WorldWideScience

Sample records for high-grade transition area

  1. Primary amyloidosis with high grade transitional cell carcinoma of bladder: A rare case report

    Directory of Open Access Journals (Sweden)

    Prashant Gupta

    2012-01-01

    Full Text Available Primary amyloidosis of bladder is a rare disease that closely resembles bladder cancer on clinical presentation with painless gross hematuria. Pathologically this is a totally benign non-neoplastic lesion and its association with urothelial carcinoma of the bladder is rare. We herein report a 64-year-old diabetic male who has been treated for primary amyloidosis of bladder for the last 26 years presented recently with high-grade solid urothelial cancer with osseous metaplasia and sarcomatoid change of bladder with area of amyloid deposition.

  2. Increased variability of watershed areas in patients with high-grade carotid stenosis

    DEFF Research Database (Denmark)

    Kaczmarz, Stephan; Griese, Vanessa; Preibisch, Christine

    2018-01-01

    . Despite of high relevance for both clinical diagnostics and research, individual in vivo WSA definition is fairly limited to date. Thus, this study proposes a standardized segmentation approach to delineate individual WSAs by use of time-to-peak (TTP) maps and investigates spatial variability...... time atlas and individual super-selective arterial spin labeling. We compared spatial variability of WSA probability maps between groups and assessed TTP differences between hemispheres in individual and group-average watershed locations. Results: Patients showed significantly higher spatial...... of individual WSAs. Methods: We defined individual watershed masks based on relative TTP increases in 30 healthy elderly persons and 28 patients with unilateral, high-grade carotid stenosis, being at risk for watershed-related hemodynamic impairment. Determined WSA location was confirmed by an arterial transit...

  3. Frequent EGFR Positivity and Overexpression in High-Grade Areas of Human MPNSTs

    Directory of Open Access Journals (Sweden)

    Séverine Tabone-Eglinger

    2008-01-01

    Full Text Available Malignant peripheral nerve sheath tumours (MPNSTs are highly malignant and resistant. Transformation might implicate up regulation of epidermal growth factor receptor (EGFR. Fifty-two MPNST samples were studied for EGFR, Ki-67, p53, and survivin expression by immunohistochemistry and for EGFR amplification by in situ hybridization. Results were correlated with clinical data. EGFR RNA was also quantified by RT-PCR in 20 other MPNSTs and 14 dermal neurofibromas. Half of the patients had a neurofibromatosis type 1 (NF1. EGFR expression, detected in 86% of MPNSTs, was more frequent in NF1 specimens and closely associated with high-grade and p53-positive areas. MPNSTs expressed more EGFR transcripts than neurofibromas. No amplification of EGFR locus was observed. NF1 status was the only prognostic factor in multivariate analysis, with median survivals of 18 and 43 months for patients with or without NF1. Finally, EGFR might become a new target for MPNSTs treatment, especially in NF1-associated MPNSTs.

  4. U-Pb isotopic systematics of zircons from prograde and retrograde transition zones in high-grade orthogneisses, Sri Lanka

    Energy Technology Data Exchange (ETDEWEB)

    Baur, N.; Liew, T.C.; Todt, W.; Hofmann, A.W. (Max-Planck-Institut fuer Chemie, Mainz (West Germany)); Kroener, A. (Univ. Mainz (West Germany)); Williams, I.S. (Australian National Univ., Canberra (Australia))

    1991-07-01

    The authors present U-Pb zircon isotopic data from locally restricted prograde (arrested in situ charnockitization) and retrograde metamorphic transition zones, which are well exposed in Proterozoic orthogneisses tectonically interbanded with granulite facies supracrustal rocks of the Highland Group in Sri Lanka. These granitoid rocks yield apparent ages of 1942 {plus minus} 22 Ma, {approximately} 770 Ma, {approximately} 660 Ma, and {approximately} 560 Ma. All samples show severe Pb-loss some 550-560 Ma ago. The main phase of granulite-formation could not be dated unambiguously but is bracketed between {approximately} 660 Ma and {approximately} 550 Ma. The pervasive Pb-loss event around 550-560 Ma reflects the end of this period of high-grade metamorphism and was associated with widespread igneous activity and retrogression. This is constrained by the 550 {plus minus} 3 Ma intrusion age for a post-tectonic granite. They relate this late phase of thermal activity to crustal uplift of the Sri Lankan granulites. This data unambiguously prove the high-grade history of the Sri Lanka gneisses to be a late Precambrian event that may be related to the Pan-African evolution along the eastern part of Africa.

  5. High-grade metamorphic rocks of the Mellid area, Galicia, NW Spain

    NARCIS (Netherlands)

    Hubregtse, J.J.M.W.

    1973-01-01

    This study concerns the petrology of the Mellid area, the SE portion of the outer zone of the Ordenes Complex which is one of the upthrusted Precambrian complexes in the axial zone of the Hercynian orogen in Galicia, NW Spain. An eugeosynclinal rock sequence is found containing units with different

  6. Capillary Transit Time Heterogeneity Is Associated with Modified Rankin Scale Score at Discharge in Patients with Bilateral High Grade Internal Carotid Artery Stenosis.

    Directory of Open Access Journals (Sweden)

    Sibu Mundiyanapurath

    Full Text Available Perfusion weighted imaging (PWI is inherently unreliable in patients with severe perfusion abnormalities. We compared the diagnostic accuracy of a novel index of microvascular flow-patterns, so-called capillary transit time heterogeneity (CTH to that of the commonly used delay parameter Tmax in patients with bilateral high grade internal carotid artery stenosis (ICAS.Consecutive patients with bilateral ICAS ≥ 70%NASCET who underwent PWI were retrospectively examined. Maps of CTH and Tmax were analyzed with a volumetric approach using several thresholds. Predictors of favorable outcome (modified Rankin scale at discharge 0-2 were identified using univariate and receiver operating characteristic (ROC curve analysis.Eighteen patients were included. CTH ≥ 30s differentiated best between patients with favorable and unfavorable outcome when both hemispheres were taken into account (sensitivity 83%, specificity 73%, area under the curve [AUC] 0.833 [confidence interval (CI 0.635; 1.000]; p = 0.027. The best discrimination using Tmax was achieved with a threshold of ≥ 4s (sensitivity 83%, specificity 64%, AUC 0.803 [CI 0.585;1.000]; p = 0.044. The highest AUC was found for left sided volume with CTH ≥ 15s (sensitivity 83%, specificity 91%, AUC 0.924 [CI 0.791;1.000]; p = 0.005.The study suggests that CTH is superior to Tmax in discriminating ICAS patients with favorable from non-favorable outcome. This finding may reflect the simultaneous involvement of large vessels and microvessels in ICAS and underscore the need to diagnose and manage both aspects of the disease.

  7. Petrology of the Teijeiro area: part of the Early Palaeozoic high-grade metamorphic Sobrado/Teijeiro complex (Galicia, NW Spain)

    NARCIS (Netherlands)

    Kuijper, R.P.

    1981-01-01

    The high-grade metamorphic Sobrado-Teijeiro complex forms part of the peripheral belt of the Ordenes basin. The fault-bounded elliptical complex consists of a central unit of highly serpentinized ultramafic rocks, surrounded by (partly retrograded) mafic granulite facies rocks, highgrade

  8. Knoxville Area Transit: Propane Hybrid Electric Trolleys

    Energy Technology Data Exchange (ETDEWEB)

    2005-04-01

    A 2-page fact sheet summarizing the evaluation done by the U.S. Department of Energy's Advanced Vehicle Testing Activity on the Knoxville Area Transit's use of propane hybrid electric trolleys.

  9. A Systematic Review and Meta-Analysis of Studies Examining the Use of Brain Laser Interstitial Thermal Therapy versus Craniotomy for the Treatment of High-Grade Tumors in or near Areas of Eloquence: An Examination of the Extent of Resection and Major Complication Rates Associated with Each Type of Surgery.

    Science.gov (United States)

    Barnett, Gene H; Voigt, Jeffrey D; Alhuwalia, Manmeet S

    2016-01-01

    The extent of resection (EOR) of high-grade gliomas (WHO grade III or IV) in or near areas of eloquence is associated with overall patient survival, but with higher major neurocognitive complications. A systematic review and meta-analysis was undertaken of the peer-reviewed literature in order to identify studies which examined EOR or extent of ablation (EOA) and major complications (defined as neurocognitive or functional complications which last >3 months duration after surgery) associated with either brain laser interstitial thermal therapy (LITT) or open craniotomy in high-grade tumors in or near areas of eloquence. Eight studies on brain LITT (n = 79 patients) and 12 craniotomy studies (n = 1,036 patients) were identified which examined either/both EOR/EOA and complications. Meta-analysis demonstrated an EOA/EOR of 85.4 ± 10.6% with brain LITT versus 77.0 ± 40% with craniotomy (mean difference: 8%; 95% CI: 2-15; p = 0.01; inverse variance, random effects model). Meta-analysis of proportions of major complications for each individual therapy demonstrated major complications of 5.7% (95% CI: 1.8-11.6) and 13.8% (95% CI: 10.3-17.9) for LITT and craniotomy, respectively. In patients presenting with high-grade gliomas in or near areas of eloquence, early results demonstrate that brain LITT may be a viable surgical alternative. © 2016 The Author(s) Published by S. Karger AG, Basel.

  10. Industrial cities in transition: Problem areas

    Directory of Open Access Journals (Sweden)

    Miletić Radmila

    2009-01-01

    Full Text Available The complex transitional process of the central and eastern European countries from the centrally-planned economy towards the market economy has been characterized by numerous conflicts and dramatic changes, particularly in the production sector. Taking into consideration that industry had the dominant significance in the economic structure shortly before the collapse of communism, the primary focus of the reforms was directed towards its restructuring. Therefore, the deindustrialization, as the process of the economic, social, spatial and ecological changes connected with the reduction of the productive activities, has been an integral part of the transitional process in these countries. While some regions/cities reacted positively on the changes and had the advantage in the newly created circumstances, others faced with serious problems, weakened their position considerably in the local and regional frames. Thus, the spatial structure of industry was also modified on different levels of the territorial hierarchy. The uncompetitive economic base, spoiled environment, together with other unfavourable factors in many-structural industrial centers/regions has slowed down the exceeding of the structural lacks by taking them into a phase of stagnation or regression. In comparison with other post-socialist countries, the transitional process in Serbia was marked by a series of uniqueness as due to different historical heritage, circumstances in which the process had begun so due to applied policies of adapting and restructuring. .

  11. Metal recovery from high-grade WEEE

    DEFF Research Database (Denmark)

    Bigum, Marianne; Brogaard, Line Kai-Sørensen; Christensen, Thomas Højlund

    2012-01-01

    Based on available data in the literature the recovery of aluminium, copper, gold, iron, nickel, palladium and silver from high-grade WEEE was modeled by LCA. The pre-treatment of WEEE included manual sorting, shredding, magnetic sorting, Eddy-current sorting, air classification and optical sorting...... and refining of ore. The resource recovery per tonne of high-grade WEEE ranged from 2 g of palladium to 386 kg of iron. Quantified in terms of person-equivalents the recovery of palladium, gold, silver, nickel and copper constituted the major environmental benefit of the recovery of metals from WEEE...... effect compared to the metallurgical treatment. However only 12-26% of silver, gold and palladium are recovered during pre-treatment, which suggest that the reduction of the apparent losses of precious metals as palladium, gold and silver during pre-treatment of WEEE is of environmental importance. Our...

  12. Permian Triassic palynofloral transition in Chintalapudi area ...

    Indian Academy of Sciences (India)

    The entire 606 m-thick sedimentary sequence in borecore MCP-7 from Chintalapudi area, Chintalapudi sub-basin has been lithologically designated as Kamthi Formation. However, the palynological inves- tigation revealed five distinct palynoassemblages, which essentially fall under two groups, one group.

  13. Permian Triassic palynofloral transition in Chintalapudi area ...

    Indian Academy of Sciences (India)

    The entire 606 m-thick sedimentary sequence in borecore MCP-7 from Chintalapudi area, Chintalapudi sub-basin has been lithologically designated as Kamthi Formation. However, the palynological investigation revealed five distinct palynoassemblages, which essentially fall under two groups, one group ...

  14. High-grade primary pulmonary leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Rodrigo Afonso da Silva Sardenberg

    2011-12-01

    Full Text Available Primary sarcomas of the lung are rare and account for 0.5% of all primary lung tumors. There were approximately 300 cases described in the literature as of 2006. All histologic types of sarcoma were described, and the most common intrathoracic types reported were angiosarcoma, leiomyosarcoma, fibrosarcoma, hemangiopericytoma, and rhabdomyosarcoma. The biological behavior of these tumors is not well-known due to their low frequency. Leiomyosarcomas represent one of the most common subtypes encountered in the lungs, and usually occur during the sixth decade, with male predominance. Although the frequency of metastatic disease is not related to tumor size, prognosis was reported to be poorer in high-grade tumors. In comparison with other sarcomas, survival after complete resection of pulmonary leiomyosarcoma was reported as longer. We report on a patient with primary leiomyosarcoma originating from the bronchus with complete resection and long-term follow-up.

  15. Posterior surgery in high-grade spondylolisthesis.

    Science.gov (United States)

    Lengert, R; Charles, Y P; Walter, A; Schuller, S; Godet, J; Steib, J-P

    2014-09-01

    High-grade L5-S1 spondylolisthesis alters sagittal spinopelvic balance, which can cause low back pain and progressive neurologic disorder. The present study assessed spondylolisthesis reduction and maintenance over time with L4-S1 versus L5-S1 fusion using a lever-arm system and posterior fusion combined with lumbosacral graft. Forty patients were operated on for symptomatic high-grade spondylolisthesis, 34 of whom had full pre- and post-operative radiological analysis, with a mean follow-up of 5.4years. There were 9 L5-S1 and 25 L4-S1 instrumentations. Analysis of spinopelvic and slipping parameters and the evolution of segmental lordosis compared results between L5-S1 and L4-S1 instrumentation. Mean Taillard spondylolisthesis index decreased from 64% to 37% (P=0.0001). Overall sagittal spinopelvic balance was not significantly changed. Overall L1-S1 and segmental L4-L5 lordosis were not affected by instrumentation. Mean L5-S1 segmental lordosis increased from 11° to 18°. There was loss of reduction from 19° to 14° with L5-S1 instrumentation, in contrast to maintained reduction with L4-S1 instrumentation (P=0.006). The lever-arm system provided anterior-posterior reduction of spondylolisthesis and corrected slippage. Postoperative change in overall sagittal spinopelvic balance was slight and constant. Posterior L4-S1 fusion provided better long-term control of L5-S1 lordosis reduction than the shorter L5-S1 fusion. Retrospective study of level IV. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Accessibility and transit-oriented development in European metropolitan areas

    NARCIS (Netherlands)

    Papa, E.; Bertolini, L.

    2015-01-01

    This study investigates how urban form is related to accessibility. In particular, it explores the relationship between Transit-Oriented Development (TOD) and rail-based accessibility in a metropolitan area. The following overarching questions are addressed: Does a TOD-informed urban spatial

  17. Alkali control of high-grade metamorphism and granitization

    Directory of Open Access Journals (Sweden)

    Oleg G. Safonov

    2014-09-01

    Full Text Available We review petrologic observations of reaction textures from high-grade rocks that suggest the passage of fluids with variable alkali activities. Development of these reaction textures is accompanied by regular compositional variations in plagioclase, pyroxenes, biotite, amphibole and garnet. The textures are interpreted in terms of exchange and net-transfer reactions controlled by the K and Na activities in the fluids. On the regional scale, these reactions operate in granitized, charnockitized, syenitized etc. shear zones within high-grade complexes. Thermodynamic calculations in simple chemical systems show that changes in mineral assemblages, including the transition from the hydrous to the anhydrous ones, may occur at constant pressure and temperature due only to variations in the H2O and the alkali activities. A simple procedure for estimating the activity of the two major alkali oxides, K2O and Na2O, is implemented in the TWQ software. Examples of calculations are presented for well-documented dehydration zones from South Africa, southern India, and Sri Lanka. The calculations have revealed two end-member regimes of alkalis during specific metamorphic processes: rock buffered, which is characteristic for the precursor rocks containing two feldspars, and fluid-buffered for the precursor rocks without K-feldspar. The observed reaction textures and the results of thermodynamic modeling are compared with the results of available experimental studies on the interaction of the alkali chloride and carbonate-bearing fluids with metamorphic rocks at mid-crustal conditions. The experiments show the complex effect of alkali activities in the fluid phase on the mineral assemblages. Both thermodynamic calculations and experiments closely reproduce paragenetic relations theoretically predicted by D.S. Korzhinskii in the 1940s.

  18. A large area transition radiation detector for the NOMAD experiment

    Science.gov (United States)

    Bassompierre, G.; Bermond, M.; Berthet, M.; Bertozzi, T.; Détraz, C.; Dubois, J.-M.; Dumps, L.; Engster, C.; Fazio, T.; Gaillard, G.; Gaillard, J.-M.; Gouanère, M.; Manola-Poggioli, E.; Mossuz, L.; Mendiburu, J.-P.; Nédélec, P.; Palazzini, E.; Pessard, H.; Petit, P.; Petitpas, P.; Placci, A.; Sillou, D.; Sottile, R.; Valuev, V.; Verkindt, D.; Vey, H.; Wachnik, M.

    1998-02-01

    A transition radiation detector to identify electrons at 90% efficiency with a rejection factor against pions of 10 3 on an area of 2.85 × 2.85 m 2 has been constructed for the NOMAD experiment. Each of its 9 modules includes a 315 plastic foil radiator and a detector plane of 176 vertical straw tubes filled with a xenon-methane gas mixture. Details of the design, construction and operation of the detector are given.

  19. A large area transition radiation detector for the NOMAD experiment

    CERN Document Server

    Bassompierre, Gabriel; Berthet, M; Bertozzi, T; Détraz, C; Dubois, J M; Dumps, Ludwig; Engster, Claude; Fazio, T; Gaillard, G; Gaillard, Jean-Marc; Gouanère, M; Manola-Poggioli, E; Mossuz, L; Mendiburu, J P; Nédélec, P; Palazzini, E; Pessard, H; Petit, P; Petitpas, P; Placci, Alfredo; Sillou, D; Sottile, R; Valuev, V Yu; Verkindt, D; Vey, H; Wachnik, M

    1997-01-01

    A transition radiation detector to identify electrons at 90% efficiency with a rejection factor against pions of 10 3 on an area of 2.85 × 2.85 m 2 has been constructed for the NOMAD experiment. Each of its 9 modules includes a 315 plastic foil radiator and a detector plane of 176 vertical straw tubes filled with a xenon-methane gas mixture. Details of the design, construction and operation of the detector are given.

  20. On Financing of Urban Transition viewed from the Oresund Area

    DEFF Research Database (Denmark)

    Haldrup, Karin; Snällfot, David

    2014-01-01

    The “urban transition” agenda is as a conglomerate of ambitions derived from international policy documents and as applied in the Oresund area. Encompassing locally set goals for (i) climate change mitigation; (ii) energy efficiency; and (iii) human wellbeing in the built environment. Its...... implementation is largely dependent on private sector joining in, since transitioning the building stock is to be financed by the market. This paper explores strategies to meet this agenda in the Oresund area. A particular focus is on the refurbishment of multi-family housing relative to these set goals...

  1. Oncocytoma-Like Renal Tumor With Transformation Toward High-Grade Oncocytic Carcinoma

    Science.gov (United States)

    Sirintrapun, Sahussapont J.; Geisinger, Kim R.; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L.; Ghazalpour, Anatole; Bender, Ryan P.; Gatalica, Zoran

    2014-01-01

    Abstract Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt–Hogg–Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the

  2. Post-treatment changes of tumour perfusion parameters can help to predict survival in patients with high-grade astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Sanz-Requena, Roberto; Marti-Bonmati, Luis [Hospital Quironsalud Valencia, Radiology Department, Valencia (Spain); Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); Revert-Ventura, Antonio J.; Salame-Gamarra, Fares [Hospital de Manises, Radiology Department, Manises (Spain); Garcia-Marti, Gracian [Hospital Quironsalud Valencia, Radiology Department, Valencia (Spain); Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); CIBER-SAM, Instituto de Salud Carlos III, Madrid (Spain); Perez-Girbes, Alexandre [Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); Molla-Olmos, Enrique [Hospital La Ribera, Radiology Department, Alzira (Spain)

    2017-08-15

    Vascular characteristics of tumour and peritumoral volumes of high-grade gliomas change with treatment. This work evaluates the variations of T2*-weighted perfusion parameters as overall survival (OS) predictors. Forty-five patients with histologically confirmed high-grade astrocytoma (8 grade III and 37 grade IV) were included. All patients underwent pre- and post-treatment T2*-weighted contrast-enhanced magnetic resonance (MR) imaging. Tumour, peritumoral and control volumes were segmented. Relative variations of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), K{sup trans-T2*}, k{sub ep-T2*}, v{sub e-T2*} and v{sub p-T2*} were calculated. Differences regarding tumour grade and surgical resection extension were evaluated with ANOVA tests. For each parameter, two groups were defined by non-supervised clusterisation. Survival analysis were performed on these groups. For the tumour region, the 90th percentile increase or stagnation of CBV was associated with shorter survival, while a decrease related to longer survival (393 ± 189 vs 594 ± 294 days; log-rank p = 0.019; Cox hazard-ratio, 2.31; 95% confidence interval [CI], 1.12-4.74). K{sup trans-T2*} showed similar results (414 ± 177 vs 553 ± 312 days; log-rank p = 0.037; hazard-ratio, 2.19; 95% CI, 1.03-4.65). The peritumoral area values showed no relationship with OS. Post-treatment variations of the highest CBV and K{sup trans-T2*} values in the tumour volume are predictive factors of OS in patients with high-grade gliomas. (orig.)

  3. Evidence of nerve sheath differentiation and high grade morphology in sclerosing epithelioid fibrosarcoma

    Science.gov (United States)

    Hanson, I; Pearson, J; Eyden, B; Slawik, S; Harris, M

    2001-01-01

    Sclerosing epithelioid fibrosarcoma is a recently described sarcoma in which ultrastructural evidence of fibroblastic differentiation forms part of the diagnostic criteria. This report describes a further case of this tumour, which showed evidence of both fibroblastic and perineurial differentiation by immunohistochemistry and electron microscopy, and which had areas of high grade morphology. The tumour metastasised and the patient died of disease 12 months after presentation. The relevance of these findings to diagnosis and differentiation in these tumours is discussed. Key Words: sclerosing epithelioid fibrosarcoma • nerve sheath differentiation • high grade morphology PMID:11533083

  4. Redundancy in Public Transit - Vol III. The Political Economy of Transit in the San Francisco Bay Area, 1945-63

    OpenAIRE

    Seymour Adler

    1980-01-01

    This report focuses on two concrete developments. One is the historical process that produced the Bay Area Rapid Transit District in 1957 and the district's particular regional rapid transit plan, approved by the voters of Alameda, Contra Costa, and San Francisco counties in November, 1962. The other is the process that produced the Alameda-Contra Costa Transit District in 1955 and 1956, and the particular transit service this District began operating in 1960. The relation between the two dis...

  5. 40 CFR 246.200 - High-grade paper recovery.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery. ...

  6. Role of radiotherapy for high grade gliomas management.

    Science.gov (United States)

    Caruso, C; Carcaterra, M; Donato, V

    2013-06-01

    We have analyzed the therapeutic standard options for high grade gliomas, with particular attention to the different radiation therapy modalities and techniques and their application considering the natural history of the disease. Of the several therapeutic options, surgical resection remains the initial treatment of choice for patients with high grade glioma; of all adjuvant treatments tested, radiotherapy offers the greatest magnitude of survival benefit, so radiotherapy, which must be started within 6 weeks of surgery, is mandatory for practically all patients with high grade gliomas. In this paper we perform an overview considering the integration between the different therapeutic modalities, with particular attention to the radiation therapy role in the management of high grade gliomas.

  7. INTERFACIAL AREA TRANSPORT AND REGIME TRANSITION IN COMBINATORIAL CHANNELS

    Energy Technology Data Exchange (ETDEWEB)

    Seugjin Kim

    2011-01-28

    . This study investigates the geometric effects of 90-degree vertical elbows and flow configurations in two-phase flow. The study shows that the elbows make a significant effect on the transport characteristics of two-phase flow, which includes the changes in interfacial structures, bubble interaction mechanisms and flow regime transition. The effect of the elbows is characterized for global and local two-phase flow parameters. The global two-phase flow parameters include two-phase pressure, interfacial structures and flow regime transition. In order to characterize the frictional pressure drop and minor loss across the vertical elbows, pressure measurements are obtained across the test section over a wide range of flow conditions in both single-phase and two-phase flow conditions. A two-phase pressure drop correlation analogous to Lockhart-Martinelli correlation is proposed to predict the minor loss across the elbows. A high speed camera is employed to perform extensive flow visualization studies across the elbows in vertical upward, horizontal and vertical downward sections and modified flow regime maps are proposed. It is found that modified flow regime maps immediately downstream of the vertical upward elbow deviate significantly from the conventional flow regime map. A qualitative assessment of the counter-current flow limitation characteristics specific to the current experimental facility is performed. A multi-sensor conductivity probe is used to measure local two-phase flow parameters such as: void fraction, bubble velocity, interfacial area concentration and bubble frequency. The local measurements are obtained for six different flow conditions at ten measurement locations along axial direction of the test section. Both the vertical-upward and vertical-downward elbows have a significant impact on bubble distribution, resulting in, a bimodal distribution along the horizontal radius of the tube cross-section and migration of bubbles towards the inside of the

  8. Alternative Fuel Transit Buses: DART's (Dallas Area Rapid Transit) LNG Bus Fleet Final Results

    Energy Technology Data Exchange (ETDEWEB)

    Chandler, K. [Battelle (US); Norton, P. [National Renewable Energy Lab., Golden, CO (US); Clark, N.

    2000-11-07

    In 1998, Dallas Area Rapid Transit, a public transit agency in Dallas, Texas, began operating a large fleet of heavy-duty buses powered by liquefied natural gas. As part of a $16 million commitment to alternative fuels, DART operates 139 LNG buses serviced by two new LNG fueling stations.

  9. MRI of high-grade astrocytic tumors: early appearance and evolution

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, K.; Takahashi, N.; Ishikawa, K.; Furusawa, T.; Sakai, K. [Department of Radiology, Niigata University Faculty of Medicine (Japan); Ito, J.; Tokiguchi, S. [Department of Radiology, Niigata University Faculty of Dentistry (Japan)

    2002-05-01

    The clinical management and prognosis of patients with diffusely infiltrating astrocytomas are dependent on neuropathological grading of the tumors. The characteristics of MR images of high-grade astrocytic tumors are well known, but the early MRI appearance and the MRI evolution of high-grade astrocytic tumors have rarely been examined. We retrospectively reviewed MR images obtained from 4 months to 3 years and 3 months before admission, as well as MR images on admission, for five patients with pathologically proven high-grade astrocytic tumors (two glioblastomas and three anaplastic astrocytomas). In two patients, neoplastic lesions were not detectable on initial MRI, even retrospectively. In the remaining three patients, however, hyperintense areas with little or no mass effect were demonstrated on T2-weighted imaging. These lesions were misinterpreted as non-neoplastic processes, such as ischemic lesion or infarction, or demyelinating processes. All tumors showed gadolinium enhancement on admission, that emerged from the previously existing hyperintense areas on T2-weighted images without gadolinium enhancement, except for one de novo glioblastoma. Development of a small central cyst without gadolinium enhancement was demonstrated in one case before the emergence of an enhancing area. (orig.)

  10. A Regional Approach to Rail Transit Training for the New York Metropolitan Area. Final Report.

    Science.gov (United States)

    McKnight, Claire E.; Rotter, Naomi

    A study examined the feasibility of a regional approach to rail transit training in the New York metropolitan area. First, case studies were collected to document existing training practices at the five agencies currently responsible for training rail transit workers in the New York metropolitan area and to identify mutual training needs that…

  11. Transition to the Work Setting in Rural Areas.

    Science.gov (United States)

    Greenwood, Reed

    1992-01-01

    Discusses two primary rural disability issues: employment needs of, and outcomes for, rural youth with disabilities; and employability development and transition methods. Suggests improvements for service delivery through effective case management, parent education and support, and collaboration among educational and rehabilitation agencies. (KS)

  12. High grade leiomyosarcoma mimicking a recurrent angiomyxoma in the perineum

    Directory of Open Access Journals (Sweden)

    Neha Sood

    2015-05-01

    Full Text Available Perineal leiomyosarcoma is an extremely rare and aggressive cancer with a high metastatic potential and no defined standard treatment. There are only a few (six reported cases in the literature. We report the case of a 67-year-old woman with a perineal leiomyosarcoma arising at the same site of a previously resected superficial angiomyxoma. Initially, she was treated for a presumptive recurrence of angiomyxoma. As she did not respond to medical therapy, she underwent repeat surgical excision. Pathology revealed a high grade leiomyosarcoma, histologically strikingly distinct from the initial diagnosis. She received adjuvant local radiation therapy, and remains without evidence of recurrent disease 36 months after completion of all therapy. This is the first reported case of a high grade perineal leiomyosarcoma originating at the same site as a resected benign superficial angiomyxoma. Our case emphasizes the necessity of a prompt histological diagnosis in cases of presumed recurrent perineal angiomyxoma.

  13. Molecular events leading to HPV-induced high grade neoplasia

    Directory of Open Access Journals (Sweden)

    Saskia M. Wilting

    2016-12-01

    Full Text Available Cervical cancer is initiated by high-risk types of the human papillomavirus (hrHPV and develops via precursor stages, called cervical intraepithelial neoplasia (CIN. High-grade CIN lesions are considered true precancerous lesions when the viral oncogenes E6 and E7 are aberrantly expressed in the dividing cells. This results in abolishment of normal cell cycle control via p53 and pRb degradation. However, it has become clear that these viral oncogenes possess additional oncogenic properties, including interference with the DNA methylation machinery and mitotic checkpoints. Identification of the resulting molecular events leading to high-grade neoplasia will 1 increase our understanding of cervical carcinogenesis, 2 yield biomarkers for early diagnosis, and 3 identify therapeutic targets for HPV-induced (pre cancerous lesions.This review will briefly summarise current advances in our understanding of the molecular alterations in the host cell genome that occur during HPV-induced carcinogenesis.

  14. Successful Nonoperative Management of High-Grade Blunt Renal Injuries.

    Science.gov (United States)

    May, Allison M; Darwish, Oussama; Dang, Brian; Monda, John J; Adsul, Prajakta; Syed, Johar; Siddiqui, Sameer A

    2016-01-01

    Current management of high-grade blunt renal trauma favors a nonoperative approach when possible. We performed a retrospective study of high grade blunt renal injuries at our level I trauma center to determine the indications and success of nonoperative management (NOM). 47 patients with blunt grade IV or V injuries were identified between October 2004 and December 2013. Immediate operative patients (IO) were compared to nonoperatively managed (NOM). Of the 47 patients, 3 (6.4%) were IO and 44 (95.6%) NOM. IO patients had a higher heart rate on admission, 133 versus 100 in NOM ( P = 0.01). IO patients had a higher rate of injury to the renal vein or artery (100%) compared to NOM group (18%) ( P = 0.01). NOM failed in 3 of 44 patients (6.8%). Two required nonemergent nephrectomy and one required emergent exploration resulting in nephrectomy. Six NOM patients had kidney-related complications (13.6%). The renal salvage rate for the entire cohort was 87.2% and 93.2% for NOM. Nonoperative management for hemodynamically stable patients with high-grade blunt renal trauma is safe with a low risk of complications. Management decisions should consider hemodynamic status and visualization of active renal bleeding as well as injury grade in determining operative management.

