Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients / 中华胃肠外科杂志

Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.

Gastrointestinal involvement due to graft-versus-host disease / Compromiso gastrointestinal por enfermedad de injerto contra huésped

Abstract Graft-versus-host disease is a common complication after stem cell transplantation. The digestive tract is affected in many patients who suffer from it, with consequences that can be fatal. The proper approach, which includes endoscopic studies, allows ruling out differential diagnoses and managing the disease early.

Resumen La enfermedad de injerto contra huésped es una complicación frecuente después del trasplante de células madre. El tracto digestivo se afecta en una gran proporción de los pacientes que la sufren, con consecuencias que pueden llegar a ser fatales. El abordaje adecuado, que incluye el uso de estudios endoscópicos, permite descartar diagnósticos diferenciales y brindar un manejo temprano de la enfermedad.

Necrosis intestinal, una complicación infrecuente de la nutrición enteral por yeyunostomía / Mesenteric necrosis, a rare complication of feeding jejunostomy

RESUMEN La nutrición enteral es parte importante del soporte vital avanzado en el paciente crítico, y ha demostrado ser más fisiológica, económica y con resultados superiores a la nutrición parenteral. La yeyunostomía para alimentación enteral está indicada cuando no es posible la alimentación por vía oral y está contraindicada la utilización de una sonda nasogástrica o nasoyeyunal de alimentación. Es una vía de alimentación con escasa morbilidad, aunque no está exenta de complicaciones, y algunas de ellas pueden ser graves. Comunicamos un caso de necrosis intestinal vinculado a la alimentación enteral por yeyunostomía en un paciente sometido a una gastrectomía oncológica.

ABSTRACT Enteral nutrition is an important component of advanced life support in the critically ill patient, and has demonstrated to be more physiologic, cheaper and with better results than parenteral nutrition. Jejunostomy for enteral nutrition is indicated when the oral route is impossible and the use of a nasogastric or nasojejunal feeding tube is contraindicated. Although the rate of complications associated with enteral nutrition through jejunostomy is low, they may occur and be serious. We report a case of bowel necrosis associated with a jejunostomy performed for enteral nutrition in a patient who underwent oncologic gastrectomy.

The effects of L-carnitine on gastrointestinal contractility and histological changes in rat intestinal ischemia-reperfusion Injury / Efectos de la l-carnitina sobre la contractilidad gastrointestinal y los cambios histológicos en la lesión por isquemia-reperfusión intestinal de rata

SUMMARY: Ischemia-reperfusion (I/R) of the small intestine causes serious abdominal pathologies including tissue dysfunction and organ failure. L-carnitine (L-C), a powerful antioxidant, may help lessen the severity of these pathological effects since it plays a key role in energy metabolism. In this work we aimed to study the effects of L-C on the isolated ileal and duodenal contractility and histological changes in intestinal ischemia and reperfusion injury. Twenty eight Wistar rats were divided into four groups. The first group is the control group. Second group, I/R group, had rats submitted to 45-minutes of intestinal ischemia and to 45-minutes reperfusion. The third group, I/R+ L-C group, rats were treated with L-C 5 minutes before reperfusion and than submitted to ischemia. The fourth group, included rats that were treated with L-C without ischemia or reperfusion. Intestinal ischemia was conducted by obstructing superior mesentery arteries by silk loop. The ileal and duodenal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (Ach) and relaxation was achieved with phenylephrine. At the same time the terminal ileal and duodenal segments were examined for histological changes. Ach-induced contraction responses were higher in the I/R+L-C group, the L-C group, and the control group compared to the I/R group, in both ileal and duodenal segments. On the other hand, the phenylephrine-induced relaxations were higher in the I/R+L-C and L-C groups, especially in duodenal segments. In I/R group intestinal morphology was observed to be severely damaged whereas in I/R+L-C group the damage was noticeably lower possibly due to protective properties of L-C. I/R injury caused severe cellular damage response within the muscularis resulting in decreased gastrointestinal motility. Treatment with the L-C has significantly affected the gastrointestinal contractility. Also L-C treatment reduced the damage in intestinal morphology that occurs after IR injury.

