RESUMO
Hot beverage consumption is a risk factor for esophageal squamous cell carcinoma, but the underlying mechanisms are still unknown. We developed an experimental mouse model to understand the mechanism of thermal lesion to esophageal carcinogenesis. Female BALB/c mice were treated by gavage with water at different temperatures three times a week and nitrosamines in the drinking water. Water at 70°C, but not at lower temperatures, initially induced an esophageal necrosis that healed and became resistant to necrosis after further administrations. However, when 70°C water was associated with N-nitrosodiethylamine at doses above 1 ppm, there was interference in epithelial regeneration, allowing recurrent thermal injury and inflammation. Recurrent thermal injury resulted in hyper proliferative premalignant lesions being induced earlier (at 4 weeks) and at a higher frequency (4-fold increase at 16 weeks) when compared to mice treated with NDEA only. Ki-67 immunostaining revealed that recurrent thermal injury induced basal cell proliferation resulting in the expansion of epithelial basal cells, confirmed by the increase in cytokeratin 14 positive cells with concomitant reduction of differentiated cytokeratin 5 positive cells. We conclude that recurrent thermal lesion may act as a tumor promoter though a strong proliferation stimulus of esophageal epithelial basal cells.
Assuntos
Proliferação de Células/efeitos dos fármacos , Água Potável/administração & dosagem , Esôfago/patologia , Temperatura Alta , Lesões Pré-Cancerosas/patologia , Animais , Dietilnitrosamina/administração & dosagem , Dietilnitrosamina/toxicidade , Água Potável/efeitos adversos , Água Potável/química , Esôfago/metabolismo , Feminino , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Camundongos Endogâmicos BALB C , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Análise de Sobrevida , Fatores de TempoRESUMO
Small children are a challenging group in whom to perform KT. This retrospective study analyzed the results of 62 KTs in children weighing <15 kg, performed between 1998 and 2010, using extraperitoneal access and anastomosis of the renal vessels of donors to the aorta and IVC or iliac vessels of the recipients. Thirty-two (51.6%) grafts were LRDTs and 30 (48.4%) were DDRTs-28 of them pediatric. The mean age at KT was 3.7 ± 2.2 yr (1-12), and the mean weight was 12.3 ± 2.1 kg (5.6-14.9). Ten children weighed <10 kg, and five (8.1%) children presented previous thrombosis of the venous system. At one and five yr, patient survival was 93.2% and 84.2%, and graft survival was 85.2% and 72.7%. There were no differences between the rates for LRDT and DDRT. There were six vascular complications (four vascular thromboses, one laceration, and one renal artery stenosis) and two perirenal collections. Extraperitoneal access is a valid KT technique in children weighing <15 kg.
Assuntos
Peso Corporal , Transplante de Rim/métodos , Anastomose Cirúrgica , Aorta/cirurgia , Criança , Pré-Escolar , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Veia Ilíaca/cirurgia , Imunossupressores/uso terapêutico , Lactente , Rim/cirurgia , Masculino , Complicações Pós-Operatórias , Insuficiência Renal , Estudos Retrospectivos , Trombose/patologia , Resultado do Tratamento , Veia Cava Inferior/cirurgiaRESUMO
