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Preliminary evidence suggests that statins may prevent major perioperative vascular complications. METHODS: We randomized 648 statin-naïve patients who were scheduled for noncardiac surgery and were at risk for a major vascular complication. Patients were randomized to a loading dose of atorvastatin or placebo (80 mg anytime within 18hours before surgery), followed by a maintenance dose of 40 mg (or placebo), started at least 12hours after the surgery, and then 40 mg/d (or placebo) for 7days. The primary outcome was a composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery, and stroke at 30days. RESULTS: The primary outcome was observed in 54 (16.6%) of 326 patients in the atorvastatin group and 59 (18.7%) of 316 patients in the placebo group (hazard ratio [HR] 0.87, 95% CI 0.60-1.26, P=.46). No significant effect was observed on the 30-day secondary outcomes of all-cause mortality (4.3% vs 4.1%, respectively; HR 1.14, 95% CI 0.53-2.47, P=.74), nonfatal myocardial infarction (3.4% vs 4.4%, respectively; HR 0.76, 95% CI 0.35-1.68, P=.50), myocardial injury after noncardiac surgery (13.2% vs 16.5%; HR 0.79, 95% CI 0.53-1.19, P=.26), and stroke (0.9% vs 0%, P=.25). CONCLUSION: In contrast to the prior observational and trial data, the LOAD trial has neutral results and did not demonstrate a reduction in major cardiovascular complications after a short-term perioperative course of statin in statin-naïve patients undergoing noncardiac surgery. We demonstrated, however, that a large multicenter blinded perioperative statin trial for high-risk statin-naïve patients is feasible and should be done to definitely establish the efficacy and safety of statin in this patient population.
Assuntos
Atorvastatina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Procedimentos Cirúrgicos Operatórios , Idoso , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/prevenção & controle , Assistência Perioperatória/métodos , Modelos de Riscos Proporcionais , Medição de Risco , Troponina/sangueRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) shows a 5-year survival rate below 10%, demonstrating the urgency in improving its treatment. Alterations in epidermal growth factor receptors are closely related to malignancy transformation in a number of tumors and recent successful targeted therapies have been directed to these molecules. Therefore, in this study, we analyzed the expression of EGFR and HER2 and evaluated EGFR mutation profile as well as the presence of mutations in hotspots of KRAS and BRAF in ESCC patients. METHODS: We performed RT-qPCR, immunohistochemistry and Fluorescent in situ hybridization to determine EGFR and HER2 expression in ESCC patients, and direct sequencing and PCR-RFLP for mutations and polymorphism analysis. RESULTS: Our results showed an increased EGFR mRNA expression in tumors compared to surrounding tissue (p <0.05), with 11% of the cases presenting at least a four-fold difference between tumor and paired adjacent mucosa. EGFR protein overexpression was present only in 4% of the cases. The median expression of HER2 mRNA was not different between tumors and adjacent mucosa. Still, 7% of the tumors presented at least a 25-fold higher expression of this gene when compared to its paired counterpart. Immunohistochemical analysis revealed that 21% of the tumors were positive for HER2 (scores 2+ and 3+), although only 3+ tumors presented amplification of this gene. Mutation analysis for EGFR (exons 18-21), KRAS (codons 12 and 13) and BRAF (V600E) showed no mutations in any of the hotspots of these genes in almost 100 patients analyzed. EGFR presented synonymous polymorphisms at codon 836 (C>T) in 2.1% of the patients, and at codon 787 (G>A) in 79.2% of the cases. This last polymorphism was also evaluated in 304 healthy controls, which presented a similar frequency (73.7%) in comparison with ESCC patients. The absence of mutations of EGFR, KRAS and BRAF as well as the overexpression of EGFR and HER2 in less than 10% of the patients suggest that this signaling pathway is altered in only a small proportion of patients with ESCC. CONCLUSION: HER receptors target therapies may have the potential to be effective in only a minor fraction of patients with ESCC.
