Aspectos histológicos, genéticos y moleculares de las lesiones preneoplásicas de la mucosa gástrica / Histological, genetic and molecular aspects of preneoplastic lesions of the gastric mucosa

Siendo el cáncer gástrico la 3ª causa de muerte por cáncer en Chile, y existiendo estrategias de tamizaje consistentes en pesquisa de lesiones preneoplásicas de la mucosa gástrica, es relevante conocer los aspectos genéticos y moleculares que puedan ser aplicados, en la optimización de dichas estrategias a grupos de mayor riesgo. El objetivo de este manuscrito fue revisar la evidencia actual en los aspectos señalados, y de la inmunohistoquímica de 4 marcadores (p53, CDX2, MUC2 y S100A9) en la mucosa gástrica normal y en las lesiones preneoplásicas de la misma.

SUMMARY: Since gastric cancer is the 3rd leading cause of death from cancer in Chile, and there are screening strategies consisting of screening for preneoplastic lesions of the gastric mucosa, it is important to know certain genetic and molecular aspects that can be applied in optimizing these strategies for higher risk groups. The aim of this manuscript was to review the current evidence on the aforementioned aspects, and on the immunohistochemistry of 4 markers (p53, CDX2, MUC2 and S100A9) in normal gastric mucosa and in its preneoplastic lesions.

Morfología y repercusiones diagnóstico-terapéuticas de las lesiones preneoplásicas gástricas / Morphology and diagnostic determinants of gastric precancerous conditions

El carcinoma gástrico (CG) de tipo intestinal se origina en un epitelio displásico, que a su vez se desarrolla en medio de una atrofia gástrica (AG) y metaplasia intestinal (MI). La infección por Helicobacter pylori (HP) es la causa más frecuente de AG, causando una pangastritis atrófica multifocal. Entre otras condiciones que producen inflamación crónica de la mucosa gástrica se encuentran también la gastritis autoinmune y la anemia perniciosa. El marco conceptual sobre el cual descansa gran parte de la investigación actual y nuestra comprensión de los cambios que ocurren en la mucosa gástrica se debe a la denominada "cascada de Correa"; quien planteó que la mucosa gástrica crónicamente inflamada, da paso a la AG, que va adquiriendo focos de MI y en dicho epitelio se desarrollará finalmente una displasia (DIS). Se ha acuñado el término lesiones preneoplásicas gástricas (LPG), para referirse a: AG, MI y DIS.Después de la erradicación de HP, se ha demostrado una reducción general de la incidencia de CG; efecto que no es tan claro, cuando la pangastritis por HP ha evolucionado a AG extensa. De tal modo que el efecto de la erradicación de HP medido a través de EC, ha sido poco consistente. La AG grave diagnosticada por histología representa la condición de mayor riesgo. Por otra parte, la MI puede ser de tipo intestinal (delgado-entérica ó incompleta) y la colónica (colónica ó completa) considerándose a esta última, como la variedad de peor pronóstico. El diagnóstico histológico de este tipo de lesiones determina que quien las padece, debe someterse a vigilancia endoscópica. El objetivo de este manuscrito fue resumir la evidencia existente respecto de las LPG, en términos de su caracterización morfológica y sus repercusiones diagnóstico-terapéuticas (significado patológico, graduación del riesgo, vigilancia recomendada; y factores de riesgo).

Gastric carcinoma (GC) of intestinal type, originates from a dysplastic epithelium, which in turn develops in the midst of gastric atrophy (GA) and intestinal metaplasia (IM). Helicobacter pylori (HP) infection is the most frequent cause of GA, causing a multifocal atrophic pangastritis. Among other conditions that produce chronic inflammation of gastric mucosa are also autoimmune gastritis and pernicious anemia. The conceptual framework on which much of current research rests and our understanding of the changes that occur in the gastric mucosa is due to the so-called "Correa waterfall"; who stated that gastric mucosa chronically inflamed, gives way to the GA, which is acquiring foci of IM and in said epithelium a dysplasia (DIS) will eventually develop. The term precancerous conditions (PCC) of the gastric mucosa have been coined to refer to: GA, IM and DIS. After HP eradication, a general reduction in the incidence of GC has been demonstrated; effect that is not so clear, when pangastritis by HP has evolved to extensive GA. Thus, the effect of HP eradication measured through clinical trials has been inconsistent. Severe GA diagnosed represents the highest risk condition. On the other hand, IM can be enteric (grade I), enterocolic (grade II) or colonic (grade III); considering IM III as the variety with the worst prognosis. Histological diagnosis of gastric PCC, determines that the one who suffers them, must undergo endoscopic surveillance. The aim of this manuscript was to update morphological aspects and diagnostic-therapeutic scope of gastric PCC.