Esophageal cancer is among the most common and fatal tumors in the world. Eighty percent of esophageal tumors are esophageal squamous cell carcinoma (ESCC). Brazil is one of the high incidence areas in the West, where tobacco and alcohol consumption have been associated with ESCC. However, polymorphisms in xenobiotic metabolizing genes may also contribute to the risk. Therefore, in this study, we analyzed the risk of ESCC associated with tobacco and alcohol consumption and with polymorphisms of CYP2A6 (CYP2A6*2), CYP2E1 (CYP2E1*5B, CYP2E1*6), GSTP1 (Ile105Val), GSTM1 and GSTT1 null genotypes in 126 cases and 252 age- and gender-matched controls. Data on the amount, length and type of tobacco and alcohol consumed were collected, and DNA was extracted from blood lymphocytes from all individuals. Polymorphisms were analyzed by polymerase chain reaction (PCR)-multiplex (GSTM1 and T1), PCR-Restriction Fragment Length Polymorphism (CYP2E1*5B and *6 and GSTP1 Ile105Val) or allele-specific PCR amplification (CYP2A6*2). Risks were evaluated by multivariate conditional regression analysis. As expected, tobacco [odds ratio (OR) = 6.71, 95% confidence interval (95% CI) 3.08-14.63] and alcohol (OR = 16.98, CI 7.8-36.98) consumption, independently or together (OR = 26.91, CI 13.39-54.05) were risk factors. GSTP1 Ile105Val polymorphism was an independent risk factor (OR = 2.12, CI 1.37-3.29), whereas GSTT1 wild-type was an independent protective factor for ESCC (OR = 0.37, CI 0.16-0.79). There was approximately 80% statistical power to detect both results. There was no risk associated with CYP2A6, CYP2E1 and GSTM1 polymorphisms. In conclusion, this study suggests an opposite role of GSTP1 and GSTT1 polymorphisms for the risk for ESCC.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Citocromo P-450 CYP2E1/genética , Neoplasias Esofágicas/genética , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Oxigenases de Função Mista/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Brasil , Estudos de Casos e Controles , Citocromo P-450 CYP2A6 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , FumarRESUMO
We aim to determine the expression of the proto-oncogene c-Myc in patients with Barrett's esophagus (BE) and esophageal adenocarcinoma, and to evaluate the prevalence of such expression in relation to the metaplasia-dysplasia-adenocarcinoma sequence. BE develops as a result of a severe esophageal mucosa injury from gastroesophageal reflux. BE is a premalignant lesion and plays an important role in the development of esophageal adenocarcinoma. Several genetic alterations have been identified in the process that transforms a normal cell into a tumorous one. In the development of human tumors, one of the most important genes is the proto-oncogene c-Myc. The c-Myc protein expression was determined by immunohistochemical analysis in four different groups: 31 patients with normal tissue, 43 patients with BE without dysplasia, 11 patients with dysplasia in BE and 37 patients with esophageal adenocarcinoma. The material was obtained from esophageal biopsies or the dissection of patient esophagectomy specimens. Demographic and endoscopic data (sex, age, race and intestinal metaplasia extension), and morphologic and histopathologic tumor characteristics (deep tumor invasion, lymph node status, and tumor differentiation) were analyzed. The c-Myc expression was assessed using the Immunoreactive Scoring System (IRS). Overexpression of c-Myc was found in only 9.6% of normal tissue specimens, 37.2% of Barrett's esophagus, 45.5% of BE patients with dysplasia and 73% of adenocarcinoma samples, with significant statistical difference among these groups. No correlation was identified when the c-Myc expression was compared with morphologic and histologic tumor features or endoscopic data. However, linear correlation of c-Myc overexpression along the metaplasia-dysplasia-adenocarcinoma sequence was observed. This study demonstrates a significant increase in the expression of c-Myc in Barrett's esophagus, dysplasia and adenocarcinoma in relation to the control group, as well as a linear progression of this gene expression in this sequence. These results point out the importance of this marker in the development of esophageal adenocarcinoma from BE.