Assuntos
Carcinoma de Células Escamosas/genética , Receptores ErbB/genética , Neoplasias Esofágicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Análise Mutacional de DNA , Receptores ErbB/metabolismo , Neoplasias Esofágicas/metabolismo , Feminino , Genes erbB-1 , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , RNA Mensageiro/análise , Receptor ErbB-2/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas ras/genéticaRESUMO
BACKGROUND: Overall survival in patients who underwent transhiatal esophagectomy submitted or not to neoadjuvant therapy. Southern Brazil has one of the highest incidences of esophageal squamous cell carcinoma in the world. Transthoracic esophagectomy allows more complete abdominal and thoracic lymphadenectomy than transhiatal. However, this one is associated with less morbidity. AIM: To analyze the outcomes and prognostic factors of squamous esophageal cancer treated with transhiatal procedure. METHODS: All patients selected for transhiatal approach were included as a potentially curative treatment and overall survival, operative time, lymph node analysis and use of neoadjuvant therapy were analyzed. RESULTS: A total of 96 patients were evaluated. The overall 5-year survival was 41.2%. Multivariate analysis showed that operative time and presence of positive lymph nodes were both associated with a worse outcome, while neoadjuvant therapy was associated with better outcome. The negative lymph-node group had a 5-year survival rate of 50.2%. CONCLUSION: Transhiatal esophagectomy can be safely used in patients with malnutrition degree that allows the procedure, in those with associated respiratory disorders and in the elderly. It provides considerable long-term survival, especially in the absence of metastases to local lymph nodes. The wider use of neoadjuvant therapy has the potential to further increase long-term survival.
Assuntos
Carcinoma de Células Escamosas , Diabetes Mellitus Tipo 2 , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The high incidence of esophageal cancer in the north of Iran has been associated to the consumption of opium and exposure to nitrosamines. Diethylnitrosamine has an established potential of producing experimental cancer in the esophagus and liver. AIM: To evaluate by histopathology the effect of oral administration of morphine and diethylnitrosamine during 23 weeks on the hepatic and esophageal carcinogenesis on 176 rats. METHODS: We divided the rats into the following groups: Morph: morphine; Den: diethylnitrosamine; Den+morph: Den and morphine in the same solution; Den/morph: Den and morphine in different solutions and days. RESULTS: Morphine did not promote neoplasias. The highest neoplastic incidents were found: a) in the esophagus, Den in relation to Den/morph and Den+morph (71.1%, 55.8%, and 50.0%); b) in the liver, Den and Den/morph in relation to Den+morph (73.8%, 81.4%, and 40.9%); c) higher incident of hepatic neoplasia than esophageal in Den/morph (81.4% and 55.8%). Different doses of diethylnitrosamine were ingested among the groups Den, Den/morph, and Den+morph, respectively 2.9, 2.8, and 2.3 mg/kg/day. CONCLUSIONS: These results show that the morphine did not promote esophageal carcinogenesis and may have stimulated the hepatic metabolism of the first pass of the carcinogen.
Assuntos
Alquilantes/toxicidade , Analgésicos Opioides/toxicidade , Dietilnitrosamina/toxicidade , Neoplasias Esofágicas/induzido quimicamente , Neoplasias Hepáticas Experimentais/induzido quimicamente , Morfina/toxicidade , Animais , Testes de Carcinogenicidade , Neoplasias Esofágicas/patologia , Neoplasias Hepáticas Experimentais/patologia , Ratos , Ratos WistarRESUMO
Esophageal squamous cell carcinoma (ESCC) presents poor prognosis, and patients diagnosed with this tumor currently lack target treatments. Therefore, in order to identify potential targets for ESCC treatment, we carried out a transcriptome analysis with ESCC and paired nonmalignant surrounding mucosa samples, followed by a master regulator analysis, and further explored the role of the identified central regulatory genes through in vivo and in vitro assays. Among the transcription factors deregulated/enriched in ESCC, we focused on FOXM1 because of its involvement in the regulation of critical biological processes. A new transcriptome analysis performed with ESCC cell lineage TE-1 showed that the modulation of FOXM1 expression resulted in PIK3R3 expression changes, whereas chromatin immunoprecipitation assay revealed that FOXM1 was capable of binding onto PIK3R3 promoter, thus demonstrating that PIK3R3 is a new FOXM1 target. Furthermore, FOXM1 overexpression resulted in the activation of PIK3/AKT signaling pathway through PIK3R3-mediated AKT phosphorylation. Finally, the analysis of the clinic-pathological data of ESCC patients revealed that overexpression of both FOXM1 and PIK3R3 was associated with poor prognosis, but only the latter was an independent prognosis factor for ESCC patients. In conclusion, our results show that FOXM1 seems to play a central role in ESCC carcinogenesis by upregulating many oncogenes found overexpressed in this tumor. Furthermore, PIK3R3 is a novel FOXM1 target that triggers the activation of the PI3K/AKT pathway in ESCC cells.
