58 research outputs found
Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers
Contains fulltext :
89346.pdf (publisher's version ) (Open Access)BACKGROUND: Colorectal, endometrial and upper urinary tract tumours are characteristic for Lynch syndrome (hereditary non-polyposis colon carcinoma, HNPCC). The aim of the present study was to establish whether carriers of mutations in mismatch repair genes MLH1, MSH2 or MSH6 are at increased risk of urinary bladder cancer. METHODS: Carriers and first degree relatives of 95 families with a germline mutation in the MLH1 (n=26), MSH2 (n=43), or MSH6 (n=26) gene were systematically questioned about the occurrence of carcinoma. The cumulative risk of cancer occurring before the age of 70 years (CR70) was compared to the CR70 of the general Dutch population. Microsatellite instability (MSI) testing and/or immunohistochemistry (IHC) for mismatch repair proteins was performed on bladder tumour tissue. RESULTS: Bladder cancer was diagnosed in 21 patients (90% men) from 19 Lynch syndrome families (2 MLH1, 15 MSH2, and 4 MSH6). CR70 for bladder cancer was 7.5% (95% CI 3.1% to 11.9%) for men and 1.0% (95% CI 0% to 2.4%) for women, resulting in relative risks for mutation carriers and first degree relatives of 4.2 (95% CI 2.2 to 7.2) for men and 2.2 (95% CI 0.3 to 8.0) for women. Men carrying an MSH2 mutation and their first degree relatives were at highest risks: CR70 for bladder and upper urinary tract cancer being 12.3% (95% CI 4.3% to 20.3%) and 5.9% (95% CI 0.7% to 11.1%). Bladder cancer tissue was MSI positive in 6/7 tumours and loss of IHC staining was found in 14/17 tumours, indicating Lynch syndrome aetiology. CONCLUSION: Patients with Lynch syndrome carrying an MSH2 mutation are at increased risk of urinary tract cancer including bladder cancer. In these cases surveillance should be considered.01 juli 201
High Diagnostic Performance of Short Magnetic Resonance Imaging Protocols for Prostate Cancer Detection in Biopsy-naive Men: The Next Step in Magnetic Resonance Imaging Accessibility
Background: To make magnetic resonance imaging (MRI) more accessible to men at risk
of high-grade prostate cancer (PCa), there is a need for quicker, simpler, and less costly
MRI protocols.
Objective: To compare the diagnostic performance of monoplanar (âfastâ biparametric MRI
[bp-MRI]) and triplanar noncontrast bp-MRI with that of the current contrast-enhanced
multiparametric MRI (mp-MRI) in the detection of high-grade PCa in biopsy-naĂŻve men.
Design, setting, and participants: A prospective, multireader, head-to-head study included 626 biopsy-naĂŻve men, between February 2015 and February 2018.
Intervention: Men underwent prebiopsy contrast-enhanced mp-MRI. Prior to biopsy,
two blinded expert readers subsequently assessed âfastâ bp-MRI, bp-MRI, and mp-MRI.
Thereafter, systematic transrectal ultrasound-guided biopsies (SBs) were performed.
Men with suspicious mp-MRI (Prostate Imaging Reporting and Data System 3â5 lesions)
also underwent MR-in-bore biopsy (MRGB).
Outcome measurements and statistical analysis: Primary outcome was the diagnostic
performance of each protocol for the detection of high-grade PCa. Secondary outcomes
included the difference in biopsy avoidance, detection of low-grade PCa, acquisition
times, decision curve analyses, inter-reader agreement, and direct costs. Results from
combined MRGB and SB were used as the reference standard. High-grade PCa was
defined as grade 2.
Results and limitations: Sensitivity for high-grade PCa for all protocols was 95% (180/
190; 95% confidence interval [CI]: 91â97%). Specificity was 65% (285/436; 95% CI: 61â70%) for âfastâ bp-MRI and 69% (299/436; 95% CI: 64â73%) for bp-MRI and mp-MRI.
With fast bp-MRI, 0.96% (6/626) more low-grade PCa was detected. Biopsy could be
avoided in 47% for the fast bp-MRI and in 49% for the bp-MRI and mp-MRI protocols.