Assuntos
Adenocarcinoma/metabolismo , Esôfago de Barrett/metabolismo , Neoplasias Esofágicas/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/patologia , Estudos de Casos e Controles , Neoplasias Esofágicas/patologia , Esôfago/metabolismo , Esôfago/patologia , Feminino , Humanos , Masculino , Metaplasia/metabolismo , Metaplasia/patologia , Pessoa de Meia-Idade , Proto-Oncogene MasRESUMO
The most common genetic alterations found in a wide variety of cancers are p53 tumor suppressor gene mutations. p53 appears to be a nuclear transcription factor that plays a role in the control of cell proliferation, apoptosis, and the maintenance of genetic stability. Angiogenesis is a critical process in solid tumor growth and metastasis. Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, may be a major tumor angiogenesis regulator. Few studies have investigated the association between p53 and VEGF expressions and prognosis in esophageal carcinoma. Forty-seven specimens resected from patients with stage II and III squamous cell carcinoma (SCC) of the esophagus were studied using immunohistochemical staining. VEGF and p53 expressions were observed in 40% and 53% of the tumors, respectively. The p53 and VEGF staining statuses were coincident in only 21% of the tumors, and no significant correlation was found between p53 and VEGF statuses. No clinicopathologic factors were significantly correlated with p53 or VEGF expression. No significant association between p53 and VEGF expressions and poor prognosis was found. In conclusion, p53 and VEGF were not correlated with prognosis in patients with stage II and III SCC of the esophagus.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Esofagectomia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Fatores de TempoRESUMO
UNLABELLED: "Matè", a popular hot infusion of a herb (Ilex paraguayensis) drunk in large volumes, is a known risk factor for squamous cell carcinoma of the esophagus and there is a suspicion that high temperature of boiled water used for the infusion may contribute for carcinogenesis. METHODS: We measured the temperature of "matè" infusion drunk by a sample of the population at risk for this carcinoma in Taquara, southern Brazil. We interviewed inhabitants for drinking habits and the temperature of the infusion was measured with high precision thermometers. Temperature of the infusion was asked to consumers and their estimate compared to our measurements. We considered 60 degrees C or higher as "hot". RESULTS: In 36 residencies, 107 individuals were drinking "matè". Most individuals drank it daily (97.2%), and the medium daily volume was 1,265 ml (SD +/- 1,132 mL) ranging from 250 to 6,000 mL. The measured temperature was 60 degrees C or higher in 72% of residencies with medium of 63.4 degrees C (51-78 degrees C) and median 64.4 degrees C. CONCLUSION: In this study, "matè" was consumed in large volumes at high temperature and individuals did not estimate correctly the temperature of infusion. High temperatures of "matè" may contribute to carcinogenesis in this population.
Assuntos
Bebidas/efeitos adversos , Carcinoma de Células Escamosas/etiologia , Neoplasias Esofágicas/etiologia , Comportamento Alimentar , Temperatura Alta/efeitos adversos , Adulto , Idoso , Brasil , Feminino , Humanos , Magnoliopsida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estatísticas não Paramétricas , Inquéritos e Questionários , Sensação Térmica , População UrbanaRESUMO
To determine long-term survival of patients with thoracic oesophageal tumor who underwent resection, and to identify possible associated prognostic factors, 58 patients underwent oesophagectomy alone (group A) and 16 combined with neo-adjuvant chemoradiotherapy (group B). Univariate and multivariate analysis of prognostic factors were performed for age, depth of oesophageal wall tumour penetration, node involvement, type of resection, TNM stage and degree of tumour differentiation. Long-term survival rates at 1-5 years were 81% versus 89%; 56% versus 67%; 30% versus 67%; 12% versus 44%; and 0% versus 33% for group A and B, respectively (P = 0.0543, NS). Univariate analysis revealed only depth of invasion (P = 0.0076) and TNM stage (P = 0.0452) as isolated prognostic factors for long-term survival and multivariate analysis did not demonstrate any independent factor. Despite the small number of cases, neoadjuvant chemoradiotherapy seems to improve prognosis as well as to allow resection in a greater number of cases due to tumor downstaging.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/terapia , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Análise de Sobrevida , Taxa de SobrevidaRESUMO
UNLABELLED: There is increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction in the USA and Europe, however, data in Brazil are scanty. OBJECTIVE AND METHODS: We reviewed all histology confirmed esophageal and esophagogastric junction cancer reports during a 10-year period (1987-1996) obtained by upper digestive endoscopy biopsies at a cancer referral center in Southern Brazil. Cancer cases were classified in three categories: adenocarcinoma, squamous cell carcinoma, and others. RESULTS: Among 349 cases, adenocarcinoma was found in 53 (15.2%), squamous cell carcinoma in 283 (81.1%) and others in 13 (3.7%). CONCLUSIONS: In this study, the prevalence of adenocarcinoma was 15%.