RESUMO
AIM: To investigate the survival rates after transarterial embolization (TAE). METHODS: One hundred third six hepatocellular carcinoma (HCC) patients [90 barcelona clinic liver cancer (BCLC) B] were submitted to TAE between August 2008 and December 2013 in a single center were retrospectively studied. TAE was performed via superselective catheterization followed by embolization with polyvinyl alcohol or microspheres. The date of the first embolization until death or the last follow-up date was used for the assessment of survival. The survival rates were calculated using the Kaplan-Meier method, and the groups were compared using the log-rank test. RESULTS: The overall mean survival was 35.8 mo (95%CI: 25.1-52.0). The survival rates of the BCLC A patients (33.7%) were 98.9%, 79.0% and 58.0% at 12, 24 and 36 mo, respectively, and the mean survival was 38.1 mo (95%CI: 27.5-52.0). The survival rates of the BCLC B patients (66.2%) were 89.0%, 69.0% and 49.5% at 12, 24 and 36 mo, respectively, and the mean survival was 29.0 mo (95%CI: 17.2-34). The survival rates according to the BCLC B sub-staging showed significant differences between the groups, with mean survival rates in the B1, B2, B3 and B4 groups of 33.5 mo (95%CI: 32.8-34.3), 28.6 mo (95%CI: 27.5-29.8), 19.0 mo (95%CI: 17.2-20.9) and 13 mo, respectively (P = 0.013). CONCLUSION: The BCLC sub-staging system could add additional prognosis information for post-embolization survival rates in HCC patients.
RESUMO
ABSTRACT Background: Southern Brazil has one of the highest incidences of esophageal squamous cell carcinoma in the world. Transthoracic esophagectomy allows more complete abdominal and thoracic lymphadenectomy than transhiatal. However, this one is associated with less morbidity. Aim: To analyze the outcomes and prognostic factors of squamous esophageal cancer treated with transhiatal procedure. Methods: All patients selected for transhiatal approach were included as a potentially curative treatment and overall survival, operative time, lymph node analysis and use of neoadjuvant therapy were analyzed. Results: A total of 96 patients were evaluated. The overall 5-year survival was 41.2%. Multivariate analysis showed that operative time and presence of positive lymph nodes were both associated with a worse outcome, while neoadjuvant therapy was associated with better outcome. The negative lymph-node group had a 5-year survival rate of 50.2%. Conclusion: Transhiatal esophagectomy can be safely used in patients with malnutrition degree that allows the procedure, in those with associated respiratory disorders and in the elderly. It provides considerable long-term survival, especially in the absence of metastases to local lymph nodes. The wider use of neoadjuvant therapy has the potential to further increase long-term survival.