Eficiência e segurança de secretagogos intestinais para constipação crônica: uma revisão sistemática e meta-análise / Efficacy and safety of intestinal secretagogues for chronic constipation: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Intestinal secretagogues have been tested for the treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The class-effect of these type of drugs has not been studied. OBJECTIVE: To determine the efficacy and safety of intestinal secretagogues for the treatment of chronic constipation and constipation-predominant irritable bowel syndrome. METHODS: A computer-based search of papers from 1966 to September 2017 was performed. Search strategy consisted of the following MESH terms: intestinal secretagogues OR linaclotide OR lubiprostone OR plecanatide OR tenapanor OR chloride channel AND chronic constipation OR irritable bowel syndrome. Data were extracted as intention-to-treat analyses. A random-effects model was used to give a more conservative estimate of the effect of individual therapies, allowing for any heterogeneity among studies. Outcome measures were described as Relative Risk of achieving an improvement in the symptom under consideration. RESULTS: Database Search yielded 520 bibliographic citations: 16 trials were included for analysis, which enrolled 7658 patients. Twelve trials assessed the efficacy of intestinal secretagogues for chronic constipation. These were better than placebo at achieving an increase in the number of complete spontaneous bowel movements per week [RR 1.87 (1.24-2.83)], at achieving three or more spontaneous bowel movements per week [RR 1.56 (1.31-1.85)] and at inducing spontaneous bowel movement after medication intake [RR 1.49 (1.07-2.06)]. Similar results were observed when assessing the efficacy of intestinal secretagogues on constipation-predominant irritable bowel syndrome based on the results of six trials. CONCLUSION: Intestinal secretagogues are useful and safe therapeutic alternatives for the treatment of constipation-related syndromes.

RESUMO CONTEXTO: Os secretagogos intestinais têm sido testados para o tratamento da constipação crônica e síndrome do intestino irritável com constipação predominante. O efeito classe desses tipos de drogas ainda não foi estudado. OBJETIVO: Determinar a eficácia e a segurança de secretagogos intestinais para o tratamento da constipação crônica e síndrome do intestino irritável de constipação predominante. MÉTODOS: Realizada pesquisa baseada em banco de dados de trabalhos publicados entre 1966 e setembro de 2017. A estratégia de pesquisa consistia dos seguintes termos MeSH: secretagogos intestinais OU linaclotide OU lubiprostona OU plecanatide OU tenapanor OU canal de cloro E constipação crônica OU síndrome do intestino irritável. Os dados foram extraídos como análises de intenção de tratar. Um modelo de efeitos aleatórios foi usado para dar uma estimativa mais conservadora do efeito das terapias individuais, permitindo a qualquer heterogeneidade entre os estudos. Os desfechos foram descritos como risco relativo de alcançar uma melhoria no sintoma em consideração. RESULTADOS: A busca no banco de dados rendeu 520 citações bibliográficas: 16 ensaios foram incluídos para análise, que incluiu 7658 pacientes. Doze trabalhos avaliaram a eficácia de secretagogos intestinais para constipação crônica. Estes foram melhores do que placebo, alcançando um aumento no número de evacuações completas espontâneas por semana [RR 1,87 (1,24-2,83)], para a aquisição de três ou mais evacuações espontâneas por semana [RR 1,56 (1,31-1,85)] e na indução espontânea do movimento intestinal após a ingestão de medicação [RR 1,49 (1,07-2,06)]. Resultados semelhantes foram observados ao avaliar a eficácia de secretagogos intestinais na síndrome do intestino irritável de constipação predominante com base em resultados de seis ensaios. CONCLUSÃO: Os secretagogos intestinais são alternativas terapêuticas úteis e seguras para o tratamento de síndromes relacionadas à constipação.