  15. High-grade surface osteosarcoma of the hand

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Kuniko; Hayashi, Tomayoshi; Kinoshita, Naoe [Nagasaki University Hospital, Department of Pathology, Nagasaki (Japan); Kumagai, Kenji; Shindo, Hiroyuki [Nagasaki University Graduate School of Biomedical Sciences, Department of Orthopedic Surgery, Nagasaki (Japan); Uetani, Masataka [Nagasaki University Graduate School of Biomedical Sciences, Department of Radiology and Radiation Biology, Nagasaki (Japan); Ishida, Tsuyoshi [National Center of Neurology and Psychiatry, Department of Pathology and Laboratory Medicine, Kohnodai Hospital, Chiba (Japan); Tokyo Medical and Dental University, Department of Molecular Bone and Cartilage Pathology, Hard Tissue Genome Research Center, Tokyo (Japan)

    2007-09-15

    A 32-year-old woman presented with a 1-year history of mild pain in the right ring finger. Radiographs and CT revealed a calcified lesion with cortical erosion on the surface of the proximal aspect of the right ring finger proximal phalanx. On magnetic resonance imaging (MRI), the lesion showed low signal intensity on T1- and T2-weighted images and slight enhancement with gadolinium. Clinically, it was diagnosed as a benign bone-forming lesion such as florid reactive periostitis, and excision was accordingly performed. However, histological examination revealed proliferation of atypical osteoblastic cells among irregularly arranged osteoid seams. Taking the imaging findings into account, a pathological diagnosis of high-grade surface osteosarcoma was established. In general, bone- and cartilage-forming lesions of the hands and feet are benign. Osteosarcoma of short tubular bones in the hands and feet is extremely rare; moreover, high-grade surface osteosarcoma is one of the rarest subtypes of osteosarcoma. Nonetheless, high-grade surface osteosarcoma should be included in the differential diagnosis, particularly if the radiological findings or clinical course are not entirely typical of a more common benign process, to avoid incorrect clinicoradiological and pathological diagnosis. (orig.)

  16. Elective neck management for high-grade salivary gland carcinoma.

    Science.gov (United States)

    Herman, Michael P; Werning, John W; Morris, Christopher G; Kirwan, Jessica M; Amdur, Robert J; Mendenhall, William M

    2013-01-01

    To determine whether patients with clinically node negative (cNo) high grade salivary gland carcinomas benefit from an elective neck dissection prior to postoperative radiotherapy (RT). Between October 1964 and October 2009, 59 previously untreated patients with cNo high-grade salivary gland carcinomas (squamous cell carcinomas were excluded) were treated with curative intent using elective neck dissection (END; n=41), or elective neck irradiation (ENI; n=18) at the University of Florida College of Medicine (Gainesville, FL). All patients underwent resection of the primary cancer followed by postoperative RT. The median follow-up period was 5.2years (range, 0.3-34years). Occult metastases were found in 18 (44%) of the 41 patients in the END group. There were 4 recurrences (10%) in the END group and 0 recurrence in the ENI group. Neck control rates at 5years were: END, 90%; ENI, 100%; and overall, 93% (p=0.1879). Cause-specific survival was 94% in the ENI group, 84% in the END group, and 86% for all patients (p=0.6998). There were 3 reported grade 3 or 4 toxicities. Two patients had a postoperative fistula and one patient had a grade 4 osteoradionecrosis that required a partial mandibulectomy. Patients with cNo high grade salivary gland carcinomas who are planned to undergo surgery and postoperative RT likely do not benefit from a planned neck dissection. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Radiologic Dilemma in an Extra-Axial Petroclival Lesion: Low Grade versus High Grade.

    Science.gov (United States)

    Karthigeyan, Madhivanan; Ahuja, Chirag Kamal; Chatterjee, Debjyoti; Salunke, Pravin

    2017-04-01

    Radiologic differentiation between a low-grade and high-grade lesion is crucial when deciding extent of resection and prognostication. Occasionally, imaging features can be confusing between the 2 lesions. We report a case that presented such a radiologic dilemma. The lesion appeared benign and extra-axial on routine magnetic resonance imaging sequences. However, subtle clinical and imaging clues pointed to a high-grade lesion. A 27-year-old woman presented with multiple cranial nerve palsies, gait ataxia, and features of increased intracranial pressure. Computed tomography and magnetic resonance imaging showed a petroclival extra-axial contrast-enhancing lesion with areas of chunky calcification. Although choline peak on spectroscopy raised suspicion of a high-grade lesion, the primary differential diagnosis included meningioma and schwannoma considering its characteristic imaging appearance. Postoperative histopathology showed the lesion to be giant cell glioblastoma. Apart from reporting a rare variant of glioblastoma in an unusual location, this case highlights atypical imaging in a glioblastoma. Brainstem edema may be a subtle indicator of the infiltrative nature of a tumor. Magnetic resonance spectroscopy may be a useful adjunct in such circumstances. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. MRI differentiation of low-grade from high-grade appendicular chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Douis, Hassan; Singh, Leanne; Saifuddin, Asif [The Royal National Orthopaedic Hospital NHS Trust, Department of Radiology, Stanmore, Middlesex (United Kingdom)

    2014-01-15

    To identify magnetic resonance imaging (MRI) features which differentiate low-grade chondral lesions (atypical cartilaginous tumours/grade 1 chondrosarcoma) from high-grade chondrosarcomas (grade 2, grade 3 and dedifferentiated chondrosarcoma) of the major long bones. We identified all patients treated for central atypical cartilaginous tumours and central chondrosarcoma of major long bones (humerus, femur, tibia) over a 13-year period. The MRI studies were assessed for the following features: bone marrow oedema, soft tissue oedema, bone expansion, cortical thickening, cortical destruction, active periostitis, soft tissue mass and tumour length. The MRI-features were compared with the histopathological tumour grading using univariate, multivariate logistic regression and receiver operating characteristic curve (ROC) analyses. One hundred and seventy-nine tumours were included in this retrospective study. There were 28 atypical cartilaginous tumours, 79 grade 1 chondrosarcomas, 36 grade 2 chondrosarcomas, 13 grade 3 chondrosarcomas and 23 dedifferentiated chondrosarcomas. Multivariate analysis demonstrated that bone expansion (P = 0.001), active periostitis (P = 0.001), soft tissue mass (P < 0.001) and tumour length (P < 0.001) were statistically significant differentiating factors between low-grade and high-grade chondral lesions with an area under the ROC curve of 0.956. On MRI, bone expansion, active periostitis, soft tissue mass and tumour length can reliably differentiate high-grade chondrosarcomas from low-grade chondral lesions of the major long bones. (orig.)

  19. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  20. Characterization of Stormwater Runoff from a Light Rail Transit Area.

    Science.gov (United States)

    Sajjad, Raja Umer; Kim, Kyoung Jin; Memon, Sheeraz; Sukhbaatar, Chinzorig; Paule, Ma Cristina; Lee, Bum-Yeon; Lee, Chang-Hee

    2015-09-01

    The monitoring of stormwater runoff from Light Rail Transit (LRT) facilities is insufficient in many regions around the world. In this study, runoff quality and quantity were monitored during operational and non-operational LRT phases during 2010-2013. The event mean concentration (EMC) of pollutants showed little statistical variability during both phases. The antecedent dry day (ADD) showed a strong to moderate positive correlation with most pollutant EMCs during the non-operational phase. The existence and magnitude of the first flush from LRT runoff was found to be similar to those from other transportation land uses. The comparison of LRT runoff data with an adjacent road bridge site showed that the pollutant EMC and unit load were 2 to 9 times higher from the road bridge. It was suggested that LRT automated operation and the elevated track makes this transportation mode a viable option for the management of non-point source pollution.

  1. Traumatic high-grade cervical dislocation: treatment strategies and outcomes.

    Science.gov (United States)

    Sribnick, Eric A; Hoh, Daniel J; Dhall, Sanjay S

    2014-12-01

    Traumatic high-grade cervical spinal dislocations are rare injuries, generally associated with severe neurological compromise. In particular, cervical spondyloptosis (>100% subluxation) is rarely reported. The object of our study is to present a case series describing presentation, management, and outcome in traumatic high-grade cervical spinal dislocations. Retrospective analysis was performed involving two level 1 trauma centers. Patients with a high-grade traumatic cervical subluxation were selected from a database, and these patients were admitted between August 2007 and July 2011. Fifteen patients were identified; three had spondyloptosis. The admission American Spinal Injury Association Impairment Scale (AIS) grade varied (A = 9; B = 2; C = 1; D = 2; E = 1). Fourteen patients underwent attempted closed reduction with six (43%) failing closed reduction. High-dose methylprednisolone was administered in nine patients (60%). All patients underwent surgical stabilization: three underwent anterior only, three underwent posterior only, and nine underwent a combined anterior-posterior approach. Postoperatively, one patient improved two AIS grades, three improved one AIS grade, nine maintained their preoperative score, and two patients worsened. In this series, 26.7% of patients had improvement in their AIS grade postoperatively, and the majority of patients (60%) maintained their preoperative AIS grade. In 57% of patients placed in traction, reduction was possible. Likely due to the severity of these injuries, there was a high incidence of complications. However, review of patient outcomes reveals that these patients can have improvement of neurological function. We recommend aggressive reduction and surgical stabilization. Our preference is either a combined anterior-posterior approach or a posterior-only approach. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Net effects of gasoline price changes on transit ridership in U.S. urban areas.

    Science.gov (United States)

    2014-12-01

    Using panel data of transit ridership and gasoline prices for ten selected U.S. urbanized areas over the time period of 2002 to 2011, : this study analyzes the effect of gasoline prices on ridership of the four main transit modesbus, light rail, h...

  3. Carlsbad Area Office Waste Isolation Division Transition Plan

    Energy Technology Data Exchange (ETDEWEB)

    1994-01-01

    In October 1993, the US Department of Energy (DOE) announced the Revised Test Strategy for the Waste Isolation Pilot Plant (WIPP). The new strategy involves conducting additional radioactive waste tests in laboratories instead of the underground at the WIPP. It will likely result in an acceleration of regulatory compliance activities needed for a disposal decision, which could result in permanent disposal of transuranic waste earlier than the previous test program and regulatory compliance strategy. The Revised Test Strategy changes the near-term program activities for the WIPP site. The revised strategy deletes radioactive waste tests at the WIPP, prior to completing all activities for initiating disposal operations, and consequently the need to maintain readiness to receive waste in the near-term. However, the new strategy enables the DOE to pursue an earlier disposal decision, supported by an accelerated regulatory compliance strategy. With the new strategy, the WIPP must prepare for disposal operations in early 1998. This Westinghouse Waste Isolation Division (WID) Transition Plan addresses the WID programmatic, budgetary, and personnel changes to conform to the Revised Test Strategy, and to support the accelerated compliance strategy and earlier disposal operations at the WIPP.

  4. Deciphering fluid inclusions in high-grade rocks

    Directory of Open Access Journals (Sweden)

    Alfons van den Kerkhof

    2014-09-01

    Full Text Available The study of fluid inclusions in high-grade rocks is especially challenging as the host minerals have been normally subjected to deformation, recrystallization and fluid-rock interaction so that primary inclusions, formed at the peak of metamorphism are rare. The larger part of the fluid inclusions found in metamorphic minerals is typically modified during uplift. These late processes may strongly disguise the characteristics of the “original” peak metamorphic fluid. A detailed microstructural analysis of the host minerals, notably quartz, is therefore indispensable for a proper interpretation of fluid inclusions. Cathodoluminescence (CL techniques combined with trace element analysis of quartz (EPMA, LA-ICPMS have shown to be very helpful in deciphering the rock-fluid evolution. Whereas high-grade metamorphic quartz may have relatively high contents of trace elements like Ti and Al, low-temperature re-equilibrated quartz typically shows reduced trace element concentrations. The resulting microstructures in CL can be basically distinguished in diffusion patterns (along microfractures and grain boundaries, and secondary quartz formed by dissolution-reprecipitation. Most of these textures are formed during retrograde fluid-controlled processes between ca. 220 and 500 °C, i.e. the range of semi-brittle deformation (greenschist-facies and can be correlated with the fluid inclusions. In this way modified and re-trapped fluids can be identified, even when there are no optical features observed under the microscope.

  5. Biomechanics of high-grade spondylolisthesis with and without reduction.

    Science.gov (United States)

    Wang, Wenhai; Aubin, Carl-Eric; Cahill, Patrick; Baran, George; Arnoux, Pierre-Jean; Parent, Stefan; Labelle, Hubert

    2016-04-01

    The clinical advantages of reducing spondylolisthesis over fusion in situ have several intuitive reasons such as restore the spinal column into a more anatomic relationship and alignment. However, there is only little evidence in the literature supporting the theoretical advantages of reduction, and its effect on spinopelvic alignment remains poorly defined. In this study, a comprehensive finite element model was developed to analyze the biomechanics of the spine after spinal fusion at L5-S1 in both types of high-grade spondylolisthesis (balanced and unbalanced pelvis). The relevant clinical indices (i.e. spondylolisthesis grade and Dubousset lumbosacral angle), the displacement of L4-L5, pressure within the annulus and nucleus, and stress at L4-L5 were evaluated and compared. The model can well predict the changes of the important clinical indices during the surgery. For a balanced pelvis, the reduction has a minimal effect on the biomechanical conditions at the adjacent level during postsurgical activities. In the unbalanced case, reduction induced larger deformation in the lumbosacral region and a higher stress concentration at adjacent level. Whether such a stress concentration can lead to long-term disc degeneration is not known. The results provide additional information for the clinician considering reduction of high-grade spondylolisthesis.

  6. Nonlinear ghost waves accelerate the progression of high-grade brain tumors

    Science.gov (United States)

    Pardo, Rosa; Martínez-González, Alicia; Pérez-García, Víctor M.

    2016-10-01

    We study a reduced continuous model describing the evolution of high grade gliomas in response to hypoxic events through the interplay of different cellular phenotypes. We show that hypoxic events, even when sporadic and/or limited in space, may have a crucial role on the acceleration of high grade gliomas growth. Our modeling approach is based on two cellular phenotypes. One of them is more migratory and a second one is more proliferative. Transitions between both phenotypes are driven by the local oxygen values, assumed in this simple model to be uniform. Surprisingly, even very localized in time hypoxia events leading to transient migratory populations have the potential to accelerate the tumor's invasion speed up to speeds close to those of the migratory phenotype. The high invasion speed persists for times much longer than the lifetime of the hypoxic event. Moreover, the phenomenon is observed both when the migratory cells form a persistent wave of cells located on the invasion front and when they form a evanescent "ghost" wave disappearing after a short time by decay to the more proliferative phenotype. Our findings are obtained through numerical simulations of the model equations both in 1D and higher dimensional scenarios. We also provide a deeper mathematical analysis of some aspects of the problem such as the conditions for the existence of persistent waves of cells with a more migratory phenotype.

  7. Sports participation and high grade renal injuries in children.

    Science.gov (United States)

    Gerstenbluth, Robert E; Spirnak, J Patrick; Elder, Jack S

    2002-12-01

    The risk of major renal injury resulting from various forms of sports participation is unknown. Urologists often recommend that children with a solitary kidney avoid contact sports. We reviewed our recent experience with pediatric renal trauma to determine if there is an association between different types of sports activity and high grade renal injury. We retrospectively reviewed the medical records of 68 consecutive children with blunt renal injury who were treated at 2 level I trauma centers. Injuries were graded using the renal injury scale of the American Association for the Surgery of Trauma. Records were reviewed for mechanism of injury, associated injuries, management and injury severity score. Statistical analysis was performed using Fisher's exact test or Wilcoxon rank sum test. Of the 68 renal lesions 13 were grade I, 15 grade II, 15 grade III, 17 grade IV and 8 grade V. The most common cause of renal trauma was motor vehicle accidents, accounting for 21 injuries (30.1%). Accidents associated with nonmotorized sports activity accounted for 14 injuries (20.6%). Bicycle riding was the most common sports etiology, accounting for 8 of 14 cases (57.1%) at an age range of 5 to 15 years (mean 9.4). None of the bicycle injuries involved collision with a motor vehicle. Bicycling accounted for 1 grade I, 1 grade II, 1 grade III, 2 grade IV and 3 grade V injuries. Football, hockey and sledding were responsible for the remaining 6 sports related injuries. High grade renal injury (grade IV or V) was identified in 5 of 8 bicycle accidents (62.5%) and 1 of 6 nonbicycle sports related injuries (16.7%, p = 0.14). Injury severity scores ranged from 4 to 50 (mean 20.6) for bicycle renal injuries and 4 to 13 (mean 6.7) for nonbicycle sports related trauma (p sports related cause of renal injury in children and is associated with a significant risk of major renal injury. Families of children with a solitary kidney should be aware of this risk factor. Team contact sports are

  8. Liver stiffness measurement predicts high-grade post-hepatectomy liver failure: A prospective cohort study.

    Science.gov (United States)

    Chong, Charing Ching-Ning; Wong, Grace Lai-Hung; Chan, Anthony Wing-Hung; Wong, Vincent Wai-Sun; Fong, Anthony Kwong-Wai; Cheung, Yue-Sun; Wong, John; Lee, Kit-Fai; Chan, Stephen L; Lai, Paul Bo-San; Chan, Henry Lik-Yuen

    2017-02-01

    Liver stiffness measurement using transient elastography appears to be an excellent tool for detection of liver fibrosis and cirrhosis with high accuracy. The aim of this study is to evaluate the efficacy of preoperative liver stiffness measurement in predicting post-hepatectomy liver failure. A prospective cohort study of all consecutive patients undergoing hepatectomy for hepatocellular carcinoma from February 2010 to August 2014 was studied. All patients received detailed preoperative assessments including liver stiffness measurement. The primary outcome was post-hepatectomy liver failure according to the International Study Group of Liver Surgery definition. A total of 255 patients were included. Liver stiffness measurement showed significant correlation with grade B or C post-hepatectomy liver failure. (P = 0.003) Using the cutoff at 12 kPa, liver stiffness measurement had a sensitivity of 52.4% and specificity of 73.3% in predication of high-grade (grade B or C) post-hepatectomy liver failure. Liver stiffness measurement > 12 kPa was also an independent prognostic factor for both high-grade post-hepatectomy liver failure and major postoperative complications by multivariate analysis. The diagnostic accuracy was better in patients without right lobe tumor with an area under the receiver operating characteristic of 0.83 compared with an area under the receiver operating characteristic of only 0.62 in patients with right lobe tumor. Liver stiffness measurement using Fibroscan is good to predict high-grade post-hepatectomy liver failure especially in patients without right lobe tumor. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  9. High Grade Myofibroblastic Sarcoma of Paratesticular Soft Tissues

    Directory of Open Access Journals (Sweden)

    Ioannis Anastasiou

    2014-01-01

    Full Text Available Tumors of the paratesticular region most often arise from the soft tissue surrounding the spermatic cord and the epididymis or from the soft tissue (dartos muscle of the scrotal wall. Paratesticular tumors, despite their rarity, present a high incidence of malignancy (30%, and the therapeutic approach of choice is surgical resection with negative margin. The grade, the histology type, the presence of metastases during the diagnosis, the size of the tumor, the age of the patients, and the surgical margins are all important prognostic factors. We present a case report of a 86-year-old patient with a high grade paratesticular and scrotum sarcoma of soft tissues which was presented as a hard painful mass of the scrotum. The patient was subjected to high ligation of the spermatic cord and received no further treatment and 6 months after the operation no local or systematic recurrence was observed.

  10. High Grade Infective Spondylolisthesis of Cervical Spine Secondary to Tuberculosis.

    Science.gov (United States)

    Hadgaonkar, Shailesh; Shah, Kunal; Shyam, Ashok; Sancheti, Parag

    2015-12-01

    Spondylolisthesis coexisting with tuberculosis is rarely reported. There is a controversy whether spondylolisthesis coexists or precedes tuberculosis. Few cases of pathological spondylolisthesis secondary to tuberculous spondylodiscitis have been reported in the lumbar and lumbosacral spine. All cases in the literature presented as anterolisthesis, except one which presented as posterolisthesis of lumbar spine. Spondylolisthesis in the cervical spine is mainly degenerative and traumatic. Spondylolisthesis due to tuberculosis is not reported in the lower cervical spine. The exact mechanism of such an occurrence of spondylolisthesis with tuberculosis is sparsely reported in the literature and inadequately understood. We report a rare case of high grade pathological posterolisthesis of the lower cervical spine due to tubercular spondylodiscitis in a 67-year-old woman managed surgically with a three-year follow-up period. This case highlights the varied and complex presentation of tuberculosis of the lower cervical spine and gives insight into its pathogenesis, diagnosis, and management.

  11. High-grading and over-quota discarding in mixed fisheries

    NARCIS (Netherlands)

    Batsleer, J.; Hamon, K.G.; Overzee, van H.M.J.; Rijnsdorp, A.D.; Poos, J.J.

    2015-01-01

    High-grading is the decision by fishers to discard fish of low value that allows them to land more valuable fish. A literature review showed high-grading is reported in commercial and non-commercial fisheries around the world, although the number of observations is small. High-grading occurs in

  12. Histological outcomes of anal high-grade cytopredictions.

    Science.gov (United States)

    Roberts, Jennifer Margaret; Jin, Fengyi; Poynten, Isobel Mary; Law, Carmella; Templeton, David James; Thurloe, Julia Kathleen; Garland, Suzanne Marie; Grulich, Andrew Edwin; Farnsworth, Annabelle; Hillman, Richard John

    2017-10-20

    Longitudinal studies of histological outcomes after anal cytological screening in men who have sex with men (MSM) are rare. This study measured the positive predictive values (PPVs) of each level of baseline cytological abnormality in MSM in Sydney, Australia, over a 12-month period. The Study of the Prevention of Anal Cancer is a 3-year prospective study of the natural history of anal human papillomavirus infection in MSM at least 35 years old. For each participant with a baseline cytological abnormality, the worst histology was recorded at the baseline high-resolution anoscopy and at 6 and 12 months. PPVs for a histological high-grade squamous intraepithelial lesion (HSIL) diagnosis were calculated for each level of baseline cytological abnormality at each time point. Among 424 men who completed 3 visits, the PPV of a cytological HSIL increased from 71.6% at the baseline to 86.4% at 6 months and to 92.6% at 12 months (P < .001). For cytological atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC-H), the PPV increased from 51.5% at the baseline to 69.7% at 6 months and to 75.8% at 12 months (P = .004). At each time point, the PPV of a cytological HSIL was significantly higher than the PPV of ASC-H. The PPV of low-grade cytology reports was significantly lower than the PPV of ASC-H at each time point. In a cohort of MSM, a baseline histological HSIL diagnosis after an HSIL cytoprediction is high, and it increases with further examinations over the course of 12 months. Lower levels of cytological abnormalities have significantly lower PPVs. These data can inform patient management and the quality assessment of each aspect of the screening pathway. Cancer Cytopathol 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  13. Transition Management and Social Innovation in Rural Areas: Lessons from Social Farming

    Science.gov (United States)

    Di Iacovo, Francesco; Moruzzo, Roberta; Rossignoli, Cristiano; Scarpellini, Paola

    2014-01-01

    Purpose: The article reflects on transition management in rural areas and the possible implications for extension services able to support social innovation and rural change, starting from experiences on social farming in different areas of Italy. Design/methodology/approach: By presenting three case studies we investigate the role of social…

  14. Bay Area Transit Agencies Propel Fuel Cell Buses Toward Commercialization (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2010-07-01

    This fact sheet describes the Zero Emission Bay Area (ZEBA) demonstration of the next generation of fuel cells buses. Several transit agencies in the San Francisco Bay Area are participating in demonstrating the largest single fleet of fuel cell buses in the United States.

  15. A note on Maxwell's equal area law for black hole phase transition

    Energy Technology Data Exchange (ETDEWEB)

    Lan, Shan-Quan; Mo, Jie-Xiong; Liu, Wen-Biao [Beijing Normal University, Department of Physics, Institute of Theoretical Physics, Beijing (China)

    2015-09-15

    The state equation of the charged AdS black hole is reviewed in the T-r{sub +} plane. With a view on the the phase transition, the T-S, P-V, P-ν graphs are plotted and then the equal area law is used in the three cases to get the phase transition point (P, T). The analytical phase transition point relations for P-T of a charged AdS black hole has been obtained successfully. By comparing the three results, we find that the equal area law possibly cannot be used directly for the P-ν plane. According to the T-S, P-V results, we plot the P-T-Q graph and find that for a highly charged black hole a very low temperature condition is required for the phase transition. (orig.)

  16. A note on Maxwell’s equal area law for black hole phase transition

    Energy Technology Data Exchange (ETDEWEB)

    Lan, Shan-Quan; Mo, Jie-Xiong; Liu, Wen-Biao, E-mail: wbliu@bnu.edu.cn [Department of Physics, Institute of Theoretical Physics, Beijing Normal University, 100875, Beijing (China)

    2015-09-09

    The state equation of the charged AdS black hole is reviewed in the T–r{sub +} plane. With a view on the the phase transition, the T–S, P–V, P–ν graphs are plotted and then the equal area law is used in the three cases to get the phase transition point (P, T). The analytical phase transition point relations for P–T of a charged AdS black hole has been obtained successfully. By comparing the three results, we find that the equal area law possibly cannot be used directly for the P–ν plane. According to the T–S, P–V results, we plot the P–T–Q graph and find that for a highly charged black hole a very low temperature condition is required for the phase transition.

  17. Transition in Education: Policy Making and the Key Educational Policy Areas in the Central-European and Baltic Countries.

    Science.gov (United States)

    Rado, Peter

    This report examines transition in educational systems and identifies key policy areas in Central-Eastern European countries. It summarizes policy implications of the transition process within the educational context of these countries. Chapter 1, "Transition and Education," outlines key characteristics of the transition process and…

  18. Role of combined circumareolar skin excision and liposuction in management of high grade gynaecomastia

    Directory of Open Access Journals (Sweden)

    Arindam Sarkar

    2014-01-01

    Full Text Available Introduction: High-grade gynaecomastia (Simon IIb and III has tissue excess (skin excess, enlarged areola, and displaced nipple, which is best managed surgically; however, results of conventional breast reduction surgeries and liposuction is not very good. Aim of our study was to describe a combined technique to manage these problems to produce a good result. Material and Method: This was a 2-year study among 12 patients of high grade gynaecomastia. Clinical and laboratory findings were normal. Pre-operatively in standing position, diameter of breast and areola, position of nipple, and amount of skin excess were marked. Under general anaesthesia, tumescent infiltration, circumareolar de-epithelisation of skin excess, and liposuction was completed. Redundant portion of the breast was sharply dissected and pulled out. Areola was fixed over pectoralis fascia at mid humerus level, just medial to the mid-clavicular line. Outer borders of the de-epithelised area were apposed by the purse-string effect of a subdermal suture, and further apposed by few half buried horizontal mattress sutures. Drains for 24 hour and compressive dressings for 6 weeks were used. Result: Mean age of presentation was 25.8 year; emotional discomfort was the chief complaint. Among 12 patients, 10 patients had bilateral gynaecomastia and 8 patients had enlarged and displaced nipple-areola complex. Average hospital stay was 2.41 days and recoveries were usually uneventful. Conclusion: The problem of tissue excess and tissue displacement in high grade gynaecomastia can be well managed by this combined circumareolar skin reduction and liposuction technique to achieve a scar-less flat male chest.

  19. Stroke and stroke mimics: a case of high grade glioma

    Directory of Open Access Journals (Sweden)

    Roberta Wolffenbüttel Argenti

    2015-01-01

    Full Text Available The clinical diagnosis of acute stroke is inaccurate approximately 10%-30% of the time, which can lead to unnecessary administration of thrombolytic therapy or delays in appropriate therapy. Rapid and accurate neuroimaging triage is essential to guide therapy and exclude mimics. Although many conditions that mimic stroke clinically have imaging appearances that can overlap acute stroke, these conditions can be differentiated in most cases by using a careful pattern-based approach. We describe a case of 67 yo male patient who had a clinic of wakeup stroke and at the first magnetic resonance image (MRI it was found that was an acute stroke of middle cerebral artery.The patient did not improve and a second MRI  revelead a two times growth of the lesion, and the MRI findings were compatible with tumor. At the surgery they found a infiltrative lesion and the anatomopathological exam showed that it was a high grade glioma.The diagnosis of ischemic stroke is often straight forward; however, the clinical diagnosis of acute stroke is inaccurate in many cases. Furthermore, many of these conditions, such as encephalitis, mass lesions, seizures, hypoglycemia, transient global amnesia (TGA,demyelinating disease, drug toxicity, and metabolic disturbances, have imaging appearances that can mimic acute or subacute infarction; however, an accurate diagnosis can often be made by using a pattern-based approach.

  20. High grade neuroendocrine neoplasm of the antrum and orbit.

    Science.gov (United States)

    MacIntosh, Peter W; Jakobiec, Frederick A; Stagner, Anna M; Gilani, Sapideh; Fay, Aaron

    2015-01-01

    Neuroendocrine malignancies-tumors characterized by the production of dense-core secretory granules-are most often encountered in the lungs and can also be found in extrapulmonary sites. Our patient had a primary neuroendocrine tumor of the antrum with an elusive cell of origin that secondarily invaded the inferior orbit. In the sinuses, neuroendocrine tumors may be confused with infectious sinusitis or squamous cell carcinoma. There are no known pathognomonic clinical or radiographic signs to distinguish these tumors from other conditions. Diagnosis depends on a biopsy with histopathologic and immunohistochemical analysis to identify biomarkers such as synaptophysin, chromogranin, CD56 and neuron specific enolase. Our patient's tumor defied precise immunohistochemical characterization because of its primitive character and erratic biomarker expression. The diagnosis oscillated between a neuroendocrine carcinoma and an ectopic esthesioneuroblastoma grade IV-hence the use of the more generic nosologic category of neuroendocrine neoplasm without specifying a neuronal or epithelial origin. Data to guide management are limited, particularly in the ophthalmic literature, and derive from experience with tumors of the sinonasal compartments. In the present case of a sino-orbital high grade neuroendocrine neoplasm, regional lymph node metastases developed shortly after presentation. The tumor has responded well to chemotherapy and radiation, but recurrence is often encountered within 2 years in this class of neoplasms. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Concurrent thermochemoradiotherapy for brain high-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Ryabova, A. I., E-mail: ranigor@mail.ru; Novikov, V. A.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Choinzonov, E. L. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Siberian State Medical University, Tomsk, 634050 (Russian Federation); Gribova, O. V. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Baranova, A. V. [National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)

    2016-08-02

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  2. High-Grade Leiomyosarcoma Arising in a Previously Replanted Limb

    Directory of Open Access Journals (Sweden)

    Tiffany J. Pan

    2015-01-01

    Full Text Available Sarcoma development has been associated with genetics, irradiation, viral infections, and immunodeficiency. Reports of sarcomas arising in the setting of prior trauma, as in burn scars or fracture sites, are rare. We report a case of a leiomyosarcoma arising in an arm that had previously been replanted at the level of the elbow joint following traumatic amputation when the patient was eight years old. He presented twenty-four years later with a 10.8 cm mass in the replanted arm located on the volar forearm. The tumor was completely resected and pathology examination showed a high-grade, subfascial spindle cell sarcoma diagnosed as a grade 3 leiomyosarcoma with stage pT2bNxMx. The patient underwent treatment with brachytherapy, reconstruction with a free flap, and subsequently chemotherapy. To the best of our knowledge, this is the first case report of leiomyosarcoma developing in a replanted extremity. Development of leiomyosarcoma in this case could be related to revascularization, scar formation, or chronic injury after replantation. The patient remains healthy without signs of recurrence at three-year follow-up.

