DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma

The pathogenesis of cystic nephroma of the kidney has interested pathologists for over 50 years. Emerging from its initial designation as a type of unilateral multilocular cyst, cystic nephroma has been considered as either a developmental abnormality or a neoplasm or both. Many have viewed cystic nephroma as the benign end of the pathologic spectrum with cystic partially differentiated nephroblastoma and Wilms tumor, whereas others have considered it a mixed epithelial and stromal tumor. We hypothesize that cystic nephroma, like the pleuropulmonary blastoma in the lung, represents a spectrum of abnormal renal organogenesis with risk for malignant transformation. Here we studied DICER1 mutations in a cohort of 20 cystic nephromas and 6 cystic partially differentiated nephroblastomas, selected independently of a familial association with pleuropulmonary blastoma and describe four cases of sarcoma arising in cystic nephroma, which have a similarity to the solid areas of type II or III pleuropulmonary blastoma. The genetic analyses presented here confirm that DICER1 mutations are the major genetic event in the development of cystic nephroma. Further, cystic nephroma and pleuropulmonary blastoma have similar DICER1 loss of function and ‘hotspot' missense mutation rates, which involve specific amino acids in the RNase IIIb domain. We propose an alternative pathway with the genetic pathogenesis of cystic nephroma and DICER1-renal sarcoma paralleling that of type I to type II/III malignant progression of pleuropulmonary blastoma

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study)

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types

Type-Specific HPV Prevalence in Cervical Cancer and High-Grade Lesions in Latin America and the Caribbean: Systematic Review and Meta-Analysis

BACKGROUND: Cervical cancer is a major public health problem in Latin America and the Caribbean (LA&C), showing some of the highest incidence and mortality rates worldwide. Information on HPV type distribution in high-grade cervical lesions (HSIL) and invasive cervical cancer (ICC) is crucial to predict the future impact of HPV16/18 vaccines and screening programmes, and to establish an appropriate post-vaccinal virologic surveillance. The aim was to assess the prevalence of HPV types in HSIL and ICC in studies in LA&C. METHODS AND FINDINGS: We performed a systematic review, following the MOOSE guidelines for systematic reviews of observational studies, and the PRISMA statement for reporting systematic reviews and meta-analyses. Inclusion criteria were at least ten cases of HSIL/ICC, and HPV-type elicitation. The search, without language restrictions, was performed in MEDLINE, Cochrane Library, EMBASE, LILACS from inception date to December 2009, proceedings, reference lists and consulting experts. A meta-analysis was performed using arc-sine transformations to stabilize the variance of simple proportions. Seventy-nine studies from 18 countries were identified, including 2446 cases of HSIL and 5540 of ICC. Overall, 46.5% of HSIL cases harbored HPV 16 and 8.9% HPV18; in ICC, 53.2% of cases harbored HPV 16 and 13.2% HPV 18. The next five most common types, in decreasing frequency, were HPV 31, 58, 33, 45, and 52. Study's limitations comprise the cross-sectional design of most included studies and their inherent risk of bias, the lack of representativeness, and variations in the HPV type-specific sensitivity of different PCR protocols. CONCLUSIONS: This study is the broadest summary of HPV type distribution in HSIL and ICC in LA&C to date. These data are essential for local decision makers regarding HPV screening and vaccination policies. Continued HPV surveillance would be useful, to assess the potential for changing type-specific HPV prevalence in the post-vaccination era in Latin America

The Canlex Project: summary and conclusions

The Canadian geotechnical engineering community has completed a major collaborative 5 year research project entitled the Canadian Liquefaction Experiment (CANLEX). The main objective of the project was to study the phenomenon of soil liquefaction, which can occur in saturated sandy soils and is characterized by a large loss of strength or stiffness resulting in substantial deformations. The intent of this paper is to compare, interpret, and summarize the large amount of field and laboratory data obtained for six sites in Western Canada as part of the CANLEX project. The sites are compared in terms of both flow-liquefaction and cyclic-softening considerations. The paper presents a number of conclusions drawn from the project as a whole, in terms of both fundamental and practical significance.published_or_final_versio

Understanding assessment on a ward for older people : a qualitative study

Aim: To explore assessment on a hospital ward for older people from the perspectives of patients and healthcare professionals. Design: A qualitative study drawing on grounded theory was undertaken between February 2015 and January 2016. Methods: Interviews with 15 patients and 22 healthcare professionals, a focus group with six healthcare professionals, 45 hours of observation, and review of 18 sets of patient notes. Analysis was conducted using initial and focused coding, continuously comparing data, emerging codes and themes. Findings: The core category was navigating, constructed through three themes: containing complexity, networking, and situating the process. Navigating assessment was a complex, flexible, context dependent and social process in which healthcare professionals used a combination of formal, informal, visible and invisible ways of working. Registered nurses were at the centre of networking and focused on gathering and sharing information within the multi-disciplinary team, whilst patients had a passive role despite a variety of preferences about their involvement. Conclusions: Navigating the assessment of older people is contextually situated, includes networking and a professional focus on containing complexity. This process may be enhanced by: 1) making informal assessment visible to others; 2) developing the nurses’ role beyond chasing information towards coordinating care; 3) asking patients and acting on how they would like to be involved in decision making. Impact: Acknowledging that navigating assessment is a social, flexible and complex process, including different ways of working to meet patient needs, may enhance the usability of current assessment guidelines and their development