RESUMEN: La isquemia-reperfusión (I/R) del intestino delgado provoca graves patologías abdominales que incluyen disfunción tisular y falla orgánica. La L-carnitina (L-C), un poderoso antioxidante, puede ayudar a disminuir la gravedad de estos efectos patológicos, ya que desempeña un papel clave en el metabolismo energético. El objetivo de este trabajo fue estudiar los efectos de L-C sobre la contractilidad ileal y duodenal aislada y los cambios histológicos en la lesión por isquemia y reperfusión intestinal. Se dividieron 28 ratas Wistar en cuatro grupos. El primer grupo fue el control. El segundo grupo, grupo I/R, de ratas sometidas durante 45 minutos de isquemia intestinal y a 45 minutos de reperfusión. El tercer grupo, grupo I/R+ L-C, las ratas se trataron con L-C, 5 minutos antes de la reperfusión y luego se sometieron a isquemia. El cuarto grupo, las ratas fueron tratadas con L-C sin isquemia ni reperfusión. La isquemia intestinal se realizó obstruyendo la arteria mesentérica superior con un asa de seda. Los segmentos ileal y duodenal se aislaron y suspendieron en un baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (Ach) y la relajación se logró con fenilefrina. Al mismo tiempo, se examinaron cambios histológicos de los segmentos del íleon terminal y del duodeno. Las respuestas de contracción inducidas por Ach fueron mayores en el grupo I/R+L-C, el grupo L-C y el grupo control en comparación con el grupo I/R, tanto en el segmento ileal como en el duodenal. Por otra parte, las relajaciones inducidas por fenilefrina fueron mayores en los grupos I/R+L-C y L-C, especialmente en los segmentos duodenales. En el grupo I/R se observó que la morfología intestinal estaba dañada significativamente, mientras que en el grupo I/R+L-C el daño fue notablemente menor, posiblemente debido a las propiedades protectoras de L-C. La lesión por I/R causó una respuesta de daño celular severo dentro de la capa muscular que resultó en una disminución de la motilidad gastrointestinal. El tratamiento con L-C afectó significativamente la contractilidad gastrointestinal. Por otra parte, el tratamiento L-C redujo el daño en la morfología intestinal que ocurre después de la lesión por IR.

¿Por qué es importante detectar la gastritis atrófica y la metaplasia intestinal gástrica? ¿Cuál es la forma adecuada de hacerlo? / Why is it important to detect atrophic gastritis and gastric intestinal metaplasia? What is the proper way to do it?

RESUMEN La metaplasia intestinal gástrica y la gastritis atrófica son condiciones precancerosas conocidas (CPCs) del estómago, lo que significa que los pacientes con CPCs están en riesgo de desarrollar cáncer gástrico y, por lo tanto, el diagnóstico y la categorización de riesgo para estos pacientes es un tema relevante. El objetivo de esta revisión es proporcionar una actualización sobre el problema, el diagnóstico y el manejo de las CPCs con énfasis en el papel de la detección endoscópica adecuada.

ABSTRACT Gastric intestinal metaplasia and atrophic gastritis are a known precancerous condition (PCC) of the stomach, meaning that patients with PCC are at risk for gastric cancer and so, diagnosis and risk categorization for these patients is relevant. The aim of this review is to provide an update regarding the problem, diagnosis, and management of PCCs with an emphasis on the role of appropriate endoscopic detection.

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.

Effects of intraperitoneal glutamine in the treatment of experimental sepsis / Efeitos da glutamina intraperitoneal no tratamento da sepse experimental

ABSTRACT Background: Sepsis is an important public health issue and is associated with high treatment costs and high mortality rates. Glutamine supplementation has proven to be beneficial to the functions of the immune system, acting beneficially in the evolution of patients in severe catabolic states. Aim: To evaluate the effect of glutamine supplementation via intraperitoneal in rats, induced sepsis, considering the following organs: intestines, liver, kidneys and lungs. Methods: Male Wistar rats subjected to sepsis by ligature and cecal puncture were divided into two groups: control C (n=6) and glutamine G (n=11), in which were administered dipeptiven 20% at a dose of 2 ml/kg/day (equivalent to 0.4g N(2)-L-alanyl-L-glutamine/kg) intraperitoneally 48 h prior to sepsis induction. After 48 h they were euthanized and intestine, liver, lung and kidney were removed for histological analysis. Results: Intestinal epithelial desquamation of the control group was more intense compared to the glutamine group (p=0.008). In the kidneys, degenerative tubular epithelial changes were less severe in the animals that received glutamine (p=0.029). Regarding to the liver, glutamine group showed lower levels of cell swelling than the control group (p=0.034). In the lung there were no results with statistical significance. Conclusion: Prior intraperitoneal supplementation with glutamine in experimental animals is able to reduce the damage to the intestinal mucosa, to the kidneys and liver's histoarchitecture.

RESUMO Racional: A sepse é importante problema de saúde pública, sendo relacionada com altos custos de tratamento e elevadas taxas de mortalidade. A suplementação de glutamina tem provado ser benéfica às funções do sistema imune, atuando em estados catabólicos graves. Objetivo: Avaliar o efeito da suplementação de glutamina via intraperitoneal em ratos induzidos à sepse. Método: Foram utilizados ratos Wistar submetidos à sepse por ligadura e punção do ceco, separados em grupo controle C (n=6) e glutamina G (n=11), aos quais foram administrados dipeptiven a 20% com dose de 2 ml/kg/dia (equivalente a 0,4 g N(2)-L-alanil-L-glutamina/kg), via intraperitoneal, 48 h antes da indução da sepse. Após 48 h todos os animais foram submetidos à eutanásia e intestino, fígado, pulmão e rim foram retirados para análise histológica. Resultados: No intestino a descamação epitelial do grupo controle foi mais intensa em comparação ao da glutamina (p=0,008). Nos rins, houve menor degeneração do epitélio tubular nos animais que receberam glutamina (p=0,029). No fígado, o grupo glutamina apresentou índices menores de tumefação celular do que o grupo controle (p=0,034). No pulmão não houve resultados com significância estatística. Conclusão: A suplementação prévia de animais experimentais com glutamina via intraperitoneal é capaz de reduzir os danos causados à mucosa intestinal, histoarquitetura dos rins e do fígado.