  3. GIS-based Approaches to Catchment Area Analyses of Mass Transit

    DEFF Research Database (Denmark)

    Andersen, Jonas Lohmann Elkjær; Landex, Alex

    2009-01-01

    Catchment area analyses of stops or stations are used to investigate potential number of travelers to public transportation. These analyses are considered a strong decision tool in the planning process of mass transit especially railroads. Catchment area analyses are GIS-based buffer and overlay...... search to simulate the actual walking distances. A refinement of the Service Area Approach is to implement additional time resistance in the network search to simulate obstacles in the walking environment. This paper reviews and compares the different GIS-based catchment area approaches, their level...

  4. Ultrasonographic evaluation of transition from normal to ectatic area: A comparison between myopic staphylomata and coloboma

    Directory of Open Access Journals (Sweden)

    Anubha Rathi

    2017-01-01

    Full Text Available Choroidal coloboma and posterior staphyloma are two clinically distinct entities, with choroidal excavation being a unifying feature. They are associated with early onset cataract which can make ophthalmoscopy difficult. This report studies the transition between the normal and ectatic area in these cases with ultrasound. We evaluate “posterior hump” as a sign of differentiation between these two conditions.

  5. Primary balloon angioplasty for symptomatic, high-grade intracranial stenosis.

    Science.gov (United States)

    Tomycz, Luke; Bansal, Neil K; Lockney, Tim; Strothers, Megan; Connors, John J; Shay, Scott; Singer, Robert J

    2013-01-01

    In light of recent controversy about the safety and efficacy of intracranial stenting, we sought to evaluate our experience with primary balloon angioplasty for symptomatic, high-grade intracranial stenosis. All intracranial angioplasty cases performed at Vanderbilt University Medical Center from 2006 to 2011 were retrospectively reviewed for degree of stenosis pre- and post-procedure. Immediate peri-procedural complications were evaluated as well as one-month and long-term outcomes. A total of 26 patients were included in the study with a mean age of 63.0 years and a mean follow-up of 350.2 days. The average pre-procedure stenosis was 71.2%. The immediate, average post-procedure stenosis was 46.6%, and the average post-procedure stenosis at last angiographic follow-up was 44.5%. Retreatment was required in only 3.8% of patients. The primary end-point of major stroke or death at 30 days was observed in 11.5%, and the overall intra-procedural complication rate was 7.7%. The incidence of stroke or death at last follow-up was 15.4%, which is comparable to the one-year stroke or death rate in the medical arm of the SAMPRISS trial. In this retrospective series, primary balloon angioplasty was found to be effective as a treatment option for symptomatic intracranial stenosis with the risk of stroke or death at 30 days higher than the medical arm of SAMPRIS but lower than the stenting arm. The one-year risk of stroke was comparable to that reported for the one-year outcomes in the SAMPRISS medical arm.

  6. Preserved splenic function after angioembolisation of high grade injury.

    Science.gov (United States)

    Skattum, Jorunn; Titze, Thomas Larsen; Dormagen, Johann Baptist; Aaberge, Ingeborg S; Bechensteen, Anne Grete; Gaarder, Per Ivar; Gaarder, Christine; Heier, Hans Erik; Næss, Pål Aksel

    2012-01-01

    After introducing splenic artery embolisation (SAE) in the institutional treatment protocol for splenic injury, we wanted to evaluate the effects of SAE on splenic function and assess the need for immunisation in SAE treated patients. 15 SAE patients and 14 splenectomised (SPL) patients were included and 29 healthy blood donors volunteered as controls. Clinical examination, medical history, general blood counts, immunoglobulin quantifications and flowcytometric analysis of lymphocyte phenotypes were performed. Peripheral blood smears from all patients and controls were examined for Howell-Jolly (H-J) bodies. Abdominal doppler, gray scale and contrast enhanced ultrasound (CEUS) were performed on all the SAE patients. Leukocyte and platelet counts were elevated in both SAE and SPL individuals compared to controls. The proportion of memory B-lymphocytes did not differ significantly from controls in either group. In the SAE group total IgA, IgM and IgG levels as well as pneumococcal serotype specific IgG and IgM antibody levels did not differ from the control group. In the SPL group total IgA and IgG Pneumovax(®) (PPV23) antibody levels were significantly increased, and 5 of 12 pneumococcal serotype specific IgGs and IgMs were significantly elevated. H-J bodies were only detected in the SPL group. CEUS confirmed normal sized and well perfused spleens in all SAE patients. In our study non-operative management (NOM) of high grade splenic injuries including SAE, was followed by an increase in total leukocyte and platelet counts. Normal levels of immunoglobulins and memory B cells, absence of H-J bodies and preserved splenic size and intraparenchymal blood flow suggest that SAE has only minor impact on splenic function and that immunisation probably is unnecessary. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Surgical treatment of esophageal high-grade dysplasia.

    Science.gov (United States)

    Reed, Michael F; Tolis, George; Edil, Barish H; Allan, James S; Donahue, Dean M; Gaissert, Henning A; Moncure, Ashby C; Wain, John C; Wright, Cameron D; Mathisen, Douglas J

    2005-04-01

    Barrett's esophagus, high-grade dysplasia (HGD), and invasive cancer are steps in the progression of esophageal adenocarcinoma. While surgery is recommended for resectable invasive adenocarcinoma, a number of treatment modalities are advocated for HGD. The purpose of this study is to determine the outcomes after surgery for HGD. We identified cases of HGD based on endoscopic biopsy in a single institution's databases from 1980 through 2001. Records were reviewed for patient characteristics, treatments, staging, and outcomes. In a 22-year period, 869 cases of esophageal adenocarcinoma and 1,614 cases of Barrett's esophagus were diagnosed. Of these, 115 had HGD without pretreatment evidence of invasion. Forty-nine patients with HGD underwent resection (mean age, 59 years) as initial treatment. Forty-seven had endoscopic treatment (mean age, 70 years) by photodynamic therapy or endoscopic mucosal resection. Seven of the endoscopically treated patients failed, with three undergoing surgery and four observation. Nineteen patients were initially observed, with six eventually having surgery. For the 49 initially treated surgically, one (2%) operative mortality occurred. Invasive adenocarcinoma was present in 18 (37%). The five-year survival was 83% for all resected HGD patients (91% for those without invasion, 68% with invasion). Three of the eight deaths in those with invasion were from recurrent adenocarcinoma. Surgical resection of esophageal HGD can be performed with low mortality and allows long-term survival. A significant percentage with an initial diagnosis of HGD will have invasive disease at resection. Surgery is the optimal treatment for HGD unless contraindicated by severe comorbidities.

  8. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia

    OpenAIRE

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-01-01

    Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case?control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men ...

  9. Perception of the Transition Zones from Urban to Suburban Area Using Mobile Eye

    Directory of Open Access Journals (Sweden)

    Paolo Magris

    2014-12-01

    Full Text Available Road users adjust their driving behavior based on the perception of the route and the surrounding environment. The eye-tracking technology allows interpreting the driver behavior, analyzing aspects otherwise not considered in the design stage. This technology has been used for transition zone analysis at town entrances along the SP 610 “Selice Montanara”, to verify the efficiency of gateway created to reduce the input speed in urban areas. Results show that the installation of traffic calming measures at transition zones leads to a change of the environment perception by drivers, and consequently safety increase.

  10. Invisible gold and arsenic in pyrite from the high-grade Hishikari gold deposit, Japan

    Science.gov (United States)

    Morishita, Y.; Shimada, N.; Shimada, K.

    2008-12-01

    Gold occurs as both electrum (a natural alloy of gold and silver) and invisible gold in arsenian pyrite in the Hishikari epithermal gold deposit in Japan. Microanalyses of arsenian pyrite from the deposit using secondary ion mass spectrometry (SIMS) and electron probe microanalysis (EPMA) revealed that Au concentrations (0.1-2600 ppm) are positively correlated with As concentrations (0.0-6.1%). A small (3 μm) area of pyrite was analyzed because the sample textures were fine and complicated. The Au/As ratio is high in the Sanjin ore zone, which has very high-grade veins, while the ratio is low in the Yamada ore zone, which has average-grade veins.

  11. Low-grade and high-grade endometrial stromal sarcoma: A National Cancer Database study.

    Science.gov (United States)

    Seagle, Brandon-Luke L; Shilpi, Arunima; Buchanan, Samuel; Goodman, Chelain; Shahabi, Shohreh

    2017-08-01

    To provide refined prognostic information from large cohorts of women with low-grade or high-grade endometrial stromal sarcoma (ESS). We performed an observational retrospective cohort analysis of women diagnosed with low-grade or high-grade ESS from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to identify prognostic factors after multiple imputation of missing data. Recursive partitioning methods were used to rank prognostic factors in high-grade ESS. Matched cohort analyses were performed to hypothesis-test effects of adjuvant treatments. We identified 2414 and 1383 women with low-grade or high-grade ESS, respectively. Women with high-grade ESS had markedly decreased survival compared to women with low-grade ESS (five-year survival (95% CI): 32.6 (30.1-35.3%) versus 90.5% (89.3-91.8%), P<0.001). Among women with high-grade ESS, median survival (95% CI) was only 19.9 (17.1-22.1) months. Increased age and tumor size were associated with decreased survival in low-grade ESS. In high-grade ESS, additional negative prognostic factors were distant or nodal metastasis, omission of lymphadenectomy, and pathologically-positive surgical margins (all P<0.001). Use of adjuvant chemotherapy (time ratio (TR) (95% CI): 1.36 (1.17-1.58), P<0.001) and radiotherapy (TR (95% CI): 1.57 (1.32-1.87), P<0.001) were associated with increased survival for high-grade ESS. The contrasting excellent versus poor prognosis of low-grade versus high-grade ESS, respectively, was confirmed. The best treatment of high-grade ESS is early and complete surgical resection including lymphadenectomy. Adjuvant chemotherapy and radiotherapy may increase survival of women with high-grade ESS. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. TRANSIT THROUGH THE SCHENGEN AREA FOR THE HOLDERS OF SPECIFIC SWISS DOCUMENTS

    CERN Multimedia

    2006-01-01

    The Swiss Permanent Mission has informed CERN of the following relaxation of the transit regulations granted by the States applying the Schengen Agreement and other European States to third-country nationals who are normally required to obtain a visa. As from 10 July 2006, those holding a Carte de légitimation or Attestation de fonctions issued by the Swiss Federal Department of Foreign Affairs or a B, C or Ci-type residence permit are exempted from the requirement to obtain a visa for transit through the Schengen area, so long as the transit period does not exceed five days (for each transit). For other circumstances (for example tourism, including for conferences), the requirement to obtain a visa remains in force. The States that form the Schengen area are: Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Italy, Luxembourg, Norway, the Netherlands, Portugal, Spain and Sweden. In addition, the following States have decided to apply the same exemption from the requirement to obtain a...

  13. An Analysis of the Impacts of British Transport Reforms on Transit Integration in the Metropolitan Areas

    OpenAIRE

    Rivasplata, Charles Richard

    2006-01-01

    By the 1990s, many experts concluded that transit privatization in Britain had produced positive impacts on service provision in London, but that deregulation outside of the capital had resulted in a number of negative impacts to passengers, most notably, rising fares, lower service frequencies in some areas, and declining levels of service integration. In an attempt to improve mobility at the local level, the incoming Labour Government effectively devolved transport planning powers to local ...

  14. Extent of high-grade prostatic intraepithelial neoplasia is not a ...

    African Journals Online (AJOL)

    Objective: High-grade prostatic intraepithelial neoplasia (PIN) is a well accepted pre-cursor of invasive prostate cancer. Most investigators agree that a diagnosis of high-grade PIN warrants repeat transrectal ultrasound guided biopsy. We set out to investigate risk factors for cancer among a modern cohort of men with ...

  15. Natural history of high-grade cervical intraepithelial neoplasia : a review of prognostic biomarkers

    NARCIS (Netherlands)

    Koeneman, Margot M.; Kruitwagen, Roy F. P. M.; Nijman, Hans W.; Slangen, Brigitte F. M.; Van Gorp, Toon; Kruse, Arnold-Jan

    The natural history of high-grade cervical intraepithelial neoplasia (CIN) is largely unpredictable and current histopathological examination is unable to differentiate between lesions that will regress and those that will not. Therefore, most high-grade lesions are currently treated by surgical

  16. Modeling platinum sensitive and resistant high grade serous ovarian cancer: development and applications of experimental systems

    Directory of Open Access Journals (Sweden)

    Paula eCunnea

    2014-04-01

    Full Text Available High grade serous ovarian cancer remains the most common sub-type of ovarian cancer and, characterized by high degrees of genomic instability and heterogeneity, is typified by a transition from early response to acquired resistance to platinum based chemotherapy. Conventional models for the study of ovarian cancer have been largely limited to a set of relatively poorly characterized immortalized cell lines and recent studies have called into question the validity of some of these as reliable models. Here we review new approaches and models systems which take into account advances in our understanding of ovarian cancer biology and advances in the technology available for their generation and study. We discuss primary cell models, 2D, 3D and organotypic models, and paired sample approaches that capture the evolution of chemotherapy failure within single cases. We also overview new methods for non-invasive collection of representative tumor material from blood samples. Adoption of such methods and models will improve the quality and clinical relevance of ovarian cancer research.

  17. Oncocytoma-like renal tumor with transformation toward high-grade oncocytic carcinoma: a unique case with morphologic, immunohistochemical, and genomic characterization.

    Science.gov (United States)

    Sirintrapun, Sahussapont J; Geisinger, Kim R; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L; Ghazalpour, Anatole; Bender, Ryan P; Gatalica, Zoran

    2014-10-01

    Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt-Hogg-Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the development of an

  18. Hydrogeology of the transition area between Prekmursko polje and Goričko (NE Slovenia

    Directory of Open Access Journals (Sweden)

    Katja Koren

    2015-12-01

    Full Text Available In April 2014 a detailed hydrogeological mapping was performed in the transition area between the hilly Goričko in the north and the fltland of Prekmursko polje in the south (NE Slovenia. The occurrence of groundwater and surface water phenomena were registered and groundwater levels determined in a number of dug wells. Some basic physico-chemical parameters of water, i.e. temperature, electrical conductivity and pH were measured. Groundwater level map of the area was drawn and groundwater flw directions determined. In the Goričko area, groundwater flws from north to south, while in Prekmursko polje groundwater flw is parallel to the flw of the Mura River, i.e. NW-SE. In the transition area between Goričko and Prekmursko polje groundwater countor lines bend substantialy indicating a change in the relief as well as change of the hydrogeological characteristic of sediments. The groundwater pH and temperatures in Goričko and Prekmursko polje, are simillar. However, the electrical conductivity of groundwater in Prekmursko polje is higher than in Goričko.

  19. Average opportunity-based accessibility of public transit systems to grocery stores in small urban areas

    Directory of Open Access Journals (Sweden)

    Nimish Dharmadhikari

    2015-12-01

    Full Text Available This research studies the accessibility of grocery stores to university students using the public transportation system, drawing from a case study of Fargo, North Dakota. Taking into consideration the combined travel time components of walking, riding, and waiting, this study measures two types of accessibilities: accessibility to reach a particular place and accessibility to reach the bus stop to ride the public transit system. These two accessibilities are interdependent and cannot perform without each other. A new method to calculate the average accessibility measure for the transit routes is proposed. A step-wise case study analysis indicates that one route provides accessibility to a grocery store in eight minutes. This also suggests that the North Dakota State University area has moderate accessibility to grocery stores.

  20. Radiological and clinical outcome of non surgical management for pediatric high grade spondylolisthesis.

    Science.gov (United States)

    Bourassa-Moreau, Etienne; Labelle, Hubert; Mac-Thiong, Jean-Marc

    2010-01-01

    To describe and compare the quality of life of patients with pediatric high-grade spondylolisthesis managed non-operatively and operatively. Some authors consider pediatric high-grade spondylolisthesis as an absolute indication for surgery, regardless of symptoms while others sometimes recommend observation in asymptomatic patients. Very little is known about the indications and outcome of non-operatively managed high-grade spondylolisthesis. A prospective database comprising all the spondylolisthesis cases from a single pediatric institution was reviewed in order to identify all cases of high grade spondylolisthesis. Quality of life data from Short form (SF)-12 and Scoliosis Research Society (SRS)-22 questionnaires were collected. Non-operatively treated patients were identified and compared to surgically treated patients at baseline and at last follow-up. 34 spondylolisthesis were identified as high grade and 5 of them were non-operatively treated. Quality of life questionnaires showed less impairment in the non-operative group when compared to the surgical group preoperatively. Moreover at last follow-up, quality of life questionnaires were similar between the two groups. There was no worsening of quality of life observed in non-operative patients during follow-up. The quality of life after surgical treatment of high grade spondylolisthesis is similar to that of patients with high grade spondylolisthesis and mild symptoms undergoing non-operative treatment.

  1. Chemical hole doping into large-area transition metal dichalcogenide monolayers using boron-based oxidant

    Science.gov (United States)

    Matsuoka, Hirofumi; Kanahashi, Kaito; Tanaka, Naoki; Shoji, Yoshiaki; Li, Lain-Jong; Pu, Jiang; Ito, Hiroshi; Ohta, Hiromichi; Fukushima, Takanori; Takenobu, Taishi

    2018-02-01

    Hole carrier doping into single-crystalline transition metal dichalcogenide (TMDC) films can be achieved with various chemical reagents. However, large-area polycrystalline TMDC monolayers produced by a chemical vapor deposition (CVD) growth method have yet to be chemically doped. Here, we report that a salt of a two-coordinate boron cation, Mes2B+ (Mes: 2,4,6-trimethylphenyl group), with a chemically stable tetrakis(pentafluorophenyl)borate anion, [(C6F5)4B]‑, can serve as an efficient hole-doping reagent for large-area CVD-grown tungsten diselenide (WSe2) films. Upon doping, the sheet resistance of large-area polycrystalline WSe2 monolayers decreased from 90 GΩ/sq to 3.2 kΩ/sq.

  2. Transition areas in the domain patterns of storeyed cambium of Tilia cordata Mill.

    Directory of Open Access Journals (Sweden)

    Wiesław Włoch

    2014-01-01

    Full Text Available The occurrence of interlocked grain, generated by storeyed cambium, was observed in the wood of linden. The inclination of the grain changed periodically every two to four years. In general, the direction of the change of grain was compatible with the occurrence of configuration Z or S of cellular events. 1f, in the cambium during the generation of a growth ring, the domain border did not pass the examined area, the events were of one configuration type only, otherwise, there were two types of events aggregated into microareas. The microareas were the result of unsynchronous activities of groups of cambium cells. A growth ring area through which a domain border passed during the year under consideration was called the transition area.

  3. Measuring Transit Oriented Development of Existing Urban Areas around Metro Stations in Faridabad City

    Directory of Open Access Journals (Sweden)

    Sat Pal

    2018-01-01

    Full Text Available Urban population in Indian cities is encouraging auto reliance and having unsafe economic, social and environmental consequences. Land-use-change patterns are the outcome of the complex relations between the human and the physical surroundings. To address these issues the planners are moving beyond land use planning to a sustainable development. Transit and Land use planning are important components to achieve sustainable future of urban development. TOD is a planning tool to encourage this integration. This paper discusses the land use scenario and opportunity around four Metro transit stations in Faridabad city. Different methods and various sets of indicators are considered to evaluate and measure TOD index in this study. This study will evaluate and measure the Faridabad city in the context of land use around Metro Stations to support TOD. This paper seeks to answer how to promote walkable communities, compact and transit-oriented development (TOD that incorporates mixed land use development, including neighbourhood schools, retail and business related space and a mix range of housing types within walkable distance. This paper concludes that the stations area which had a low TOD score needs to have policy for improvement. If planned efficiently, TODs can realize the sustainable development with considerable change in the urban development that focuses on pedestrian based neighbourhood planning.

  4. Zircon Ion Microprobe Dating of High-Grade Rocks in Sri Lanka

    National Research Council Canada - National Science Library

    A. Kröner; I. S. Williams; W. Compston; N. Baur; P. W. Vitanage; L. R. K. Perera

    1987-01-01

    The high-grade gneisses of Sri Lanka display spectacular in-situ granulitization phenomena similar to those observed in southern India and of current interest for evolutionary models of the lower continental crust...

  5. Non-operative management attempted for selective high grade blunt hepatosplenic trauma is a feasible strategy

    OpenAIRE

    Hsieh, Ting-Min; Cheng Tsai, Tsung; Liang, Jiun-Lung; Che Lin, Chih

    2014-01-01

    Background There is growing evidence of clinical data recently for successful outcomes of non-operative management (NOM) for blunt hepatic and spleen injuries (BHSI). However, the effectiveness of NOM for high-grade BHSI remains undefined. The aim of the present study was to review our experience with NOM in high-grade BHSI and compare results with the existing related data worldwide. Methods In this retrospectively protocol-driven study, 150 patients with grade 3–5 BHSI were enrolled during ...

  6. High-grade renal injuries are often isolated in sports-related trauma

    OpenAIRE

    Patel, DP; Redshaw, JD; Breyer, BN; Smith, TG; Erickson, BA; Majercik, SD; Gaither, TW; Craig, JR; Gardner, S.; Presson, AP; Zhang, C.; Hotaling, JM; Brant, WO; Myers, JB

    2015-01-01

    © 2015 Elsevier Ltd. All rights reserved. Introduction: Most high-grade renal injuries (American Association for Surgery of Trauma (AAST) grades III-V) result from motor vehicle collisions associated with numerous concomitant injuries. Sports-related blunt renal injury tends to have a different mechanism, a solitary blow to the flank. We hypothesized that high-grade renal injury is often isolated in sports-related renal trauma. Material and methods: We identified patients with AAST grades III...

  7. Surgical Versus Nonsurgical Treatment for High-Grade Spondylolisthesis in Children and Adolescents

    OpenAIRE

    Xue, Xuhong; Wei, Xiaochun; Li, Li

    2016-01-01

    Abstract The optimal management of high-grade spondylolisthesis in children and adolescent is controversial. There is a paucity of literature regarding operatively or nonoperative management in this setting. To assessment of the current state of evidence regarding high-grade spondylolisthesis treatment with the goal of obtaining outcome comparisons in these patients managed either operatively or nonoperatively. We performed a systematic literature search up to November 2014, using Medline, Em...

  8. Montachusett Area Regional Transit Authority (MART) automatic vehicle location and mobile data terminal (AVL/MDT) pilot program report

    Science.gov (United States)

    2003-02-14

    The Montachusett Area Regional Transit Authority (MART) MART was established in 1978 to provide public transportation to the 18 Massachusetts communities. MART fixed-route service operates with 26 buses. Its paratransit services are more extensive, a...

  9. Multiperiod Hierarchical Location Problem of Transit Hub in Urban Agglomeration Area

    Directory of Open Access Journals (Sweden)

    Ting-ting Li

    2017-01-01

    Full Text Available With the rapid urbanization in developing countries, urban agglomeration area (UAA forms. Also, transportation demand in UAA grows rapidly and presents hierarchical feature. Therefore, it is imperative to develop models for transit hubs to guide the development of UAA and better meet the time-varying and hierarchical transportation demand. In this paper, the multiperiod hierarchical location problem of transit hub in urban agglomeration area (THUAA is studied. A hierarchical service network of THUAA with a multiflow, nested, and noncoherent structure is described. Then a multiperiod hierarchical mathematical programming model is proposed, aiming at minimizing the total demand weighted travel time. Moreover, an improved adaptive clonal selection algorithm is presented to solve the model. Both the model and algorithm are verified by the application to a real-life problem of Beijing-Tianjin-Hebei Region in China. The results of different scenarios in the case show that urban population migration has a great impact on the THUAA location scheme. Sustained and appropriate urban population migration helps to reduce travel time for urban residents.

  10. Pediatric High Grade Glioma (HGG: a Review and Update on Tumor Clinical Characteristics and Biology

    Directory of Open Access Journals (Sweden)

    Jason eFangusaro

    2012-08-01

    Full Text Available High grade gliomas (HGG are one of the most common central nervous system (CNS tumors encountered in adults, but they only represent approximately 8-12% of all pediatric CNS tumors. Historically, pediatric HGG were thought similar to adult HGG since they appear histologically identical; however, molecular, genetic, and biologic data reveal that they are distinct. Similar to adults, pediatric HGG are very aggressive and malignant lesions with few patients achieving long-term survival despite a variety of therapies. Initial treatment strategies typically consist of a gross total resection (GTR when feasible followed by focal radiotherapy combined with chemotherapy. Over the last few decades, a wealth of data has emerged from basic science and pre-clinical animal models helping to better define the common biologic, genetic and molecular make-up of these tumors. These data have not only provided a better understanding of tumor biology, but they have also provided new areas of research targeting molecular and genetic pathways with the potential for novel treatment strategies and improved patient outcomes. Here we provide a review of pediatric non-brainstem HGG, including epidemiology, presentation, histology, imaging characteristics, treatments, survival outcomes and an overview of both basic and translational research. An understanding of all relevant pre-clinical tumor models, including their strengths and pitfalls is essential in realizing improved patient outcomes in this population.

  11. Overexpression of CD47 predicts poor prognosis and promotes cancer cell invasion in high-grade serous ovarian carcinoma

    Science.gov (United States)

    Li, Yinuo; Lu, Shuhua; Xu, Ying; Qiu, Chunping; Jin, Chengjuan; Wang, Yuqiong; Liu, Zhaojian; Kong, Beihua

    2017-01-01

    CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. CD47 is overexpressed in various human malignancies. However, the expression and functional significance of CD47 in high-grade serous ovarian carcinoma (HGSOC) has not been completely understood. In this study, we reported that CD47 was commonly overexpressed in HGSOC. Higher CD47 expression was significantly correlated with poor prognosis of HGSOC patients. Functional investigations revealed that CD47 overexpression in ovarian cancer cells significantly promoted migration and invasion. Moreover, CD47 induced epithelial-mesenchymal transition (EMT) through modulating E-cadherin and N-cadherin. Our findings suggest that up-regulation of CD47 is correlated with ovarian cancer progression and it might be a potential biomarker for predicting clinical outcomes. PMID:28670378

  12. Centralised or decentralised sanitation in Swedish summerhouse areas in transition to permanent living?

    Science.gov (United States)

    Kärrman, E; Erlandsson, A; Hellström, D; Björlenius, B; Tidåker, P

    2007-01-01

    The standard of wastewater management is high in Sweden. Around 90% of the population is connected to central wastewater treatment plants with high requirements of nutrients removal; however, still the problem with algae blooms in the Baltic Sea exists. The aim of the VeVa project was to develop a simple and user-friendly Excel-based model to support environmental decisions of how to select wastewater systems for housing areas where no central sewer system exists. The VeVa model deals with two types of environmental issues: substance flow analysis and energy analysis. Six system structures were studied for the transition area Lillängsdal in Värmdö municipality sorted in three categories: 1) on-site systems for single households; 2) local collective systems; 3) connection to central systems. All studied system structures, except for a Sand filter system, fulfilled the goals of reducing phosphorus and BOD7 according to Swedish guidelines for on-site systems in sensitive areas. All studied systems, except for the Sand filter system, have the potential to fulfil the Swedish National Environmental goal to recycle 60% phosphorus to productive land. The systems with central wastewater treatment plant and local wastewater treatment are the most energy efficient alternatives that also fulfil the requirements of discharges and environmental goals regarding phosphorus recycling.

  13. Maxwell’s Equal Area Law and the Hawking-Page Phase Transition

    Directory of Open Access Journals (Sweden)

    Euro Spallucci

    2013-01-01

    Full Text Available We study the phases of a Schwarzschild black hole in the Anti-deSitter background geometry. Exploiting fluid/gravity duality, we construct the Maxwell equal area isotherm   in the temperature-entropy plane, in order to eliminate negative heat capacity BHs. The construction we present here is reminiscent of the isobar cut in the pressure-volume plane which eliminates unphysical part of the Van der Walls curves below the critical temperature. Our construction also modifies the Hawking-Page phase transition. Stable BHs are formed at the temperature , while pure radiation persists for . turns out to be below the standard Hawking-Page temperature and there are no unstable BHs as in the usual scenario. Also, we show that, in order to reproduce the correct BH entropy , one has to write a black hole equation of state, that is, , in terms of the geometrical volume .

  14. Tendencies in the development of operational quality of ballasted and ballastless track superstructure and transition areas

    Science.gov (United States)

    Ižvolt, Libor; Šestáková, Janka; Šmalo, Michal

    2017-09-01

    Department of Railway Engineering and Track Management is cooperating with Slovak Railways (Železnice Slovenskej republiky - ŽSR) on assessment of quality of railway tracks, structures of railway tracks and parts of these structures. One of diagnostics methods is monitoring of track geometry focused on durability of ballastless track quality and its transition area to ballasted track. The diagnostics is carried out by continuous method and results are used for prediction of future degradation of construction. The first part of the paper deals with a brief recapitulation of information about the experimental sections and the methods of diagnostics of track geometry. The second part of the paper is carrying out the analysis and prognosis of development of the quality of construction of the experimental sections, which is a tool for the track superstructure maintenance planning.