RESUMO Racional: O sul do Brasil tem uma das maiores incidências de carcinoma epidermoide do esôfago no mundo. A esofagectomia transtorácica permite linfadenectomia abdominal e torácica mais completa do que a transhiatal. No entanto, esta está associado à menor morbidade. Objetivo: Analisar os desfechos e fatores prognósticos do câncer epidermoide do esôfago que foram tratados com procedimento transhiatal. Métodos: Foram incluídos todos os pacientes selecionados para abordagem transhiatal como tratamento potencialmente curativo correlacionando sobrevida geral, tempo operatório, análise de linfonodos e uso de terapia neoadjuvante. Resultados: Foram avaliados 96 pacientes. A sobrevida geral em cinco anos foi de 41,2%. A análise multivariada mostrou que o tempo operatório e a presença de linfonodos positivos foram associados a pior resultado, enquanto a terapia neoadjuvante contribuiu para melhor resultado. O grupo de linfonodos negativos teve taxa de sobrevivência em cinco anos de 50,2%. Conclusão: A esofagectomia transhiatal pode ser empregada com segurança em pacientes que apresentem desnutrição com grau que permita o procedimento, nos com distúrbios respiratórios associados e nos idosos. Proporciona sobrevida em longo prazo considerável, especialmente na ausência de metástases para linfonodos locais. O uso mais amplo da terapia neoadjuvante tem o potencial de aumentar ainda mais a sobrevida em longo prazo.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas/cirurgia , Esofagectomia , Diabetes Mellitus Tipo 2 , Carcinoma de Células Escamosas do Esôfago/cirurgia , Brasil , Estudos Retrospectivos , Resultado do Tratamento , Excisão de LinfonodoRESUMO
Transarterial chemoembolization (TACE) and transarterial embolization (TAE) have improved the survival rates of patients with unresectable hepatocellular carcinoma (HCC); however, the optimal TACE/TAE embolic agent has not yet been identified. The aim of this study was to compare the effect of two different embolic agents such as microspheres (ME) and polyvinyl alcohol (PVA) on survival, tumor response, and complications in patients with HCC submitted to transarterial embolization (TAE). Eighty HCC patients who underwent TAE between June 2008 and December 2012 at a single center were retrospectively studied. A total of 48 and 32 patients were treated with PVA and ME, respectively. There were no significant differences in survival (P = 0.679) or tumoral response (P = 0.369) between groups (PVA or ME). Overall survival rates at 12, 18, 24, 36, and 48 months were 97.9, 88.8, 78.9, 53.4, and 21.4% in the PVA-TAE group and 100, 92.9, 76.6, 58.8, and 58% in the ME-TAE group (P = 0.734). Patients submitted to TAE with ME presented postembolization syndrome more frequently when compared with the PVA group (P = 0.02). According to our cohort, the choice of ME or PVA as embolizing agent had no significant impact on overall survival.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Microesferas , Álcool de Polivinil/uso terapêutico , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: In Brazil, gastric cancer is the fourth most common malignancy among men and sixth among women. The cause is multivariate and the risks are well known. It has prognosis and treatment defined by the location and staging of the tumor and number of lymph nodes resected and involved. AIM: The Brazilian Consensus on Gastric Cancer promoted by ABCG was designed with the intention to issue guidelines that can guide medical professionals to care for patients with this disease. METHODS: Were summarized and answered 43 questions reflecting consensus or not on diagnosis and treatment that may be used as guidance for its multidisciplinary approach. The method involved three steps. Initially, 56 digestive surgeons and related medical specialties met to formulate the questions that were sent to participants for answers on scientific evidence and personal experience. Summaries were presented, discussed and voted in plenary in two other meetings. They covered 53 questions involving: diagnosis and staging (six questions); surgical treatment (35 questions); chemotherapy and radiotherapy (seven questions) and anatomopathology, immunohistochemistry and perspective (five questions). It was considered consensus agreement on more than 70% of the votes in each item. RESULTS: All the answers were presented and voted upon, and in 42 there was consensus. CONCLUSION: It could be developed consensus on most issues that come with the care of patients with gastric cancer and they can be transformed in guidelines.
