intraabdominal [P.I.A.] por vía vesical a través de una sonda Foley. Clasificados en dos grupos de estudio: 30 del grupo de control; sin patología abdominal: 22 hombres y 8 mujeres con un promedio de edad 49 años, diagnosticados de; T.E.C., trauma raquimedular, meningitis, absceso cerebral y mal formación arteriovenoso, que necesitaban de sonda vesical. Obteníendose una media normal o valor referencial de normalidad de 2.7 cm. H20 o 1.98 mmHg. El segundo grupo experimental: 30 pacientes diagnosticados de abdomen agudo quirúrgico: 21 hombres y 9 mujeres, con un promedio de edad de 46 años, clasificados en 5 tipos de abdomen agudo: AAOI, AAT,AAP AAI. AAOV. se les mediÓ la presión intraabdominal transvesical, obteniéndose los siguientes resultados. P.I.A.: Prequirúrgico medio: 19.29 cm H20 [14.18 mmHg.]. P.IA.: Posquirúrgico media: 8.97 cm H20 [6.59 mmHg.]. Todos sometidos a laparotomía exploratoria. Mejorando 28 pacientes, uno empeoró y solicitÓ el alta, un paciente falleció. En el grupo de control los 30 pacientes presentaron la presiÓn intraabdominal en valores normales

Prevalence of Barrett Esophagus in Adolescents and Young Adults With Esophageal Atresia

International audience

Hemorrhagic Shock Secondary To Button Battery Ingestion.

Button battery ingestion is a frequent pediatric complaint. The serious complications resulting from accidental ingestion have increased significantly over the last two decades due to easy access to gadgets and electronic toys. Over recent years, the increasing use of lithium batteries of diameter 20 mm has brought new challenges, because these are more detrimental to the mucosa, compared with other types, with high morbidity and mortality. The clinical complaints, which are often nonspecific, may lead to delayed diagnosis, thereby increasing the risk of severe complications. A five-year-old boy who had been complaining of abdominal pain for ten days, was brought to the emergency service with a clinical condition of hematemesis that started two hours earlier. On admission, he presented pallor, tachycardia and hypotension. A plain abdominal x-ray produced an image suggestive of a button battery. Digestive endoscopy showed a deep ulcerated lesion in the esophagus without active bleeding. After this procedure, the patient presented profuse hematemesis and severe hypotension, followed by cardiorespiratory arrest, which was reversed. He then underwent emergency exploratory laparotomy and presented a new episode of cardiorespiratory arrest, which he did not survive. The battery was removed through rectal exploration. This case describes a fatal evolution of button battery ingestion with late diagnosis and severe associated injury of the digestive mucosa. A high level of clinical suspicion is essential for preventing this evolution. Preventive strategies are required, as well as health education, with warnings to parents, caregivers and healthcare professionals.

Gastrointestinal Involvement In Lipoid Proteinosis: A Ten-year Follow-up Of A Brazilian Female Patient.

Lipoid proteinosis is a rare autosomal recessive disease characterized by the deposition of hyaline material in the skin and internal organs. The main clinical features are hoarseness and typical skin lesions. In this report we describe the endoscopic and radiologic findings in a Brazilian female patient presenting extensive gastrointestinal involvement and the evolution of the detected lesions in ten years of follow-up. Initial upper endoscopy and colonoscopy showed a similar pattern of multiple yellowish nodules throughout the esophagus, stomach, duodenum, and colons. Histological analysis confirmed the diagnosis of lipoid proteinosis. In addition, small bowel follow through demonstrated numerous well defined, round, small filling defects throughout the jejunum. Ten years later, the esophageal lesions remained the same, but none of the previous alterations were detected in the stomach, duodenum, and colons. In conclusion, lipoid proteinosis may affect all gastrointestinal organs with the same pattern of macroscopic and microscopic lesions. Some lesions may regress with increasing age.

Dysphagia After Antireflux Fundoplication: Endoscopic, Radiological And Manometric Evaluation.

The transient dysphagia after fundoplication is common and most often disappears until six weeks postoperatively. Analyze a group of patients who presented late and persistent dysphagia postoperatively. Forty-one patients after Nissen fundoplication, 14 male and 27 female, mean age 48 year, were evaluated based on medical history, esophagogastroduodenoscopy, contrast radiographic examination and esophageal manometry. The results were compared with another 19 asymptomatic individuals. Contrast radiographic examination of the esophagus revealed in six cases delayed emptying, characterizing that four patients had achalasia and two diffuse spasm of the esophagus. Esophageal manometry showed that maximal expiratory pressure of the lower sphincter ranged from 10 to 38 mmHg and mean respiratory pressure from 14 to 47 mmHg, values similar to controls. Residual pressure ranged from 5 to 31 mmHg, and 17 patients had the same values as the control group. The residual pressure of the lower sphincter was higher and statistically significant in patients with dysphagia compared with those operated without dysphagia. Future studies individualizing and categorizing each motility disorder, employing other techniques of manometry, and the analysis of the residual pressure may contribute to understand of persistent dysphagia in the postoperative fundoplication.