Are there differences in the growth adaptation processes of growing and mature organism models of short bowel syndrome?

OBJECTIVES: The purpose of this study was to present an experimental model of short bowel syndrome (SBS) in weaning rats and to compare the adaptative mechanisms of the remaining bowel in weaning rats and adult animals by means of morphometric, histologic and molecular methods. METHODS: Twenty-four weaning rats were divided into 3 groups of 8 animals, one control group and two short bowel groups (euthanasia after 4 and 21 days), and were compared with similar adult groups. Morphometric evaluations of the animals and histopathological and molecular studies of the remaining bowel were performed. RESULTS: The weight of young rats increased after enterectomy, whereas that of adult rats decreased after enterectomy (p<0.0001). The ratio of intestinal length/body weight was significantly higher in weaning rats than in adults (p<0.002), showing that intestinal growth was more intense in weaning rats. Intestinal resection promoted increased thickness of the small bowel lamina propria (p=0.001) and reduced thickness of the colon lamina propria (p=0.04) in weaning rats relative to those in adults. In addition, intestinal resection promoted increased expression of the Bcl-xl gene (antiapoptotic) in adult animals compared with that in weaning rats (p=0.001). CONCLUSION: Morphometric, histological and molecular differences were shown in the adaptation processes of growing and mature organisms.

Fallo intestinal agudo en el paciente crítico / Insuficiência intestinal aguda em pacientes críticos / Acute intestinal failure in critically patients

Introducción: el fallo intestinal agudo determina en gran medida la mortalidad del paciente crítico. Objetivo: brindar a los profesionales de la salud las bases teóricas esenciales que sustenten su autopreparación para la prevención, diagnóstico y tratamiento del fallo intestinal agudo. Método: se realizó una revisión bibliográfica en la Facultad de Ciencias Médicas de Guantánamo, entre enero y julio de 2018, con una sistematización teórica sobre el tema. Se estudiaron 45 artículos de los 145 que se encontraron publicados entre los años 2010 y 2018 en las bases de datos electrónicas. Resultados: se elaboró una monografía sobre el fallo intestinal agudo que contuvo los siguientes núcleos de conocimientos: definición, fisiopatología, etiología, diagnóstico y tratamiento. Conclusiones: es ineludible la habilitación de los profesionales para la prevención y diagnóstico precoz del fallo intestinal agudo porque este determina en gran medida la sepsis, el fallo multiorgánico y la mortalidad del paciente crítico(AU)

Introduction: acute intestinal failure can cause mortality n critically patients. Objective: provide the health professionals essential theoretical foundations that support their selfpreparation for the prevention, diagnosis and treatment of acute intestinal failure. Method: a literature review was done at the Faculty of Medical Sciences of Guantanamo, between January and July 2018, with a theoretical systematization on the subject. 45 articles found 145 that were published between 2010 and 2018 in electronic databases that were studied. Results: a case - study on the acute intestinal failure was developed which contained the following kernel of knowledges: definition, pathophysiology, etiology, diagnosis and treatment: Conclusions: it is unavoidable enabling professionals to prevention and early diagnosis of acute intestinal failure because it is determined sepsis, multiple organ failure and mortality on critically ill patients(AU)

Introdução: a insuficiência intestinal aguda determina em grande parte a mortalidade do paciente crítico. Objetivo: fornecer aosprofissionais de saúde as bases teóricas essenciais que sustentam sua autopreparação para a prevenção, diagnóstico e tratamento da insuficiência intestinal aguda. Método: revisão bibliográfica realizada na Faculdade de Ciências Médicas de Guantánamo, no período de janeiro a julho de 2018, com uma sistematização teórica sobre o tema. Estudamos 45 artigos dos 145 publicados entre 2010 e 2018 nas bases de dados eletrônicas. Resultados: foi elaborada uma monografia sobre insuficiência intestinal aguda que continha os seguintes núcleos de conhecimento: definição, fisiopatologia, etiologia, diagnóstico e tratamento. Conclusões: a qualificação de profissionais para a prevenção e diagnóstico precoce da insuficiência intestinal aguda é inescapável, pois determina em grande parte sepse, falência de múltiplos órgãos e mortalidade do paciente crítico(AU)

