Recurrent acute thermal lesion induces esophageal hyperproliferative premalignant lesions in mice esophagus.

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.

Kidney transplantation in children weighing less than 15 kg: extraperitoneal surgical access-experience with 62 cases.

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.

Polymorphisms of GSTP1 and GSTT1, but not of CYP2A6, CYP2E1 or GSTM1, modify the risk for esophageal cancer in a western population.

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.

c-Myc overexpression is strongly associated with metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.

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.

Neoplasias associadas ao carcinoma epidermóide do esôfago / Neoplasms associated to esophageal epidermoid carcinoma

INTRODUÇÄO. O carcinoma epidermóide de esôfago (CEE) tem uma importante associaçäo com neoplasias do trato aerodigestivo e, provavelmente, compartilham dos mesmos fatores de risco. Além destes, outras neoplasias podem estar associadas com o carcinoma de esôfago. OBJETIVO. Analisar, retrospectivamente, pacientes com carcinoma epidermóide de esôfago tratados pelo Grupo de Cirurgia do Esôfago, Estômago e Intestino Delgado (GCEEID) do Hospital de Clínicas de Porto Alegre (HCPA), no período de janeiro/88 a junho/95, os quais tinham neoplasias associadas ao CEE. PACIENTES E MÉTODOS. Dentre os 261 pacientes estudados, 19 (7,28 por cento) tinham neoplasia associada ao CEE. Dez pacientes apresentaram tumores sincrônicos e 9, metacrônicos. O sexo predominante foi o masculino, com 17 casos. A média de idade ficou em 62,52 anos no momento do diagnóstico da neoplasia esofágica. RESULTADOS. Os tumores aerodigestivos, na sua totalidade carcinomas escamosos, representaram o tipo histológico predominante da neoplasia associada em 68,42 por cento dos casos. O sítio mais freqüente da neoplasia aerodigestiva associada foi a árvore respiratória (53,8 por cento), seguido da cavidade oral e orofaringe (23 por cento) e laringe (23 por cento). Dos 19 pacientes, 12 eram tabagistas e nove ingeriam bebidas alcoólicas regularmente. Para o tratamento do CEE, optou-se por cirurgia em seis pacientes. A neoplasia associada foi tratada com cirurgia radical em 11 pacientes e radioterapia em cinco. Surpreendentemente, foram diagnosticados quatro casos (21 por cento) de adenocarcinomas gßstricos associados ao CEE, tratados com cirurgia radical em três pacientes. CONCLUSÄO. Os autores ressaltam a importância do estadiamento criterioso dos pacientes com CEE devido a associaçäo significativa com outras neoplasias, principalmente com tumores aerodigestivos. Alertam para o seguimento desses pacientes e discutem a possibilidade de fatores de risco comuns: fumo e álcool. Nesta casuística, encontrou-se associaçäo importante com neoplasias gástricas.