  15. Nitrogen fertilisation of durum wheat: a case study in Mediterranean area during transition to conservation agriculture

    Directory of Open Access Journals (Sweden)

    Angelica Galieni

    2016-03-01

    Full Text Available Nitrogen (N nutrition plays a key role for high yields and quality in durum wheat (Triticum turgidum L. subsp. durum (Desf. Husn; in Mediterranean environments, data regarding N fertilisation management during the transition phase to conservation agriculture (CA are limited. The aim of this work was to study the effects of N fertiliser forms and rates on yield and some quality traits of durum wheat, during the transition period to CA in Mediterranean areas; moreover, indication on the recommendable N form/rate combinations have been given. Field trials were carried out in south of Italy, during the first two years of transition to CA (from 2010 to 2012 in a durum wheat-based rotation. Following a split-plot design arranged on a randomised complete blocks with three replications, two N forms (main plots - urea and calcium nitrate - and four N rates (sub-plots - 50, 100, 150 and 200 kg N ha–1 - plus an un-fertilised Control, were compared. The following parameters were analysed: grain yield, N-input efficiency, grains protein concentration (GPC, total gluten, gluten fractions and minerals concentration in kernels. Calcium nitrate gave the highest yield (4.48 t ha–1, as predicted by the quadratic model, at 146 kg N ha–1, on average. This was particularly noticeable in 2012, when the distribution of rainfall and temperatures regimes as well as residues’ status could have favoured such N-form. These results were confirmed by the observed higher values of all indices describing N-input efficiency. High GPC values (14.8% were predicted at slightly higher N-rates (173 kg N ha–1, averaging both N forms. In particular, gluten proteins and glutenin/gliadin ratio accrued as the N doses increased, reaching the highest values at 150 kg N ha–1, also positively affecting the quality of durum wheat flour. Iron and zinc concentrations were noticeably increased (38% and 37% on average by N supply, probably due to the enhanced water use efficiency under

  16. Overdiagnosis of high-grade dysplasia in Barrett's esophagus: a multicenter, international study.

    Science.gov (United States)

    Sangle, Nikhil A; Taylor, Shari L; Emond, Mary J; Depot, Michelle; Overholt, Bergein F; Bronner, Mary P

    2015-06-01

    Numerous histological mimics of high-grade dysplasia in Barrett's esophagus predispose to overdiagnosis and potential serious mismanagement, including unnecessary esophagectomy. This study investigates the prevalence and sources of this problem. Biopsies from 485 patients diagnosed with Barrett's high-grade dysplasia were screened for a multi-institutional, international Barrett's endoscopic ablation trial. Screening included review of the original diagnostic slides and an additional protocol endoscopy with an extensive biopsy sampling. Observer variability by the study pathologists was assessed through two blinded diagnostic rounds on 437 biopsies from 26 random study endoscopies. Study diagnostic reassessments revealed significantly lower rates of high-grade dysplasia. Only 248 patients (51%) were confirmed to have high-grade dysplasia. The remaining patients had inflamed gastric cardia without Barrett's (n=18; 7%), Barrett's without dysplasia (n=35; 15%), indefinite change (n=61; 26%), low-grade dysplasia (n=79; 33%), adenocarcinoma (n=43; 18%), and other (n=1; overdiagnosis included Barrett's inflammatory atypia (n=182), atypia limited to the basal metaplastic glands (n=147), imprecise criteria for low grade neoplasia (n=102), tangential sectioning artifact (n=59), and reactive gastric cardiac mucosa (n=38). A total of 194 patients (40%) were overdiagnosed with Barrett's high-grade dysplasia, as affirmed by the extensive screening process and high-level study pathologist agreement. The multiple diagnostic pitfalls uncovered should help raise pathologists' awareness of this problem and improve diagnostic accuracy.

  17. Intravenous flat-detector computed tomography angiography for high-grade carotid stenosis.

    Science.gov (United States)

    Jeon, Jin Sue; Sheen, Seung Hun; Kim, Heung Cheol

    2013-01-01

    The significant feature of intravenous flat-detector computed tomography (IV FDCT) angiography is its role in neurointerventional setting without patient transfer. However, few studies have addressed the accuracy of IV FDCT in estimating carotid stenosis and length. This study examined the reliability of IV FDCT in the diagnosis of high-grade carotid stenosis and stenosis length with digital subtraction angiography (DSA) as the reference. Intravenous flat-detector CT and DSA were conducted simultaneously for 33 patients with 42 stenosed carotid arteries who were suspected of having symptomatic high-grade stenosis by carotid duplex ultrasound, magnetic resonance angiography, or CT angiography. The degree of stenosis and length discrepancy between 2 tests were recorded by 2 readers. The intraobserver and interobserver agreements were excellent for measuring high-grade carotid stenosis (κ = 0.87 and 0.82). Intravenous flat-detector CT had a sensitivity of 96.3%, specificity of 93.3%, and negative predictive value of 93.3% for detecting high-grade stenosis (≥70%) compared with DSA. Bland-Altman plots demonstrated excellent correlation of the degree of stenosis IV FDCT with DSA. Length discrepancy (IV FDCT - DSA, in millimeters) did not differ significantly according to degree of stenosis (Spearman rank test; r = 0.18, P = 0.26). Intravenous flat-detector CT can be a feasible and time-saving test for evaluating high-grade carotid stenosis and stenosis length.

  18. Differentiating high-grade from low-grade chondrosarcoma with MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hye Jin; Hong, Sung Hwan; Choi, Ja-Young; Choi, Jung-Ah; Kang, Heung Sik [Seoul National University College of Medicine, Department of Radiology and Institute of Radiation Medicine, Seoul (Korea); Moon, Kyung Chul [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea); Kim, Han-Soo [Seoul National University College of Medicine, Department of Orthopedic Surgery, Seoul (Korea)

    2009-12-15

    The purpose of the study was to evaluate the MR imaging features that differentiate between low-grade chondrosarcoma (LGCS) and high-grade chondrosarcoma (HGCS) and to determine the most reliable predictors for differentiation. MR images of 42 pathologically proven chondrosarcomas (28 LGCS and 14 HGCS) were retrospectively reviewed. There were 13 male and 29 female patients with an age range of 23-72 years (average age 51 years). On MR images, signal intensity, specific morphological characteristics including entrapped fat, internal lobular architecture, and outer lobular margin, soft tissue mass formation and contrast enhancement pattern were analysed. MR imaging features used to identify LGCS and HGCS were compared using univariate analysis and multivariate stepwise logistic regression analysis. On T1-weighted images, a central area of high signal intensity, which was not seen in LGCS, was frequently observed in HGCS (n = 5, 36%) (p < 0.01). Entrapped fat within the tumour was commonly seen in LGCS (n = 26, 93%), but not in HGCS (n = 1, 4%) (p < 0.01). LGCS more commonly (n = 24, 86%) preserved the characteristic internal lobular structures within the tumour than HGCSs (n = 4, 29%) (p < 0.01). Soft tissue formation was more frequently observed in HGCS (n = 11, 79%) than in LGCS (n = 1, 4%) (p < 0.01). On gadolinium-enhanced images, large central nonenhancing areas were exhibited in only two (7.1%) of LGCS, while HGCS frequently (n = 9, 64%) had a central nonenhancing portion (p < 0.01). Results of multivariate stepwise logistic regression analysis showed that soft tissue formation and entrapped fat within the tumour were the variables that could be used to independently differentiate LGCS from HGCS. There were several MR imaging features of chondrosarcoma that could be helpful in distinguishing HGCS from LGCS. Among them, soft tissue mass formation favoured the diagnosis of HGCS, and entrapped fat within the tumour was highly indicative of LGCS. (orig.)

  19. Is fluorescein-guided technique able to help in resection of high-grade gliomas?

    Science.gov (United States)

    Acerbi, Francesco; Broggi, Morgan; Eoli, Marica; Anghileri, Elena; Cavallo, Claudio; Boffano, Carlo; Cordella, Roberto; Cuppini, Lucia; Pollo, Bianca; Schiariti, Marco; Visintini, Sergio; Orsi, Chiara; La Corte, Emanuele; Broggi, Giovanni; Ferroli, Paolo

    2014-02-01

    Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45-74 years), enrolled in the study since September 2011. In all cases fluorescein (5-10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. The median preoperative tumor volume was 30.3 cm(3) (range 2.4-87.8 cm(3)). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT).

  20. Convection-enhanced delivery catheter placements for high-grade gliomas: complications and pitfalls.

    Science.gov (United States)

    Shahar, Tal; Ram, Zvi; Kanner, Andrew A

    2012-04-01

    Convection-enhanced delivery (CED) of compounds into brain tumors reportedly circumvents the blood brain barrier. CED intends to increase drug delivery to malignant cells, reaching high local therapeutic concentration and decreasing or eliminating systemic side effects. Clinical experience and published data on catheter placement (CP) surgery are scarce. We propose practical and technical guidelines for planning CED based on our experience. We retrospectively analyzed the medical charts and relevant neuroimages of 25 patients following the insertion of 64 CED catheters. The patients were enrolled in at least one of four clinical trials using CED for treating recurrent glioblastoma multiforme in our institution between 2003-2006. Intra- and postoperative complications related to CP surgery and the difficulties and pitfalls of planning were evaluated. There were 29 CP surgeries. Forty-four peritumoral brain tissue catheters were inserted in 16 CP surgeries following tumor resection in 16 patients, and 20 catheters were placed into the tumor in 13 procedures in 10 patients. The lesions were in or near eloquent brain tissue areas in 13 of all CP surgeries. Complications included increased edema (31%), infection (6.9%), bleeding (6.9%) and seizures (13.8%). Significant neurological deterioration occurred in 4 patients (13.8%). Difficulties in adhering to CP surgery guidelines included lesion site (superficial, mesial temporal lobe, proximity to CSF spaces), proximity to eloquent cortical areas, tissue density that interfered with the trajectory, and technical limitations of stereotactic instruments. CED procedures for high-grade gliomas may be associated with surgical morbidity. Adherence to guidelines might be difficult because of lesion site and complicated by brain and tumor tissue characteristics. This should be considered while planning clinical trials that use convection-based technology.

  1. Connectivity of larval cod in the transition area between North Sea and Baltic Sea and potential implications for fisheries management

    DEFF Research Database (Denmark)

    Huwer, Bastian; Hinrichsen, H.-H.; Hüssy, Karin

    2016-01-01

    in the transition area between North Sea and Baltic were investigated to (i) determine long-term trends and variability in advective transport of larvae from spawning grounds to juvenile nursery areas, (ii) estimate the degree of exchange between different management areas, and (iii) compare the results...... settlement areas, with observed distributions of juveniles in bottom trawl surveys suggests that the drift simulations provide reasonable estimates of early life stage connectivity between cod populations in the investigated areas. High exchange rates of particles between management areas of up to ca. 70...

  2. Safety and effectiveness of emergency carotid artery stenting for a high-grade carotid stenosis with intraluminal thrombus under proximal flow control in hyperacute and acute stroke.

    Science.gov (United States)

    Iwata, Tomonori; Mori, Takahisa; Tajiri, Hiroyuki; Miyazaki, Yuichi; Nakazaki, Masahito

    2013-01-01

    A study was undertaken to investigate the feasibility, safety and effectiveness of emergency carotid artery stenting (eCAS) for a high-grade carotid stenosis with intraluminal thrombus (ILT) with or without proximal flow control (PFC). Patients with acute ischemic stroke included in the analysis were those who were admitted between 2001 and 2010 with serious neurological symptoms, without a large high-intensity area of diffusion-weighted images and who underwent eCAS for a high-grade carotid stenosis with ILT. Patients underwent eCAS without PFC until 2004 (group C) and under PFC after 2004 (group P). The National Institutes of Health Stroke Scale (NIHSS) score on admission, just before CAS and 7 days after CAS as well as the 3-month modified Rankin Scale were investigated. Fifty-six patients underwent eCAS, eight of whom had a high-grade stenosis with ILT. Four of the eight patients were in group C and four were in group P. Probable distal embolism associated with eCAS occurred in two cases in group C and in none in group P. In groups C and P the median 7-day NIHSS scores were 15 and 5, respectively (padmission and just before CAS. In stroke patients with a high-grade carotid stenosis with ILT, eCAS under PFC is safer and more effective in achieving a favorable clinical outcome than eCAS without PFC.

  3. Ferroelectricity and the phase transition in large area evaporated vinylidene fluoride oligomer thin films

    Science.gov (United States)

    Foreman, K.; Poddar, Shashi; Ducharme, Stephen; Adenwalla, S.

    2017-05-01

    Organic ferroelectric materials, including the well-known poly(vinylidene fluoride) and its copolymers, have been extensively studied and used for a variety of applications. In contrast, the VDF oligomer has not been thoroughly investigated and is not widely used, if used at all. One key advantage the oligomer has over the polymer is that it can be thermally evaporated in vacuum, allowing for the growth of complex heterostructures while maintaining interfacial cleanliness. Here, we report on the ferroelectric properties of high-quality VDF oligomer thin films over relatively large areas on the order of mm2. The operating temperature is identified via differential scanning calorimetry and pyroelectric measurements. Pyroelectric measurements also reveal a stable remanent polarization for these films which persists over very long time scales, an important result for non-volatile data storage. Temperature dependent pyroelectric and capacitance measurements provide compelling evidence for the phase transition in these films. Capacitance-voltage and current-voltage measurements are used to confirm ferroelectricity, quantify the dielectric loss, and calculate the spontaneous polarization. Finally, piezoresponse force microscopy is used to demonstrate large area, low-voltage ferroelectric domain reading/writing in VDF oligomer thin films. This work enables new channels for VDF oligomer applications and research.

  4. Low tortoise abundances in pine forest plantations in forest-shrubland transition areas

    Science.gov (United States)

    Rodríguez-Caro, Roberto C.; Oedekoven, Cornelia S.; Graciá, Eva; Anadón, José D.; Buckland, Stephen T.; Esteve-Selma, Miguel A.; Martinez, Julia; Giménez, Andrés

    2017-01-01

    In the transition between Mediterranean forest and the arid subtropical shrublands of the southeastern Iberian Peninsula, humans have transformed habitat since ancient times. Understanding the role of the original mosaic landscapes in wildlife species and the effects of the current changes as pine forest plantations, performed even outside the forest ecological boundaries, are important conservation issues. We studied variation in the density of the endangered spur-thighed tortoise (Testudo graeca) in three areas that include the four most common land types within the species’ range (pine forests, natural shrubs, dryland crop fields, and abandoned crop fields). Tortoise densities were estimated using a two-stage modeling approach with line transect distance sampling. Densities in dryland crop fields, abandoned crop fields and natural shrubs were higher (>6 individuals/ha) than in pine forests (1.25 individuals/ha). We also found large variation in density in the pine forests. Recent pine plantations showed higher densities than mature pine forests where shrub and herbaceous cover was taller and thicker. We hypothesize that mature pine forest might constrain tortoise activity by acting as partial barriers to movements. This issue is relevant for management purposes given that large areas in the tortoise’s range have recently been converted to pine plantations. PMID:28273135

  5. Research and development of intelligent controller for high-grade sanitary ware

    Science.gov (United States)

    Bao, Kongjun; Shen, Qingping

    2013-03-01

    With the social and economic development and people's living standards improve, more and more emphasis on modern society, people improve the quality of family life, the use of intelligent controller applications in high-grade sanitary ware physiotherapy students. Analysis of high-grade sanitary ware physiotherapy common functions pointed out in the production and use of the possible risks, proposed implementation of the system hardware and matching, given the system software implementation process. High-grade sanitary ware physiotherapy intelligent controller not only to achieve elegant and beautiful, simple, physical therapy, water power, deodorant, multi-function, intelligent control, to meet the consumers, the high-end sanitary ware market, strong demand, Accelerate the enterprise product Upgrade and improve the competitiveness of enterprises.

  6. Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial.

    Science.gov (United States)

    Koeneman, M M; Kruse, A J; Kooreman, L F S; Zur Hausen, A; Hopman, A H N; Sep, S J S; Van Gorp, T; Slangen, B F M; van Beekhuizen, H J; van de Sande, A J M; Gerestein, C G; Nijman, H W; Kruitwagen, R F P M

    2017-02-07

    The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia (CIN). The lagging inclusions were mainly due to a strong patient preference for either of the two treatment modalities. This prompted us to initiate a new study on the same subject, with a non-randomized, open-label design: the 'TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC)-3' study. Original TOPIC-trial: Medical Ethics Committee approval number METC13231; ClinicalTrials.gov Identifier: NCT02329171, 22 December 2014. TOPIC-3 study: Medical Ethics Committee approval number METC162025; ClinicalTrials.gov Identifier: NCT02917746, 16 September 2016.

  7. Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment

    Directory of Open Access Journals (Sweden)

    Daniela Rizzo

    2015-01-01

    Full Text Available High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas.

  8. Prostatectomy-based validation of combined urine and plasma test for predicting high grade prostate cancer

    DEFF Research Database (Denmark)

    Albitar, Maher; Ma, Wanlong; Lund, Lars

    2018-01-01

    BACKGROUND: Distinguishing between low- and high-grade prostate cancers (PCa) is important, but biopsy may underestimate the actual grade of cancer. We have previously shown that urine/plasma-based prostate-specific biomarkers can predict high grade PCa. Our objective was to determine the accuracy...... of a test using cell-free RNA levels of biomarkers in predicting prostatectomy results. METHODS: This multicenter community-based prospective study was conducted using urine/blood samples collected from 306 patients. All recruited patients were treatment-naïve, without metastases, and had been biopsied......, designated a Gleason Score (GS) based on biopsy, and assigned to prostatectomy prior to participation in the study. The primary outcome measure was the urine/plasma test accuracy in predicting high grade PCa on prostatectomy compared with biopsy findings. Sensitivity and specificity were calculated using...

  9. Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia.

    Science.gov (United States)

    Lendvai, Ágnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J H; Wardenaar, René; Volders, Haukeline H; Klip, Harry G; Hollema, Harry; Jansen, Ritsert C; Schuuring, Ed; Wisman, G Bea A; van der Zee, Ate G J

    2012-11-01

    Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection.

  10. Obesity increases the risk for high-grade prostate cancer: results from the REDUCE study.

    Science.gov (United States)

    Vidal, Adriana C; Howard, Lauren E; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

    2014-12-01

    Studies suggest that obesity is associated with lower risk of prostate cancer but more aggressive cancers. As obesity lowers PSA levels, these observations may be influenced by detection bias. We examined the association between obesity and risk of low- and high-grade prostate cancer in REDUCE, in which biopsies were largely independent of PSA. The REDUCE study tested dutasteride for prostate cancer risk reduction in men with a PSA of 2.5 to 10.0 ng/mL and a negative biopsy. Study participants included 6,729 men who underwent at least one on-study biopsy. The association between baseline body mass index (BMI obese) and risk of high-grade (Gleason ≥7) or low-grade prostate cancer (Gleason cancer was examined using multinomial logistic regression. Overall, 1,739 men (27%) were normal weight, 3,384 (53%) overweight, and 1,304 (20%) were obese. Obesity was associated with lower risk of low-grade prostate cancer in both univariable (OR, 0.74; P = 0.001) and multivariable analyses (OR, 0.79; P = 0.01). In univariable analysis, obesity was not associated with high-grade prostate cancer (OR, 1.08; P = 0.50). However, in multivariable analysis, obesity was associated with increased risk of high-grade prostate cancer (OR, 1.28; P = 0.042). This analysis was not able to address how obesity may influence prostate cancer progression. Obesity is associated with decreased risk of low-grade and increased risk of high-grade prostate cancer. These data provide further support to the hypothesis that obesity is associated with aggressive prostate cancer. Obesity is linked with aggressive prostate cancer. Avoiding obesity may prevent the risk of developing high-grade prostate cancer. ©2014 American Association for Cancer Research.

  11. Particulate Matter Concentrations in San Francisco Bay Area Rapid Transit (BART) Train Stations

    Science.gov (United States)

    Newsome, L.; Macias, S.; Romero, N.; Lockett, N.; Polar, J.; Madrigal, C.; Lopez, F.; Sanchez, R.; Webster, D.; Torio, M.; Rios, V.; Marks-Block, T.; Toli, F.

    2012-12-01

    As part of a general effort to assess air quality in different regions of the San Francisco Bay Area, we collected Particulate Matter (PM) data within passenger train cars along multiple commuter train lines simultaneously during the summer and fall of 2012. We visited numerous Bay Area Rapid Transit (BART) system stations, including those along the Fremont, Pittsburg and SF/Daly City lines. In conducting this study we used a Dustrak 8530 aerosol sensor equipped with a Global Positioning System (GPS) receiver to measure PM size 2.5 μm concentrations every second. Of all the BART stations we visited, average PM concentration levels at the Embarcadero station in San Francisco were the highest during multiple visits, with a value of 104.95 μg/m3. We also noted that high levels of PM 2.5 were released when the cloth seats on the trains were struck, which resulted in significant, temporary increases of hazardous PM levels of up to 3000 μg/m3! Embarcadero station's high PM concentration correlates to past research in other underground train stations throughout the world, where PM produced through the abrasive interaction of train wheels and tracks or brake pads becomes trapped. Compared to levels measured at outdoor stations (average of 8.52μg/m3) and other underground stations, levels detected at the Embarcadero station are particularly alarming. We believe this is due to the fact that this station is located at one end of a long, underground and underwater transbay tunnel that connects the East San Francisco Bay area to San Francisco to the west. To reduce PM exposure risk to BART employees and passengers, we suggest increasing and/or installing filtration and ventilation systems, which should substantially reduce PM concentrations at Embarcadero station.

  12. Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

    Science.gov (United States)

    Sopracordevole, Francesco; Mancioli, Francesca; Clemente, Nicolò; De Piero, Giovanni; Buttignol, Monica; Giorda, Giorgio; Ciavattini, Andrea

    2015-10-01

    The aim of this study was to analyze the correlation between the first diagnosis of high-grade Vaginal Intraepithelial Neoplasia (HG-VaIN: VaIN 2-VaIN 3) and the cytological abnormalities on the referral pap smear.All the women with histological diagnosis of HG-VaIN consecutively referred to the Gynecological Oncology Unit of the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014 and with a pap smear performed in the 3 months before the diagnosis were considered, and an observational cohort study was performed.A total of 87 women with diagnosis of HG-VaIN were identified. Major cytological abnormalities (HSIL and ASC-H) on the referral pap smear were significantly more frequent than lesser abnormalities (ASC-US and LSIL) in postmenopausal women (64.9% vs 36.7%, P = 0.02) and in women with a previous diagnosis of HPV-related cervical preinvasive or invasive lesions (70.5% vs 39.5%, P = 0.01). Diagnosis of VaIN 3 was preceded by major cytological abnormalities in most of the cases (72.7% vs 27.3%, P pap smear. Major abnormalities are usually reported in postmenopausal women and in women with previous cervical HPV-related disease. However, ASC-US or LSIL do not exclude HG-VaIN, especially VaIN2. An accurate examination of the whole vaginal walls (or vaginal vault) must be performed in all the women who underwent colposcopy for an abnormal pap smear, and a biopsy of all suspicious areas is mandatory.

  13. Selective-area growth and controlled substrate coupling of transition metal dichalcogenides

    Science.gov (United States)

    Bersch, Brian M.; Eichfeld, Sarah M.; Lin, Yu-Chuan; Zhang, Kehao; Bhimanapati, Ganesh R.; Piasecki, Aleksander F.; Labella, Michael, III; Robinson, Joshua A.

    2017-06-01

    Developing a means for true bottom-up, selective-area growth of two-dimensional (2D) materials on device-ready substrates will enable synthesis in regions only where they are needed. Here, we demonstrate seed-free, site-specific nucleation of transition metal dichalcogenides (TMDs) with precise control over lateral growth by utilizing an ultra-thin polymeric surface functionalization capable of precluding nucleation and growth. This polymer functional layer (PFL) is derived from conventional photoresists and lithographic processing, and is compatible with multiple growth techniques, precursors (metal organics, solid-source) and TMDs. Additionally, we demonstrate that the substrate can play a major role in TMD transport properties. With proper TMD/substrate decoupling, top-gated field-effect transistors (FETs) fabricated with selectively-grown monolayer MoS2 channels are competitive with current reported MoS2 FETs. The work presented here demonstrates that substrate surface engineering is key to realizing precisely located and geometrically-defined 2D layers via unseeded chemical vapor deposition techniques.

  14. Over-expression of β-catenin is associated with high grade of ...

    African Journals Online (AJOL)

    W. Said

    2017-04-28

    Apr 28, 2017 ... a Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya b Department of Urology, ... by 2030 basically due to the growth and aging of the global population [1]. .... Over-expression of ß-catenin is associated with high grade of prostatic cancer in Libyan patients. 135. Table 1.

  15. Fluctuating fetal or neonatal renal pelvis: marker of high-grade vesicoureteral reflux.

    Science.gov (United States)

    Anderson, Nigel G; Allan, Richard B; Abbott, George D

    2004-07-01

    Fetal renal pelvic dilatation is a predictor of vesicoureteral reflux (VUR), but has low specificity. The aim of this study was to determine the clinical significance of fluctuating size of the renal pelvis on sonography, particularly in relationship to VUR. We prospectively recorded fetal renal pelvic diameter >/=4 mm in 1,092 fetuses (692 boys), from May 1989 to December 1995, with a minimum follow-up of 7 years. Fluctuation, defined as size of renal pelvis changing by more than 4 mm during the course of obstetric (23), postnatal (128), and both pre- and postnatal (7) renal sonograms, was recorded prospectively in 159 (117 boys). Of the 1,092, 849 (593 boys) had a voiding cystourethrogram at a mean age of 7 weeks (range 3-20 weeks). Of the 31 (16 girls) with high-grade VUR, fluctuation was observed in 20 (9 girls). Fluctuation was strongly associated with high-grade VUR (odds ratio 11.1, P=0.0000003) and with renal damage (sensitivity 61%, positive predictive value 31%). Primary high-grade VUR was persistent, seen equally in boys and girls, and required surgery in the majority. Fluctuation was associated with renal duplication anomalies ( P=0.00009) and megaureter ( P<0.00000001). Fluctuation of the renal pelvis on sonography is a marker for persistent high-grade VUR and renal damage in girls and boys.

  16. Cognitive impairments in patients with low grade gliomas and high grade gliomas

    Directory of Open Access Journals (Sweden)

    Eliane C. Miotto

    2011-08-01

    Full Text Available OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19 and high-grade glioma (G2, n=8 patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

  17. Organizing the Cellular and Molecular Heterogeneity in High-Grade Serous Ovarian Cancer by Mass Cytometry

    Science.gov (United States)

    Tumor heterogeneity in high grade serous ovarian cancer (HG-SOC) represents a significant barrier for successful therapeutic intervention. To further...understand the cell types contributing to this heterogeneity we performed a comprehensive phenotypic characterization of 22 primary ovarian tumor...also showed greater overall phenotypic heterogeneity quantified by Simpsons Diversity Index. Importantly the novel cell types identified have the

  18. Profiles of Genomic Instability in High-Grade Serous Ovarian Cancer Predict Treatment Outcome

    DEFF Research Database (Denmark)

    Wang, Zhigang C.; Birkbak, Nicolai Juul; Culhane, Aedín C.

    2012-01-01

    Purpose: High-grade serous cancer (HGSC) is the most common cancer of the ovary and is characterized by chromosomal instability. Defects in homologous recombination repair (HRR) are associated with genomic instability in HGSC, and are exploited by therapy targeting DNA repair. Defective HRR cause...

  19. L5 pedicle subtraction osteotomy for high-grade isthmic spondylolisthesis.

    Science.gov (United States)

    Radcliff, Kristen E; Jakoi, Andre M

    2015-04-01

    To the authors' knowledge, this is the first article to present a pedicle subtraction osteotomy in the lumbar spine to correct and stabilize a high-grade isthmic spondylolisthesis, which poses many challenges with regard to treatment options and outcomes. The optimal surgical treatment for high-grade spondylolisthesis is controversial, but the goals of treatment are to stabilize the affected spinal levels and to decompress the neural elements. A pedicle subtraction osteotomy is a reconstructive procedure that addresses fixed sagittal imbalance by increasing lumbar lordosis through posterior spinal column shortening. The authors report a 46-year-old patient with chronic, progressively worsening back and leg radiculopathy accompanied by sagittal plane malalignment and for which a pedicle subtraction osteotomy was performed. The procedure yielded stabilization of the patient's lumbar spondylolisthesis and sagittal plane alignment was restoration. At 3 months postoperatively, the patient's pain had fully resolved and her motor and neurologic examination exhibited no deficits. At 24 months postoperatively, she was still symptom-free and ambulating without assistance. This report is the first documented successful pedicle subtraction osteotomy in the treatment of high-grade spondylolisthesis. This report indicates that certain patient populations may be amenable to pedicle subtraction osteotomy as a treatment option for pathology involving high-grade isthmic spondylolisthesis. Copyright 2015, SLACK Incorporated.

  20. Residual high-grade stenosis after recanalization of extracranial carotid occlusion in acute ischemic stroke

    NARCIS (Netherlands)

    Luitse, M.J.; Velthuis, B.K.; Dauwan, M.; Dankbaar, J.W.; Biessels, G.J.; Kappelle, L.J.; Meijer, F.J.; Dijk, E.J. van

    2015-01-01

    BACKGROUND AND PURPOSE: Residual stenosis after recanalization of an acute symptomatic extracranial occlusion of the internal carotid artery (ICA) might be an indication for carotid endarterectomy. We evaluated the proportion of residual high-grade stenosis (>/=70%, near occlusions not included)

  1. Effect of High-Grade Preoperative Knee Laxity on Anterior Cruciate Ligament Reconstruction Outcomes.

    Science.gov (United States)

    Magnussen, Robert A; Reinke, Emily K; Huston, Laura J; Hewett, Timothy E; Spindler, Kurt P

    2016-12-01

    Knee laxity in the setting of suspected anterior cruciate ligament (ACL) injury is frequently assessed through physical examination using the Lachman, pivot-shift, and anterior drawer tests. The degree of laxity noted on these examinations may influence treatment decisions and prognosis. Increased preoperative knee laxity would be associated with increased risk of subsequent revision ACL reconstruction and worse patient-reported outcomes 2 years postoperatively. Cohort study; Level of evidence, 2. From an ongoing prospective cohort study, 2333 patients who underwent primary isolated ACL reconstruction without collateral or posterior cruciate ligament injury were identified. Patients reported by the operating surgeons as having an International Knee Documentation Committee (IKDC) grade D for Lachman, anterior drawer, or pivot-shift examination were classified as having high-grade laxity. Multiple logistic regression modeling was used to evaluate whether having high-grade preoperative laxity was associated with increased odds of undergoing revision ACL reconstruction within 2 years of the index procedure, controlling for patient age, sex, Marx activity level, level of competition, and graft type. Multiple linear regression modeling was used to evaluate whether having high-grade preoperative laxity was associated with worse IKDC score or Knee injury and Osteoarthritis Outcome Score Knee-Related Quality of Life subscale (KOOS-QOL) scores at a minimum 2 years postoperatively, controlling for baseline score, patient age, ethnicity, sex, body mass index, marital status, smoking status, sport participation, competition level, Marx activity rating score, graft type, and articular cartilage and meniscus status. Pre-reconstruction laxity data were available for 2325 patients (99.7%). Two-year revision data were available for 2259 patients (96.8%), and patient-reported outcomes were available for 1979 patients (84.8%). High-grade preoperative laxity was noted in 743 patients

  2. Identifying patients at risk for high-grade intra-abdominal hypertension following trauma laparotomy.

    Science.gov (United States)

    Strang, Steven G; Van Imhoff, Diederik L; Van Lieshout, Esther M M; D'Amours, Scott K; Van Waes, Oscar J F

    2015-05-01

    Abdominal Compartment Syndrome (ACS) is an uncommon but deleterious complication after trauma laparotomy. Early recognition of patients at risk of developing ACS is crucial for their outcome. The aim of this study was to compare the characteristics of patients who developed high-grade intra-abdominal hypertension (IAH) (i.e., grade III or IV; intra-abdominal pressure, IAP >20 mm Hg) following an injury-related laparotomy versus those who did not (i.e., IAP ≤20 mm Hg). A retrospective analysis of consecutive trauma patients admitted to a level 1 trauma centre in Australia between January 1, 1995 and January 31, 2010 was performed. A comparison was made between characteristics of patients who developed high-grade IAH following trauma laparotomy versus those who did not. A total of 567 patients (median age 31 years) were included in this study. Of these patients 10.2% (58/567) developed high-grade IAH of which 51.7% (30/58) developed ACS. Patients with high-grade IAH were older (pgrade IAH received larger volumes of crystalloids (pgrade IAH suffered higher mortality rates (25.9% (15/58) vs. 12.2% (62/509); p=0.012). Of all patients who underwent a trauma laparotomy, 10.2% developed high-grade IAH, which increases the risk of mortality. Patients with acidosis, coagulopathy, and hypothermia were especially at risk. In these patients, the abdomen should be left open until adequate resuscitation has been achieved, allowing for definitive surgery. This is a level III retrospective study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Risk factors for high-grade envenomations after French viper bites in children.

