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991.
Palmero EI Schüler-Faccini L Caleffi M Achatz MI Olivier M Martel-Planche G Marcel V Aguiar E Giacomazzi J Ewald IP Giugliani R Hainaut P Ashton-Prolla P 《Cancer letters》2008,261(1):21-25
Germline TP53 mutations predispose to a rare familial cancer syndrome, the Li-Fraumeni Syndrome (LFS), characterized by the early onset of multiple cancers including childhood adrenocortical carcinomas, sarcomas and brain tumors, and breast and colon cancer in young adults. An identical germline mutation at codon 337 in TP53 (R337H) has been shown to be causally related to an increased risk of multiple cancers in unrelated subjects with familial cancer risk in Southern Brazil. Here we have assessed the prevalence of R337H in 750 healthy women participating in a community-based breast cancer screening program in the area of Porto Alegre. The mutant was detected in two participants (0.3%) who were fourth-degree relatives and reported a familial history of cancer at multiple sites that did not match classical criteria for LFS and its variants. Testing in additional family members detected the mutation in three subjects, one of whom developed breast cancer at the age of 36. These findings indicate that R337H may be a low penetrance mutant which predisposes to multiple cancers and occurs in the population of Southern Brazil at a frequency 10-20 times higher than other TP53 mutants commonly associated with LFS. 相似文献
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Justin K. Scheer Malla Keefe Virginie Lafage Michael P. Kelly Shay Bess Douglas C. Burton Robert A. Hart Amit Jain Baron S. Lonner Themistocles S. Protopsaltis Richard Hostin Christopher I. Shaffrey Justin S. Smith Frank Schwab Christopher P. Ames 《The spine journal》2017,17(10):1397-1405
Background Context
Current metrics to assess patients' health-related quality of life (HRQOL) may not reflect a true change in the patients' specific perception of what is most important to them.Purpose
This study aimed to describe the initial experience of a Patient Generated Index (PGI) in which patients create their own outcome domains.Study Design
This is a single-center prospective study.Patient Sample
Patients with adult spinal deformity (ASD) comprise the study sample.Outcome Measures
Oswestry Disability Index (ODI), Short Form-36 (SF-36 Physical Component Score [PCS] and Mental Component Score [MCS]), Scoliosis Research Society-22r (SRS-22r), and PGI.Methods
Oswestry Disability Index, SF-36, SRS-22r, and PGI were administered preoperatively and postoperatively at 6 weeks, 3 months, 6 months, and 1 and 2 years. PGI correlations with ODI, SF-36, SRS total score, free-text frequency analysis of PGI exact response with text in ODI and SRS-22r questionnaires, and the responsiveness (effect size [ES]) of the HRQOL metrics were analyzed. No funding was used for this study and there are no conflicts of interest.Results
A total of 59 patients with 209 clinical encounters produced 370 PGI written response topics that included affect or emotions, relationships, activities of daily life, personal care, work, and hobbies. Mean preoperative PGI score was 18.6±13.5 (0–71.7 out of 100 [best]), and mean scores significantly improved at every postoperative time point (p<.05). Preoperative PGI scores significantly correlated with preoperative ODI (r=?0.28, p=.03), MCS (r=0.48, p<.01), and SRS total (r=0.57, p<.01). Postoperative PGI scores correlated with all HRQOL measures (p<.0001): ODI (r=?0.65), PCS (r=0.50), MCS (r=0.55), and SRS total (r=0.63). PGI responses exactly matched ODI and SRS-22r text at 47.8% and 35.4%, respectively, and at 63.2% and 58.9%, respectively, for categories. Patient Generated Index ES at a minimum of 1-year follow-up was ?2.39, indicating substantial responsiveness (|ES|>0.8). Effect sizes for ODI, SRS-22r total, SF-36 PCS, and SF-36 MCS were 2.16, ?2.06, ?2.05, and ?0.80, respectively.Conclusions
The PGI is easy to administer and offers additional information about the patients' perspective not captured in standard HRQOL metrics. Patient Generated Index scores correlated with all of the standard HRQOL scores and were more responsive than ODI, SF-36, and SRS-22r, suggesting that the PGI may be a step closer to one HRQOL measure that better encompasses concerns and goals of the individual patients. 相似文献994.