Ocurrence of equine cavitary myiasis (Gasterophilus spp) and its relation with secondary gastric ulcers of the squamous mucosa in Temuco, Chile / Ocurrencia de miasis cavitaria equina (Gasterophilus Spp) y su relación con las úlceras gástricas secundarias en la mucosa escamosa en Temuco, Chile / Ocorrência da miíase cavitária equina (Gasterophilus spp) e sua relação com as ulceras gástricas secundarias na mucosa escamosa em Temuco, Chile

The aim of this study was to determine the ocurrence of equine cavitary myiasis (Gasterophilus spp) in the CholChol slaughtering house in Temuco, Chile and its relation with the presentation of secondary gastric ulcers in the non-glandular squamous mucosa of the horses' (Equus caballus) stomachs. Of 240 stomachs evaluated post mortem, 145 were selected and characterized as positive to gasterophilosis (60.4%), of which 75 were males (20 stallions and 55 geldings) and 70 were mares, with ages ranging from 1 to 16 years. Every stomach was evaluated, characterized and photographed post mortem. Information about sex, age, location of the Gasterophilus larvae, presence and degree of ulceration of the squamous mucosa, were recorded in the respective forms and posteriorly digitalized. Global analysis of the location of larvae in the stomach of horses positive to gasterophilosis, established that 91.7% were located in the glandular mucosa, while 8.3% were located in the squamous mucosa. In the stomachs with presence of larvae in the antral/piloric regions of the glandular mucosa, 87.6% had secondary ulcers in the nonglandular squamous mucosa, due to the increase in the gastric fill line following alterations in gastric emptying, of which 69% were classified in categories 3 to 4 with a number of larvae higher tan 30, while 18.6% were found in categories 1 or 2 with less than 30 larvae per site. Regarding the location of larvae in the squamous mucosa, 8.3% of the stomachs showed primary mechanic ulcers, all classified between grades 1 and 2. Of all the animals evaluated, 62.1% had more tan 60 larvae, of which 60.1% had grade 3 or 4 secondary squamous ulcers, 15.9% had between 30 and 60 larvae per site, and 14.5% had less than 30 larvae per site. The study showed significant statistical dependence (p<0.05) between the number of larvae located in the glandular mucosa and the degree of severity of the secondary gastric ulcers in the squamous mucosa. Concluding, a high ocurrence of cavitary gastric myiasis was observed in slaughtering horses in the south of Chile, with squamous ulcers secondary to abnormal gastric emptying being the most frequent observation, which makes evident the need to continue research and management control of this pathology in horses.> <0.05) between the number of larvae located in the glandular mucosa and the degree of severity of the secondary gastric ulcers in the squamous mucosa. Concluding, a high ocurrence of cavitary gastric myiasis was observed in slaughtering horses in the south of Chile, with squamous ulcers secondary to abnormal gastric emptying being the most frequent observation, which makes evident the need to continue research and management control of this pathology in horses.