Alterações do trato digestório de cães da raça Golden Retriever afetados pela distrofia muscular

O modelo experimental canino Golden Retriever portador da Distrofia Muscular (GRMD) é o melhor substituto entre os modelos animais para estudar a Distrofia Muscular de Duchenne. Além da musculatura estriada, a doença pode afetar a musculatura estriada cardíaca e a musculatura lisa, e desta forma, o funcionamento do trato digestório, já que o músculo liso é o elemento primário dos órgãos tubulares. Através de estudo morfológico descritivo, o objetivo deste trabalho foi verificar se a distrofia muscular afeta a arquitetura geral do trato digestório e como se dispõe sua estrutura muscular em animais afetados. Foram realizadas avaliações descritivas macro e microscópicas com colorações de Hematoxilina-Eosina, Tricrômio de Masson e Picrosirius. Entre os resultados apresentados, verificou-se que o esôfago e o fígado dos animais afetados encontraram-se alterados, assim como o estômago não ocupava seu lugar habitual. O músculo diafragma apresentava-se atrofiado e diferenças histológicas foram encontradas na camada muscular do sistema gastrointestinal, em geral. Outras estruturas do tubo digestório de GRMDs apresentaram-se de maneira similar a de um animal normal.

Análise morfométrica da transição esôfago-gástrica de eqüinos submetidos a diferentes manejos alimentares e atividade física

O objetivo deste trabalho foi identificar se diferentes tipos de manejo físico e alimentar determinaram mudanças adaptativas na morfometria da região de transição esôfago-gástrica (TEG) em eqüinos. Foram utilizados 15 conjuntos de animais adultos com raça, sexo e idade não identificados, divididos em três grupos de acordo com a dieta e a atividade física: grupo I - composto por cinco conjuntos da TEG de eqüinos em treinamento intensivo e alimentados principalmente à base de concentrado; grupo II - com cinco conjuntos da TEG de eqüinos que não desempenhavam atividade física intensa e eram alimentados principalmente à base de concentrado, e o grupo III - composto por cinco conjuntos da TEG de eqüinos mantidos a pasto e que não desempenhavam atividade física intensa. A região de transição esôfago-gástrica teve a estrutura do seu epitélio avaliada morfometricamente, onde foram feitas mensurações para identificar a espessura do epitélio estratificado pavimentoso queratinizado. A espessura do grupo I teve como média 122,3µm, do grupo II foi de 173,4µm e do grupo III foi de 281,7µm. Os resultados encontrados para a espessura do epitélio estratificado pavimentoso queratinizado dos eqüinos mostraram a existência de diferenças estatisticamente significativas dos eqüinos do grupo I, quando comparados aos eqüinos do grupo III.

Tabagismo e câncer no Brasil: evidências e perspectivas

Neste artigo analisa-se a tendência temporal da prevalência do tabagismo no Brasil, bem como as assimetrias da prevalência de acordo com as regiões do país, a idade, o gênero e o nível socioeconômico da população. Desde o estabelecimento da relação entre tabagismo e câncer de pulmão há 60 anos, o número de tumores malignos com evidências de associação causal com o tabagismo ascendeu a vinte. O declínio da prevalência do tabagismo na população brasileira tem sido constante desde o final da década de 80. Até 2003, foi mais intenso entre os homens. A partir daquele ano, a queda tornou-se mais pronunciada entre as mulheres. As mais altas prevalências de tabagismo encontram-se no Sudeste e Sul, as duas regiões com maiores incidências de neoplasias estritamente relacionadas ao tabaco (cavidade oral, esôfago e pulmão). A exposição ambiental à fumaça do tabaco também foi examinada considerando-se os efeitos para os adultos não fumantes, que apresentam maior risco de tumores de pulmão, laringe e faringe, e entre crianças de pais fumantes, suscetíveis ao risco de hepatoblastoma e leucemia linfocítica aguda. Apesar do incontestável sucesso da política de controle do tabagismo no país, as ações de prevenção devem considerar que as parcelas da população com piores condições socioeconômicas e com baixo nível educacional são as que apresentam taxas mais altas de prevalência de tabagismo. Dentro destes segmentos populacionais os adolescentes representam uma prioridade

Effects of perinatal protein deprivation and recovery on esophageal myenteric plexus