Assuntos
Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Brasil , HumanosRESUMO
The role of HPV in esophageal squamous cell carcinoma (ESCCs) is controversial. Therefore, we determined, through different methodologies, the prevalence of HPV in 264 ESCC samples from Brazil, and correlated it with the presence of surrogate markers and clinicopathological characteristics. HPV is present in 13% of ESCC, and with a 3-fold variation between high and medium incidence areas. Most HPV positive tumors were infected with HPV16, but this was not associated with p16 expression, TP53 mutation status, patient age, amount of tobacco or alcohol consumption, or overall survival. We conclude that HPV infection may not have a role in ESCC.
Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias Esofágicas/virologia , Infecções por Papillomavirus/complicações , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas , Brasil/epidemiologia , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Feminino , Genes p16 , Genes p53 , Papillomavirus Humano 16/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prevalência , FumarRESUMO
BACKGROUND: The venous thromboembolism is a common complication after surgical treatment in general and, in particular, on the therapeutic management on cancer. Surgery of the digestive tract has been reported to induce this complication. Patients with digestive cancer have substantial increased risk of initial or recurrent thromboembolism. AIM: To provide to surgeons working in digestive surgery and general surgery guidance on how to make safe thromboprophylaxis for patients requiring operations in the treatment of their gastrointestinal malignancies. METHODS: The guideline was based on 15 relevant clinical issues and related to the risk factors, treatment and prognosis of the patient undergoing surgical treatment of cancer on digestive tract. They focused thromboembolic events associated with operations and thromboprophylaxis. The questions were structured using the PICO (Patient, Intervention or Indicator, Comparison and Outcome), allowing strategies to generate evidence on the main primary bases of scientific information (Medline / Pubmed, Embase, Lilacs / Scielo, Cochrane Library, PreMedline via OVID). Evidence manual search was also conducted (BDTD and IBICT). The evidence was recovered from the selected critical evaluation using discriminatory instruments (scores) according to the category of the question: risk, prognosis and therapy (JADAD Randomized Clinical Trials and New Castle Ottawa Scale for studies not randomized). After defining potential studies to support the recommendations, they were selected by the strength of evidence and grade of recommendation according to the classification of Oxford, including the available evidence of greater strength. RESULTS: A total of 53,555 papers by title and / or abstract related to issue were found. Of this total were selected (1st selection) 478 studies that were evaluated as full-text. From them to support the recommendations were included in the consensus 132 papers. The 15 questions could be answered with evidence grade of articles with 31 A, 130 B, 1 C and 0 D. CONCLUSION: It was possible to prepare safe recommendations as guidance for thromboembolism prophylaxis in operations on the digestive tract malignancies, addressing the most frequent topics of everyday work of digestive and general surgeons.
Assuntos
Neoplasias Gastrointestinais/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia/prevenção & controle , Humanos , Guias de Prática Clínica como AssuntoRESUMO
OBJECTIVE: To review the evidence of safety and effectiveness of endoscopic and surgical treatment of Zenker's diverticulum. METHODS: Searches of MEDLINE, LILACS and SciELO by "Zenker's diverticulum" or "pharyngoesophageal diverticulum," and selection of studies for quality assessment and data extraction to a meta-analysis. RESULTS: The study did not find any randomized clinical trial. We found five comparative, non-randomized studies, with a total of 630 patients, 339 in the endoscopic arms and 291 in the surgical ones. The values for safety were a 0.29% mortality and 7% morbidity for the endoscopic treatment, and 0.34% mortality and 5% morbidity for surgical treatment. The values for effectiveness were 84% and 85%, respectively. The effect of endoscopic and surgical approaches for the treatment of Zenker's diverticulum was comparable, the odds ratio for morbidity was 1.24 (0.56 to 2.74), and the odds ratio for success was 0.66 (0.41 -1.05). CONCLUSION: The studies on the treatment of Zenker's diverticulum have a low level of evidence and are not able to establish the best treatment in terms of safety and effectiveness.