Altintas S Toussaint J Durbecq V Lambein K Huizing MT Larsimont D Van Marck E Vermorken JB Tjalma WA Sotiriou C 《The breast journal》2011,17(4):343-351
Ductal carcinoma in situ (DCIS) is considered a heterogeneous premalignant condition of the breast with a certain probability for progressing to malignancy. There is no standard of care. The updated Van Nuys Prognostic Index (VNPI) 2003 is a clinical tool in treatment decision making. This study assessed the prognostic value of the VNPI after integration of proliferative biomarkers (GGI and Ki-67). DCIS samples were divided into three VNPI subgroups (low risk [score 4-6], intermediate risk [score 7-9], high risk [score 10-12]) based on nuclear grade ± necrosis, tumor size, margin width, and age. Nuclear grade was substituted by the genomic grade index (GGI) to generate the VNPI-GGI and combined with the Ki-67 to generate the VNPI-Ki67. Disease-free survival was calculated by Kaplan-Meier survival plots with log-rank significance. Multiple regression analysis was carried out using Cox proportional hazard regression analysis. A total of 88 cases (median age 54 years) with representative tissue were identified out of 168 DCIS patients. Median follow-up was more than 5 years. Ten patients developed an ipsilateral recurrence of whom nine were invasive: six patients were classified in the VNPI subgroup 2 and three patients in the VNPI subgroup 3. One non-invasive recurrence (DCIS) was classified in the VNPI subgroup III. A statistical association was observed between a high VNPI score and a higher risk of recurrence (HR = 7.72 [95% CI 1.01-58.91], p = 0.049). Ki-67 did not improve the prognostic value of VNPI (HR = 6.5, [95% CI 0.80-53.33], p = 0.08). In contrast, the VNPI-GGI could identify more accurately high-risk DCIS patients with early relapses within 5 years (HR = 18.14 [95% CI 1.75-188], p = 0.015). GGI incorporated into the VNPI improved its prognostic value for DCIS, especially for identifying early relapses. This method should be validated and incorporated in future prospective clinical DCIS trials. 相似文献
995.
Scotet V Duguépéroux I Audrézet MP Blayau M Boisseau P Journel H Parent P Férec C 《Prenatal diagnosis》2008,28(3):197-202
OBJECTIVE: This study reports 18 years of experience in prenatal diagnosis (PD) of cystic fibrosis (CF) in a region where CF is frequent and the uptake of PD is common (Brittany, western France). METHOD: All PDs made over the period 1989-2006 in women living in Brittany were collected. RESULTS: We recorded 268 PDs made in 1 in 4 risk couples, plus 22 PDs directly made following the sonographic finding of echogenic bowel. Most of the 268 PDs were done in couples already having CF child(ren) (n = 195, 72.8%). Close to one-fifth followed cascade screening (n = 49, 18.3%), which identified 26 new 1 in 4 risk couples among the relatives of CF patients or of carriers identified through newborn screening (NBS). The remaining PDs were mainly made in couples whose 1 in 4 risk was evidenced following the diagnosis of echogenic bowel in a previous pregnancy (n = 22, 8.2%). Although patients' life expectancy has considerably improved, in our population the great majority of couples chose pregnancy termination when PD indicated that the foetus had CF (95.9%). CONCLUSION: This study describes the distribution of PDs according to the context in which the 1 in 4 risk was discovered and highlights the real decisions of couples as regards pregnancy termination after a positive PD. 相似文献
996.
