RESUMO
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RESUMO
New biological tools are required to understand the functional significance of genetic events revealed by whole genome sequencing (WGS) studies in oesophageal adenocarcinoma (OAC). The MFD-1 cell line was isolated from a 55-year-old male with OAC without recombinant-DNA transformation. Somatic genetic variations from MFD-1, tumour, normal oesophagus, and leucocytes were analysed with SNP6. WGS was performed in tumour and leucocytes. RNAseq was performed in MFD-1, and two classic OAC cell lines FLO1 and OE33. Transposase-accessible chromatin sequencing (ATAC-seq) was performed in MFD-1, OE33, and non-neoplastic HET1A cells. Functional studies were performed. MFD-1 had a high SNP genotype concordance with matched germline/tumour. Parental tumour and MFD-1 carried four somatically acquired mutations in three recurrent mutated genes in OAC: TP53, ABCB1 and SEMA5A, not present in FLO-1 or OE33. MFD-1 displayed high expression of epithelial and glandular markers and a unique fingerprint of open chromatin. MFD-1 was tumorigenic in SCID mouse and proliferative and invasive in 3D cultures. The clinical utility of whole genome sequencing projects will be delivered using accurate model systems to develop molecular-phenotype therapeutics. We have described the first such system to arise from the oesophageal International Cancer Genome Consortium project.
Assuntos
Adenocarcinoma/patologia , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Genoma Humano/genética , Adenocarcinoma/genética , Sequência de Bases/genética , Neoplasias Esofágicas/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , FenótipoRESUMO
A best evidence topic in surgery was written according to a structured protocol. The question addressed was whether the initial surgical management of chylothorax after oesophagectomy results in a better outcome. Altogether 357 papers were found as a result of the reported search, of which 4 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. Three studies were retrospective and from single centres with small patient numbers, while one study was a prospective, randomized controlled trial, from which a subgroup analysis was included in our results. We conclude that although all studies to date have had very small patient numbers and some contradictory results, there is some evidence that early surgical intervention of chylothorax following oesophagectomy reduces hospital stay when compared with conservative treatment.
Assuntos
Quilotórax/cirurgia , Esofagectomia/efeitos adversos , Ducto Torácico/cirurgia , Tempo para o Tratamento , Benchmarking , Quilotórax/diagnóstico , Quilotórax/etiologia , Medicina Baseada em Evidências , Humanos , Tempo de Internação , Ligadura , Reoperação , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
A best evidence topic in surgery was written according to a structured protocol. The question addressed was whether prophylactic thoracic duct ligation during oesophagectomy results in a lower incidence of post-operative chylothorax. 29 relevant papers were found using the reported search, of which 5 papers represented the best evidence to answer the clinical question. The authors, date and country of publication, patient group, study type, relevant outcomes and results of these papers are tabulated. Of these studies, only one was a prospective randomised controlled study with sizeable patient numbers. This was also the most recent study and demonstrated a significant decrease in post-operative chylothorax incidence following intra-operative thoracic duct ligation. Of the four remaining retrospective studies, one showed an increase in chylothorax rate following ligation whilst three showed a reduction in the incidence of chylothorax (although in only one of these three studies was this decrease statistically significantly). We conclude that for patients undergoing oesophagectomy, although there are conflicting results from retrospective studies, prospective randomised controlled trial evidence points to prophylactic ligation of the thoracic duct as an effective measure to reduce the incidence of post-operative chylothorax.