Contribution of flagella and motility to gut colonisation and pathogenicity of Salmonella Enteritidis in the chicken

ABSTRACT Salmonella Enteritidis causes fowl paratyphoid in poultry and is frequently associated to outbreaks of food-borne diseases in humans. The role of flagella and flagella-mediated motility into host-pathogen interplay is not fully understood and requires further investigation. In this study, one-day-old chickens were challenged orally with a wild-type strain Salmonella Enteritidis, a non-motile but fully flagellated (SE ΔmotB) or non-flagellated (SE ΔfliC) strain to evaluate their ability to colonise the intestine and spread systemically and also of eliciting gross and histopathological changes. SE ΔmotB and SE ΔfliC were recovered in significantly lower numbers from caecal contents in comparison with Salmonella Enteritidis at early stages of infection (3 and 5 dpi). The SE ΔmotB strain, which synthesises paralysed flagella, showed poorer intestinal colonisation ability than the non-flagellated SE ΔfliC. Histopathological analyses demonstrated that the flagellated strains induced more intense lymphoid reactivity in liver, ileum and caeca. Thus, in the present study the flagellar structure and motility seemed to play a role in the early stages of the intestinal colonisation by Salmonella Enteritidis in the chicken.

The expression of endothelial and inducible nitric oxide synthase and apoptosis in intestinal ischemia and reperfusion injury under the action of ischemic preconditioning and pentoxifylline

Abstract Purpose: To investigate the expression of nitric oxide synthase (NOS) and apoptosis associated with ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal ischemia (I) and reperfusion (R) injury. Methods: Thirty male rats were assigned to 5 groups: (CG), no clamping of the superior mesenteric artery (90 minutes); (IR-SS) saline + ischemia (30 minutes) + reperfusion (60 minutes); (IR-PTX) PTX + ischemia (30 minutes) + reperfusion (60 minutes); (IPC-IR-SS) 5 minutes of ischemia + 5 minutes of reperfusion (IPC) + saline + I(30 minutes)+R(60 minutes); and (IPC-IR-PTX) IPC + PTX + I(30 minutes)+ R(60 minutes). Results: The application of IPC and PTX showed a significantly lower immunohistochemistry reaction for active caspase-3 (P<0.05) compared to IR+SS. The number of cells immunoreactive to BCL-2 was higher in the IR-PTX group (P>0.05). The NOS-2 expression (qRTPCR) in the IR-PTX group (P<0.05) was higher than the values for the IPC+IR-SS and IPC-IR-PTX groups. The NOS-3 expression was significantly upper in the IPC-IR-PTX group than in the CG (P<0.05), the IR-SS (P<0.05) and the IR-PTX (P<0.05) groups. Conclusions: The BCL-2 and active caspase-3 showed beneficial effects on PTX and IPC. The expression of NOS-2 and NOS-3 in the IPC and IPC-PTX groups showed no synergistic effect.

The role of ischemic preconditioning and pentoxifylline in intestinal ischemia/reperfusion injury of rats

Abstract Purpose: To investigate the role of ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal mucosa ischemia/reperfusion injury (IR). Methods: Thirty rats were assigned to 5 groups (N=6): (CG): no clamping of the superior mesenteric artery (90 min.); (IR-SS): saline + ischemia (30 min.) + reperfusion (60 min.); (IR-PTX): PTX + ischemia (30min.) + reperfusion (60 min.); (IPC-IR-SS): 5 min. of ischemia + 5 minutes of reperfusion (IPC) + saline + ischemia (30 min.) + reperfusion (60 min.); (IPC-IR-PTX ): 5 min. of ischemia + 5 min. of reperfusion (IPC) + PTX + 30 min. of I + 60 minutes of R. Results: The IR-PTX, IPC-IR-SS and IPC-IR-PTX groups had significantly lower scores of mucosa damage than the IR-SS group. IR-PTX group showed higher scores than the IPC-IR-PTX group, in accordance with the hypothesis of a favorable effect of IPC alone or in association with PTX. Additionally, IPC-IR-SS had a higher damage score than the IPC-IR-PTX. The villi height and crypt depth were similar in all groups. The villi height in the IR-SS was significantly lower. Conclusion: Ischemic preconditioning or pentoxifylline alone protect the intestinal mucosa from ischemia/reperfusion injury. However, they do not have a synergistic effect when applied together.