    Science.gov (United States)

    Claudet, Isabelle; Maréchal, Céline; Gurrera, Emmanuel; Cordier, Laurie; Honorat, Raphaele; Grouteau, Erick

    2012-07-01

    Viper bites and subsequent evolution to severe envenomations are more frequent in children. The aims of this study were to describe the clinical, biological, and therapeutic characteristics of children bitten by vipers in France and to identify risk factors associated with severe envenomations. A retrospective study was conducted between 2001 and 2009 in the pediatric emergency department of a tertiary-level children hospital. Collected data were age and sex of children; day and time of admission; day, time, and circumstances of the accident; snake identification; bite location; envenomation severity; presence of fang marks; prehospital care; use of specific immunotherapy and associated treatments; length of stay; and hospital course. Fifty-eight children were included (43 boys, 15 girls). The mean age was 7.8 ± 4.1 years. Bites were most often located on the lower extremities (77%). The classification of envenomation was: 83% low grade (absence or minor envenomation) and 17% high-grade (moderate to severe envenomations). All high-grade envenomations received specific immunotherapy (Viperfav). Being bitten on an upper extremity (P level (P = 0.016) were associated with a significant risk of high-grade envenomation. In the multivariate analysis, 3 factors remained significant: upper-extremity location (relative risk [RR], 60.5 [3.5-1040]; P = 0.005), immediate violent pain (RR, 21.5 [1.3-364.5]; P = 0.03), and female sex (RR, 17.5 [0.9-320.3]; P = 0.053). A certain number of criteria seem related to more significant risk of progression to high-grade envenomation. Bites to the upper extremities should be carefully observed because of the risk of evolution to a high-grade envenomation.

  4. High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

    Science.gov (United States)

    Grand, Bertrand; Cazes, Aurélie; Mordant, Pierre; Foucault, Christophe; Dujon, Antoine; Guillevin, Elizabeth Fabre; Barthes, Françoise Le Pimpec; Riquet, Marc

    2013-09-01

    Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Active MMP-2 Activity Discriminates Colonic Mucosa, Adenomas with and without High Grade Dysplasia and Cancers

    Science.gov (United States)

    Murnane, Mary Jo; Cai, Jinguo; Shuja, Sania; McAneny, David; Willett, John B.

    2010-01-01

    Pathologic assessment of colorectal adenomas, a complex task with significant inter-observer variability, typically defines the scheduling of surveillance colonoscopies following removal of adenomas. We have characterized the activity levels of pro- and active matrix metalloproteinase-2 and matrix metalloproteinase-9 in colorectal adenomas and carcinomas, as potential markers of pathologic progression during colorectal tumorigenesis. Endogenous fully activated matrix metalloproteinase-2, in particular, has been studied less frequently in adenomas due to difficulties in detection. For this report, tissues (n=119) from 51 individuals were extracted and assayed on gelatin zymograms with digital standardization to nanogram quantities of purified active controls. Resulting data were assessed by graphical and multinomial logit regression analyses to test whether matrix metalloproteinase-2 or matrix metalloproteinase-9 activities could discriminate among four different types of colorectal tissue (normal mucosa, adenomas with or without high grade dysplasia and invasive carcinomas). Active matrix metalloproteinase-2 successfully discriminated among these tissue categories. Median activity for active matrix metalloproteinase-2 increased in a stepwise fashion with pathologic progression from normal mucosa to adenoma without high grade dysplasia to adenoma with high grade dysplasia to cancer. Although pro-matrix metalloproteinase-2 and pro-matrix metalloproteinase-9 activities could discriminate to some extent among tissue categories, those effects did not contribute additional information. Active matrix metalloproteinase-2 activity correlated significantly with histopathologic assessment of colorectal tissues. The ability of active matrix metalloproteinase-2 to distinguish adenomas with high grade dysplasia from adenomas without high grade dysplasia may be particularly useful in predicting future colorectal cancer risk for an individual, thus optimizing scheduling of

  6. Blood Magnesium, and the Interaction with Calcium, on the Risk of High-Grade Prostate Cancer

    Science.gov (United States)

    Motley, Saundra S.; Smith, Joseph A.; Concepcion, Raoul; Barocas, Daniel; Byerly, Susan

    2011-01-01

    Background Ionized calcium (Ca) and magnesium (Mg) compete as essential messengers to regulate cell proliferation and inflammation. We hypothesized that inadequate Mg levels, perhaps relative to Ca levels (e.g. a high Ca/Mg ratio) are associated with greater prostate cancer risk. Study Design In this biomarker sub-study of the Nashville Men's Health Study (NMHS), we included 494 NMHS participants, consisting of 98 high-grade (Gleason≥7) and 100 low-grade cancer cases, 133 prostate intraepithelial neoplasia (PIN) cases, and 163 controls without cancer or PIN at biopsy. Linear and logistic regression were used to determine associations between blood Ca, Mg, and the Ca/Mg ratio across controls and case groups while adjusting for potential confounding factors. Results Serum Mg levels were significantly lower, while the Ca/Mg ratio was significantly higher, among high-grade cases vs. controls (p = 0.04, p = 0.01, respectively). Elevated Mg was significantly associated with a lower risk of high-grade prostate cancer (OR = 0.26 (0.09, 0.85)). An elevated Ca/Mg ratio was also associated with an increased risk of high-grade prostate cancer (OR = 2.81 (1.24, 6.36) adjusted for serum Ca and Mg). In contrast, blood Ca levels were not significantly associated with prostate cancer or PIN.Mg, Ca, or Ca/Mg levels were not associated with low-grade cancer, PIN, PSA levels, prostate volume, or BPH treatment. Conclusion Low blood Mg levels and a high Ca/Mg ratio were significantly associated with high-grade prostate cancer. These findings suggest Mg affects prostate cancer risk perhaps through interacting with Ca. PMID:21541018

  7. Tropical forest transitions: structural changes in forest area, composition and landscape

    NARCIS (Netherlands)

    Wiersum, K.F.

    2014-01-01

    Most studies on tropical forest dynamics focus on the processes of deforestation and forest degradation and its associated ecological impacts; comparatively little attention is given to the emergence of forest transitions. This review gives an overview of forest transitions in the tropics as

  8. Diagnostics of Track Quality of Ballastless Track and Transition Areas in Vicinity of Portals of Tunnel Turecky vrch

    Directory of Open Access Journals (Sweden)

    Šmalo Michal

    2016-05-01

    Full Text Available The paper deals with the partial results of diagnostics of experimental sections of ballastless track Rheda 2000® and transition areas between ballastless and ballasted track structure around portals of tunnel Turecky vrch after six measurement cycles. The paper presents differences between each operational measurement and the measurement before putting sections into operation, which indicates a development of track geometry quality.

  9. A Gastrointestinal Stromal Tumor of the Stomach Demonstrating a Stepwise Progression from Low- to High-Grade Malignancy

    Directory of Open Access Journals (Sweden)

    Takahiko Nakajima

    2012-01-01

    Full Text Available We report a case of a gastrointestinal stromal tumor (GIST of the stomach that demonstrated a stepwise progression from low- to high-grade malignancy. The patient had been followed for a small gastric submucosal tumor that had turned malignant after 8 years of indolence, manifested by tarry stools. The tumor was enucleated, and gastric GIST was diagnosed. The most significant histological finding was that the tumor comprised two clearly demarcated areas, one with less aggressive characteristics and the other with highly aggressive characteristics. The patient exhibited multiple liver metastases 24 months after surgery. Imatinib mesylate was not administered throughout the clinical course because it was not available for clinical use at that time. The patient followed an unfavorable clinical course and died of liver dysfunction 55 months after surgery. Autopsy was performed. By comparing the immunohistochemical profiles of primary and metastatic tumors, it was established that only the tumor cells with highly aggressive characteristics had metastasized.

  10. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia

    Science.gov (United States)

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-01-01

    Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case–control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted. After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24–2.81) and women (adjusted OR = 2.72, 95% CI = 1.44–5.16). The 2 highest BMI categories (27.5–29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5–29.9: adjusted OR = 1.78, 95% CI = 1.02–3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27–5.08) and women (BMI = 27.5–29.9: adjusted OR = 2.88, 95% CI = 1.27–6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36–5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25–3.14) and women (adjusted OR = 2.88, 95% CI = 1.43–5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25–2.69) in women. Increased BMI was associated with an increased risk

  11. Fe-phyllosilicate redox cycling organisms from a redox transition zone in Hanford 300 Area sediments

    Directory of Open Access Journals (Sweden)

    Jason eBenzine

    2013-12-01

    Full Text Available Microorganisms capable of reducing or oxidizing structural iron (Fe in Fe-bearing phyllosilicate minerals were enriched and isolated from a subsurface redox transition zone at the Hanford 300 Area site in eastern Washington, USA. Both conventional and in situ i-chip enrichment strategies were employed. One Fe(III-reducing Geobacter (G. bremensis strain R1, Deltaproteobacteria and six Fe(II phyllosilicate-oxidizing isolates from the Alphaproteobacteria (Bradyrhizobium japonicum strains 22, is5, and in8p8, Betaproteobacteria (Cupriavidus necator strain A5-1, Dechloromonas agitata strain is5, and Actinobacteria (Nocardioides sp. strain in31 were recovered. The G. bremensis isolate grew by oxidizing acetate with the oxidized form of NAu-2 smectite as the electron acceptor. The Fe(II-oxidizers grew by oxidation of chemically reduced smectite as the energy source with nitrate as the electron acceptor. The Bradyrhizobium isolates could also carry out aerobic oxidation of biotite. This is the first report of the recovery of a Fe(II-oxidizing Nocardioides, and to date only one other Fe(II-oxidizing Bradyrhizobium is known. The 16S rRNA gene sequences of the isolates were similar to ones found in clone libraries from Hanford 300 sediments and groundwater, suggesting that such organisms may be present and active in situ. Whole genome sequencing of the isolates is underway, the results of which will enable comparative genomic analysis of mechanisms of extracellular phyllosilicate Fe redox metabolism, and facilitate development of techniques to detect the presence and expression of genes associated with microbial phyllosilicate Fe redox cycling in sediments.

  12. 76 FR 30997 - National Transit Database: Amendments to Urbanized Area Annual Reporting Manual

    Science.gov (United States)

    2011-05-27

    ... proposed recertification requirements. One public transit agency requested clarification of the logistics... connecting a small UZA to a large UZA may be allocated 100% to the large UZA, but the reverse is not true...

  13. Salivary gland hybrid tumour revisited: could they represent high-grade transformation in a low-grade neoplasm?

    Science.gov (United States)

    Hellquist, Henrik; Skalova, Alena; Azadeh, Bahram

    2016-12-01

    Salivary gland hybrid tumour, first described in 1996, is a very rare neoplasm for which exact morphological criteria have not been universally agreed upon. In contrast, the concept of high-grade transformation (HGT) in salivary neoplasms has been widely accepted during the last decade, and the number of reported cases is rapidly increasing. A review of the literature revealed 38 cases of hybrid tumour reported in 22 publications. During approximately the same time period, well over 100 cases of HGT in salivary neoplasms have been reported. There are important histological similarities between hybrid tumours and salivary tumours with HGT. In the latter, containing one tumour component of low-grade malignancy and the other of high grade, the two tumour components are not entirely separated and appear to originate in the same area. Virtually, all cases reported as hybrid tumour had no clear lines of demarcation between the two tumour types. We are inclined to suggest that most of the 38 cases of hybrid tumours described in the literature would today better be called tumour with HGT rather than hybrid tumour. The relative proportion of the two components may vary, and the high-grade component is sometimes very small, which emphasises the importance of very generous sampling of the surgical specimen. The molecular genetic mechanisms responsible for HGT, including what used to be called hybrid tumour, remain largely unknown. Abnormalities of a few genes (including p53, C-MYC, cyclin D1, HER-2/neu) have been documented. As insufficient data exist on gene abnormalities in these lesions, conclusions as to whether or not they have a common origin and which mechanisms are involved in transformation cannot be drawn. Due to the small number of cases reported, many of which lack follow-up details; indicators of prognosis of hybrid tumours are not available, but their behaviour seems to be similar to that of tumours with HGT, i.e. an accelerated aggressive course. HGT of

  14. Severity and Spatial Distribution of Boron Toxicity in Barley Cultivated Areas of Central Anatolia and Transitional Zones

    OpenAIRE

    Avci, Muzaffer; AKAR, Taner

    2014-01-01

    The aim of this study was to determine the severity and spatial distribution of boron toxicity symptoms on barley cultivated areas in Central Anatolia and Transitional Zones (CATZs). Boron concentrations of plants sampled from barley cultivated areas of the CATZs region at 189 sites during springs 1996 and 1997 were determined. Boron toxicity symptoms were observed mainly in small areas near Konya-Çumra, Ankara-Gölbaşı, Yenikent and Yozgat-Yerköy and between the provinces of Konya and Aksaray...

  15. Proposal for the award of two blanket contracts for the supply of high-grade helium

    CERN Document Server

    2003-01-01

    This document concerns the supply of up to 280 000 kg of high-grade helium. Following a call for tenders (IT-3235/AT) sent on 4 July 2003 to seven firms, in four Member States, CERN had, by the closing date, received six tenders from six firms in four Member States. The Finance Committee is invited to agree to the negotiation of two blanket contracts for the supply of up to 280 000 kg of high-grade helium with AIR PRODUCTS (FR) and CARBAGAS (CH) for a total maximum amount for both contracts of 5 577 800 US dollars (7 736 400 Swiss francs), not subject to revision, for a period of four years starting 1 January 2004. The rates of exchange used are those stipulated in the tenders. The firms have indicated the following distribution by country of the contract value covered by this adjudication proposal: AIR PRODUCTS : PL - 100%; CARBAGAS : PL - 100%.

  16. A population-based study of high-grade gliomas and mutated isocitrate dehydrogenase 1

    DEFF Research Database (Denmark)

    Dahlrot, Rikke H; Kristensen, Bjarne W; Hjelmborg, Jacob

    2012-01-01

    High-grade gliomas have a dismal prognosis, and prognostic factors are needed to optimize treatment algorithms. In this study we identified clinical prognostic factors as well as the prognostic value of isocitrate dehydrogenase 1 (IDH1) status in a population-based group of patients with high......-grade gliomas. Using the Danish Cancer Registry and the Danish Pathology Databank we identified 359 patients: 234 had WHO grade IV gliomas, 58 had WHO grade III gliomas, and 67 were diagnosed clinically. Mutated IDH1 was predominantly observed in oligodendroglial tumors (WHO grade III). Patients with mutated...... IDH1 had a significantly better outcome than patients with wildtype IDH1: 2-year OS 59% and 18%, respectively (HR 0.38, 95% CI 0.21-0.68). However, when adjusting for other prognostic factors, IDH1 status was not a significant independent prognostic factor (HR=0.58, 95% CI 0.32-1.07). Young age...

  17. P-COMM-B induction chemotherapy in intermediate and high grade non-Hodgkin's lymphoma.

    Science.gov (United States)

    Phillips, J K; Sherlaw-Johnson, C; Davies, J M; Clough, J V; Parry, H; Nash, J R; Cawley, J C

    1995-06-01

    57 patients with newly diagnosed intermediate or high grade non-Hodgkin's lymphoma with stage II to IV disease were treated with P-COMM-B (prednisolone, cyclophosphamide, vincristine, mitozantrone, methotrexate and bleomycin). 46% patients achieved a complete remission and 26% achieved a partial remission. Projected disease-free survival in complete remission at 5 years is 56% and projected overall survival at 5 years is 37%. Neutropenia and proximal myopathy were the commonest severe toxicities encountered and two deaths were clearly related to treatment (3.5%). P-COMM-B is effective first-line chemotherapy in intermediate and high grade non-Hodgkin's lymphoma. The efficacy and toxicity of P-COMM-B appear to be comparable to those of the best contemporary regimen, CHOP.

  18. BRCA and early events in the development of high grade serous ovarian cancer

    Directory of Open Access Journals (Sweden)

    Sophia HL George

    2014-01-01

    Full Text Available Women who have an inherited mutation in the BRCA1 or BRCA2 genes have a substantial increased lifetime risk of developing epithelial ovarian cancer, and epidemiological factors related to parity, ovulation and hormone regulation have a dramatic effect on the risk in both BRCA mutation carriers and non-carriers. The most common and most aggressive histotype of epithelial ovarian cancer, high-grade serous carcinoma, is also the histotype associated with germline BRCA mutations. In recent years, evidence has emerged indicating that the likely tissue of origin of high-grade serous carcinoma is the fallopian tube. We have reviewed what is known about the fallopian tube in BRCA mutation carriers at both the transcriptional and translational aspect of their biology. We propose that changes of the transcriptome in BRCA heterozygotes reflect an altered response to the ovulatory stresses from microenvironment, which may include the post-ovulation inflammatory response and altered reproductive hormone physiology.

  19. Rare earth element patterns in Archean high-grade metasediments and their tectonic significance

    Science.gov (United States)

    Taylor, Stuart Ross; Rudnick, Roberta L.; Mclennan, Scott M.; Eriksson, Kenneth A.

    1986-01-01

    REE data on metasedimentary rocks from two different types of high-grade Archean terrains are presented and analyzed. The value of REEs as indicators of crustal evolution is explained; the three geologic settings (in North America, Southern Africa, and Australia) from which the samples were obtained are described; and the data are presented in extensive tables and graphs and discussed in terms of metamorphic effects, the role of accessory phases, provenance, and tectonic implications (recycling, the previous extent of high-grade terrains, and a model of Archean crustal growth). The diversity of REE patterns in shallow-shelf metasediments is attributed to local provenance, while the Eu-depleted post-Archean patterns are associated with K-rich plutons from small, stable early Archean terrains.

  20. Immunotherapy for high-grade glioma: how to go beyond Phase I/II clinical trials.

    Science.gov (United States)

    van Gool, Stefaan

    2013-10-01

    Evaluation of: Lasky JL 3rd, Panosyan EH, Plant A et al. Autologous tumor lysate-pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed or recurrent high-grade gliomas. Anticancer Res. 33, 2047-2056 (2013). Immunotherapy for children and adults with high-grade glioma (HGG) is an emerging innovative treatment approach, which aims at stimulating the body's own immune system against HGG by using autologous dendritic cells pulsed with autologous tumor lysate as a therapeutic vaccine. This is the third report on immunotherapy for HGG in children, bringing additional knowledge and experience to the scientific community. However, at the same time, this and other manuscripts urge for the next step in treatment development.

  1. Topical 5-Fluorouracil for Women With High-Grade Vaginal Intraepithelial Neoplasia.

    Science.gov (United States)

    Fiascone, Stephen; Vitonis, Allison F; Feldman, Sarah

    2017-12-01

    To examine success rates of 5-fluorouracil, excision, and laser ablation as the initial and secondary management strategies for women with high-grade vaginal intraepithelial neoplasia. We conducted a retrospective case series of women referred to a single center for management of biopsy-proven, high-grade vaginal intraepithelial neoplasia between April 1994 and May 2016. Data including demographic characteristics, human papillomavirus risk factors, antecedent Pap cytology, concurrent or prior cervical and vulvar dysplasia, and treatment outcome including follow-up Pap cytology were recorded. All women were counseled on options of excision, laser ablation, or 5-fluorouracil, which was administered intravaginally according to a standardized regimen. Recurrence was defined as a biopsy showing any vaginal intraepithelial neoplasia diagnosis after primary treatment. Forty-seven patients were treated initially with 5-fluorouracil, 35 were treated with excision, and 22 were treated with laser ablation. Demographics were similar between groups. No recurrence was noted in 35 women treated with 5-fluorouracil (74%; 95% CI 62-87%), 20 treated with excision (57%; 95% CI 41-74%), and nine treated with laser ablation (41%; 95% CI 20-61%). Among 13 patients treated with 5-fluorouracil for recurrence, eight (62%) did not experience a second recurrence. Nine of 58 (16%) patients ever treated with 5-fluorouracil reported a side effect, most commonly irritation and dyspareunia. 5-fluorouracil was associated with a 74% success rate as the initial treatment modality for high-grade vaginal dysplasia. There is also a role for 5-fluorouracil in the management of recurrent or persistent high-grade vaginal intraepithelial neoplasia.

  2. Prognostic value of endocervical sampling following loop excision of high grade intraepithelial neoplasia.

    Science.gov (United States)

    Cui, Yiwen; Sangi-Haghpeykar, Haleh; Patsner, Bruce; Bump, Jennifer M M; Williams-Brown, Marian Y; Binder, Gary L; Masand, Ramya P; Anderson, Matthew L

    2017-03-01

    To assess the role of additional biopsies performed with loop electrosurgical excisional procedure (LEEP) in predicting the likelihood of persistent high grade intraepithelial neoplasia. Clinicopathologic data were abstracted from women who underwent excision of high grade intraepithelial lesions between 2001 and 2014. Persistent disease was defined as uninterrupted high grade intraepithelial neoplasia, whereas recurrent disease was defined as disease diagnosed ≥1year after treatment with intervening normal evaluation. Chi-square and Fisher's exact tests were used to examine associations between demographic and histologic parameters and clinical outcomes. A total of 606 women underwent LEEP for high grade intraepithelial neoplasia (HSIL), of whom, 178 (29%) were additionally evaluated by endocervical curettage, 80 (13%), top hat and 99 (16%), both procedures. With mean follow-up of 1.9±1.5years, persistent disease was identified in 87 women (14%) while recurrent disease was diagnosed in 20 (3%). After adjusting for age, HIV status and histologic grade of disease, the presence of disease at the endocervical margin (aOR=2.2, 95% CL 1.8-5.5, p<0.0001), with endocervical curettage (aOR=2.39, 95% CL 1.2-9.9, p=0.025) or on top hat (aOR=4.0, 95% CL 1.1-16.2, p=0.04) correlated with the likelihood of persistent but not recurrent disease. Only endocervical margin status remained predictive (p=0.03) of outcome after controlling for pre-procedure likelihood of endocervical disease. Sensitivity of endocervical margin status for persistent disease was 56.9% with specificity of 72.2%. Positive predictive value (PPV) was 24.9% and negative predictive value (NPV) 90.9%. Despite frequent use of additional procedures to sample the endocervix, these strategies do not improve the ability of endocervical margin status to predict persistent or recurrent dysplasia. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Primary undifferentiated high-grade pleomorphic sarcoma in the perihepatic space: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Beom; Kim, Song Hoon [Dept. of Radiology, Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2015-07-15

    Undifferentiated high-grade pleomorphic sarcoma (UPS) is a pleomorphic soft tissue sarcoma derived from histiocytes capable of fibroblastic transformation. UPS affects soft tissues of the body, especially the extremities and retroperitoneum, and primary UPS in the perihepatic space is extremely rare. We report a case of primary perihepatic UPS in a 44-year-old male, who presented with fever and right upper abdominal discomfort.

  4. Radiologic and Clinical Outcomes of Surgery in High Grade Spondylolisthesis Treated with Temporary Distraction Rod

    Science.gov (United States)

    Hootkani, Alireza; Jarahi, Lida; Rezvan, Manizheh; Moayedpour, Amir

    2015-01-01

    Background Surgical techniques used in the treatment of patients with high grade lumbar spondylolisthesis (> 50% slippage) are usually associated with a great deal of controversies. We aim to evaluate the surgical outcomes of high grade spondylolisthesis treated with an intraoperative temporary distraction rod. Methods We retrospectively studied 21 patients (14 females and 7 males), aged 50.4 ± 9.2 years, who had high grade lumbar spondylolisthesis that was treated with intraoperative temporary distraction rods, neural decompression, pedicular screw fixation, and posterolateral fusion involving one more intact upper vertebra. The mean follow-up period was 39.2 months. Radiologic and clinical outcomes were measured by slip angle, slip percentage, correction rate, Oswestry Disability Index (ODI), visual analogue scale (VAS), patient's satisfaction rate in the pre- and postoperative period. Data were analyzed by SPSS ver. 11.5. Results Analysis of the preoperative visits and final follow-up visits indicated that surgery could improve ODI, lumbar VAS, and leg VAS from 60.5% to 8.2%, from 6.7 to 2.2, and from 6.9 to 1.3, respectively. Slip angle and slip percentage were also changed from -8° to -15° and from 59.2% to 21.4%, respectively. Mean correction rate at the final follow-up visit was 64.1%. Loss of correction was insignificant and a neurologic complication occurred in one patient due to misplacement of one screw. Excellent and good levels of satisfaction were observed in 90.5% of the patients. Conclusions In the surgical treatment of refractory high grade spondylolisthesis, the use of a temporary distraction rod to reduce the slipped vertebra in combination with neural decompression, posterolateral fusion, and longer instrumentation is associated with satisfactory clinical and radiologic outcomes. PMID:25729523

  5. A dosimetric comparison of four treatment planning methods for high grade glioma

    Directory of Open Access Journals (Sweden)

    Miller Robert W

    2009-10-01

    Full Text Available Abstract Background High grade gliomas (HGG are typically treated with a combination of surgery, radiotherapy and chemotherapy. Three dimensional (3D conformal radiotherapy treatment planning is still the main stay of treatment for these patients. New treatment planning methods suggest better dose distributions and organ sparing but their clinical benefit is unclear. The purpose of the current study was to compare normal tissue sparing and tumor coverage using four different radiotherapy planning methods in patients with high grade glioma. Methods Three dimensional conformal (3D, sequential boost IMRT, integrated boost (IB IMRT and Tomotherapy (TOMO treatment plans were generated for 20 high grade glioma patients. T1 and T2 MRI abnormalities were used to define GTV and CTV with 2 and 2.5 cm margins to define PTV1 and PTV2 respectively. Results The mean dose to PTV2 but not to PTV1 was less then 95% of the prescribed dose with IB and IMRT plans. The mean doses to the optic chiasm and the ipsilateral globe were highest with 3D plans and least with IB plans. The mean dose to the contralateral globe was highest with TOMO plans. The mean of the integral dose (ID to the brain was least with the IB plan and was lower with IMRT compared to 3D plans. The TOMO plans had the least mean D10 to the normal brain but higher mean D50 and D90 compared to IB and IMRT plans. The mean D10 and D50 but not D90 were significantly lower with the IMRT plans compared to the 3D plans. Conclusion No single treatment planning method was found to be superior to all others and a personalized approach is advised for planning and treating high-grade glioma patients with radiotherapy. Integral dose did not reflect accurately the dose volume histogram (DVH of the normal brain and may not be a good indicator of delayed radiation toxicity.

  6. Proposal for the award of three contracts for the supply of high-grade helium

    CERN Document Server

    2001-01-01

    This document concerns the award of three contracts for the supply of high-grade helium. Following a market survey carried out among 27 firms in ten Member States, a call for tenders (IT-2855/LHC) was sent on 15 November 2000 to five firms in three Member States. By the closing date, CERN had received tenders from four firms in three Member States. For the reasons explained in this document, the Finance Committee is invited to agree to the negotiation of the following three contracts: - a contract with MESSER GRIESHEIM (DE), the lowest bidder, for the supply of up to 26 000 kg of high-grade helium over a period of three years for an estimated amount of 655 200 Swiss francs, not subject to revision. - a contract with BOC (GB), the second lowest bidder, for the supply of up to 26 000 kg of high-grade helium over a period of three years for an estimated amount of 493 300 US dollars (808 080 Swiss francs), not subject to revision. The rate of exchange which has been used is that stipulated in the tender. - a cont...

  7. Significant worsening sperm parameters are associated to testicular hypotrophy in patients with a high grade varicocele.

    Science.gov (United States)

    Guzel, O; Aslan, Y; Balci, M; Tuncel, A; Unal, B; Atan, A

    2015-01-01

    To investigate the relationship between testicular volume and semen parameter sin patients with unilateral high grade left varicocele. One hundred eighty seven patients who had left high grade varicocele aged 19-to-25 years were included in this study. All patients underwent a standard evaluation, including medical history and physical examination. The percentage testicular volume difference between the right and left testicles was calculated. The patients were divided into the following three groups; Group 1 (n=72) testicular volume difference 20% Group 3 (n=41). The mean age and BMI of the patients were 21.5 years and 23.1kg/m(2), respectively (P=.596, P=.943). The semen parameters and testicular volumes of the three groups were compared. The total motile sperm count, percentage of motile sperm, percentage of normal morphology sperm were found to be lower in Group 3 (P=.011, P=.012, P=.029 respectively). The mean testicular volumes for the left and the right testis were found to be 15.2cm(3) and 17.7cm(3) (P<.001), respectively. No significant difference was found in the right testicular volumes between groups (17.4, 17.7 and 18.1cm(3), P=.573). A high grade left testicular varicocele is associated with ipsilateral testicular hypotrophy and parallel to worsened sperm parameters. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Increased incidence of penile cancer and high-grade penile intraepithelial neoplasia in Denmark 1978-2008

    DEFF Research Database (Denmark)

    Baldur-Felskov, Birgitte; Hannibal, Charlotte Gerd; Munk, Christian

    2012-01-01

    To assess the trends in incidence of penile cancer during 1978-2008 and high-grade penile intraepithelial neoplasia (PIN2/3) during 1998-2008 in Denmark.......To assess the trends in incidence of penile cancer during 1978-2008 and high-grade penile intraepithelial neoplasia (PIN2/3) during 1998-2008 in Denmark....

  9. High-grade dysplasia in sporadic fundic gland polyps : a case report and review of the literature

    NARCIS (Netherlands)

    Jalving, M; Koornstra, JJ; Gotz, JM; van der Waaij, LA; de Jong, S; Zwart, N; Karrenbeld, Arend; Kleibeuker, JH

    2003-01-01

    We present a case of fundic gland polyps (FGPs) containing high-grade dysplasia in a 68-year-old man. High-grade dysplasia, and even gastric adenocarcinoma, associated with FGPs have been described in patients with familial adenomatous polyposis (FAP) and attenuated familial adenomatous polyposis

  10. The use of 18F-FDG PET to differentiate progressive disease from treatment induced necrosis in high grade glioma

    NARCIS (Netherlands)

    Dankbaar, J. W.; Snijders, T. J.; Robe, P. A.; Seute, T.; Eppinga, W.; Hendrikse, J.; De Keizer, B.

    2015-01-01

    In the follow-up of patients treated for high grade glioma, differentiation between progressive disease (PD) and treatment-induced necrosis (TIN) is challenging. The purpose of this study is to evaluate the diagnostic accuracy of FDG PET for the differentiation between TIN and PD after high grade

  11. Comparable outcome between endometrioid and non-endometrioid tumors in patients with early-stage high-grade endometrial cancer

    NARCIS (Netherlands)

    Reynaers, E. A. E. M.; Ezendam, N. P. M.; Pijnenborg, J. M. A.

