| 1. |
|
|
| 2. |
|
|
| 3. |
- Abe, O, et al.
(författare)
-
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
-
Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
-
Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Bahi, R., et al.
(författare)
-
Ischemia is not an independent predictive factor of chronic renal failure after partial nephrectomy in a solitary kidney in patients without pre-operative renal insufficiency
- 2015
-
Ingår i: Progrès en urologie (Paris). - : Elsevier BV. - 1166-7087. ; 25:1, s. 27-33
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the influence of vascular clamping and ischemia time on long-term post-operative renal function following partial nephrectomy (PN) for cancer in a solitary kidney.Patients and methods: This is a retrospective study including 259 patients managed by PN between 1979 and 2010 in 13 centers. Clamping use, technique choice (pedicular or parenchymal clamping), ischemia time, and peri-operative data were collected. Pre-operative and last follow-up glomerular filtration rates were compared. A multivariate analysis using a Cox model was performed to assess the impact of ischemia on post-operative chronic renal failure risk.Results: Mean tumor size was 4.0 ± 2.3 cm and mean pre-operative glomerular filtration rate was 60.8 ± 18.9 mL/min. One hundred and six patients were managed with warm ischemia (40.9%) and 53 patients with cold ischemia (20.5%). Thirty patients (11.6%) have had a chronic kidney disease. In multivariate analysis, neither vascular clamping (P = 0.44) nor warm ischemia time (P = 0.1) were associated with a pejorative evolution of renal function. Pre-operative glomerular filtration rate (P < 0.0001) and blood loss volume (P = 0.02) were significant independent predictive factors of long-term renal failure.Conclusion: Renal function following PN in a solitary kidney seems to depend on non-reversible factors such as pre-operative glomerular filtration rate. Our findings minimize the role of vascular clamping and ischemia time, which were not significantly associated with chronic renal failure risk in our study.
|
|
| 8. |
- Pignot, G., et al.
(författare)
-
L’Ischémie n’est pas un facteur d’insuffisance rénale chronique après néphrectomie partielle sur rein unique
- 2014
-
Ingår i: Progrès en urologie (Paris). - : Elsevier. - 1166-7087. ; 24:13, s. 822-822
-
Tidskriftsartikel (refereegranskat)abstract
- Objectifs Déterminer l‘influence du clampage pédiculaire et de sa durée sur la fonction rénale à long terme après néphrectomie partielle (NP) pour cancer sur rein unique.Méthodes L’étude a inclus rétrospectivement 259 patients opérés par NP entre 1979 et 2010 dans 13 centres. L’utilisation d’un clampage, son type (pédiculaire ou parenchymateux), sa durée ainsi que les données pré-, intra- et postopératoires ont été recueillies. Les valeurs de débit de filtration glomérulaire (DFG) préopératoire et au dernier suivi ont été comparés. Une analyse multivariée selon le modèle de Cox a été réalisée afin de déterminer l’impact de l’ischémie sur le risque d’insuffisance rénale (IR) chronique postopératoire.Résultats La taille moyenne des tumeurs était de 4,0±2,3cm et le DFG préopératoire moyen de 60,8±18,9ml/min. Au total, 106 patients ont été opérés en ischémie chaude (40,9 %) et 53 en ischémie froide (20,5 %). Trente patients (11,6 %) ont évolué vers l’insuffisance rénale chronique. En analyse multivariée, ni le clampage pédiculaire (p=0,44), ni la durée d’ischémie chaude (p=0,1) n’étaient associés à une évolution vers l’insuffisance rénale. Les facteurs indépendants d’insuffisance rénale à long terme étaient le DFG préopératoire (p<0,0001) et les pertes sanguines (p=0,02).Conclusion La fonction rénale après NP sur rein unique apparaît principalement liée à des facteurs non modifiables et notamment le DFG préopératoire. Ce travail relativise l’importance du clampage pédiculaire et du temps d’ischémie qui n’étaient pas significativement liés au risque d’IR dans notre étude.
|
|
| 9. |
- Van Wijk, Rob C., 1991-, et al.
(författare)
-
Anti‐tuberculosis effect of isoniazid scales accurately from zebrafish to humans
- 2020
-
Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 177:24, s. 5518-5533
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purposeThere is a strong need for innovation in anti-tuberculosis drug development. The zebrafish larva is an attractive disease model in tuberculosis research. To translate pharmacological findings to higher vertebrates, including humans, the internal exposure of drugs needs to be quantified and linked to observed response.Experimental approachIn zebrafish studies, drugs are commonly dissolved in the external water, posing a challenge to quantify internal exposure. We developed experimental methods to quantify internal exposure, including nano-scale blood sampling, and to quantify the bacterial burden, using automated fluorescence imaging analysis, with isoniazid as paradigm compound. We used pharmacokinetic-pharmacodynamic modelling to quantify the exposure-response relationship responsible for the antibiotic response. To translate isoniazid response to humans, the quantitative exposure-response relationship in zebrafish was linked to simulated concentration-time profiles in humans, and two quantitative translational factors on sensitivity to isoniazid and stage of infection were included.Key resultsBlood concentration was only 20% of the external drug concentration. The bacterial burden increased exponentially and an isoniazid dose corresponding to 15 mg·L-1internal concentration (minimum inhibitory concentration) lead to bacteriostasis of the mycobacterial infection in the zebrafish. The concentration-effect relationship was quantified, and based on that relationship and the translational factors, the isoniazid response was translated to humans, which correlated well with observed data.Conclusions and implicationsThis proof-of-concept confirms the potential of the zebrafish larvae as tuberculosis disease model in translational pharmacology, and contributes to innovative anti-tuberculosis drug development which is strongly needed.
|
|
| 10. |
|
|