Changes in mast cell infiltration: a possible mechanism in detrusor overactivity induced by visceral hypersensitivity

ABSTRACT Objective: To establish the detrusor overactivity (DO) model induced by visceral hypersensitivity (VH) and investigate the relationship between mast cell (MC) infiltration and DO. Materials and Methods: Sixty rats are divided into 4 groups randomly: Group 1:Baseline group; Group 2: DO group; Group 3: CON group; Group 4: VH group. The colorectal distension (CRD) and abdominal withdral reflex (AWR) scores are performed to evaluate VH. The cystometric investigation and histological test of MC infiltration are assessed. Results: The threshold pressure of CRD in the VH group is significantly lower than that in the CON group (P<0.001). At the distension pressure ≥20 mmHg, the AWR scores of the VH group are significantly higher than those of the CON group (10 mmHg: P=0.33; 20 mmHg: P=0.028; 40 mmHg: P<0.001; 60 mmHg: P<0.001; 80 mmHg: P<0.001). DO model is successfully established in the VH group (DO rate=100%). Compared with the CON group, the numbers of MC infiltration are significantly increased in the VH group, including submucosa of bladder (P<0.001), mucosa lamina propria/mesentery of small intestine (P<0.001), and mucosa lamina propria/mesentery of large intestine (P<0.001). Furthermore, more MC activation as well as degranulation are observed in the VH group. Conclusions: It is indicated that DO model can be established in the VH rats. The MC infiltration may play an important role in DO induced by VH, and may be helpful to understand the mechanisms of DO in VH patients.

Ausencia segmentaria del músculo intestinal con membrana ileal en un recién nacido de extremadamente bajo peso al nacer: A propósito de un caso / Segmental absence of intestinal muscle with ileal web in an extremely low birth weight infant: Case report

Las perforaciones intestinales espontáneas son perforaciones localizadas sin las características clínicas, radiológicas e histopatológicas típicas de la enterocolitis necrosante. La perforación intestinal espontánea es una entidad clínica de reciente definición. El factor de riesgo más conocido es la prematurez. Se presenta en el 2-3% de los recién nacidos de muy bajo peso al nacer y en el 5% de los neonatos de extremadamente bajo peso. En este artículo presentamos el caso de un recién nacido de extremadamente bajo peso al nacer con perforación intestinal espontánea, ausencia segmentaria del músculo intestinal y membrana ileal como causas subyacentes. Nuestro objetivo es llamar la atención a la ausencia segmentaria del músculo intestinal, una afección rara pero que se informa cada vez más como causa de perforación intestinal espontánea, y a la importancia del examen histopatológico de las muestras obtenidas durante una cirugía.

Spontaneous intestinal perforations are localized perforations without the typical clinical, radiological, and histopathological features of necrotizing enterocolitis. Spontaneous intestinal perforation is a recently defined clinical entity. The best-known risk factor is prematurity. It is seen 2-3% in very low birthweight infants and 5 % of extremely low birthweight infants. Herein we report an extremely low birthweight infant with spontaneous intestinal perforation, segmental absence of intestinal muscle and an ileal web as an underlying cause. We aimed to draw attention to the segmental absence of intestinal muscle which is rare but increasingly reported cause of spontaneous intestinal perforation and the importance of histopathologic examination of surgical specimens.

Effects of Potentilla Fulgens as Prophylactic Agent in Intestinal Ischemia Reperfusion Injury / Efectos de Potentilla fulgens como Agente Profiláctico en la Lesión por Isquemia-Reperfusión Intestinal

The purpose of this study, ischemia reperfusion injury in rats, Potentilla fulgens is to investigate the protective effects. Wistar albino rats (n= 30) weighing 180-220 g were used in the experiment. Group 1 animals underwent sham laparotomy without ischemia-reperfusion injury. Group 2 animals underwent laparotomy and occlusion of superior mesenteric arteries for 30 min followed by 20 min of reperfusion without pretreatment. The Potentilla fulgens group received 400 mg/kg/day Potentilla fulgens intraperitoneally 5 days before Ischemia-reperfusion injury. There was a significant difference between the group with ischemia-reperfusion group Potentilla fulgens (p<0.0001). In statistical analysis of the MDA level, data were obtained after a respective measurement in all groups. Potentilla fulgens group with ischemia-reperfusion group was a significant decrease in MDA (p<0.001). In the period after ischemia-reperfusion, marked PCNA immunoreactivities were observed in the nuclei of crypt and villus cell. In ischemia reperfusion group, the number of PCNA immunoreactivity is quite advanced and they extended throughout the middle part of the intestine folds. The number of TUNEL-positive nuclei were also developed. In ischemia-reperfusion plus P. fulgens group, the intestinal epithelium with only a few PCNA immunoreactive nuclei. TUNEL positive nuclei were noted in the gut lumen and mucosal close differentiated goblet cells. We showed that Potentilla fulgens extract significantly prevented mucosal lesions caused by intestinal ischemia-reperfusion.