El objetivo del presente estudio fue determinar la ocurrencia de miasis cavitaria equina (Gasterophilus spp) en el centro de faenado Chol-Chol de Temuco, Chile y su relación con la presentación de úlceras gástricas secundarias en la mucosa escamosa (aglandular) del estómago de caballos (Equus caballus). De 240 estómagos evaluados post mortem, fueron seleccionados y caracterizados 145 estómagos positivos a Gasterophilosis (60,4%), de los cuales 75 provenían de animales machos (20 enteros y 55 castrados) y 70 hembras, con un rango de edad entre 1 y 16 años. Cada estómago fue evaluado, caracterizado y fotografiado post mortem. Los datos de sexo, edad, ubicación de las larvas de Gasterophilus, presencia y grado de ulceración en la mucosa escamosa, fueron diligenciados en los formatos respectivos y posteriormente digitalizados. Al analizar en forma global la ubicación de las larvas en el estómago de caballos positivos a Gasterophilosis, se estableció que el 91,7% (133/145) se ubicaron en la mucosa glandular, mientras que el 8,3% (12/145) se ubicaron en la mucosa escamosa. En los estómagos con presencia de larvas en la región antro pilórica de la mucosa glandular, el 87,6 (127/145) presentaron ulceraciones secundarias en la mucosa escamosa (aglandular), debido al aumento de la línea de llenado por alteración en el vaciamiento gástrico, de las cuales 69,0% (100/145) estuvieron clasificadas entre los categorías 3 y 4 con un numero de larvas mayores a 30, mientras que el 18,6% (27/145) se encontraron en las categorías 1 y 2 con un numero de larvas por sitio menor de 30. Con respecto a la ubicación de las larvas en la mucosa escamosa, evidencio la presencia de úlceras primarias de carácter mecánico en el 8,3% (12/145), siendo clasificadas en su totalidad entre los grados 1 y 2. El 62,1% de los animales tuvo una cantidad de larvas mayor a 60, de los cuales el 60,1% (88/145), presentaron úlceras escamosa secundarias en los grados 3 y 4. El 15,9% (23/145) presentaron una población de larvas por sitio entre 30 y 60 y el 14,5% (21/145) presento una población de menos de 30 larvas por sitio. El estudio demostró que hubo dependencia estadística significativa (p<0,05) entre el número de larvas ubicadas en la mucosa glandular y el grado de severidad de las úlceras gástricas secundarias en la mucosa escamosa. Se puede concluir que existe una elevada ocurrencia de miasis cavitarias gástricas en los caballos de faenados en el sur de Chile, siendo las ulceras escamosas secundarias al mal vaciamiento gástrico las de mayor frecuencia, por lo que se hace necesario realizar más investigaciones y concientización sobre el manejo de estas patologías en este tipo de animales.> <0,05) entre el número de larvas ubicadas en la mucosa glandular y el grado de severidad de las úlceras gástricas secundarias en la mucosa escamosa. Se puede concluir que existe una elevada ocurrencia de miasis cavitarias gástricas en los caballos de faenados en el sur de Chile, siendo las ulceras escamosas secundarias al mal vaciamiento gástrico las de mayor frecuencia, por lo que se hace necesario realizar más investigaciones y concientización sobre el manejo de estas patologías en este tipo de animales.

O objetivo do presente estudo foi determinar a ocorrência da miíase cavitária equina (Gasterophilus spp) no centro do abatedouro Chol-Chol de Temuco, Chile, e sua relação com a apresentação de ulceras gástricas secundárias na mucosa escamosa (aglandular) do estomago de cavalos (Equus caballus). Dos 240 estômagos avaliados post mortem, foram selecionados e caracterizados 145 estômagos positivos a gasterofilose (60,4%), dos quais 75 provinham de animais machos (20 inteiros e 55 castrados) e 70 fêmeas com um rango de idade entre 1 e 16 anos. Cada estomago foi avaliado, caracterizado e fotografado post mortem. Os dados de sexo, idade, localização das larvas de Gasterophilus, presencia e grau de ulceração na mucosa escamosa, foram diligenciados nos formatos respectivos e posteriormente digitalizados. Ao analisar em forma global a localização das larvas no estomago de cavalos positivos a gasterofilose. Se estabeleceu que o 91,7% (133/145) se localizaram na mucosa glandular, enquanto que o 8,3% (12/145) se localizaram na mucosa escamosa. Nos estômagos com presença de larvas na região antro pilórica da mucosa glandular, o 87,6% (127/145) apresentaram ulcerações secundarias na mucosa escamosa (aglandular), devido ao aumento da linha de preenchimento por alteração no esvaziamento gástrico, das quais 69% (100/145) estiveram classificadas entre as categorias 3 e 4 com um número de larvas maiores a 30, enquanto que o 18,6% (27/145) se encontraram nas categorias 1 e 2 com um número de larvas por sitio menor de 30. Com respeito a localização das larvas na mucosa escamosa, se evidenciou a presença de ulceras primarias de carácter mecânico em 8,3 (12/145), sendo assim classificadas em sua totalidade entre os graus 1 e 2. O 62,1% dos animais teve uma quantidade de larvas maior a 60, dos quais o 60,1% (88/145), apresentaram ulceras escamosas secundarias nos graus 3 e 4. O 15,9% (23/145) apresentaram uma população de larvas por sitio entre 30 e 60; e o 14,5% (21/145) apresentou uma população de menos de 30 larvas por sitio. O estudo demostrou que houve dependência estatística significativa (p<0,05) entre o número de larvas localizadas na mucosa glandular e o grau de severidade das ulceras gástricas secundarias na mucosa escamosa. Pode-se concluir que existe uma elevada ocorrência de miíase cavitária gástrica nos cavalos de abatedouros no sul do Chile, sendo as ulceras escamosas secundarias ao esvaziamento defeituoso, as de maior frequência, pelo que se faz necessário realizar mais pesquisas e conscientização sobre o manejo de estas patologias em este tipo de animais.> <0,05) entre o número de larvas localizadas na mucosa glandular e o grau de severidade das ulceras gástricas secundarias na mucosa escamosa. Pode-se concluir que existe uma elevada ocorrência de miíase cavitária gástrica nos cavalos de abatedouros no sul do Chile, sendo as ulceras escamosas secundarias ao esvaziamento defeituoso, as de maior frequência, pelo que se faz necessário realizar mais pesquisas e conscientização sobre o manejo de estas patologias em este tipo de animais.