Fast bp-MRI and bp-MRI can be performed in 8 and 13 min, respectively, instead of
16
Characteristics and outcome of pediatric renal cell carcinoma patients registered in the International Society of Pediatric Oncology (SIOP) 93â01, 2001 and UKâIMPORT database: A report of the SIOPâRenal Tumor Study Group
In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric OncologyâRenal Tumor Study Group (SIOPâRTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93â01, 2001 and UKâIMPORT databases, were included. Eventâfree survival (EFS) and overall survival (OS) were analyzed using the KaplanâMeier method. Between 1993 and 2019, 122 pediatric patients with RCC were registered. Available detailed data (n = 111) revealed 56 localized, 30 regionally advanced, 25 metastatic and no bilateral cases. Histological classification according to World Health Organization 2004, including immunohistochemical and molecular testing for transcription factor E3 (TFE3) and/or EB (TFEB) translocation, was available for 65/122 patients. In this group, the most common histological subtypes were translocation type RCC (MiTâRCC) (36/64, 56.3%), papillary type (19/64, 29.7%) and clear cell type (4/64, 6.3%). One histological subtype was not reported. In the remaining 57 patients, translocation testing could not be performed, or TFEâcytogenetics and/or immunohistochemistry results were missing. In this group, the most common RCC histological subtypes were papillary type (21/47, 44.7%) and clear cell type (11/47, 23.4%). Ten histological subtypes were not reported. Estimated 5âyear (5y) EFS and 5yâOS of the total group was 70.5% (95% CI = 61.7%â80.6%) and 84.5% (95% CI = 77.5%â92.2%), respectively. Estimated 5yâOS for localized, regionally advanced, and metastatic disease was 96.8%, 92.3%, and 45.6%, respectively. In conclusion, the registered pediatric patients with RCC showed a reasonable outcome. Survival was substantially lower for patients with metastatic disease. This descriptive study stresses the importance of full, prospective registration including TFEâtesting
Artificial intelligence for diagnosis and Gleason grading of prostate cancer: the PANDA challenge
Through a community-driven competition, the PANDA challenge provides a curated diverse dataset and a catalog of models for prostate cancer pathology, and represents a blueprint for evaluating AI algorithms in digital pathology.Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge-the largest histopathology competition to date, joined by 1,290 developers-to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted kappa, 95% confidence interval (CI), 0.840-0.884) and 0.868 (95% CI, 0.835-0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials
El narcoperiodismo de GarcĂa MĂĄrquez: uma anĂĄlise dos aspectos da narcoliteratura no livro-reportagem NotĂcia de um sequestro
Desde os anos 1970, a cobertura da mĂdia tradicional sobre o narcotrĂĄfico caracterizou-se pela superficialidade de suas narrativas cujo processo impossibilita a profundidade de anĂĄlise. PorĂ©m, alguns repĂłrteres foram bem-sucedidos ao aproximar o narcotrĂĄfico e o jornalismo literĂĄrio, rompendo com essa barreira limitante, principalmente, a partir da produção de livros-reportagem. O tema influenciou a literatura do continente (originando termos como narcoliteratura, narconarrativa e narcocultura), bem como o contexto do trĂĄfico de drogas proporcionou a produção editorial de obras de nĂŁo ficção, a partir dos final dos anos 80, atingindo o ĂĄpice nos anos 90 e 2000. Desta forma, este artigo discute o papel do livro-reportagem para a produção cultural da narcoliteratura, a partir de uma anĂĄlise de seus aspectos dentro da obra jornalĂstica NotĂcia de um sequestro (1996), de Gabriel GarcĂa MĂĄrquez. O artigo estĂĄ apoiado nos conceitos de livro-reportagem, de Edvaldo Pereira Lima e nas discussĂ”es sobre narcocultura, de Omar RincĂłn e de Diana Palaversich
Monitoring international migration flows in Europe. Towards a statistical data base combining data from different sources
The paper reviews techniques developed in demography, geography and statistics that are useful for bridging the gap between available data on international migration flows and the information required for policy making and research. The basic idea of the paper is as follows: to establish a coherent and consistent data base that contains sufficiently detailed, up-to-date and accurate information, data from several sources should be combined. That raises issues of definition and measurement, and of how to combine data from different origins properly. The issues may be tackled more easily if the statistics that are being compiled are viewed as different outcomes or manifestations of underlying stochastic processes governing migration. The link between the processes and their outcomes is described by models, the parameters of which must be estimated from the available data. That may be done within the context of socio-demographic accounting. The paper discusses the experience of the U.S. Bureau of the Census in combining migration data from several sources. It also summarizes the many efforts in Europe to establish a coherent and consistent data base on international migration.
The paper was written at IIASA. It is part of the Migration Estimation Study, which is a collaborative IIASA-University of Groningen project, funded by the Netherlands Organization for Scientific Research (NWO). The project aims at developing techniques to obtain improved estimates of international migration flows by country of origin and country of destination
Artificial intelligence for diagnosis and Gleason grading of prostate cancer: The PANDA challenge
Through a community-driven competition, the PANDA challenge provides a curated diverse dataset and a catalog of models for prostate cancer pathology, and represents a blueprint for evaluating AI algorithms in digital pathology.
Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge-the largest histopathology competition to date, joined by 1,290 developers-to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted kappa, 95% confidence interval (CI), 0.840-0.884) and 0.868 (95% CI, 0.835-0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials.KWF Kankerbestrijding ; Netherlands Organization for Scientific Research (NWO) ; Swedish Research Council European Commission ; Swedish Cancer Society ; Swedish eScience Research Center ; Ake Wiberg Foundation ; Prostatacancerforbundet ; Academy of Finland ; Cancer Foundation Finland ; Google Incorporated ; MICCAI board challenge working group ; Verily Life Sciences ; EIT Health ; Karolinska Institutet ; MICCAI 2020 satellite event team ; ERAPerMe
Association of Chromosome 9p21 with Subsequent Coronary Heart Disease events:A GENIUS-CHD study of individual participant data
BACKGROUND:Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS:A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103,357 Europeans with established CHD at baseline from the GENIUS-CHD Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/MI), occurred in 13,040 of the 93,115 participants with available outcome data. Effect estimates were compared to case/control risk obtained from CARDIoGRAMPlusC4D including 47,222 CHD cases and 122,264 controls free of CHD. RESULTS:Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/MI among those with established CHD at baseline (GENIUS-CHD OR 1.02; 95% CI 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D OR 1.20; 95% CI 1.18-1.22; p for interaction Conclusions: In contrast to studies comparing individuals with CHD to disease free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development
- âŠ