El objetivo fue investigar los efectos protectores de Potentilla fulgens sobre la lesión por isquemia-reperfusión en ratas albinas Wistar (n= 30) con un peso de 180 g. En el grupo 1, los animales fueron sometidos a laparotomía simulada sin lesión por isquemia-reperfusión. En el Grupo 2, los animales fueron sometidos a laparotomía y oclusión de las arteria mesentérica superior durante 30 min seguido de 20 min de reperfusión sin pretratamiento. El grupo Potentilla fulgens recibió 400 mg/kg/día de P. fulgens por vía intraperitoneal 5 días antes de la lesión por isquemia-reperfusión. Hubo diferencias significativas entre el grupo de grupo con isquemia-reperfusión y el tratado con Potentilla fulgens (p<0,0001). En el análisis estadístico del nivel de malondialdehído (MDA), los datos se obtuvieron después de una medición respectiva en todos los grupos. Los grupos Potentilla fulgens y con isquemia-reperfusión tuvieron una disminución significativade MDA (p<0,0001). En el periodo después de la isquemia-reperfusión, se observó inmunorreactividad del marcador PCNA en los núcleos de las células de las criptas y vellosidades. En el grupo de isquemia-reperfusión, la inmunoreactividad a PCNA fue bastante avanzada y se extendió a lo largo de la parte media de los plieges intestinales. También aumentó el número de núcleos positivos a TUNEL. En el grupo isquemia-reperfusión tratado con P. fulgens, el epitelio intestinal mostró pocos núcleos inmunorreactivos a PCNA; núcleos positivos a TUNEL se observaron en el lumen intestinal y la mucosa, cerca de las células caliciformes diferenciadas. Demostramos que el extracto de P. fulgens disminuye significativamente lesiones de la mucosa intestinal causadas por la isquemia-reperfusión.

Avaliação da resposta imunológica da mucosa intestinal de frangos de corte desafiados com diferentes sorovares de Salmonella / Evaluation of immune response of the intestinal mucosa in broilers challenged with different Salmonella serovars

Objetivou-se com o presente estudo comparar o efeito de diferentes sorovares de Salmonella na resposta imune local da mucosa do intestino de frangos de corte. Aos sete dias de idade, as aves foram desafiadas com os sorovares S. Enteritidis, S. Typhimurium, S. Senftenberg, S. Mbandaka e S. Minnesota. Foi observado que todos os sorovares testados foram capazes de colonizar o intestino das aves sendo possível o isolamento de Salmonella em suabes de cloaca, 48 h após inoculação. De maneira geral, as aves do grupo controle negativo, que não foram desafiados apresentaram quantidade significativamente menor de células imunológicas na mucosa intestinal do que as aves desafiadas. Porém, verificou-se que os sorovares de Salmonella, utilizados neste estudo, apresentaram diferentes efeitos sobre a dinâmica celular da mucosa do íleo e ceco e afetaram de modo diferente o ganho de peso e ganho médio diário das aves demonstrando distintos graus de patogenicidade. Os sorovares Enteritidis e Typhimurium apresentaram um efeito mais intenso tanto no desempenho quanto na mobilização de células imunológicas na mucosa intestinal de frangos de corte.

The study was designed to compare the effect of different Salmonella serovars in immune response across the count of CD8+ cells, CD4+ cells, goblet cells and macrophages in the gut mucosa of broilers. During the experimental inoculation at 7 day-old were used Salmonella enterica subspecies enterica sorovars Enteritidis, Typhimurium, Senftenberg, Mbandaka and Minnesota. It was observed that all serovars tested were capable of contaminating the poultry being possible counts of Salmonella in cloacal swabs, 48 h after inoculation and into the crop and cecum, at 14 and 20 day-old. Serovars tested had different effects on broiler performance assessed at 20 days. In the mucosa of the ileum and cecum of broilers, it was observed that some of the serotypes increased CD8 + cells, CD4 + cells, goblet cells and macrophages compared to the negative control group both at 14 and at 20 day-old. S. Enteritidis and S. Typhimurium are the serovars that showed the more intense effect in live performance and in the immune system of birds showing pathogenic characteristic; generally the broilers of the negative control showed significantly less immune cells on the intestinal mucosa than broilers inoculated experimentally. However, it was found that the Salmonella serovars used in this study had different effects on the cellular dynamics of the mucosa of the ileum and cecum and differently affect weight gain and average daily gain of poultry showing different levels of pathogenicity.

A Rare Case of Bowel Gangrene in Pregnancy : A Surgical and Obstetric Catastrophe.

An unusual case of bowel gangrene involving jejunum upto the middescending colon leading to septicaemic shock, presented as a case of placental abruption with IUD with shock. Case Report : The 25 year old primigravida patient with 34 weeks of gestation was referred from peripheral obstetrician to SVNGMC, in a state of shock with clinical features suggestive of concealed type of placental abruption with IUD. In view of placental abruption with shock, emergency caesarean section was performed. Per Operative Findings: Foul smelling peritoneal fluid, IUD. Baby with placental separation with RP clot and gangrenous bowel from jejunum to middescending colon. As such long segment of bowel was involved; surgeon decided resection and end to end anastomosis was not possible. Propable diagnosis like superior mesenteric artery thrombosis/ Embolism was made. pt was put on low dose inj. Heparin and later managed in Surgical I.C.U. & succumbed on day 3 postop. Conclusion: Hypercoagulable state normally found in pregnant women which is believed to result in superior mesenteric vessel thrombosis and then intestinal ischaemia. It is extremely important not to miss any complaint like pain in abdomen and other G.I. complaints that may have any surgical or medical pathology associated with pregnancy.