Effect of calcium channel blockers on stress-induced gastrointestinal pathophysiological changes in rats

Forty adult male albino rats [200 +/- 20 g each] were used in this study. Animals were equally divided into 4 groups [n = 10]; normal control [CON] group was intraesophageally [i.o.] administered with distilled water [0.5 mL/d] for 1 week [wk]; L-type calcium-channel blocker [CCB] group that i.o. administered with otilonium [octylonium] bromide [OB, 2 mg/kg rat/d dissolved in 0.5 mL distilled water] for 1 wk; a cold-restraint stress [CRS] group that i.o. administered with distilled water as CON group but also restrained for 3 hs/d at 4- 6 degreeC in individual wire-mesh cylinders for 1 wk; and combined group [CCB+CRS group] that i.o. administered with OB as in CCB group and also restrained as in CRS group. The number of fecal pellets expelled by each animal was counted and examined for its consistency every 30 min for 3 hs, starting at 5 min after the induction of CRS or transporting to individual cages. At the end of the 1 -wk period, each rat was sacrificed by stunning and cervical dislocation, the abdominal cavity was opened along the midline, the stomach, upper segment of small intestine [US], lower segment of small intestine [W and a segment from distal colon [DCS] were rapidly excised and soaked in warm [37 degreeC], carbonated Tyrode s solution. Stomach was further used for measuring the areas of erosion [ulcers] if present, while UIS, LIS and DCS were further used for motility study of both spontaneous and evoked contractility in response to ACh and KCl: CRS produced significant increase the spontaneous motility of the UIS when compared to the CON values. Contractile response to ACh and KCl of both UIS and DCS were also significantly increased by CRS. Also, fecal pellet output was increased significantly by CRS when compared with the corresponding values in CON rats. Moreover, CRS induced gastric ulceration which appeared to be scattered along the mucosa of the stomach, On the other hand, the motility of LIS insignificantly changed by CRS. Administration to OB [L-type CCB] produced significant decrease in spontaneous contractions and contractile responses to ACh and KCl of UIS, LIS and DCS, together with decreased fecal pellets output when compared with the corresponding values in CON rats. Administration to OB to CRS rats reduced significantly both spontaneous and evoked motility in response to ACh and KCl of UIS and DCS, while the LIS did not affect significantly when compared with the corresponding values of non-treated CRS group. Also, OB administration reduced significantly the increased fecal pellet output caused by CRS. On the other hand, OB administration to CRS rats produced significant reduction or almost complete protection of the gastric mucosa from the development of ulceration. It can be concluded that OB [L-CCB] could help in prevention and treatment of GIT motility disorders caused by different stressors as CRS. Also, OB could prevent the development of stress gastric ulceration in different forms of stressors