Assuntos
Esofagoscopia , Divertículo de Zenker/cirurgia , HumanosRESUMO
Esophageal squamous cell carcinoma (ESCC) is believed to arise from esophageal mucosa through accumulation of both genetic and epigenetic changes. DNA methylation is a critical epigenetic mechanism involved in key cellular processes and its deregulation has been linked to many human cancers, including ESCC. The aim of this study is to examine the global deregulation of methylation states in ESCC and identify potential early biomarkers. With this purpose, we performed a bead array analysis of more than 800 cancer-related genes in ten ESCC samples, ten matched surrounding tissues and four esophageal mucosa from healthy individuals. Pyrosequencing was used for validation of DNA methylation changes in up to 106 cases and 27 controls. A total of 37 CpG sites were found to be differentially methylated between tumors and surrounding tissues. These CpG sites were significantly enriched in genes related to several pathways including IL-10 anti-inflammatory signaling pathway and cell communication pathway. In addition, by comparing with healthy esophageal mucosa, we identified TFF1 gene as a potential early marker of ESCC. This is the first study to address methylation changes in ESCC in a large set of genes. Methylome analysis is shown as a sensitive and powerful tool to identify molecular players in ESCC. These data should prove to be the reference for future studies identifying potential biomarkers and molecular targets in ESCC.
Assuntos
Carcinoma de Células Escamosas/genética , Metilação de DNA , Epigênese Genética , Neoplasias Esofágicas/genética , Proteínas Supressoras de Tumor/genética , Ilhas de CpG , Marcadores Genéticos , Humanos , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Fator Trefoil-1 , Proteínas Supressoras de Tumor/químicaRESUMO
OBJECTIVE: To evaluate the expression of P53 and Ki-67 during esophageal diethylnitrosamine (DEN)-induced carcinogenesis in 100 mice by immunohistochemistry. METHODS: The animals were assigned to 4 groups, receiving water and food ad libitum. Control groups I and II received weekly esophageal gavage with cold (room temperature) or hot (60-70 degrees C) water, respectively. Experimental groups III and IV were treated with DEN for 3 consecutive days during the week, and one weekly gavage as above. The mice were sacrificed in different periods from day 30 to day 150 after the beginning of the experiment, for collection of esophageal samples which were then submitted to microscopic and immunohistochemical analyses. The temperature of the water administered by gavage was not related to the frequency of esophageal tumors. RESULTS: The expression of Ki-67 was significantly higher in high-grade intraepithelial lesion (I.L.), and the expression of P53 was also higher in low-grade I.L. CONCLUSION: The results emphasize the direct relationship of the carcinogenic process with early cell alterations detected by immunohistochemistry.
Assuntos
Carcinoma de Células Escamosas/imunologia , Neoplasias Esofágicas/imunologia , Antígeno Ki-67/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Animais , Carcinoma de Células Escamosas/induzido quimicamente , Dietilnitrosamina/administração & dosagem , Neoplasias Esofágicas/induzido quimicamente , Feminino , Imuno-Histoquímica , CamundongosRESUMO
PURPOSE: To study the expression of heme-oxygenase-1 (HO-1), an enzyme induced by oxidative stress, in specimens obtained from an experimental model in rats that evaluated the role of gastric and duodenal reflux in esophageal carcinogenesis. METHODS: Esophageal specimens embedded in paraffin obtained from different experimental groups of rats were used for immunohistochemistry analysis of HO-1 expression. The rats had been divided into the following groups and were killed after 22 weeks: (1) cardioplasty to induce acid reflux; (2) esophagoduodenal anastomosis to induce duodenal reflux; (3) no treatment; (4) cardioplasty + diethylnitrosamine (DEN); (5) esophagoduodenal anastomosis + DEN; and (6) DEN. The study sample comprised 3 specimens from each group with the most severe histopathological lesions found on each study branch. RESULTS: The expression of HO-1 was seen only in rat specimens submitted to esophagoduodenal anastomosis (Groups 2 and 5), and the analysis of mean fluorescence intensity revealed a significant increase of HO-1 expression (4.8 and 4.6 fold, respectively) when compared with the control group (Group 3) (p<0.05). The main target for HO-1 induction was the inflammatory cells inside the tumor or in subepithelial areas. Rats exposed to gastric reflux had no HO-1 expression. CONCLUSION: Reflux esophagitis induced by reflux of duodenal contents, which provoked considerable oxidative stress, may play an important role in esophageal carcinogenesis. Acid reflux did not induce oxidative stress in this experimental model.