AIM: To evaluate effects of pre- and postnatal protein deprivation and postnatal recovery on the myenteric plexus of the rat esophagus. METHODS: Three groups of young Wistar rats (aged 42 d) were studied: normal-fed (N42), protein-deprived (D42), and protein-recovered (R42). The myenteric neurons of their esophagi were evaluated by histochemical reactions for nicotinamide adenine dinucleotide (NADH), nitrergic neurons (NADPH)-diaphorase and acetylcholinesterase (AChE), immunohistochemical reaction for vasoactive intestinal polypeptide (VIP), and ultrastructural analysis by transmission electron microscopy. RESULTS: The cytoplasms of large and medium neurons from the N42 and R42 groups were intensely reactive for NADH. Only a few large neurons from the D42 group exhibited this aspect. NADPH detected in the D42 group exhibited low reactivity. The AChE reactivity was diffuse in neurons from the D42 and R42 groups. The density of large and small varicosities detected by immunohistochemical staining of VIP was low in ganglia from the D42 group. In many neurons from the D42 group, the double membrane of the nuclear envelope and the perinuclear cisterna were not detectable. NADH and NADPH histochemistry revealed no group differences in the profile of nerve cell perikarya (ranging from 200 to 400 mu m(2)). CONCLUSION: Protein deprivation causes a delay in neuronal maturation but postnatal recovery can almost completely restore the normal morphology of myenteric neurons. (C) 2010 Baishideng. All rights reserved.

Could Cyclophosphamide exert a protective role avoiding esophagic neuron loss in Calomys callosus infected with Trypanosoma cruzi?

The protective role of Cyclophosphamide was studied in this work. Young male Calomys callosus were infected with Trypanosoma cruzi and allowed to age. Cyclophosphamide therapy was administered to animals during acute and late chronic phases of infection. Esophageal neurons were counted, displaying enhanced neuronal loss for the young and treated infected groups. For aged and cyclophosphamide treated animals, a protection was observed through a reduced loss of neurons as compared to the young and infected groups. Enhanced nitric oxide concentrations were observed for young animals as compared to aged counterparts. Splenocyte proliferation was reduced during the acute phase in comparison with those found in the chronic phase. Morphometry of neuronal body displayed a significant reduction concerning the area, perimeter, diameter and volume for aged animals as compared to young groups. These results indicate that the protective effects of cyclophosphamide together with process of neuroplasty of peripheral nervous system could lead to a protection against neuronal loss.

Contraction of the human diaphragm during rapid postural adjustments

1. The response of the diaphragm to the postural perturbation produced by rapid flexion of the shoulder to a visual stimulus was evaluated in standing subjects. Gastric, oesophageal and transdiaphragmatic pressures were measured together with intramuscular and oesophageal recordings of electromyographic activity (EMG) in the diaphragm. To assess the mechanics of contraction of the diaphragm, dynamic changes in the length of the diaphragm were measured with ultrasonography. 2. With rapid flexion of the shoulder in response to a visual stimulus, EMG-activity in the costal and crural diaphragm occurred about 20 ms prior to the onset of deltoid EMG. This anticipatory contraction occurred irrespective of the phase of respiration in which arm movement began. The onset of diaphragm EMG-coincided with that of transversus abdominis. 3. Gastric and transdiaphragmatic pressures increased in association with the rapid arm flexion by 13.8 +/- 1.9 (mean +/- S.E.M.) and 13.5 +/- 1.8 cmH(2)O, respectively. The increases occurred 49 +/- 4 ms after the onset of diaphragm EMG, but preceded the onset of movement of the limb by 63 +/- 7 ms. 4. Ultrasonographic measurements revealed that the costal diaphragm shortened and then lengthened progressively during the increase in transdiaphragmatic pressure. 5. This study provides definitive evidence that the human diaphragm is involved in the control of postural stability during sudden voluntary movement of the limbs.

Delayed postural contraction of transversus abdominis in low back pain associated with movement of the lower limb

The temporal parameters of the response of the trunk muscles associated with movement of the lower limb were investigated in people with and without low back pain (LBP). The weight shift component of the task was completed voluntarily prior to a stimulus to move to allow investigation of the movement component of the response. In the control subjects the onset of electromyographic (EMG) activity of all trunk muscles preceded that of the muscle responsible for limb movement, thus contributing to the feed forward postural response. The EMG onset of transversus abdominis was delayed in the LBP subjects with movement in each direction, while the EMG onsets of rectus abdominis, erector spinae, and oblique abdominal muscles were delayed with specific movement directions. This result provides evidence of a change in the postural control of the trunk in people with LBP.

Preparatory trunk motion accompanies rapid upper limb movement

Evaluation of trunk movements, trunk muscle activation, intra-abdominal pressure and displacement of centres of pressure and mass was undertaken to determine whether trunk orientation is a controlled variable prior to and during rapid bilateral movement of the upper limbs. Standing subjects performed rapid bilateral symmetrical upper limb movements in three directions (flexion, abduction and extension). The results indicated a small (0.4-3.3 degrees) but consistent initial angular displacement between the segments of the trunk in a direction opposite to that produced by the reactive moments resulting from limb movement. Phasic activation of superficial trunk muscles was consistent with this pattern of preparatory motion and with the direction of motion of the centre of mass. In contrast, activation of the deep abdominal muscles was independent of the direction of limb motion, suggesting a non-direction specific contribution to spinal stability. The results support the opinion that feedforward postural responses result in trunk movements, and that orientation of the trunk and centre of mass are both controlled variables in relation to rapid limb movements.