Are there gender differences in left ventricular remodeling after myocardial infarction in rats? / Há diferenças entre os gêneros no remodelamento ventricular esquerdo após infarto do miocárdio em ratos?

Objective: An unclear issue is whether gender may influence at cardiac remodeling after myocardial infarction (MI). We evaluated left ventricle remodeling in female and male rats post-MI. Methods: Rats were submitted to anterior descending coronary occlusion. Echocardiographic evaluations were performed on the first and sixth week post-occlusion to determine myocardial infarction size and left ventricle systolic function (FAC, fractional area change). Pulsed Doppler was applied to analyze left ventricle diastolic function using the following parameters: E wave, A wave, E/A ratio. Two-way ANOVA was applied for comparisons, complemented by the Bonferroni test. A P≤=0.05 was considered significant. Results: There were no significant differences between genders for morphometric parameters on first (MI [Female (FE): 44.0±5.0 vs. Male (MA): 42.0±3.0%]; diastolic [FE: 0.04±0.003 vs. MA: 0.037±0.005, mm/g] and systolic [FE: 0.03±0.0004 vs. MA: 0.028±0.005, mm/g] diameters of left ventricle) and sixth (MI [FE: 44.0±5.0 vs. MA: 42.0±3.0, %]; diastolic [FE: 0.043±0.01 vs. MA: 0.034±0.005, mm/g] and systolic [FE: 0.035±0.01 vs. MA: 0.027±0.005, mm/g] of LV) week. Similar findings were reported for left ventricle functional parameters on first (FAC [FE: 34.0±6.0 vs. MA: 32.0±4.0, %]; wave E [FE: 70.0±18.0 vs. MA: 73.0±14.0, cm/s]; wave A [FE: 20.0±12.0 vs. MA: 28.0±13.0, cm/s]; E/A [FE: 4.9±3.4 vs. MA: 3.3±1.8]) and sixth (FAC [FE: 29.0±7.0 vs. MA: 31.0±7.0, %]; wave E [FE: 85.0±18.0 vs. MA: 87.0±20.0, cm/s]; wave A [FE: 20.0±11.0 vs. MA: 28.0±17.0, cm/s]; E/A [FE: 6.2±4.0 vs. MA: 4.6±3.4]) week. Conclusion: Gender does not influence left ventricle remodeling post-MI in rats. .

Objetivo: A influência do gênero no remodelamento cardíaco após o infarto do miocárdio é uma questão em intenso debate. Nós avaliamos o remodelamento ventricular esquerdo em ratos infartados de ambos os gêneros. Métodos: O infarto do miocárdio foi induzido por oclusão da artéria coronária descendente anterior (fêmeas [FM]; machos [MC]). A ecocardiografia foi realizada na primeira e sexta semana pós-oclusão para determinar o tamanho do infarto do miocárdio e a função sistólica do ventricular esquerdo (mudança na área fracional [FAC]). A função diastólica derivou dos seguintes parâmetros: onda E; onda A; razão E/A. ANOVA duas vias com pós-teste de Bonferroni foi aplicado nas comparações (P≤=0,05). Resultados: Todas variáveis morfométricas foram similares (P>0,05) entre os gêneros com uma (infarto do miocárdio [FM: 44,0±5,0 vs. MC: 42,0±3,0, %]; diâmetro diastólico [FM: 0,04±0,003 vs. MC: 0,037±0,005, mm/g] e sistólico [FM: 0,03±0,0004 vs. MC: 0,028±0,005, mm/g] do VE) e seis (IM [FM: 44,0±5,0 vs. MC: 42,0±3,0, %]; diâmetro diastólico [FM: 0,043±0,01 vs. MC: 0,034±0,005, mm/g] e sistólico [FM: 0,035±0,01 vs. MC: 0,027±0,005, mm/g] do ventricular esquerdo) semanas. Achado similar ocorreu para os dados funcionais com uma (FAC [FM: 34,0±6,0 vs. MC: 32,0±4,0, %]; onda E [FM: 70,0±18,0 vs. MC: 73,0±14,0, cm/s]; onda A [FM: 20,0±12,0 vs. MC: 28,0±13,0, cm/s]; E/A [FM: 4,9±3,4 vs. MC: 3,3±1,8]) e seis (FAC [FM: 29,0±7,0 vs. MC: 31,0±7,0, %]; onda E [FM: 85,0±18,0 vs. MC: 87,0±20,0, cm/s]; onda A [FM: 20,0±11,0 vs. MC: 28,0±17,0 cm/s]; E/A [FM: 6,2±4,0 vs. MC: 4,6±3,4]) semanas. Conclusão: O gênero não é determinante para o remodelamento ventricular esquerdo pós-infarto do miocárdio em ratos. .

