RESUMO
BACKGROUND: Recommended strategies to screen for Lynch syndrome in colorectal cancer are not applied in daily practice and most of Lynch cases remain undiagnosed. AIMS: We investigated in routine conditions a strategy that uses simplified clinical criteria plus detection of MisMatch Repair deficiency in tumours to identify Lynch carriers. METHODS: Colorectal cancer patients that met at least one of three clinical criteria were included: (1) colorectal cancer before 50 years, (2) personal history of colorectal or endometrial cancer, (3) first-degree relative history of colorectal or endometrial cancer. All tumours underwent an MisMatch Repair test combining microsatellite instability analysis and MisMatch Repair immunohistochemistry. Patients with an MisMatch Repair-deficient tumour were offered germline testing. RESULTS: Of the 307 patients fulfilling the clinical criteria, 46 (15%) had a MisMatch Repair-deficient tumour. Amongst them 27 were identified as Lynch carriers (20 with germline mutation: 12 MLH1, 7 MSH2, 1 MSH6; 7 highly suspected cases despite failure of genetic testing). The simplified clinical criteria selected a population whose MisMatch Repair-deficient status was highly predictive (59%) of Lynch syndrome. CONCLUSION: This bio-clinical strategy based on simplified clinical criteria combined with an MisMatch Repair test efficiently detected LS cases and is easy to use in clinical practice, outside expert centres.
Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias do Endométrio/genética , Testes Genéticos , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Fatores Etários , Reparo de Erro de Pareamento de DNA , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Feminino , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Seleção de Pacientes , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
OBJECTIVE: Recent guidelines on the management of patients chronic hepatitis C virus (HCV) infection recommend the same anti-HCV therapy for active intravenous drug users and other patients, however some physicians are reluctant to treat active drug users. The aim of this study was to compare hepatitis C management practices and clinical outcome after treatment between active intravenous drug users and other patients. METHODS: Four hundred and thirty-five naive HCV seropositive patients were recruited from 1990 to 2000 and followed up for a mean period of 2.5 years (SD 1 Year). At the beginning of the study, 116 of the patients were active intravenous drug users. Social, clinical, biological and histological data were collected. The different steps of HCV management and responses to treatment were compared between active intravenous drug users and other patients. RESULTS: There was no statistically significant difference in HCV management practices and compliance between active intravenous drug users and other patients: search for viral RNA (85% versus 67%), liver biopsy performed when indicated (82% versus 87%), initiation of anti-HCV treatment (33.6% versus 43.2%), loss to follow up during treatment (24% vs 16%). The rate of sustained viral response was not significantly different between active intravenous drug users and other patients (28% versus 21%). At multivariate analysis, factors independently associated with sustained viral response were female gender (OR=5.6 [1.02-41.2]), genotype 3 (OR=29.7 [1.4-61.7]), low viral load (OR=33.3 [2.25-100]), low fibrosis score (OR=1.4 [1.0-2.0]), elevated transaminase level (OR=12.7 [0.9-97.2]), and bitherapy protocol (OR=10 [1.18-85.3]). CONCLUSION: This study illustrates that active intravenous drug use does not affect either patient compliance with proposed management or viral response to treatment, but pluridisciplinary care should focus both on drug addiction and HCV infection.