    2015-01-01

    Background Approximately 25% of endometrial cancer patients present with high-grade tumors. Unlike the clearly defined work-up for non-endometrioid endometrial cancer, no consensus exists for surgical staging and adjuvant therapy in high-grade endometrioid endometrial cancer. We compared the

  12. Comparable outcome between endometrioid and non-endometrioid tumors in patients with early-stage high-grade endometrial cancer

    NARCIS (Netherlands)

    Reynaers, E.A.; Ezendam, N.P.; Pijnenborg, J.M.A.

    2015-01-01

    BACKGROUND: Approximately 25% of endometrial cancer patients present with high-grade tumors. Unlike the clearly defined work-up for non-endometrioid endometrial cancer, no consensus exists for surgical staging and adjuvant therapy in high-grade endometrioid endometrial cancer. We compared the

  13. Complications of high grade liver injuries: management and outcomewith focus on bile leaks

    Directory of Open Access Journals (Sweden)

    Bala Miklosh

    2012-03-01

    Full Text Available Abstract Background Although liver injury scale does not predict need for surgical intervention, a high-grade complex liver injury should alert the physician to expect an increased risk of hepatic complications following trauma. The aim of the current study was to define hepatic related morbidity in patients sustaining high-grade hepatic injuries that could be safely managed non-operatively. Patients and methods This is a retrospective study of patients with liver injury admitted to Hadassah-Hebrew University Medical Centre over a 10-year period. Grade 3-5 injuries were considered to be high grade. Collected data included the number and types of liver-related complications. Interventions which were required for these complications in patients who survived longer than 24 hours were analysed. Results Of 398 patients with liver trauma, 64 (16% were found to have high-grade liver injuries. Mechanism of injury was blunt trauma in 43 cases, and penetrating in 21. Forty patients (62% required operative treatment. Among survivors 22 patients (47.8% developed liver-related complications which required additional interventional treatment. Bilomas and bile leaks were diagnosed in 16 cases post-injury. The diagnosis of bile leaks was suspected with abdominal CT scan, which revealed intraabdominal collections (n = 6, and ascites (n = 2. Three patients had continuous biliary leak from intraabdominal drains left after laparotomy. Nine patients required ERCP with biliary stent placement, and 2 required percutaneous transhepatic biliary drainage. ERCP failed in one case. Four angioembolizations (AE were performed in 3 patients for rebleeding. Surgical treatment was found to be associated with higher complication rate. AE at admission was associated with a significantly higher rate of biliary complications. There were 24 deaths (37%, the majority from uncontrolled haemorrhage (18 patients. There were only 2 hepatic-related mortalities due to liver failure

  14. Improving polio vaccination during supplementary campaigns at areas of mass transit in India

    Directory of Open Access Journals (Sweden)

    Bahl Sunil

    2010-05-01

    Full Text Available Abstract Background In India, children who are traveling during mass immunization campaigns for polio represent a substantial component of the total target population. These children are not easily accessible to health workers and may thus not receive vaccine. Vaccination activities at mass transit sites (such as major intersections, bus depots and train stations, can increase the proportion of children vaccinated but the effectiveness of these activities, and factors associated with their success, have not been rigorously evaluated. Methods We assessed data from polio vaccination activities in Jyotiba Phule Nagar district, Uttar Pradesh, India, conducted in June 2006. We used trends in the vaccination results from the June activities to plan the timing, locations, and human resource requirements for transit vaccination activities in two out of the seven blocks in the district for the July 2006 supplementary immunization activity (SIA. In July, similar data was collected and for the first time vaccination teams also recorded the proportion of children encountered each day who were vaccinated (a new monitoring system. Results In June, out of the 360,937 total children vaccinated, 34,643 (9.6% received vaccinations at mass transit sites. In the July SIA, after implementation of a number of changes based on the June monitoring data, 36,475 children were vaccinated at transit sites (a 5.3% increase. Transit site vaccinations in July increased in the two intervention blocks from 18,194 to 21,588 (18.7% and decreased from 16,449 to 14,887 (9.5% in the five other blocks. The new monitoring system showed the proportion of unvaccinated children at street intersection transit sites in the July campaign decreased from 24% (1,784/7,405 at the start of the campaign to 3% (143/5,057 by the end of the SIA, consistent with findings from the more labor-intensive post-vaccination coverage surveys routinely performed by the program. Conclusions Analysis of

  15. PRIORITY AREAS FOR FOREST CONSERVATION IN AN URBAN LANDSCAPE AT THE TRANSITION BETWEEN ATLANTIC FOREST AND CERRADO

    OpenAIRE

    Mello, Kaline de; Toppa, Rogério Hartung; Cardoso-Leite, Eliana

    2016-01-01

    ABSTRACT Urbanization and agriculture growth are some of the major causes of natural ecosystems depletion and biodiversity loss. Conservation efforts can be developed through the prioritization of areas for forest conservation in order to minimize this process. Here, we establish conservation strategies based on a spatial analysis of forest fragments in an urban landscape at the transition between two important Brazilian biodiversity hotspots: Atlantic Forest and Cerrado. A high-resolution ma...

  16. The Transportation Crossroads: Influence of Urban Area Form And Composition on Mass Transit

    OpenAIRE

    Gasana, Parfait

    2009-01-01

    In the wake of economic restructuring and decentralization of cities America has come to rely on automobiles, contributing to high levels of traffic congestion, carbon emissions, poor quality places, and a declining public infrastructure. Policymakers and planners recognize that mass transit, an alternative mode of travel, can alleviate America’s strained transportation system. However, public transportation is an infrequently used service for commuters’ work and nonwork related trips. The pu...

  17. p53 immunohistochemistry in high-grade urothelial carcinoma of the bladder is prognostically significant.

    Science.gov (United States)

    Hodgson, Anjelica; Xu, Bin; Downes, Michelle R

    2017-08-01

    TP53 mutations are characteristic of the high-grade pathway in the dual pathway of urothelial carcinogenesis. These mutations have been correlated with aberrant accumulation of p53 protein; however the definition and significance of this vary in the literature. The aim of this study was to assess p53 immunostaining in a cohort of high-grade urothelial carcinomas by using standard published cut-offs and a novel binarized method that included assessment of the null phenotype. Each scoring method was correlated with oncological outcome. A triplicate core tissue microarray was constructed from 207 cases of high-grade urothelial carcinoma treated by cystectomy, and was stained with p53. The percentage nuclear staining was recorded for each core and averaged for every case (206 cases were evaluable). Cases were categorized as positive/negative according to published cut-offs (10%, 40%) or by binarizing them as abnormal (null phenotype or >50% positivity) and wild type (1-49% positivity). Correlation with disease-specific survival was not significant according to standard definitions of p53 positivity. When a 40% cut-off was used, a correlation with relapse-free survival was significant on univariate analysis (P = 0.038) but not on multivariate analysis (P = 0.079). Abnormal p53 expression showed a near-significant trend for association with disease-specific survival (P = 0.052) and was a significant predictor for relapse-free survival on both univariate analysis (P = 0.047) and multivariate analysis (P = 0.035). Prior to this study, the p53 null phenotype was not well described in urothelial carcinoma of the bladder. Abnormal p53 immunoexpression (null staining pattern or staining in >50% of cells) is prognostic in terms of oncological outcome. © 2017 John Wiley & Sons Ltd.

  18. Relationship Between Cytogenetic Complexity and Peritumoral Edema in High-Grade Astrocytoma.

    Science.gov (United States)

    Jeong, Kyung Ho; Song, Young Jin; Han, Jin Yeong; Kim, Ki Uk

    2016-11-01

    The purpose of the study is to reveal the association of cytogenetic compltyexi and peritumoral edema volume (PTEV) and its prognostic significance in high-grade astrocytoma patients by culturing patient tumor cells. Twenty-seven high-grade astrocytoma patients were divided into three groups according to karyotype complexity: normal, non-complex karyotype (NCK), and complex karyotype (CK). Endothelial growth factor receptor (EGFR) amplification was detected by FISH, and its association with chromosome 7 abnormalities was analyzed. Mean PTEV of each group was compared by ANOVA to evaluate the relationship between PTEV and cytogenetic complexity. The PTEV of patients in normal (n=6), NCK (n=8), and CK (n=13) groups were 24.52±17.73, 34.26±35.04, and 86.31±48.7 cm³, respectively (P=0.005). Ten out of 11 patients with EGFR amplification showed abnormalities in chromosome 7. The mean PTEV of EGFR-amplified and non-amplified groups were 80.4±53.7 and 41.3±37.9 cm³, respectively (P=0.035). The average survival of patients with PTEV less than 90 cm³ was 30.52±26.11 months, while in patients with PTEVs over or equal to 90 cm³, it was 10.83±5.53 months (P=0.007). The results show an association of complex karyotype with the PTEV of high-grade astrocytoma. EGFR amplification plays a significant role in the formation of peritumoral edema, causing PTEV to increase, which is related with survival. This implies that cytogenetic karyotype can be applied as a prognostic factor.

  19. Comparison of predictors for high-grade cervical intraepithelial neoplasia in women with abnormal smears.

    Science.gov (United States)

    Szarewski, Anne; Ambroisine, Laurence; Cadman, Louise; Austin, Janet; Ho, Linda; Terry, George; Liddle, Stuart; Dina, Roberto; McCarthy, Julie; Buckley, Hilary; Bergeron, Christine; Soutter, Pat; Lyons, Deirdre; Cuzick, Jack

    2008-11-01

    The detection of high-risk human papillomavirus (HPV) DNA provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). This study compared the sensitivity and specificity of several adjunctive tests for the detection of high-grade CIN in a population referred to colposcopy because of abnormal cytology. 953 women participated in the study. Up to seven tests were carried out on a liquid PreservCyt sample: Hybrid Capture II (Digene), Amplicor (Roche), PreTect HPV-Proofer (NorChip), APTIMA HPV assay (Gen-Probe), Linear Array (Roche), Clinical-Arrays (Genomica), and CINtec p16INK4a Cytology (mtm Laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology seen on either the biopsy or the treatment specimen after central review. 273 (28.6%) women had high-grade disease (CIN2+) on worst histology, with 193 (20.2%) having CIN3+. For the detection of CIN2+, Hybrid Capture II had a sensitivity of 99.6%, specificity of 28.4%, and PPV of 36.1%. Amplicor had a sensitivity of 98.9%, specificity of 21.7%, and PPV of 33.5%. PreTect HPV-Proofer had a sensitivity of 73.6%, specificity of 73.1%, and PPV of 52.0%. APTIMA had a sensitivity of 95.2%, specificity of 42.2%, and PPV of 39.9%. CINtec p16INK4a Cytology had a sensitivity of 83.0%, specificity of 68.7%, and PPV of 52.3%. Linear Array had a sensitivity of 98.2%, specificity of 32.8%, and PPV of 37.7%. Clinical-Arrays had a sensitivity of 80.9%, specificity of 37.1%, and PPV of 33.0%.

  20. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Anders eOhman

    2014-11-01

    Full Text Available The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early stages and improving the disease prognosis.

  1. High-grade spondylolisthesis treated using a modified Bohlman technique: results among multiple surgeons.

    Science.gov (United States)

    Hart, Robert A; Domes, Christopher M; Goodwin, Brady; D'Amato, Charles R; Yoo, Jung U; Turker, Ronald J; Halsey, Matthew F

    2014-05-01

    The ideal surgical management of high-grade spondylolisthesis remains unclear. Concerns regarding the original Bohlman transsacral interbody fusion technique with stand-alone autologous fibular strut include late graft fracture and incomplete reduction of lumbosacral kyphosis. The authors' goal was to evaluate the radiographic and surgical outcomes of patients treated for high-grade spondylolisthesis with either transsacral S-1 screws or standard pedicle screw fixation augmenting the Bohlman posterior transsacral interbody fusion technique. A retrospective review of patients who underwent fusion for high-grade spondylolisthesis in which a Bohlman oblique posterior interbody fusion augmented with either transsacral or standard pedicle screw fixation was performed by 4 spine surgeons was completed. Estimated blood loss, operating time, perioperative complications, and need for revision surgery were evaluated. Upright pre- and postsurgical lumbar spine radiographs were compared for slip percent and slip angle. Sixteen patients (12 female and 4 male) with an average age of 29 years (range 9-66 years) were evaluated. The average clinical follow-up was 78 months (range 5-137 months) and the average radiographic follow-up was 48 months (range 5-108 months). Ten L4-S1 and 6 L5-S1 fusions were performed. Five fibular struts and 11 titanium mesh cages were used for interbody fusion. Six patients had isolated transsacral screws placed, with 2 (33%) of the 6 requiring revision surgery for nonunion. No nonunions were observed in patients undergoing spanning pedicle screw fixation augmenting the interbody graft. Six patients experienced perioperative complications including 3 iliac crest site infections, 1 L-5 radiculopathy without motor involvement, 1 deep vein thrombosis, and 1 epidural hematoma requiring irrigation and debridement. The average estimated blood loss and operating times were 763 ml and 360 minutes, respectively. Slip percent improved from an average of 62% to 37

  2. Comparison of T2 and FLAIR imaging for target delineation in high grade gliomas

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    Miller Robert W

    2010-01-01

    Full Text Available Abstract Background FLAIR and T2 weighted MRIs are used based on institutional preference to delineate high grade gliomas and surrounding edema for radiation treatment planning. Although these sequences have inherent physical differences there is limited data on the clinical and dosimetric impact of using either or both sequences. Methods 40 patients with high grade gliomas consecutively treated between 2002 and 2008 of which 32 had pretreatment MRIs with T1, T2 and FLAIR available for review were selected for this study. These MRIs were fused with the treatment planning CT. Normal structures, clinical tumor volume (CTV and planning tumor volume (PTV were then defined on the T2 and FLAIR sequences. A Venn diagram analysis was performed for each pair of tumor volumes as well as a fractional component analysis to assess the contribution of each sequence to the union volume. For each patient the tumor volumes were compared in terms of total volume in cubic centimeters as well as anatomic location using a discordance index. The overlap of the tumor volumes with critical structures was calculated as a measure of predicted toxicity. For patients with MRI documented failures, the tumor volumes obtained using the different sequences were compared with the recurrent gross tumor volume (rGTV. Results The FLAIR CTVs and PTVs were significantly larger than the T2 CTVs and PTVs (p Conclusions Although both T2 and FLAIR MRI sequences are used to define high grade glial neoplasm and surrounding edema, our results show that the volumes generated using these techniques are different and not interchangeable. These differences have bearing on the use of intensity modulated radiation therapy (IMRT and highly conformal treatment as well as on future clinical trials where the bias of using one technique over the other may influence the study outcome.

  3. Prevalence of concomitant intraarticular lesions in patients treated operatively for high-grade acromioclavicular joint separations.

    Science.gov (United States)

    Pauly, Stephan; Gerhardt, Christian; Haas, Norbert P; Scheibel, Markus

    2009-05-01

    The purpose of this study is to investigate the prevalence of concomitant intraarticular lesions to the glenohumeral joint or to surrounding soft tissue structures with non-randomized prospective case series. High-grade acromioclavicular (AC) joint dislocations result from direct or indirect force impact to the shoulder girdle. Fourty consecutive patients (2 female, 38 male) with high-grade acromioclavicular joint dislocations (Rockwood III: n = 3; IV: n = 3; V: n = 34) who underwent diagnostic arthroscopy at the time of acromioclavicular joint repair were evaluated. Associated pathologic lesions were documented and treated by an all-arthroscopic approach. As a result, traumatic intraarticular lesions were found in 15% (n = 6/40) of cases. Two patients had an isolated partial tear of the subscapularis tendon. One patient had a combined tear of the subscapularis and supraspinatus tendon (PASTA type lesion). Two patients showed a type II SLAP-lesion and one patient had a type VI SLAP-lesion. Arthroscopic treatment included rotator cuff reconstruction in two cases and debridement of the partially torn tendon in one case. Two patients underwent an arthroscopic SLAP-repair and in one patient a debridement of a labral flap tear was performed. Acromioclavicular joint reconstruction was achieved via an open technique using suture anchors in 14 cases and via an all-arthroscopic approach using a double Tight-rope technique in 26 cases. To conclude, in number of cases, high-grade AC-separations may be associated with traumatic concomitant glenohumeral pathologies resulting from the same trauma impact to the shoulder girdle. A combined or an all-arthroscopic approach allows to accurately diagnose and treat associated intraarticular pathologies.

  4. Associations between circulating carotenoids, genomic instability and the risk of high-grade prostate cancer.

    Science.gov (United States)

    Nordström, Tobias; Van Blarigan, Erin L; Ngo, Vy; Roy, Ritu; Weinberg, Vivian; Song, Xiaoling; Simko, Jeffry; Carroll, Peter R; Chan, June M; Paris, Pamela L

    2016-03-01

    Carotenoids are a class of nutrients with antioxidant properties that have been purported to protect against cancer. However, the reported associations between carotenoids and prostate cancer have been heterogeneous and lacking data on interactions with nucleotide sequence variations and genomic biomarkers. To examine the associations between carotenoid levels and the risk of high-grade prostate cancer, also considering antioxidant-related genes and tumor instability. We measured plasma levels of carotenoids and genotyped 20 single nucleotide polymorphisms (SNP) in SOD1, SOD2, SOD3, XRCC1, and OGG1 among 559 men with non-metastatic prostate cancer undergoing radical prostatectomy. We performed copy number analysis in a subset of these men (n = 67) to study tumor instability assessed as Fraction of the Genome Altered (FGA). We examined associations between carotenoids, genotypes, tumor instability and risk of high-grade prostate cancer (Gleason grade ≥ 4 + 3) using logistic and linear regression. Circulating carotenoid levels were inversely associated with the risk of high-grade prostate cancer; odds ratios (OR) and 95% confidence intervals (CI) comparing highest versus lowest quartiles were: 0.34 (95% CI: 0.18-0.66) for α-carotene, 0.31 (95% CI: 0.15-0.63) for β-carotene, 0.55 (0.28-1.08) for lycopene and 0.37 (0.18-0.75) for total carotenoids. SNPs rs25489 in XRCC1, rs699473 in SOD3 and rs1052133 in OGG1 modified these associations for α-carotene, β-carotene and lycopene, respectively (P ≤ 0.05). The proportion of men with a high degree of FGA increased with Gleason Score (P levels were associated with lower FGA (P = 0.04). Circulating carotenoids at diagnosis, particularly among men carrying specific somatic variations, were inversely associated with risk of high-grade prostate cancer. In exploratory analyses, higher lycopene level was associated with less genomic instability among men with low-grade disease which is novel and

  5. Wellens' syndrome can indicate high-grade LAD stenosis in case of left bundle branch block.

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    Grautoff, Steffen

    2017-03-01

    Diagnosing acute myocardial infarction (AMI) in left bundle branch block (LBBB) is challenging. Modified Sgarbossa criteria are known to help detect AMI in LBBB. This is a report about an electrocardiogram (ECG) with Wellens' signs in combination with a pre-existing LBBB. The ECG of a patient with fluctuating chest pain showed very subtle and one day later more obvious Wellens'signs. A left anterior descending artery (LAD) stenosis was diagnosed and successfully treated. Wellens' syndrome can be diagnosed in a case of LBBB and help detect a high-grade LAD stenosis even if modified Sgarbossa criteria are not met.

  6. Patient outcomes in the operative and nonoperative management of high-grade spondylolisthesis in children.

    Science.gov (United States)

    Lundine, Kristopher M; Lewis, Stephen J; Al-Aubaidi, Zaid; Alman, Benjamin; Howard, Andrew W

    2014-01-01

    The optimal management of high-grade spondylolisthesis in the growing child is controversial. Some authors have advocated for surgery in all cases regardless of symptoms. Surgical intervention results in a >10% risk of complications with increased risk of neurological injury associated with slip reduction maneuvers. There is a paucity of literature regarding nonoperative management in this setting. This study sought to obtain outcome measures in pediatric patients with high-grade spondylolisthesis managed either operatively or nonoperatively. Database review was performed to identify patients with a high-grade (Meyerding grade III to V) spondylolisthesis managed either operatively or nonoperatively. Retrospective radiographic and chart review was performed. Patients were then contacted by phone to obtain current quality-of-life measurements using the Scoliosis Research Society (SRS)-30 questionnaire. Fifty-three patients were identified for inclusion in the study and 49 were contacted for 92% follow-up. Twenty-four patients were treated with operative intervention, and 25 patients were initially treated nonoperatively, but 10 went on to require surgical intervention. Mean age at presentation was 12.6 years (range, 8 to 17 y) and mean age at follow-up was 20.1 years (range, 10 to 29 y). There were no outcome differences between the groups. A more kyphotic slip angle was associated with worse SRS-30 outcome scores across all groups. In the nonoperative group, the slip angle was significantly larger in patients who failed conservative treatment (34 ± 17 degrees) than in those who remained nonsurgical at final follow-up (20 ± 14 degrees). Slip angle in the operative group was 27 ± 14 degrees. In surgical patients, an older age at surgery was associated with better SRS-30 outcome scores. Nonoperative management or "watchful waiting" of the minimally symptomatic or asymptomatic child with a high-grade spondylolisthesis is safe and does not lead to significant problems

  7. Variability of the Leaf Area Index in natural fields and transition forest in Southern Amazonas State, Brazil

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    Walleson Higor Corrêa Jordão

    2015-04-01

    Full Text Available The Leaf Area Index (LAI has strong influence on ecosystems’ energy and mass exchange and is fundamental to the understanding of regional climate changes and ecosystem dynamics. The main goal of this work was to establish, based on geostatistical analyses, the variability and spatial dependence of LAI in the natural fields and transitional forest in southern Amazonas State, in Brazil. The LAI was measured in a regular grid with 33 points at each studied area. Field measurements were done using the canopy analyser LAI-2000, which calculates the structure of the vegetation based on the radiation beneath the tree canopy. The average values of LAI varied according to the studied sites: the highest values were found in the transitional forest (4.42 m²m -2 , followed by the high (2.03 m²m -2 and low (1.72 m²m -2 natural fields. All studied sites showed spatial dependence according to the kriging methods, but with different degrees of dependence: spatial dependence was moderate at the transition forest and weak at the natural fields. In the more arboreal open field, the maximum limit at which the points are correlated reached a distance of 35.3 m. The kriging maps proved to be very important tools for describing the spatial distribution of LAI in the Amazon.

  8. Dallas area rapid transit impact study: A framework for assessing land use and development impacts. Research report

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, P.J.; Euritt, M.A.; Walton, C.M.

    1993-05-01

    Seven transit system impact reports were reviewed in an effort to identify strategies for measuring land-use impacts for Dallas Area Rapid Transit's (DART) light rail starter line. These systems were selected on the basis of impact study quality, system characteristics (type, size, and age), and city demographics. From these existing studies some commonly used techniques are identified and then used to form the basis for the land use component of the DART impact study design. The report concludes that DART's success in fostering economic growth will depend on many factors, including interagency coordination and, perhaps most importantly, how public/private opportunities are promoted. Other variables range from the tangible (ridership, on-time performance, operating efficiency) to the abstract (civic pride, world-class-city status, desirable urban form).

  9. Mass transit development for small urban areas; a case study: Tompkins County, N. Y. Second-year final report

    Energy Technology Data Exchange (ETDEWEB)

    Meyburg, A.H.

    1976-11-01

    This report presents the results of the second-year effort within a three-year research project to develop a transportation planning methodology for small urban areas concerned with the provision of public transportation service. This phase of the research concentrates on problems of access to health services, transportation service for the disadvantaged, potential coordination and integration of existing transportation systems, alternative systems designs and their evaluation, and suitable marketing and monitoring programs for public transportation service in small urban areas. This effort, together with elements of the first-year research will culminate in the preparation of a transit planning manual suitable for use by the transportation planner in small to medium-size urban areas.

  10. Agriculture adjustment, land-use transition and protected areas in Northwestern Argentina.

    Science.gov (United States)

    Izquierdo, Andrea E; Grau, H Ricardo

    2009-02-01

    Land-use change is the main component of regional environmental change, while protected areas represent a direct land use policy to prevent its potentially negative effects on biodiversity and environmental services. We combined an analysis of trends in land use and human demography with trends in creation of protected areas during the last three decades in northwestern Argentina, a subtropical region including a wide range of environments. The eighty nine administrative analysis units of the region were classified into four ecological groups based on their percentage of cover by the six eco-regions of the study area: (1) "Dry valleys"; dominated by Middle-elevation deserts; (2) "Highlands", dominated by High-elevation alpine zones and plateaus; (3) "Humid ecosystems", dominated by Foggy grasslands and Humid forests, and (4) "Dry forests". Between 1970 and 2002, human population became concentrated in urban areas and land use trends varied greatly among the four ecological groups. Agricultural area decreased in the Highlands and increased in the other regions, particularly in the Dry forests. Domestic animals decreased in Humid ecosystems, Highlands and the Dry valleys; and remained constant in the Dry forests. Several protected areas were created, but most of them were established in regions undergoing a decreasing intensity of land use. Overall, the analysis shows that agricultural production is becoming concentrated in the areas more suitable for modern agriculture while marginal agriculture areas and, particularly, extensive grazing are decreasing. The creation of protected areas reflects the decreasing opportunity costs of marginal areas and is failing to protect the eco-regions most threatened by current land-use trends.

  11. Cerebral vasomotor reactivity and apnea test in symptomatic and asymptomatic high-grade carotid stenosis

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    Lučić-Prokin Aleksandra

    2015-01-01

    Full Text Available Introduction. Cerebral vasomotor reactivity (VMR represents an autoregulatory response of the arterial trunks on the specific vasoactive stimuli, most commonly CO2. Objective. The aim of this retrospective study was to compare VMR in high-grade symptomatic (SCAS and asymptomatic carotid stenosis (ACAS, using the apnea test to evaluate the hemodynamic status. Methods. The study included 50 patients who were hospitalized at the neurology and vascular surgery departments as part of preparation for carotid endarterectomy. We evaluated VMR by calculating the breath holding index (BHI in 34 patients with SCAS and 16 patients with ACAS, with isolated high-grade carotid stenosis. We evaluated the impact of risk factors and collateral circulation on BHI, as well as the correlation between the degree of carotid stenosis and BHI. Results. A pathological BHI was more frequent in the SCAS group (p<0.01. There was no difference in the range of BHI values between the groups, both ipsilaterally and contralaterally. Only male gender was associated with pathological BHI in both groups (p<0.05. Collateral circulation did not exist in over 60% of all subjects. We confirmed a negative correlation between the degree of carotid stenosis and BHI. Conclusion. SCAS and ACAS patients present with different hemodynamics. While ACAS patients have stable hemodynamics, combination of hemodynamic and thromboembolic effects is characteristic of SCAS patients.

  12. Functional assessment of high-grade ICA stenosis with duplex ultrasound and transcranial Doppler.

    Science.gov (United States)

    Zachrisson, Helene; Fouladiun, Marita; Blomstrand, Christian; Holm, Jan; Volkmann, Reinhard

    2012-05-01

    Duplex ultrasound (DUS) has shown a >90% accuracy compared to angiography, concerning the degree of internal carotid artery (ICA) stenosis. However, uncertainty may occur in a severe stenosis, in which peak systolic velocity (PSV) may decrease owing to high flow resistance or high backward pressure. We investigated intracranial collateral flows using transcranial Doppler (TCD) to further evaluate the hemodynamic significance of high-grade ICA stenosis. In this retrospective study, 320 consecutive symptomatic patients were examined. The degree of ICA stenosis and collateral capacity in the circle of Willis was investigated by DUS and TCD. In addition, magnetic resonance angiography (MRA) was added in a subgroup of 204 patients. The criterion for hemodynamic significant ICA stenosis was established collateral flow. In 91% of all symptomatic vessels (291 vessels), an ICA stenosis of ≥70% was found. Established collateral flow always indicated precerebral carotid artery disease of ≥70%. Furthermore, in 11% of the whole study material, collateral reserve capacity was found despite high-grade (≥70%) ICA stenosis. PSV in ICA ICA stenosis is of hemodynamic significance and to assess collateral patterns. Established collateral blood flow will help to identify patients with ≥70% (ECST) carotid artery disease. TCD might be of value when flow velocity criteria combined with plaque assessment by DUS are inclusive. Other diagnostic methods may also be considered. © 2012 The Authors. Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  13. Dating of zircon from high-grade rocks: Which is the most reliable method?

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    Alfred Kröner

    2014-07-01

    Full Text Available Magmatic zircon in high-grade metamorphic rocks is often characterized by complex textures as revealed by cathodoluminenscence (CL that result from multiple episodes of recrystallization, overgrowth, Pb-loss and modifications through fluid-induced disturbances of the crystal structure and the original U-Th-Pb isotopic systematics. Many of these features can be recognized in 2-dimensional CL images, and isotopic analysis of such domains using a high resolution ion-microprobe with only shallow penetration of the zircon surface may be able to reconstruct much of the magmatic and complex post-magmatic history of such grains. In particular it is generally possible to find original magmatic domains yielding concordant ages. In contrast, destructive techniques such as LA-ICP-MS consume a large volume, leave a deep crater in the target grain, and often sample heterogeneous domains that are not visible and thus often yield discordant results which are difficult to interpret. We provide examples of complex magmatic zircon from a southern Indian granulite terrane where SHRIMP II and LA-ICP-MS analyses are compared. The SHRIMP data are shown to be more precise and reliable, and we caution against the use of LA-ICP-MS in deciphering the chronology of complex zircons from high-grade terranes.

  14. Detection of high-grade small bowel obstruction on conventional radiography with convolutional neural networks.

    Science.gov (United States)

    Cheng, Phillip M; Tejura, Tapas K; Tran, Khoa N; Whang, Gilbert

    2017-08-21

    The purpose of this pilot study is to determine whether a deep convolutional neural network can be trained with limited image data to detect high-grade small bowel obstruction patterns on supine abdominal radiographs. Grayscale images from 3663 clinical supine abdominal radiographs were categorized into obstructive and non-obstructive categories independently by three abdominal radiologists, and the majority classification was used as ground truth; 74 images were found to be consistent with small bowel obstruction. Images were rescaled and randomized, with 2210 images constituting the training set (39 with small bowel obstruction) and 1453 images constituting the test set (35 with small bowel obstruction). Weight parameters for the final classification layer of the Inception v3 convolutional neural network, previously trained on the 2014 Large Scale Visual Recognition Challenge dataset, were retrained on the training set. After training, the neural network achieved an AUC of 0.84 on the test set (95% CI 0.78-0.89). At the maximum Youden index (sensitivity + specificity-1), the sensitivity of the system for small bowel obstruction is 83.8%, with a specificity of 68.1%. The results demonstrate that transfer learning with convolutional neural networks, even with limited training data, may be used to train a detector for high-grade small bowel obstruction gas patterns on supine radiographs.