Thibault Vieira Martine Antoine Anne-Marie Ruppert Vincent Fallet Michael Duruisseaux Etienne Giroux Leprieur Virginie Poulot Nathalie Rabbe Laurene Sclick Michele Beau-Faller Roger Lacave Armelle Lavole Jacques Cadranel Marie Wislez 《Lung cancer (Amsterdam, Netherlands)》2014
Objectives
Pulmonary sarcomatoid carcinomas (SC) are highly disseminated types of non-small-cell lung carcinoma. Their prognosis is poor. New therapeutic targets are needed to improve disease management.Materials and methods
From 1995 to 2013, clinical and survival data from all consecutive patients with surgically treated SC were collected. Pathological and biomarker analyses were performed: TTF1, P63, c-MET and ALK expression (immunohistochemistry), PAS staining, ALK rearrangement (FISH), and EGFR, KRAS, HER2, BRAF, PIK3CA, and MET genes mutations (PCR).Results
Seventy-seven patients were included. Median age was 61 years (53–69). Histological subtypes were pleomorphic carcinoma (78%), carcinosarcoma (12%), and giant-cell and/or spindle-cell carcinoma (10%). Blood vessel invasion (BVI) was present in 90% of cases. Morphology and immunohistochemistry were indicative of an adenocarcinoma, squamous, and adenosquamous origin in 41.5%, 17% and 11.5%, respectively, 30% remained not-otherwise-specified. KRAS, PIK3CA, EGFR, and MET mutations were found in 31%, 8%, 3%, and 3%, respectively. No tumors had HER2 or BRAF mutations, or ALK rearrangement, whereas 34% had a c-MET positive score. Five-year overall survival (OS) was 29% for the whole population. At multivariate analysis, tumor size <50 mm (HR = 1.96 [1.04–3.73], p = 0.011), no lymph-node metastasis (HR = 3.25 [1.68–6.31], p < 0.0001), no parietal pleural invasion (HR = 1.16 [1.06–1.28], p = 0.002), no BVI (HR = 1.22 [1.06–1.40], p = 0.005), and no squamous component (HR = 3.17 [1.48–6.79], p = 0.01) were associated with longer OS. Biomarkers did not influence OS.Conclusion
Dedifferentiation in NSCLC could lead to SC and an epithelial subtype component could influence outcome. BVI was present in almost all SCs and was an independent factor of poor prognosis. 相似文献997.
Anne C.M. Thiébaut Véronique Chajès Mariette Gerber Marie‐Christine Boutron‐Ruault Virginie Joulin Gilbert Lenoir Franco Berrino Elio Riboli Jacques Bénichou Françoise Clavel‐Chapelon 《International journal of cancer. Journal international du cancer》2009,124(4):924-931
Experimental studies suggest detrimental effects of ω‐6 polyunsaturated fatty acids (PUFA), and beneficial effects of ω‐3 PUFAs on mammary carcinogenesis, possibly in interaction with antioxidants. However, PUFA food sources are diverse in human diets and few epidemiologic studies have examined whether associations between dietary PUFAs and breast cancer risk vary according to food sources or antioxidant intakes. The relationship between individual PUFA intakes estimated from diet history questionnaires and breast cancer risk was examined among 56,007 French women. During 8 years of follow‐up, 1,650 women developed invasive breast cancer. Breast cancer risk was not related to any dietary PUFA overall; however, opposite associations were seen according to food sources, suggesting other potential effects than PUFA per se. Breast cancer risk was inversely associated with α‐linolenic acid (ALA) intake from fruit and vegetables [highest vs. lowest quintile, hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63, 0.88; p trend < 0.0001], and from vegetable oils (HR 0.83; 95% CI 0.71, 0.97; p trend 0.017). Conversely, breast cancer risk was positively related to ALA intake from nut mixes (p trend 0.004) and processed foods (p trend 0.068), as was total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between ω‐6 and long‐chain ω‐3 PUFAs, with breast cancer risk inversely related to long‐chain ω‐3 PUFAs in women belonging to the highest quintile of ω‐6 PUFAs (p interaction 0.042). These results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and breast cancer risk. © 2008 Wiley‐Liss, Inc. 相似文献
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