Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

<p>Abstract</p> <p>Background</p> <p>It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis.</p> <p>Methods</p> <p>We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body ¹⁸F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression.</p> <p>Results</p> <p>No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does.</p

Linear stability analysis of miscible two-fluid flow in a channel with velocity slip at the walls

The linear stability characteristics of pressure-driven miscible two-fluid flow with same density and varying viscosities in a channel with velocity slip at the wall are examined.Aprominent feature of the instability is that only a band ofwave numbers is unstable whatever the Reynolds number is, whereas shorter wavelengths and smaller wave numbers are observed to be stable. The stability characteristics are different from both the limiting cases of interface dominated flows and continuously stratified flows in a channel with velocity slip at the wall. The flow system is destabilizing when a more viscous fluid occupies the region closer to the wall with slip. For this configuration a new mode of instability, namely the overlap mode, appears for high mass diffusivity of the two fluids. This mode arises due to the overlap of critical layer of dominant instability with the mixed layer of varying viscosity. The critical layer contains a location in the flowdomain atwhich the base flowvelocity equals the phase speed of themost unstable disturbance. Such amode also occurs in the corresponding flow in a rigid channel, but absent in either of the above limiting cases of flow in a channel with slip. The flow is unstable at low Reynolds numbers for a wide range of wave numbers for low mass diffusivity, mimicking the interfacial instability of the immiscible flows. A configuration with less viscous fluid adjacent to the wall is more stable at moderate miscibility and this is also in contrast with the result for the limiting case of interface dominated flows in a channel with slip, where the above configuration ismore unstable. It is possible to achieve stabilization or destabilization of miscible two-fluid flow in a channel with wall slip by appropriately choosing the viscosity of the fluid layer adjacent to the wall. In addition, the velocity slip at the wall has a dual role in the stability of flow system and the trend is influenced by the location of the mixed layer, the location of more viscous fluid and the mass diffusivity of the two fluids. It is well known that creating a viscosity contrast in a particularway in a rigid channel delays the occurrence of turbulence in a rigid channel. The results of the present study show that the flow system can be either stabilized or destabilized by designing the walls of the channel as hydrophobic surfaces, modeled by velocity slip at the walls. The study provides another effective strategy to control the flow syste

Is Microsporidial keratitis an emerging cause of stromal keratitis? – a case series study

BACKGROUND: Microsporidial keratitis is a rare cause of stromal keratitis. We present a series of five cases of microsporidial keratitis from a single centre in southern India with microbiologic and histopathologic features. CASE PRESENTATION: Patient charts of five cases of microsporidial stromal keratitis diagnosed between January 2002 and June 2004 were reviewed retrospectively for clinical data, microbiologic and histopathologic data. The presence of microsporidia was confirmed by special stains on corneal scrapings and/or corneal tissues, and electron microscopy. All patients were immunocompetent with a preceding history of trauma in three. Four patients presented with unilateral, small, persisting deep stromal infiltrates, of uncertain etiology, in the cornea, which were not responding to conventional antimicrobial treatment and required penetrating keratoplasty in three. Fifth case was unsuspected and underwent keratoplasty for post-traumatic scar. Three of five cases were diagnosed on corneal scrapings, prior to keratoplasty, while two were diagnosed only on histology. The microsporidia appeared as oval well defined bodies with dense staining at one pole. None of the patients showed recurrence following keratoplasty. CONCLUSION: Microsporidia, though rare, should be suspected in chronic culture-negative stromal keratitis. Organisms could lie dormant without associated inflammation

Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136359/1/ijc30600_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136359/2/ijc30600.pd

Construing the child reader: a cognitive stylistic analysis of the opening to Neil Gaiman’s The Graveyard Book

Neil Gaiman’s The Graveyard Book (2009) charts the story of Nobody Owens, a boy who is adopted by supernatural entities in the local graveyard after his family is murdered. This article draws on the notion of the “construed reader,” and combines two cognitive stylistic frameworks to analyse the opening section of the novel. In doing so, the article explores the representation and significance of the family home in relation to what follows in the narrative. The analysis largely draws on Text World Theory (Werth, 1999; Gavins, 2007), but also integrates some aspects of Cognitive Grammar (Langacker, 2008), which allows for a more nuanced discussion of textual features. The article pays particular attention to the way Gaiman frames his narrative and positions his reader to view the fictional events from a distinctive vantage point and subsequently demonstrates that a stylistic analysis of children’s literature can lay bare how such writing is designed with a young readership in mind

Assessing the genetic architecture of epithelial ovarian cancer histological subtypes.

Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The Nurses’ Health Studies would like to thank the participants and staff of the Nurses' Health Study and Nurses' Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. Funding of the constituent studies was provided by the California Cancer Research Program (00-01389V-20170, N01-CN25403, 2II0200); the Canadian Institutes of Health Research (MOP-86727); Cancer Australia; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124); the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; the Norwegian Cancer Society; the Norwegian Research Council; the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; the L & S Milken Foundation; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); the Roswell Park Cancer Institute Alliance Foundation; the US National Cancer Institute (K07-CA095666, K07-CA80668, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC67001, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA072720, P30-CA15083, P30-CA008748, P50-CA159981, P50-CA105009, P50-CA136393, R01-CA149429, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063678, R01-CA063682, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044, R01-CA095023, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA136924, R03-CA113148, R03-CA115195, U01-CA069417, U01-CA071966, UM1-CA186107, UM1-CA176726 and Intramural research funds); the NIH/National Center for Research Resources/General Clinical Research Center (MO1-RR000056); the US Army Medical Research and Material Command (DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-07-0449, W81XWH-10-1-02802); the US Public Health Service (PSA-042205); the National Health and Medical Research Council of Australia (199600 and 400281); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01GB 9401); the State of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P.685); the German Cancer Research Center; the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; Eve Appeal; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital ‘Womens Health Theme’ and the Royal Marsden Hospital; and WorkSafeBC 14. Investigator-specific funding: G.C.P receives scholarship support from the University of Queensland and QIMR Berghofer. Y.L. was supported by the NHMRC Early Career Fellowship. G.C.T. is supported by the National Health and Medical Research Council. S.M. was supported by an ARC Future Fellowship

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.Other Research Uni