Assuntos
Carcinoma/induzido quimicamente , Neoplasias Esofágicas/induzido quimicamente , Esofagite/induzido quimicamente , Refluxo Gastroesofágico/complicações , Heme Oxigenase-1/análise , Animais , Biomarcadores/análise , Carcinógenos , Dietilnitrosamina , Modelos Animais de Doenças , Esôfago/enzimologia , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
PURPOSE: Evaluation of the Mean Arterial Pressure (MAP) and body temperature changes in a new model of liver ischemia-reperfusion applying topical Hypothermia and Ischemic Preconditioning (IPC). METHODS: Rats (n= 32) were divided in 5 groups: Control (C), Normothermic Ischemia (NI), Ischemic Preconditioning (IPC), Hypothermia 26 degrees C plus IPC (H+IPC) and Hypothermia 26 degrees C (H). MAP and body temperature were recorded at 30 minutes intervals throughout the entire experiment. The study groups underwent 90 minutes partial hepatic ischemia followed by 120 minutes of reperfusion. The median and lateral left lobes were isolated and topical 26 degrees C hypothermia was induced by superfusion of cooled saline solution in H+IPC and H groups. A 10 minutes protocol of ischemia and reperfusion was applied in the IPC and H+IPC groups before the major ischemic insult. RESULTS: There was no significant difference in MAP and body temperature means between the groups throughout the experiments. CONCLUSION: The present model allows the induction of topical hepatic hypothermia associated or not to IPC. New studies to evaluate the possible synergistic effects of these tools can be reproduced without significant changes in macrohemodynamics and body temperature, or in other words, under stable conditions.
Assuntos
Pressão Sanguínea/fisiologia , Temperatura Corporal/fisiologia , Hipotermia Induzida/métodos , Isquemia/fisiopatologia , Precondicionamento Isquêmico , Fígado/irrigação sanguínea , Análise de Variância , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos WistarRESUMO
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.
Assuntos
Esôfago de Barrett/patologia , Células Caliciformes/patologia , Queratina-20/metabolismo , Queratina-7/metabolismo , Azul Alciano , Esôfago de Barrett/metabolismo , Corantes , Células Caliciformes/metabolismo , Humanos , Imuno-HistoquímicaRESUMO
OBJECTIVES: To test lumiracoxib used preemptively against a placebo,and to analyse the analgesic administration (dipirona and tramadol) in the 24 first postoperative hours. METHODS: Sixty patients undergone to a breast aumentation, under epidural anesthesia, were selected and put randomly in two groups - GI and GII. Sixty minutes before the surgery, it was administered orally, one pill of lumiracoxib 400mg to the 30 GI patients and one pill of placebo to the 30 GII patients. The postoperative pain was evaluated through the visual analogic scale, ranged from 0 (painless) to 10 (most intensive pain), being applied to the patient whenever having pain. For the same scores or under 4, it was administered intravenously 15mg/kg of dipirona up to a maximum of 1g. For scores of 5, 6 or 7, the patient had intravenously 50mg of tramadol.Scores 8 or more were treated intravenously with 0,5 mg/kg of meperidine. RESULTS: The scores in GI were significantly lower than the ones obtained in GII within the first 24 hours, with the need of 20% less dipirona and 56% of tramadol in this period of time. In the same way, it was observed that analgesic solicitation for the first time had a delay of 191 minutes in GI in comparison to GII. CONCLUSION: The use of lumiracoxib preemptively, was effective in the treatment of postoperative pain, reducing considerably the consume of analgesics, and enlarging the time for the first medication.