  15. High grade prostatic intraepithelial neoplasia in military working dogs with and without prostate cancer.

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    Aquilina, J W; McKinney, L; Pacelli, A; Richman, L K; Waters, D J; Thompson, I; Burghardt, W F; Bostwick, D G

    1998-08-01

    High grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer and is commonly found in men undergoing prostatic needle biopsy for suspected cancer. Recent work has demonstrated that pet dogs, like humans, develop PIN spontaneously and in association with prostate cancer. Pet dogs are the most domesticated animal, sharing the habitat and oftentimes the diet of their owners. If PIN and prostate cancer are strongly related to environmental factors, then the prevalence of these findings might differ in a population of dogs such as military working dogs which is not exposed to the habitat and diet of humans. In this study, we determined the prevalence of PIN in prostates of aged military working dogs with and without prostatic adenocarcinoma. Cases were selected from the military working dog slide and tissue archive at the Armed Forces Institute of Pathology, Washington, DC. The most recent 329 necropsies (1991 to 1996) were examined histologically by multiple reviewers; of these, 199 dogs (60%) were found to have evaluable prostatic tissue. In addition, the most recent 50 necropsies (1958 to 1996) with the diagnosis of prostatic cancer were examined, of which 25 cases (50%) were found to have evaluable prostatic adenocarcinoma. In most cases, a single large transverse section of prostatic tissue was available for review. Medical records for each dog were reviewed independently, and age, clinical history, indications for euthanasia, and other health problems were recorded. High grade PIN was identified in 3% of dogs (6 of 199 dogs) without prostate cancer. A total of 50.8% of dogs in this study group (101 of 199 dogs) were known to be sexually intact, 26.7% of dogs (53 of 199 dogs) were castrated, and the status of the remaining 22.6% of dogs (45 of 199 dogs) was unknown. High grade PIN was present in 18 of 25 dogs (72%) with prostatic adenocarcinoma. Of these cases, 11 dogs (44%) were castrated, 4 dogs (16%) were intact, and

  16. Classification of high-grade spondylolistheses based on pelvic version and spine balance: possible rationale for reduction.

    Science.gov (United States)

    Hresko, Michael T; Labelle, Hubert; Roussouly, Pierre; Berthonnaud, Eric

    2007-09-15

    Retrospective review of a radiographic database of high-grade spondylolisthesis patients in comparison with asymptomatic controls. To analyze the sagittal spinopelvic alignment in high-grade spondylolisthesis patients and identify subgroups that may require reduction to restore sagittal balance. High-grade spondylolisthesis is associated with an abnormally high pelvic incidence (PI); however, the spatial orientation of the pelvis, determined by sacral slope (SS) and pelvic tilt (PT), is not known. We hypothesized that sagittal spinal alignment would vary with the pelvic orientation. Digitized sagittal radiographs of 133 high-grade spondylolisthesis patients (mean age, 17 years) were measured to determined sagittal alignment. K-means cluster analysis identified 2 groups based on the PT and SS, which were compared by paired t test. Comparisons were made to asymptomatic controls matched for PI. High-grade spondylolisthesis patients had a mean PI of 78.9 degrees +/- 12.1 degrees . Cluster analysis identified a retroverted, unbalanced pelvis group with high PT (36.5 degrees +/- 8.0 degrees )/low SS (40.3 degrees +/- 9.0 degrees ) and a balanced pelvic group with low PT (mean 21.3 degrees +/- 8.2 degrees )/high SS (59.9 degrees +/- 11.2 degrees ). The retroverted pelvis group had significantly greater L5 incidence and lumbosacral angle with less thoracic kyphosis than the balanced pelvic group. A total of 83% of controls had a "balanced pelvis" based on the categorization by SS and PT. Analysis of sagittal alignment of high-grade spondylolisthesis patients revealed distinct groups termed "balanced" and "unbalanced" pelvis. The PT and SS were similar in controls and balanced pelvis patients. Unbalanced pelvis patients had a sagittal spinal alignment that differed from the balanced pelvis and control groups. Treatment strategies for high-grade spondylolisthesis should reflect the different mechanical strain on the spinopelvic junction in each group; reduction techniques

  17. Highly Flexible and High-Performance Complementary Inverters of Large-Area Transition Metal Dichalcogenide Monolayers

    KAUST Repository

    Pu, Jiang

    2016-03-23

    Complementary inverters constructed from large-area monolayers of WSe2 and MoS2 achieve excellent logic swings and yield an extremely high gain, large total noise margin, low power consumption, and good switching speed. Moreover, the WSe2 complementary-like inverters built on plastic substrates exhibit high mechanical stability. The results provide a path toward large-area flexible electronics. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Laterally Stitched Heterostructures of Transition Metal Dichalcogenide: Chemical Vapor Deposition Growth on Lithographically Patterned Area

    KAUST Repository

    Li, Henan

    2016-10-31

    Two-dimensional transition metal dichalcogenides (TMDCs) have shown great promise in electronics and optoelectronics due to their unique electrical and optical properties. Heterostructured TMDC layers such as the laterally stitched TMDCs offer the advantages of better electronic contact and easier band offset tuning. Here, we demonstrate a photoresist-free focused ion beam (FIB) method to pattern as-grown TMDC monolayers by chemical vapor deposition, where the exposed edges from FIB etching serve as the seeds for growing a second TMDC material to form desired lateral heterostructures with arbitrary layouts. The proposed lithographic and growth processes offer better controllability for fabrication of the TMDC heterostrucuture, which enables the construction of devices based on heterostructural monolayers. © 2016 American Chemical Society.

  19. A Community Energy Transition Model for Urban Areas: The Energy Self-Reliant Village Program in Seoul, South Korea

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    Hana Kim

    2017-07-01

    Full Text Available While community energy initiatives are on the rise, community actions for energy transition in Asian countries have rarely been studied. While it is difficult for community energy initiatives to develop spontaneously in Seoul, there are some success stories there. This study places these successes in context. It analyzes municipal documents, including unpublished materials from municipal meetings, in order to examine how the Seoul Metropolitan Government (SMG created enabling conditions for promoting community energy initiatives. This study also conducted interviews to explore unsolved issues related to the Energy Self-Reliant Village (ESV program. The SMG encouraged collective action through financial, administrative, and informational support. Also, this study found that Seoul’s ESV program fostered communities by raising the sense of locality and responsibility and community spirit through various educational programs. The ESV program supported the continuity of community by providing guidelines that relieved the burden on community members. The SMG played a significant role in promoting community engagement in energy transition by affecting internal and external conditions. This study provides meaningful insights that other municipalities, especially large urban areas, can follow to foster community actions for energy transition.

  20. A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development.

    Science.gov (United States)

    Sherman-Baust, Cheryl A; Kuhn, Elisabetta; Valle, Blanca L; Shih, Ie-Ming; Kurman, Robert J; Wang, Tian-Li; Amano, Tomokazu; Ko, Minoru S H; Miyoshi, Ichiro; Araki, Yoshihiko; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G; Morin, Patrice J

    2014-07-01

    Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp-TAg transgenic mouse, which expresses the SV40 large T-antigen (TAg) under the control of the mouse müllerian-specific Ovgp-1 promoter. Histological analysis of the fallopian tubes of mogp-TAg mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian HGSC. We identified areas of normal-appearing p53-positive epithelium that are similar to 'p53 signatures' in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (STIC), a potential precursor of ovarian HGSC. Beside these non-invasive precursor lesions, we also identified invasive adenocarcinoma in the ovaries of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp-TAg and wild-type (WT) C57BL/6. One of these genes, Top2a, which encodes topoisomerase IIα, was shown by immunohistochemistry to be concurrently expressed with elevated p53 and was specifically elevated in mouse STICs but not in the surrounding tissues. TOP2A protein was also found elevated in human STICs, low-grade and high-grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive HGSC in the ovary, and therefore closely simulates the current emerging model of human ovarian HGSC pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumourigenesis, as well as

  1. Formation conditions of high-grade gold-silver ore of epithermal Tikhoe deposit, Russian Northeast

    Science.gov (United States)

    Volkov, A. V.; Kolova, E. E.; Savva, N. E.; Sidorov, A. A.; Prokof'ev, V. Yu.; Ali, A. A.

    2016-09-01

    The Tikhoe epithermal deposit is located in the Okhotsk-Chukotka volcanic belt (OChVB) 250 km northeast of Magadan. Like other deposits belonging to the Ivan'insky volcanic-plutonic depression (VTD), the Tikhoe deposit is characterized by high-grade Au-Ag ore with an average Au grade of 23.13 gpt Au and Au/Ag ratio varying from 1: 1 to 1: 10. The detailed explored Tikhoe-1 orebody is accompanied by a thick (20 m) aureole of argillic alteration. Pyrite is predominant among ore minerals; galena, arsenopyrite, sphalerite, Ag sulfosalts, fahlore, electrum, and küstelite are less abundant. The ore is characterized by abundant Sebearing minerals. Cu-As geochemical specialization is noted for silver minerals. Elevated Se and Fe molar fractions of the main ore minerals are caused by their formation in the near-surface argillic alteration zone. The veins and veinlets of the Tikhoe-1 ore zone formed stepwise at a temperature of 230 to 105°C from Nachloride solution enriched in Mg and Ca cations with increasing salinity. The parameters of the ore-forming fluid correspond to those of epithermal low-sulfidation deposits and assume the formation of high-grade ore under a screening unit of volcanic rocks. In general, the composition of the ore-forming fluid fits the mineralogy and geochemistry of ore at this deposit. The similarity of the ore composition and parameters of the ore-forming fluid between the Tikhoe and Julietta deposits is noteworthy. Meanwhile, differences are mainly related to the lower temperature and fluid salinity at the Julietta deposit with respect to the Tikhoe deposit. The fluid at the Julietta deposit is depleted in most components compared with that at the Tikhoe deposit except for Sb, Cd, and Ag. The results testify to a different erosion level at the deposits as derivatives of the same ore-forming system. The large scale of the latter allows us to predict the discovery of new high-grade objects, including hidden mineralization, which is not exposed at

  2. The Role of Halogens in High-Grade Metamorphism and Anatexis

    Science.gov (United States)

    Aranovich, L.; Safonov, O.

    2016-12-01

    We review factors controlling the distribution of the two major halogens, F and Cl, in high-grade metamorphic rocks; their compositional correlations and partitioning between minerals; experimental data on stability and phase equilibria of the halogen-bearing minerals; the influence of halogens on Fe-Mg exchange reactions; and the means of estimating concentrations/activity of halogen species concentration/ activity in the fluid phase ("chlorimetry and fluorimetry") via calculation of equilibrium conditions for mineral assemblages containing halogen-bearing phases. Clear negative correlation between the F content and XFe=Fe/(Fe+Mg) suggests that natural biotite and amphibole obey the Fe-F avoidance rule. A strong positive correlation exists between K and Cl in amphibole. A scattering of points on the XFe -Cl and TiO2- Cl diagrams indicate the possible involvement of an exotic Cl-rich phase (fluid or melt) during the formation of Cl-bearing biotite and amphibole. Fluorine and Cl substituting for OH-groups substantially stabilize minerals relative to dehydration and melting. They should also strongly affect partitioning of Fe and Mg between biotite, amphibole and anhydrous minerals. This effect is quantified for Fe-Mg exchange reactions involving biotite (Zhu and Sverjensky, 1992), but remains to be evaluated for amphibole. Calculations based on recent thermodynamic systematics show that the relatively Mg-rich, Cl-poor biotite (for example, XFe = 0.4 and about 0.2 wt.% Cl) may coexist with a fairly Cl-rich fluid, i.e. total Cl/(Cl+H2O) from 0.1-0.3, depending on the assemblage, under granulite facies P-T conditions. Alkali (and Ca) metasomatism caused by interaction of high grade rocks with halogen-bearing fluids has major impact on the subsolidus phase transformations and melting processes during high-grade metamorphism and anatexis. For example, an increase in sodium content in plagioclase (Pl) by 20 mol% due to infiltration of Na- fluid into the quartz (Qtz

  3. Tumor blood flow from arterial spin labeling perfusion MRI: a key parameter in distinguishing high-grade gliomas from primary cerebral lymphomas, and in predicting genetic biomarkers in high-grade gliomas.

    Science.gov (United States)

    Yoo, Roh-Eul; Choi, Seung Hong; Cho, Hye Rim; Kim, Tae Min; Lee, Se-Hoon; Park, Chul-Kee; Park, Sung-Hye; Kim, Il Han; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho; Han, Moon Hee; Chang, Kee Hyun

    2013-10-01

    To evaluate the usefulness of pseudo-continuous arterial spin labeling (pCASL) imaging in differentiating high-grade gliomas from lymphomas and in noninvasively predicting genetic biomarkers in high-grade gliomas. Twelve glioblastoma multiforme (GBM), 3 anaplastic astrocytoma (AA), 5 recurred GBM, and 9 lymphoma patients underwent conventional MR and pCASL imaging. On pCASL perfusion map, mean absolute tumor blood flow (mTBF) was calculated from five regions of interest (ROIs) within the enhancing portion of the tumor. Relative TBF (rTBF = mTBF/mBFgm × 100) was also calculated. mTBF and rTBF of high-grade gliomas and lymphomas were compared using unpaired Student's t-test and receiver operating characteristic (ROC) analysis. Additionally, the association of TBF and six immunohistochemically confirmed genetic biomarkers was analyzed by Pearson correlation analysis in the group of high-grade gliomas. Both mTBF and rTBF of the high-grade gliomas were significantly higher than those of the lymphomas: 92.1 ± 34.7 versus 53.6 ± 30.5 mL/min/100 mg (P = 0.008) and 182.3 ± 69.5 versus 92.5 ± 44.9 (P = 0.002), respectively. Only epidermal growth factor receptor (EGFR) expression status showed a significant positive correlation with mTBF(P = 0.015) and rTBF(P = 0.007). pCASL imaging may facilitate differentiation of high-grade gliomas from lymphomas and prediction of EGFR expression status in high-grade gliomas. Copyright © 2013 Wiley Periodicals, Inc.

  4. Precursor Lesions of High-Grade Serous Ovarian Carcinoma: Morphological and Molecular Characteristics

    Directory of Open Access Journals (Sweden)

    Amy L. Gross

    2010-01-01

    Full Text Available The lack of proven screening tools for early detection and the high mortality of ovarian serous carcinoma (OSC, particularly high grade, have focused attention on identifying putative precursor lesions with distinct morphological and molecular characteristics. The finding of occult invasive and intraepithelial fallopian tube carcinomas in prophylactically removed specimens from asymptomatic high-risk BRCA 1/2-mutation carriers supports the notion of an origin for OSC in the fallopian tube. The intraepithelial carcinomas have been referred to as serous intraepithelial carcinomas (STICs but our own findings (unpublished data and recent reports have drawn attention to a spectrum of changes that fall short of STICs that we have designated serous tubal intraepithelial lesions (STILs.

  5. High grade hemangioendothelioma of the temporal bone in a child: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo Lim; Im, Soo Ah; Lim, Gye Yeon; Chun, Ho Jong; Lee, Hee Jeong; Park, Hyun Jin; Byun, Jae Young [The Catholic University of Korea, College of Medicine, Seoul (Korea, Republic of)

    2004-09-15

    Hemangioendothelioma is a rare vascular tumor characterized by endothelial tumor cells and variable malignant behavior, and it's not common for this lesion to involve the bone. Although there are a few reports of cranial involvement by hemangioendothelioma, only rare cases arising in temporal bone have been published. We present the radiologic findings of a 7-year-old boy who had a high grade hemangioendothelioma involving the temporal bone with intracranial extension. Evidence of flow voids on MR images suggested a tumor of vascular origin, and the ill-defined margins, cortical destruction and intracranial extension on the CT and MR images were correlated with the tumor's high histologic grade.

  6. Surgical Treatment as a Principle for Patients with High-Grade Pancreatic Neuroendocrine Carcinoma

    DEFF Research Database (Denmark)

    Haugvik, Sven-Petter; Janson, Eva Tiensuu; Österlund, Pia

    2016-01-01

    BACKGROUND: This study aimed to evaluate the role of surgery for patients with high-grade pancreatic neuroendocrine carcinoma (hgPNEC) in a large Nordic multicenter cohort study. Prior studies evaluating the role of surgery for patients with hgPNEC are limited, and the benefit of the surgery...... is uncertain. METHODS: Data from patients with a diagnosis of hgPNEC determined between 1998 and 2012 were retrospectively registered at 10 Nordic university hospitals. Kaplan-Meier curves were used to compare the overall survival of different treatment groups, and Cox-regression analysis was used to evaluate....... Patients selected for resection of the primary tumor and synchronous liver metastases had a high 3-year survival rate. Selected patients with both localized hgPNEC and metastatic hgPNEC should be considered for radical surgical treatment....

  7. Health-related quality of life in patients with high-grade gliomas

    DEFF Research Database (Denmark)

    Piil, K; Jakobsen, J; Christensen, Karl Bang

    2015-01-01

    The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity...... levels, prevalence and severity of anxiety and depressive symptoms and health-related quality of life among patients with a highgrade glioma. This paper is based on a longitudinal mixed methods study. Patients (n = 30) completed questionnaires at 5 time points from time of diagnosis until the final...... follow-up after 1 year. Scores of Karnofsky Performance Status (KPS), physical activity, anxiety and depression and health-related quality of life (FACT-Br) are obtained. Patients' physical activity level and KPS decrease during the disease- and treatment trajectory. The majority of patients did...

  8. Total Artificial Heart Implantation After Undifferentiated High-Grade Sarcoma Excision.

    Science.gov (United States)

    Kremer, Jamila; Farag, Mina; Arif, Rawa; Brcic, Andreas; Sabashnikov, Anton; Schmack, Bastian; Popov, Aron-Frederik; Karck, Matthias; Dohmen, Pascal M; Ruhparwar, Arjang; Weymann, Alexander

    2016-11-02

    BACKGROUND Total artificial heart (TAH) implantation in patients with aggressive tumor infiltration of the heart can be challenging. CASE REPORT We report on a patient with a rare primary undifferentiated high-grade spindle cell sarcoma of the mitral valve and in the left atrium, first diagnosed in 2014. The referring center did a first resection in 2014. In the course of 17 months, computer tomography (CT) scan again showed massive invasion of the mitral valve and left atrium. Partial resection and mitral valve replacement was not an option. We did a subtotal heart excision with total artificial heart implantation. In this report we discuss complications, risk factors, and perioperative management of this patient. CONCLUSIONS Patients with aggressive tumors of the heart can be considered for TAH implantation.

  9. Cerebral Connectivity and High-grade Gliomas: Evolving Concepts of Eloquent Brain in Surgery for Glioma

    Directory of Open Access Journals (Sweden)

    Sanjay Konakondla

    2017-02-01

    Full Text Available Technological advances in imaging the human brain help us map and understand the intricacies of cerebral connectivity. Current techniques and specific imaging sequences, however, do come with limitations. Image resolution, variability of techniques and interpretation of images across institutions are just a few concerns. In the setting of high-grade gliomas, understanding how these pathways are affected during tumor growth, surgical resection, and in the brain plasticity presents an even greater challenge. Clinical symptoms, tumor growth, and intraoperative electrical stimulation are important peri-operative considerations to assist in determining neuronal re-wiring and establish a basis of anatomic and functional correlation. The application of functional mapping coupled with the understanding of the natural history of gliomas and implications of neural plasticity, is critical in achieving the goals of maximal tumor resection while minimizing post operative deficits and improving quality of life.

  10. A High-Grade Chondrosarcoma of Calcaneum Mimicking as a Benign Pathology: Delayed Diagnosis and Management.

    Science.gov (United States)

    Baba, Muzamil Ahmad; Nazir, Naila; Shabeer, Maajid; Mir, Bashir Ahmed; Kawoosa, Altaf Ahmad

    2016-10-01

    This case is presented to highlight a rare case of chondrosarcoma of calcaneum in a young adult mimicking as a benign pathology and to highlight the diagnosis and early management of such cases to prevent complications and even death. Chondrosarcoma constitutes less than 10% of all primary malignancies of bone and occurs mostly in proximal locations such as pelvis, proximal femur, and proximal humerus. We present a case of high-grade chondrosarcoma at a very rare site, calcaneum of a 40-year-old male that was mimicking as a benign pathology. This case report highlights the importance of proper clinical examination, evaluation, and suspicion for benign occurring lesions to prevent complications related to a delay in diagnosis. Therapeutic, Level IV: Case study. © 2016 The Author(s).

  11. "Reverse Bohlman" technique for the treatment of high grade spondylolisthesis in an adult population.

    Science.gov (United States)

    Macagno, Angel E; Hasan, Saqib; Jalai, Cyrus M; Worley, Nancy; de Moura, Alexandre B; Spivak, Jeffrey; Bendo, John A; Passias, Peter G

    2016-03-01

    Surgical techniques for effective high-grade spondylolisthesis (HGS) remain controversial. This study aims to evaluate radiographic/clinical outcomes in HGS patients treated using modified "Reverse Bohlman" (RB) technique. Review of consecutive HGS patients undergoing RB at a single university-center from 2006 to 2013. Clinical, surgical, radiographic parameters collected. Six patients identified: five with L5-S1 HGS with L4-L5 instability and one had an L4-5 isthmic spondylolisthesis and grade 1 L5-S1 isthmic spondylolisthesis. Two interbody graft failures and one L5-S1 pseudoarthrosis. Postoperative improvement of anterolisthesis (62.3% vs. 49.6%, p = 0.003), slip angle (10 vs. 5°, p = 0.005), and lumbar lordosis (49 vs. 57.5°, p = 0.049). RB technique for HGS recommended when addressing adjacent level instability/slip.

  12. Daily Life Experiences of Patients With a High-Grade Glioma and Their Caregivers

    DEFF Research Database (Denmark)

    Piil, Karin; Juhler, Marianne; Jakobsen, Johannes

    2015-01-01

    BACKGROUND: There is a lack of knowledge regarding the breadth of needs for rehabilitation and supportive care across the disease and treatment trajectory for patients with a high-grade glioma (HGG) and their caregivers. OBJECTIVE: The aim of this study was to elucidate the experiences and needs...... for rehabilitation and supportive care in patients with HGG and their caregivers. METHODS: Patients with malignant glioma (N = 30) and their caregivers (N = 33) were interviewed five times during the first year of the HGG trajectory. A thematic analysis of interviews at five time points revealed five main themes...... describing the experiences related to the illness trajectory and needs for rehabilitation and supportive care. RESULTS: The five main themes identified were (a) individual strategy for acquiring prognostic information, (b) shared hope, (c) engagement in health promotion activities, (d) adjustment to symptom...

  13. Patient Outcomes in the Operative and Nonoperative Management of High-Grade Spondylolisthesis in Children

    DEFF Research Database (Denmark)

    Lundine, K. M.; Lewis, S. J.; Al-Aubaidi, Zaid

    2014-01-01

    (SRS)-30 questionnaire.Results:Fifty-three patients were identified for inclusion in the study and 49 were contacted for 92% follow-up. Twenty-four patients were treated with operative intervention, and 25 patients were initially treated nonoperatively, but 10 went on to require surgical intervention....... Mean age at presentation was 12.6 years (range, 8 to 17 y) and mean age at follow-up was 20.1 years (range, 10 to 29 y). There were no outcome differences between the groups. A more kyphotic slip angle was associated with worse SRS-30 outcome scores across all groups. In the nonoperative group...... SRS-30 outcome scores.Conclusions:Nonoperative management or watchful waiting of the minimally symptomatic or asymptomatic child with a high-grade spondylolisthesis is safe and does not lead to significant problems. Operative intervention for the symptomatic patient achieves similar long-term results...

  14. STAR and AKR1B10 are down-regulated in high-grade endometrial cancer.

    Science.gov (United States)

    Sinreih, Maša; Štupar, Saša; Čemažar, Luka; Verdenik, Ivan; Frković Grazio, Snježana; Smrkolj, Špela; Rižner, Tea Lanišnik

    2017-07-01

    Endometrial cancer is the most frequent gynecological malignancy in the developed world. The majority of cases are estrogen dependent, and are associated with diminished protective effects of progesterone. Endometrial cancer is also related to enhanced inflammation and decreased differentiation. In our previous studies, we examined the expression of genes involved in estrogen and progesterone actions in inflammation and tumor differentiation, in tissue samples from endometrial cancer and adjacent control endometrium. The aims of the current study were to examine correlations between gene expression and several demographic characteristics, and to evaluate changes in gene expression with regard to histopathological and clinical characteristics of 51 patients. We studied correlations and differences in expression of 38 genes involved in five pathophysiological processes: (i) estrogen-stimulated proliferation; (ii) estrogen-dependent carcinogenesis; (iii) diminished biosynthesis of progesterone: (iv) enhanced formation of progesterone metabolites; and (v) increased inflammation and decreased differentiation. Spearman correlation coefficient analysis shows that expression of PAQR7 correlates with age, expression of SRD5A1, AKR1B1 and AKR1B10 correlate with body mass, while expression of SRD5A1 and AKR1B10 correlate with body mass index. When patients with endometrial cancer were stratified based on menopausal status, histological grade, myometrial invasion, lymphovascular invasion, and FIGO stage, Mann-Whitney U tests revealed significantly decreased expression of STAR (4.4-fold; adjusted p=0.009) and AKR1B10 (9-fold; adjusted p=0.003) in high grade versus low grade tumors. Lower levels of STAR might lead to decreased de-novo steroid hormone synthesis and tumor differentiation, and lower levels of AKR1B10 to diminished elimination of toxic electrophilic carbonyl compounds in high-grade endometrial cancer. These data thus reveal the potential of STAR and AKR1B10 as

  15. Preparation of High-Grade Powders from Tomato Paste Using a Vacuum Foam Drying Method.

    Science.gov (United States)

    Sramek, Martin; Schweiggert, Ralf Martin; van Kampen, Andreas; Carle, Reinhold; Kohlus, Reinhard

    2015-08-01

    We present a rapid and gentle drying method for the production of high-grade tomato powders from double concentrated tomato paste, comparing results with powders obtained by foam mat air drying and freeze dried powders. The principle of this method consists of drying tomato paste in foamed state at low temperatures in vacuum. The formulations were dried at temperatures of 50, 60, and 70 °C and vacuum of 200 mbar. Foam stability was affected by low serum viscosity and the presence of solid particles in tomato paste. Consequently, serum viscosity was increased by maltodextrin addition, yielding optimum stability at tomato paste:maltodextrin ratio of 2.4:1 (w/w) in dry matter. Material foamability was improved by addition of 0.5% (w/w, fresh weight) egg white. Because of solid particles in tomato paste, foam air filling had to be limited to critical air volume fraction of Φ = 0.7. The paste was first pre-foamed to Φ = 0.2 and subsequently expanded in vacuo. After drying to a moisture content of 5.6% to 7.5% wet base (w.b.), the materials obtained were in glassy state. Qualities of the resulting powders were compared with those produced by freeze and air drying. Total color changes were the least after vacuum drying, whereas air drying resulted in noticeable color changes. Vacuum foam drying at 50 °C led to insignificant carotenoid losses, being equivalent to the time-consuming freeze drying method. In contrast, air drying caused lycopene and β-carotene losses of 18% to 33% and 14% to 19% respectively. Thus, vacuum foam drying enables production of high-grade tomato powders being qualitatively similar to powders obtained by freeze drying. © 2015 Institute of Food Technologists®

  16. Impact of intraoperative MRI on the surgical results for high-grade gliomas.

    Science.gov (United States)

    Hirschberg, H; Samset, E; Hol, P K; Tillung, T; Lote, K

    2005-04-01

    The impact of intraoperative MRI (iMRI) on the surgical procedure, patient outcome and median survival for a series of patients harbouring high-grade gliomas forms the basis of this study. Their outcome has been compared to a matched cohort of patients operated in a conventional manner to determine if the use of intraoperative MRI can be shown to improve the results of surgery and prognosis for this type of patient. 32 microsurgical open craniotomies, performed in the intraoperative iMRI scanner for grade IV supratentorial gliomas, with follow-up periods of more than 2 months, were analyzed for this study. A group of 32 primary high-grade glioma patients (no recurrent tumors) were matched for age, preoperative clinical grade, gender and histology and operated during a corresponding time interval in a conventional manner acted as controls. All 64 patients were examined and analyzed for the occurrence of postoperative increased neurological morbidity or death. No complications directly related to the intraoperative scanning procedures were observed and no intraoperative death occurred in either group. The average operating time in the intraoperative scanner was 5.1 hours and was significantly longer than in the conventional OR (3.4 hours). The mean overall survival time for the 32 patients in the study group was 14.5 months (95 % confidence interval 12.0 - 16.6) compared to 12.1 months (95 % confidence interval 10.2 - 14.1) for the matched control group. Although iMRI is an effective way of imaging residual tumor, this study could not demonstrate an increased efficacy of surgery utilizing this technique for patients harbouring grade IV gliomas compared to more conventional methods. No statistical significance was noted between the two groups (p = 0.14). The complication rate was within the range reported for other series, in both control as well as the study group.

  17. Metal recovery from high-grade WEEE: a life cycle assessment.

    Science.gov (United States)

    Bigum, Marianne; Brogaard, Line; Christensen, Thomas H

    2012-03-15

    Based on available data in the literature the recovery of aluminium, copper, gold, iron, nickel, palladium and silver from high-grade WEEE was modeled by LCA. The pre-treatment of WEEE included manual sorting, shredding, magnetic sorting, Eddy-current sorting, air classification and optical sorting. The modeled metallurgical treatment facility included a Kaldo plant, a converter aisle, an anode refinery and a precious metal refinery. The metallurgic treatment showed significant environmental savings when credited the environmental load from avoided production of the same amount of metals by mining and refining of ore. The resource recovery per tonne of high-grade WEEE ranged from 2g of palladium to 386kg of iron. Quantified in terms of person-equivalents the recovery of palladium, gold, silver, nickel and copper constituted the major environmental benefit of the recovery of metals from WEEE. These benefits are most likely underestimated in the model, since we did not find adequate data to include all the burdens from mining and refining of ore; burdens that are avoided when metals are recovered from WEEE. The processes connected to the pre-treatment of WEEE were found to have little environmental effect compared to the metallurgical treatment. However only 12-26% of silver, gold and palladium are recovered during pre-treatment, which suggest that the reduction of the apparent losses of precious metals as palladium, gold and silver during pre-treatment of WEEE is of environmental importance. Our results support in a quantitative manner that metal recovery from WEEE should be quantified with respect to the individual metals recovered and not as a bulk metal recovery rate. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. High-grade renal injuries are often isolated in sports-related trauma.

    Science.gov (United States)

    Patel, Darshan P; Redshaw, Jeffrey D; Breyer, Benjamin N; Smith, Thomas G; Erickson, Bradley A; Majercik, Sarah D; Gaither, Thomas W; Craig, James R; Gardner, Scott; Presson, Angela P; Zhang, Chong; Hotaling, James M; Brant, William O; Myers, Jeremy B

    2015-07-01

    Most high-grade renal injuries (American Association for Surgery of Trauma (AAST) grades III-V) result from motor vehicle collisions associated with numerous concomitant injuries. Sports-related blunt renal injury tends to have a different mechanism, a solitary blow to the flank. We hypothesized that high-grade renal injury is often isolated in sports-related renal trauma. We identified patients with AAST grades III-V blunt renal injuries from four level 1 trauma centres across the United States between 1/2005 and 1/2014. Patients were divided into "Sport" or "Non-sport" related groups. Outcomes included rates of hypotension (systolic blood pressure 110bpm), concomitant abdominal injury, and procedural/surgical intervention between sports and non-sports related injury. 320 patients met study criteria. 18% (59) were sports-related injuries with the most common mechanisms being skiing, snowboarding and contact sports (25%, 25%, and 24%, respectively). Median age was 24 years for sports and 30 years for non-sports related renal injuries (p=0.049). Males were more commonly involved in sports related injuries (85% vs. 72%, p=0.011). Median injury severity score was lower for sports related injuries (10 vs. 27, ptrauma was more likely to be isolated without other significant injury (69% vs. 39% (ptrauma is more likely to occur in isolation without other abdominal or thoracic injuries and clinicians must have a high suspicion of renal injury with significant blows to the flank during sports activities. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Zircon ion microprobe dating of high-grade rocks in Sri Lanka

    Energy Technology Data Exchange (ETDEWEB)

    Kroener, A.; Williams, I.S.; Compston, W.; Baur, N.; Vitanage, P.W.; Perera, L.R.K.