Growth Patterns of Signet Ring Cell Carcinoma of the Stomach for Endoscopic Resection

BACKGROUND/AIMS: It is difficult to precisely detect the lateral margin during endoscopic submucosal dissection (ESD) for signet ring cell carcinoma (SRC) because SRC often expands to lateral direction through the lamina propria. Thus, the aim of this study was to classify the intramucosal spreading patterns of SRC and to analyze the patients' clinicopathological findings according to the spreading patterns. METHODS: The intramucosal spreading patterns of SRC were classified as expansive or infiltrative types. A total of 100 surgical and 42 ESD specimens were reviewed. RESULTS: In the surgical specimens, the proportions of expansive and infiltrative types were 44% and 56%, respectively. The infiltrative type was more commonly associated with old age, atrophy, and intestinal metaplasia in surrounding mucosa and the absence of Helicobacter pylori compared with the expansive type. In ESD specimens, the proportions of expansive and infiltrative types were each 50%. When lateral margin-positive lesions were compared with -negative lesions, larger size, residual lesion, and the lack of a neutrophil infiltration were more significantly associated with lateral margin-positive lesions. All cases with residual tumors in lateral margin-positive lesions were classified as the infiltrative type. CONCLUSIONS: SRC surrounded with atrophy and/or intestinal metaplasia often spreads subepithelially in the margin. This finding may suggest that a larger safety margin is necessary in this type during ESD.

Very short cycles of postconditioning have no protective effect against reperfusion injury. Experimental study in rats / Ciclos muito curtos de pós-condicionamento não protegem contra lesão de reperfusão. Estudo experimental em ratos

Introduction: Ischemic postconditioning has been recognized as effective in the prevention of reperfusion injury in situations of ischemia and reperfusion in various organs and tissues. However, it remains unclear what would be the best way to accomplish it, since studies show great variation in the method of their application. Objective: To assess the protective effect of ischemic postconditioning on ischemia and reperfusion in rats undergoing five alternating cycles of reperfusion and ischemia of 30 seconds each one. Methods: We studied 25 Wistar rats distributed in three groups: group A (10 rats), which underwent mesenteric ischemia (30 minutes) and reperfusion (60 minutes); Group B (10 rats), undergoing ischemia (30 minutes) and reperfusion (60 minutes), intercalated by postconditioning (5 alternating cycles of reperfusion and ischemia of 30 seconds each one); and group C - SHAM (5 rats), undergoing only laparotomy and manipulation of mesenteric artery. All animals underwent resection of an ileum segment for histological analysis. Results: The mean lesions degree according to Chiu et al. were: group A, 2.77, group B, 2.67 and group C, 0.12. There was no difference between groups A and B (P>0.05). Conclusion: Ischemic postconditioning was not able to minimize or prevent the intestinal tissue injury in rats undergoing ischemia and reperfusion process when used five cycles lasting 30 seconds each one. .

Introdução: O pós-condicionamento isquêmico tem sido reconhecido como eficaz na prevenção das lesões de reperfusão em situações de isquemia e reperfusão em vários órgãos e tecidos. Entretanto, não está ainda claro qual seria a melhor maneira de realizá-lo, já que as publicações mostram grande variação de método no seu emprego. Objetivo: Avaliar o efeito protetor do pós-condicionamento isquêmico na isquemia e reperfusão intestinal em ratos, através de cinco ciclos alternados de 30 segundos de isquemia e 30 segundos de reperfusão. Métodos: Foram estudados 25 ratos Wistar, distribuídos em três grupos: grupo A (10 ratos), em que se realizou isquemia (30 minutos) e reperfusão (60 minutos) mesentérica; grupo B (10 ratos), isquemia e reperfusão, seguidos de pós-condicionamento isquêmico com 5 ciclos alternados de reperfusão e reoclusão, de 30 segundos cada; e grupo C (5 ratos), controle (SHAM). Ao final, ressecou-se um segmento do intestino delgado para análise histológica. Avaliaram-se os resultados pela classificação de Chiu et al. e procedeu-se ao tratamento estatístico. Resultados: As médias dos graus de lesão tecidual segundo a classificação de Chiu et al. foram: no grupo A, 2,77; no grupo B, 2,67; e no grupo C, 0,12. A diferença entre o resultado do grupo A com o resultado do grupo B não teve significância estatística (P>0,05). Conclusão: O pós-condicionamento isquêmico não foi capaz de minimizar ou prevenir a lesão tecidual intestinal de ratos submetidos ao processo de isquemia e reperfusão mesentérica quando utilizados cinco ciclos com duração de 30 segundos cada. .