Assuntos
Adenocarcinoma/epidemiologia , Neoplasias Esofágicas/epidemiologia , Junção Esofagogástrica , Brasil/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Estudos RetrospectivosRESUMO
It is known that some nitrosamines preferably affect particular organs because of their organospecificity. Diethylnitrosamine (DEN) is one of the most powerful nitrosamines for experimentally inducing esophagus cancer. The present study aimed to evaluate the rate and type of epithelial lesions induced by DEN in mice. We also assessed the role of alcohol and N-nitrosonornicotine (NNN) as promoters of this carcinogenesis. A total of 208 female mice (Mus musculus) were allocated to five experimental groups: group 1, water only (controls); group 2, DEN + water; group 3, DEN + NNN; group 4, DEN + 6% alcohol solution; group 5, DEN + NNN + 6% alcohol solution. Animals in groups 2, 3, 4 and 5 received DEN (0.04 ml/l) three times per week, and during the following 4 days they received the other solutions. NNN was provided at a final concentration of 30 mg/l. The overall experimental period was 180 days. At the end of this time, the animals were killed and their esophagus was dissected for macro- and microscopic analysis. There was no significant difference in relation to the size of the esophagus and to the average DEN intake by the animals (p > 0.05). A statistically significant difference (p < 0.0001) was observed between controls and all other experimental groups. There was no significant difference among experimental groups treated with carcinogens (p > 0.05). The average incidence of cancer was 85.4%. The experimental model used in the present study is a very potent indicator of esophagus cancer. Owing to the high incidence for cancer observed in the present study, it was not possible to assess the effect of alcohol and NNN as inducers for the development of esophageal cancer.
Assuntos
Carcinógenos , Carcinoma de Células Escamosas/induzido quimicamente , Dietilnitrosamina , Neoplasias Esofágicas/induzido quimicamente , Etanol , Nitrosaminas , Animais , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Esôfago/patologia , Feminino , Camundongos , Fatores de TempoRESUMO
Studies in human beings and animals have shown that esophageal exposure to duodenal and gastric contents may be important for the development of Barrett's esophagus and its complications, including adenocarcinoma and epidermoid carcinoma. Diethylnitrosamine (DEN) is a carcinogen that stimulates the development of epidermoid carcinoma in the esophagus of mice. The aim of this study was to evaluate the effect of gastroduodenal and gastric content reflux on induction of esophageal carcinogenesis. Gastroesophageal reflux (GER) and gastroduodenoesophageal reflux (GDER) were produced by cardioplasty and esophagoduodenostomy. The chosen carcinogen was DEN, diluted in drinking water, given 3 days a week for 20 consecutive weeks. One hundred Wistar female rats were divided into six groups, as follows: group 1 (18 rats), cardioplasty without DEN; group 2 (18 rats), cardioplasty with DEN; group 3 (10 rats), only water; group 4 (17 rats), cardioplasty with DEN; group 5 (17 rats), esophagoduodenostomy with DEN; group 6 (20 rats), only DEN. GER in isolation induced papillomatosis or ulceration in 22.2% of rats and, when associated with DEN, induced papillomatosis in 61.1% of rats. GDER in isolation induced marked esophagitis in 61.1% of rats, Barrett's esophagus in 16.7% and esophageal adenocarcinoma in 16.7%; when associated with DEN, 23.5% of rats presented marked esophagitis, papillomatosis or ulceration, whereas 76.5% had esophageal carcinoma, with 70.6% epidermoid carcinoma and 5.9% adenocarcinoma. Rats treated with water alone did not show histologic abnormalities of the esophageal mucosa. Rats treated with DEN alone developed papillomas in 50.0% of the cases and remained histologically unchanged in 50.0%. There was no development of low- or high-grade dysplasia in any group. The conclusions are that (1) GDER is significantly more deleterious to esophageal mucosa than GER; (2) in this study, GER did not present carcinogenic potential in relation to the esophagus; (3) GDER in isolation is an esophageal carcinogen, producing Barrett's esophagus and esophageal adenocarcinoma; (4) esophageal oncogenesis caused by GDER is potentiated by DEN, inducing esophageal epidermoid carcinoma; (5) in this study, DEN in isolation did not generate tumors in the esophagus of rats.