RESUMEN
Transurethral resection of bladder tumour is the initial, most critical step in the management of bladder cancer; as such, this is a call to arms for the urological community to it the due diligence it deserves regarding technology and training.
Asunto(s)
Cistectomía/métodos , Neoplasias de la Vejiga Urinaria/cirugía , Tecnología Biomédica , Humanos , UretraRESUMEN
BACKGROUND: Prostate cancer is a key driver of cancer-related global disability-adjusted life-years. Androgen-deprivation therapy (ADT) for advanced disease is linked to fatigue, reduced physical function, and quality of life (QoL). OBJECTIVE: To evaluate the effect of a lifestyle intervention on disease-specific QoL, diastolic blood pressure, and cancer-related fatigue in sedentary men receiving long-term ADT for advanced prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A total of 100 hundred sedentary men with locally advanced or metastatic prostate cancer on long-term ADT were randomised to an intervention or usual care group. INTERVENTION: A 12-wk lifestyle intervention consisting of aerobic and resistance exercise with parallel dietary advice. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Disease-specific QoL was measured using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaires at 12 wk postintervention and at 6 mo following withdrawal of support. Analysis of covariance and mixed regression were conducted. RESULTS AND LIMITATIONS: Clinically relevant improvements in FACT-P were seen at 12 wk in the intervention group compared with controls (mean difference: 8.9 points; 95% confidence interval [CI], 3.7-14.2; adjusted p=0.001). No difference was apparent at 6 mo (mean difference: 3.3 points; 95% CI, -2.6 to 9.3; adjusted p=0.27). No difference in diastolic blood pressure was seen at either follow-up (all p > 0.05). Clinically relevant improvements in FACT-F were seen at 12 wk (mean difference: 5.3 points; 95% CI, 2.7-7.9; adjusted p<0.001) and maintained following withdrawal of supervision (mean difference: 3.9 points; 95% CI, 1.1-6.8; adjusted p=0.007). Improvements in exercise tolerance and behaviour were maintained at 6 mo (adjusted p<0.001 and 0.038). CONCLUSIONS: A lifestyle intervention resulted in a clinically meaningful improvement in disease-specific QoL that was not maintained postintervention. No effect on blood pressure occurred. Durability of response was seen in fatigue and exercise behaviour. Further evaluation of support structures is essential. TRIAL REGISTRATION: ISRCTN88605738.
Asunto(s)
Antagonistas de Andrógenos/efectos adversos , Terapia por Ejercicio , Fatiga/terapia , Neoplasias de la Próstata/tratamiento farmacológico , Calidad de Vida , Conducta Sedentaria , Anciano , Antagonistas de Andrógenos/uso terapéutico , Presión Sanguínea , Dieta , Grasas de la Dieta , Tolerancia al Ejercicio/fisiología , Fatiga/inducido químicamente , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/fisiopatología , Entrenamiento de Fuerza , Método Simple Ciego , Encuestas y CuestionariosRESUMEN
BACKGROUND: Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse. OBJECTIVE: To assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations. DESIGN, SETTING, AND PARTICIPANTS: Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors. RESULTS AND LIMITATIONS: Eleven of 177 patients with MSH2 mutations (6.21%, p<0.001 compared with the Canadian population) were found to have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p>0.05). Of these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the matched sporadic cases, which all displayed normal expression of MSH2 and MLH1. The incidence of UTUC among MSH2 carriers was 3.95% (p<0.001), and all tumors were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5 splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer. Limitations include possible inflated risk estimates due to ascertainment bias. CONCLUSIONS: LS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma de Células Transicionales/genética , Reparación de la Incompatibilidad de ADN/genética , Neoplasias Renales/genética , Síndrome de Lynch II/genética , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Neoplasias Ureterales/genética , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/epidemiología , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Renales/epidemiología , Pelvis Renal , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Ontario/epidemiología , Sistema de Registros , Factores de Riesgo , Neoplasias Ureterales/epidemiología , Neoplasias de la Vejiga Urinaria/epidemiologíaRESUMEN
OBJECTIVES: To establish whether high microsatellite instability (MSI) (present in almost 20% of cases) and loss of MSH2 protein expression (sometimes used to predict MSI status) are prognostic factors of overall survival for patients with invasive upper urinary tract transitional cell carcinoma (UUT-TCC). UUT-TCC has a poor prognosis (overall survival less than 50% at 5 years). METHODS: The files of 80 patients who underwent nephroureterectomy for invasive UUT-TCC (Stage pT2 or worse) between 1990 and 2002 were reviewed. The following data were collated: age at diagnosis, prior history of cancer, tobacco consumption, tumor stage and grade, and disease progression. MSI was determined by polymerase chain reaction/fragment analysis and MSH2 protein expression by immunohistochemistry on retrieved tumor tissue. RESULTS: The median patient age was 71.5 years. The male/female ratio was 2.8. High MSI and loss of MSH2 expression were encountered in the tumors of 14 (17%) and 21 (26%) of the 80 patients, respectively. High MSI was significantly associated with patients with a better prognosis (Stage T2-T3N0M0; P = 0.02). The mean overall survival was 22.5 +/- 18 months (range 6 to 78). In univariate analyses, age, stage, tumor grade, high MSI, and loss of MSH2 expression were related to better overall survival (37 +/- 22 months, P = 0.003; 34 +/- 22 months, P = 0.02). Only stage, age, and high MSI were prognostic factors in a multivariate analysis (P < 0.05). CONCLUSIONS: MSI and expression of MSH2 are useful prognostic factors in invasive UUT-TCC. However, other than age and stage, only MSI was an independent factor. High MSI indicates a better prognosis, especially in patients younger than 71 years with Stage T2-T3N0M0.