    1987-11-01

    The high-grade gneisses of Sri Lanka display spectacular in-situ granulitization phenomena similar to those observed in southern India and of current interest for evolutionary models of the lower continental crust. The absolute ages of these rocks are poorly constrained and so, using the SHRIMP ion microprobe, the authors have analyzed small spots on zircons from upper amphibolite to granulite grade quartzitic and pelitic metasediments. Detrital grains from a metaquartzite of the Highland Group preserve premetamorphic U-Pb ages of between 3.17 and 2.4 Ga and indicate derivation of the sediment from an unidentified Archean source terrain. The Pb-loss patterns of these zircons and the other samples suggest severe disturbance at ca 1100 Ma ago, which the authors attribute to high-grade regional metamorphism. Two pelitic gneisses contain detrital zircons with ages up to 2.04 Ga and also record an approx. = 1100 Ma event that is also apparent from metamorphic rims around old cores and new zircon growth. A granite intrusive into the Highland Group granulites records an emplacement age of 1000-1100 Ma as well as metamorphic disturbance some 550 Ma ago but also contains older, crustally derived xenocrysts. Zircons from a metaquartzite xenolith within the granitoid Vijayan Complex are not older than approx. 1100 Ma; therefore the Vijayan is neither Archean in age nor acted as basement to the Highland Group, as previously proposed. The authors suggest that the Vijayan Complex formed significantly later than the Highland Group and that the two units were brought into contact through post-1.1 Ga thrusting. Although the granulitization phenomena in India and Sri Lanka are similar, the granulite event in Sri Lanka is not Archean in age but took place in the late Proterozoic.

  20. Fluorescence-guided surgery in high grade gliomas using an exoscope system.

    Science.gov (United States)

    Belloch, José Piquer; Rovira, Vicente; Llácer, Jose L; Riesgo, Pedro A; Cremades, Antonio

    2014-04-01

    Fluorescence-guided microsurgical resections of high-grade gliomas using 5-aminolevulinic acid (5-ALA) is superior to conventional microsurgery. An optical device, usually a modified microscope, is needed for these procedures. However, an exoscope may be implemented for fluorescence techniques. We present the use of an exoscope to perform tumor resection guided by 5-ALA fluorescence in 21 consecutive patients with high-grade glioma and two neuronavigation-guided biopsies. Twenty-three patients underwent operations. Tumor volume and localization were quantified with pre- and postoperative volumetric MRI in non-biopsy cases. In non-biopsy cases, the age range was 20 to 79 years, with a median of 56 (interquartile range = 45-66). Histological analysis indicated that 14 had glioblastoma multiforme, 2 grade-III oligodendrogliomas and 1 anaplastic astrocytoma, 3 metastases and 1 low-grade astrocytoma. Total resection was achieved in 15 cases; subtotal resection was performed in 5 patients. The result was partial resection in one case. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1-5, was 4.5 in the GBM group (IQR = 4-5), 3 (IQR = 2.5-3.5) in anaplastic glioma, and 2.5 (IQR = 2.25-2.75) for oligodendrogliomas. Of the three metastases, one showed fluorescence level 4. As for the two biopsy cases, one was anaplastic astrocytoma and one glioblastoma multiforme. The samples obtained were fluorescent in both cases. An exoscope can be also used for fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) and neuronavigation-guided biopsy. With an important advantage of low cost, this allows the surgeon to perform collaborative surgeries and adds agility to the procedure.

  1. Minimal access bilateral transforaminal lumbar interbody fusion for high-grade isthmic spondylolisthesis.

    Science.gov (United States)

    Quraishi, N A; Rampersaud, Y Raja

    2013-08-01

    Minimally invasive or "minimal access surgery" (MAS) is being utilized with increasing frequency to reduce approach-related morbidity in the lumbar spine. This paper describes our minimal access technique for posterior bilateral transforaminal lumbar interbody fusion (TLIF) and spinal instrumentation in a patient with high-grade spondylolisthesis grade (Myerding Grade III) with 5-year follow-up. A 24-year-old lady presented with mechanical back pain and left leg L5 radiculopathy. On examination, she was a thin lady with an obvious step deformity in the lower lumbar spine and otherwise, a normal neurological examination. Imaging showed a grade III isthmic L5-S1 spondylolisthesis with foraminal stenosis and focal kyphotic alignment of 20° [slip angle (SA) = 70°]. Conservative measures had failed, and a decision was made to proceed with a MAS-TLIF approach. The estimated blood loss was less than 100 ml, operating time 150 min, and post-operative hospital stay was 4 days. Post-operatively the patient had significant improvement of back and radicular pain. Improvement in ODI was substantial and sustained at 5 years. A solid fusion was achieved at 8 months. The slip percentage improved from 68 % (pre-op) to 28 % (post-op) and the focal alignment to 20° lordosis (SA = 110°). A MAS approach for selected patients with a mobile high-grade spondylolisthesis is feasible, safe and clinically effective, with the added benefit of reduced soft-tissue disruption. Our result of this technique suggests that the ability to correct focal deformity, and achieve excellent radiographic and clinical outcome is similar to the open procedure.

  2. Radiological assessment of lumbosacral dystrophic changes in high-grade spondylolisthesis

    Energy Technology Data Exchange (ETDEWEB)

    Vialle, Raphael [Armand Trousseau Hospital, Department of Paediatric Orthopaedics, Paris Cedex 12 (France); Schmit, Pierre [Necker-Enfants Malades Hospital, Department of Paediatric Radiology, Paris (France); Dauzac, Cyril; Guigui, Pierre [Beaujon Hospital, Department of Orthopaedic Surgery, Clichy Cedex (France); Wicart, Philippe [Saint-Vincent de Paul Hospital, Department of Paediatric Orthopaedics, Paris (France); Glorion, Christophe [Necker-Enfants Malades Hospital, Department of Paediatric Orthopaedics, Paris (France)

    2005-09-01

    To analyse radiographic correlates for the clinical status of patients and the deformation reducibility of high-grade lumbosacral spondylolisthesis. We also clarify the clinical and radiographic correlates of a new parameter for S1 dystrophy, the ''S1 index''. One hundred cases of high-grade isthmic lumbosacral spondylolisthesis were reviewed. We noted the dystrophic changes in the cranial sacral endplate, and the caudal endplate of L5. The severity of the spondylolisthesis was evaluated by measuring the lumbosacral kyphosis. The clinical status and the deformation reducibility (dependent on the stiffness of the deformation) were compared with these dystrophic patterns, the sagittal slope of S1 and S2 endplates and a sacral morphological marker, the S1 index. Lumbosacral kyphosis was less severe in cases with dystrophic changes of the posterior cranial edge of S1 and/or of the posterior caudal edge of L5 but its reducibility was worse. These patients were more functionally impaired. We describe and analyse this situation as a partial lumbosacral disc failure responsible for the less severe L5 slipping. The S1 index was strongly correlated with the grade of slipping, the lumbosacral kyphosis and its reducibility. We noted the same configuration among patients with a smaller S1 index, i.e. vertical S1 and S2 vertebral bodies associated with more severe but more reducible lumbosacral kyphosis. Analysing specific criteria, we think it is possible to note progressive dystrophic changes according to the natural history of lumbosacral spondylolisthesis. We think that repeated measurements of these morphological parameters in patients diagnosed with a low-grade lumbosacral spondylolisthesis could be helpful in the early detection of evolving lumbosacral kyphosis and L5 slipping. (orig.)

  3. [SPINO-PELVIC SAGITTAL ALIGNMENT IN PATIENTS WITH HIGH-GRADE L5 ISTHMIC SPONDYLOLISTHESIS].

    Science.gov (United States)

    Yang, Xi; Kong, Qingquan; Song, Yueming; Liu, Limin; Li, Tao; Gong, Quan; Zeng, Jiancheng; Liu, Hao

    2016-01-01

    To observe the character of spino-pelvic sagittal alignment in patients with high-grade L5 isthmic spondylolisthesis, and to analyze the sagittal alignment alteration after operation. Between January 2009 and June 2014, 25 patients with high-grade L5 isthmic spondylolisthesis underwent posterior surgery, and the clinical data were retrospectively analyzed as study group. There were 14 males and 11 females with a mean age of 42.5 years (range, 20-65 years). The mean disease duration was 6 months (range, 3-12 months). According to the Meyerding evaluating system, 15 cases were rated as degree III, and 10 cases as degree IV. Eighty healthy adult volunteers were recruited simultaneously as control group. The lumbar sacral angle (LSA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), and sagittal vertical axis (SVA) were measured on preoperative and last follow-up standing full length lateral X-ray films. And these parameters were compared between study group (preoperative parameters) and control group. Then the patients in study group were divided into 2 subgroups according to Hresko's method: the balanced pelvis subgroup (n = 14) and unbalanced pelvis subgroup (n = 11). The sagittal parameters were compared between 2 subgroups, and the alteration of sagittal parameters before surgery and at last follow-up was analyzed in each subgroup respectively. All patients in study group were followed up 18 months on average (range, 6-48 months). After surgery, spondylolisthesis was reduced from degree III to degree 0 in 12 cases and to degree I in 3 cases, and from degree IV to degree 0 in 6 cases and to degree I in 4 cases. Bone fusion was obtained in all patients at last follow-up. The preoperative PI, SS, PT, and SVA of study group were significantly greater than those of control group (P spondylolisthesis have greater PI, abnormal lumbosacral kyphosis, and sagittal imbalance.

  4. Comparison and correlation of pelvic parameters between low-grade and high-grade spondylolisthesis.

    Science.gov (United States)

    Min, Woo-Kie; Lee, Chang-Hwa

    2014-05-01

    This study was retrospectively conducted on 51 patients with L5-S1 spondylolisthesis. This study was conducted to compare a total of 11 pelvic parameters, such as the level of displacement by Meyerding method, lumbar lordosis, sacral inclination, lumbosacral angle, slip angle, S2 inclination, pelvic incidence (PI), L5 inclination, L5 slope, pelvic tilt (PT), and sacral slope (SS) between low-grade and high-grade spondylolisthesis, and to investigate a correlation of the level of displacement by Meyerding method with other pelvic parameters. Pelvic parameters were measured using preoperational erect lateral spinal simple radiographs. The patients were divided into 39 patients with low-grade spondylolisthesis and 12 patients with high-grade spondylolisthesis before analysis. In all patients of both groups, 11 radiographic measurements including the level of displacement by Meyerding method, lumbar lordosis, sacral inclination, lumbosacral angle, slip angle, S2 inclination, PI, L5 inclination, L5 slope, PT, and SS were performed. T test and Pearson correlation analysis were conducted to compare and analyze each measurement. As for the comparison between the 2 groups, a statistically great significance in the level of displacement by Meyerding method, lumbosacral angle, slip angle, L5 incidence, PI, and L5 slope (P≤0.001) was shown. Meanwhile, a statistical significance in the sacral inclination and PT (Pspondylolisthesis and patients with low-grade spondylolisthesis. Among the aforementioned measurements, the PI showed a significant difference between the 2 groups and also had a significant correlation with the dislocation level in all the patients.

  5. Surgical Versus Nonsurgical Treatment for High-Grade Spondylolisthesis in Children and Adolescents

    Science.gov (United States)

    Xue, Xuhong; Wei, Xiaochun; Li, Li

    2016-01-01

    Abstract The optimal management of high-grade spondylolisthesis in children and adolescent is controversial. There is a paucity of literature regarding operatively or nonoperative management in this setting. To assessment of the current state of evidence regarding high-grade spondylolisthesis treatment with the goal of obtaining outcome comparisons in these patients managed either operatively or nonoperatively. We performed a systematic literature search up to November 2014, using Medline, Embase, and The Cochrane Library. The analysis and eligibility criteria were documented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-guidelines) and Cochrane Back Review Group editorial board. We used the Newcastle–Ottawa quality assessment scale (NOS-scale) to assess the quality. Five observational studies were considered eligible for analysis based on the evaluation of 1596 identified papers. The mean overall difference in the Scoliosis Research Society questionnaire 22 between the surgical and nonsurgical groups was not statistically significant (95% CI: −0.17 to 0.21, P = 0.84). The pooled mean difference in progression of slip between the surgical and nonsurgical groups was no significant difference (OR: 0.47, 95% CI: 0.12–1.81, P = 0.27, I2 = 0%). Because of the preponderance of uncontrolled case series, low-quality evidence indicates that the quality of life and progression of slips was no significant difference between surgery and nonoperation group. Nonoperative patients had no radiologic progression of their slip during the follow-up period. PMID:26986134

  6. Prevalence and pattern of glenohumeral injuries among acute high-grade acromioclavicular joint instabilities.

    Science.gov (United States)

    Pauly, Stephan; Kraus, Natascha; Greiner, Stefan; Scheibel, Markus

    2013-06-01

    With increasing numbers of arthroscopically assisted acromioclavicular (AC) joint stabilization procedures has come an increase in reports of concomitant glenohumeral injuries among AC joint separations. The aim of the present study was to evaluate the prevalence, pattern, and cause of glenohumeral pathologies among a large patient population with acute high-grade AC joint instability. A total of 125 patients (13 women, 112 men) with high-grade AC joint dislocation (6 Rockwood II; 119 Rockwood V) underwent diagnostic glenohumeral arthroscopy before AC joint repair. Pathologic lesions were evaluated for acute or degenerative origin and, if considered relevant, treated all-arthroscopically. Concomitant glenohumeral pathologies were found in 38 of 125 patients (30.4%). Analysis of pathogenesis distinguished different patterns of accompanying injuries: acute intra-articular lesions, related to the recent shoulder trauma, were found in 9 patients (7.2%), degenerative lesions, considered to be unrelated to the recent trauma, were found in 18 (14.4%), and 11 (8.8%) had an unclear traumatic correlation (intermediate group). Within the acute and the degenerative group, affected structures were predominantly partial, articular-sided tears of the anterosuperior rotator cuff, including instabilities of the pulley complex, followed by pathologies of the long head of the biceps and superior labrum anteroposterior lesions. The intermediate group presented mainly with articular-sided partial tears of the subscapularis tendon. This prospective study showed a high prevalence (30%) of concomitant glenohumeral pathologies, of which some indicate additional surgical therapy and could be missed by an isolated open AC repair. Hence, the arthroscopic approach for AC joint stabilization allows for the diagnosis and treatment of associated intra-articular pathologies. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  7. Efficacy of spermatic vein ligation in patients affected by high grade left varicocele

    Directory of Open Access Journals (Sweden)

    Marco Grasso

    2014-01-01

    Full Text Available Purpose: To study the effect of high grade varicocele treatment in infertile patients. Materials and Methods: Seventy-five patients were selected by the following criteria: infertility persisting for more than 1 year; abnormal semen parameters; no other infertility-related disease; no obvious causes of infertility in the subject’s partner; basal eco-color Doppler ultrasound demonstrating continuous reflux in the spermatic vein. All patients considered for the study had at least a six months period from the diagnosis to the surgery due to waiting list, choice of the patient or time needed to complete diagnostic evaluation of the couple. The surgical procedure was performed through an inguinal approach. All enrolled patients were counseled to have unprotected intercourse during the ovulation period in order to maximize the probability of pregnancy within the 6-month preoperative period. The achievement of pregnancy and semen parameters were recorded during the preoperative and postoperative period. Results: Two of the seventy-five patients were excluded because of persistent varicocele after surgery. The preoperative pregnancy rate was 1.3% (1 couple. The postoperative pregnancy rate was 42.5%. The stratification of pregnancies by semester showed a significantly higher rate in the first postoperative period (p = 0.0012. Mean time to conception was 13.5 months. Mean preoperative sperm count was 17.6x10 6 /mL compared to 19.7x10 6 /mL in the postoperative period (p < 0.0001. Mean percentage of progressive sperm motility was 13.7%, compared to 17.6% in the postoperative period (p < 0.0001. Mean percentage of normal sperm morphology was 7.6%, compared to 15.2% postoperatively (p < 0.0001. Conclusion: Surgical treatment of high grade varicocele proved to effectively treat associated infertility by improving seminal parameters and pregnancy rate in our patient cohort.

  8. Mapping Urban Transitions in the Greater Beirut Area Using Different Space Platforms

    Directory of Open Access Journals (Sweden)

    Ghaleb Faour

    2014-08-01

    Full Text Available A particular challenge for undertaking urbanization mapping of Beirut is the absence of a unified understanding of the city. Migration, informal settlements, a lack of urban planning, political corruption, as well as internal conflict have made this task even harder. The population in Lebanon is unevenly distributed among regions, where one third of the population resides in the Greater Beirut Area (GBA, whereas it occupies only 233 km2 (2% of Lebanon’s total area. The Greater Beirut Area is subject to pressures arising from population growth and economic expansion. This study aims to follow the evolution of urbanization from 1963 till 2005 by processing and interpreting topographical maps and satellite images acquired by different space platforms. Satellite imagery change analysis shows that average annual urban growth surpassed 1.8 km2∙yr−1. Actually, a variety of factors triggers urban growth in the GBA (i.e., transportation, public policies, economic activities and environmental variables. The logistic regression method has been applied to model future urban growth in the region of Greater Beirut. Consequently, an urban growth scenario map has been generated. To validate our results, we compared an urban map derived from RapidEye satellite acquired in 2010 to our model’s outcome of the same year. The output shows a satisfactory rate of success (~61%. This research aims to provide policy makers and urban planners in Lebanon an essential decision tool to support upcoming urban planning in this study area or in others major cities in Lebanon.

  9. Snow season variability in a boreal-Arctic transition area monitored by MODIS data

    Science.gov (United States)

    Malnes, Eirik; Rune Karlsen, Stein; Johansen, Bernt; Bjerke, Jarle W.; Tømmervik, Hans

    2016-12-01

    The duration and extent of snow cover is expected to change rapidly with climate change. Therefore, there is a need for improved monitoring of snow for the benefit of forecasting, impact assessments and the population at large. Remotely sensed techniques prove useful for remote areas where there are few field-based monitoring stations. This paper reports on a study of snow season using snow cover area fraction data from the two northernmost counties in Norway, Troms and Finnmark. The data are derived from the daily 500 m standard snow product (MOD10A1) from the NASA Terra MODerate Resolution Imaging Spectroradiometer (MODIS) sensor for the 2000-2010 period. This dataset has been processed with multi-temporal interpolation to eliminate clouds. The resulting cloud-free daily time series of snow cover fraction maps, have subsequently been used to derive the first and last snow-free day for the entire study area. In spring, the correlation between the first snow-free day mapped by MODIS data and snow data from 40 meteorological stations was highly significant (p climate change studies and ecology. Therefore refinement and further testing of this method should be encouraged.

  10. Greater percent-free testosterone is associated with high-grade prostate cancer in men undergoing prostate biopsy.

    Science.gov (United States)

    Albisinni, Simone; De Nunzio, Cosimo; Tubaro, Andrea; Barry, William T; Banez, Lionel L; Freedland, Stephen J

    2012-07-01

    To analyze the serum androgen concentrations in men who underwent an initial prostate biopsy, focusing on the percent-free testosterone (%FT) as a predictor of low- and high-grade prostate cancer (PCa). Most studies have suggested that the absolute serum testosterone and free testosterone levels are not related to PCa risk. However, to date, the concurrent effect of free and total testosterone levels has not been evaluated. In particular, the association of the %FT (free testosterone/total testosterone) with PCa risk has not been explored. From 2006 to 2010, we collected data on 812 white Italian men with no history of PCa who underwent 12-core biopsy. The testosterone, free testosterone, and %FT (free testosterone/total testosterone) were examined as predictors of low-grade (Gleason score of ≤ 6) and high-grade (Gleason score ≥ 7) PCa using crude and adjusted multinomial logistic regression analysis. On multivariate analysis, testosterone (P ≥ .11) and free testosterone (P ≥ .45) were not significantly associated with low- or high-grade PCa. A greater %FT level significantly predicted high-grade PCa on both crude (P = .01) and multivariate (P = .02) analysis but not low-grade PCa (P ≥ .38). When examined in tertiles, men in the greatest %FT tertile had a significant twofold increased risk of high-grade PCa (odds ratio 2.04, 95% confidence interval 1.23-3.37, P = .005). In white Italian men, a greater %FT level was associated with an increased risk of high-grade PCa on initial prostate biopsy. These findings suggest that a high %FT level, rather than the absolute androgen levels, might be associated with high-grade PCa. Additional studies are needed to confirm our findings. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Area law violations and quantum phase transitions in modified Motzkin walk spin chains

    Science.gov (United States)

    Sugino, Fumihiko; Padmanabhan, Pramod

    2018-01-01

    Area law violations for entanglement entropy in the form of a square root have recently been studied for one-dimensional frustration-free quantum systems based on the Motzkin walks and their variations. Here we consider a Motzkin walk with a different Hilbert space on each step of the walk spanned by the elements of a symmetric inverse semigroup with the direction of each step governed by its algebraic structure. This change alters the number of paths allowed in the Motzkin walk and introduces a ground state degeneracy that is sensitive to boundary perturbations. We study the frustration-free spin chains based on three symmetric inverse semigroups, \

  12. Impact of the integration of proton magnetic resonance imaging spectroscopy to PI-RADS 2 for prediction of high grade and high stage prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Leapman, Michael S.; Wang, Zhen J.; Behr, Spencer C.; Kurhanewicz, John; Zagoria, Ronald J.; Carroll, Peter R.; Westphalen, Antonio C., E-mail: antonio.westphalen@ucsf.edu [University of California, San Francisco, CA (United States)

    2017-09-15

    Objective: To compare the predictions of dominant Gleason pattern ≥ 4 or non-organ confined disease with Prostate Imaging Reporting and Data System (PI-RADS v2) with or without proton magnetic resonance spectroscopic imaging ({sup 1}H-MRSI). Materials and Methods: Thirty-nine men underwent 3-tesla endorectal multiparametric MRI including {sup 1}H-MRSI and prostatectomy. Two radiologists assigned PI-RADS v2 and {sup 1}H-MRSI scores to index lesions. Statistical analyses used logistic regressions, receiver operating characteristic (ROC) curves, and 2 x 2 tables for diagnostic accuracies. Results: The sensitivity and specificity of {sup 1}H-MRSI and PI-RADS v2 for high-grade prostate cancer (PCa) were 85.7% (57.1%) and 92.9% (100%), and 56% (68.0%) and 24.0% (24.0%). The sensitivity and specificity of {sup 1}H-MRSI and PI-RADS v2 for extra-prostatic extension (EPE) were 64.0% (40%) and 20.0% (48%), and 50.0% (57.1%) and 71.4% (64.3%). The area under the ROC curves (AUC) for prediction of high-grade prostate cancer were 0.65 and 0.61 for PI-RADS v2 and 0.72 and 0.70 when combined with {sup 1}H-MRSI (readers 1 and 2, p = 0.04 and 0.21). For prediction of EPE the AUC were 0.54 and 0.60 for PI-RADS v2 and 0.55 and 0.61 when combined with {sup 1}H-MRSI (p > 0.05). Conclusion: {sup 1}H-MRSI might improve the discrimination of high-grade prostate cancer when combined to PI-RADS v2, particularly for PI-RADS v2 score 4 lesions, but it does not affect the prediction of EPE. (author)

  13. Metamorphic evolution of the Maud Belt: P- T- t path for high-grade gneisses in Gjelsvikfjella, Dronning Maud Land, East Antarctica

    Science.gov (United States)

    Bisnath, Avinash; Frimmel, Hartwig E.

    2005-12-01

    A metamorphic petrological study, in conjunction with recent precise geochronometric data, revealed a complex P- T- t path for high-grade gneisses in a hitherto poorly understood sector of the Mesoproterozoic Maud Belt in East Antarctica. The Maud Belt is an extensive high-grade, polydeformed, metamorphic belt, which records two significant tectono-thermal episodes, once towards the end of the Mesoproterozoic and again towards the late Neoproterozoic/Cambrian. In contrast to previous models, most of the metamorphic mineral assemblages are related to a Pan-African tectono-thermal overprint, with only very few relics of late Mesoproterozoic granulite-facies mineral assemblages (M 1) left in strain-protected domains. Petrological and mineral chemical evidence indicates a clockwise P- T- t path for the Pan-African orogeny. Peak metamorphic (M 2b) conditions recorded by most rocks in the area ( T = 709-785 °C and P = 7.0-9.5 kbar) during the Pan-African orogeny were attained subsequent to decompression from probably eclogite-facies metamorphic conditions (M 2a). The new data acquired in this study, together with recent geochronological and geochemical data, permit the development of a geodynamic model for the Maud Belt that involves volcanic arc formation during the late Mesoproterozoic followed by extension at 1100 Ma and subsequent high-grade tectono-thermal reworking once during continent-continent collision at the end of the Mesoproterozoic (M 1; 1090-1030 Ma) and again during the Pan-African orogeny (M 2a, M 2b) between 565 and 530 Ma. Post-peak metamorphic K-metasomatism under amphibolite-facies conditions (M 2c) followed and is ascribed to post-orogenic bimodal magmatism between 500 and 480 Ma.

  14. Development and External Validation of the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer: Comparison with Two Western Risk Calculators in an Asian Cohort.

    Science.gov (United States)

    Park, Jae Young; Yoon, Sungroh; Park, Man Sik; Choi, Hoon; Bae, Jae Hyun; Moon, Du Geon; Hong, Sung Kyu; Lee, Sang Eun; Park, Chanwang; Byun, Seok-Soo

    2017-01-01

    We developed the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer (KPCRC-HG) that predicts the probability of prostate cancer (PC) of Gleason score 7 or higher at the initial prostate biopsy in a Korean cohort (http://acl.snu.ac.kr/PCRC/RISC/). In addition, KPCRC-HG was validated and compared with internet-based Western risk calculators in a validation cohort. Using a logistic regression model, KPCRC-HG was developed based on the data from 602 previously unscreened Korean men who underwent initial prostate biopsies. Using 2,313 cases in a validation cohort, KPCRC-HG was compared with the European Randomized Study of Screening for PC Risk Calculator for high-grade cancer (ERSPCRC-HG) and the Prostate Cancer Prevention Trial Risk Calculator 2.0 for high-grade cancer (PCPTRC-HG). The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots. PC was detected in 172 (28.6%) men, 120 (19.9%) of whom had PC of Gleason score 7 or higher. Independent predictors included prostate-specific antigen levels, digital rectal examination findings, transrectal ultrasound findings, and prostate volume. The AUC of the KPCRC-HG (0.84) was higher than that of the PCPTRC-HG (0.79, pKorean population and showed similar performance with ERSPCRC-HG in a Korean population. This prediction model could help avoid unnecessary biopsy and reduce overdiagnosis and overtreatment in clinical settings.

  15. Is Age an Independent Predictor of High-Grade Histopathology in Women Referred for Colposcopy after Abnormal Cervical Cytology?

    Science.gov (United States)

    Kingnate, Chalita; Supoken, Amornrat; Kleebkaow, Pilaiwan; Chumworathayi, Bundit; Luanratanakorn, Sanguanchoke; Kietpeerakool, Chumnan

    2015-01-01

    This study was conducted to determine whether advancing age is an independent predictor of increased risk of high-grade pathologies among women referred for colposcopy after abnormal cervical cytology. Medical records were reviewed for women with abnormal cervical cytology who underwent colposcopy at Khon Kaen University Hospital. Logistic regression was used to determine the independent impact of age on the risk of high-grade pathologies. Mean age of the women was 42.8 years. Of 482 women, 97 (20.1%) were postmenopausal, and 92 (19.1%) were nulliparous. The rate of high-grade pathologies included cervical intraepithelial neoplasia 2-3, 99 (20.5%), adenocarcinoma in situ, 4 (0.8%), cervical cancer, 30 (6.2%), and endometrial cancer, 1 (0.2%). The prevalence of significant lesions was 26.9% (95% CI, 23.1%-31.2%). In total, 31 women had cancers (6.4%; 95% CI, 4.4%-9.0%). When controlling for smear types and parity, age was noted to be a significant independent predictor of high-grade histopathology. Women older than 35-40 years were approximately 2 times as likely to have severe histopathology as the younger women. This study illustrates the substantial risk of underlying significant lesions especially invasive cancer in Thai women with abnormal cervical cytology. Age was a significant independent factor predicting the risk of high-grade pathologies.

  16. Prognostic value of preoperative dynamic contrast-enhanced MRI perfusion parameters for high-grade glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Ulyte, Agne [Vilnius University, Faculty of Medicine, Vilnius (Lithuania); Katsaros, Vasileios K. [General Anticancer and Oncological Hospital ' ' St. Savvas' ' , Department of Advanced Imaging Modalities - CT and MRI, Athens (Greece); University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); Liouta, Evangelia; Stranjalis, Georgios [University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); Boskos, Christos [University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); General Anticancer and Oncological Hospital ' ' St. Savvas' ' , Department of Radiation Oncology, Athens (Greece); Papanikolaou, Nickolas [Champalimaud Foundation, Department of Radiology, Centre for the Unknown, Lisbon (Portugal); Usinskiene, Jurgita [National Cancer Institute, Vilnius (Lithuania); Affidea Lietuva, Vilnius (Lithuania); Bisdas, Sotirios [University College London Hospitals, Department of Neuroradiology, The National Hospital for Neurology and Neurosurgery, London (United Kingdom)

    2016-12-15

    The prognostic value of the dynamic contrast-enhanced (DCE) MRI perfusion and its histogram analysis-derived metrics is not well established for high-grade glioma (HGG) patients. The aim of this prospective study was to investigate DCE perfusion transfer coefficient (K{sup trans}), vascular plasma volume fraction (v{sub p}), extracellular volume fraction (v{sub e}), reverse transfer constant (k{sub ep}), and initial area under gadolinium concentration time curve (IAUGC) as predictors of progression-free (PFS) and overall survival (OS) in HGG patients. Sixty-nine patients with suspected anaplastic astrocytoma or glioblastoma underwent preoperative DCE-MRI scans. DCE perfusion whole tumor region histogram parameters, clinical details, and PFS and OS data were obtained. Univariate, multivariate, and Kaplan-Meier survival analyses were conducted. Receiver operating characteristic (ROC) curve analysis was employed to identify perfusion parameters with the best differentiation performance. On univariate analysis, v{sub e} and skewness of v{sub p} had significant negative impacts, while k{sub ep} had significant positive impact on OS (P < 0.05). v{sub e} was also a negative predictor of PFS (P < 0.05). Patients with lower v{sub e} and IAUGC had longer median PFS and OS on Kaplan-Meier analysis (P < 0.05). K{sup trans} and v{sub e} could also differentiate grade III from IV gliomas (area under the curve 0.819 and 0.791, respectively). High v{sub e} is a consistent predictor of worse PFS and OS in HGG glioma patients. v{sub p} skewness and k{sub ep} are also predictive for OS. K{sup trans} and v{sub e} demonstrated the best diagnostic performance for differentiating grade III from IV gliomas. (orig.)

  17. Predicting high grade lesions of sinusoidal obstruction syndrome related to oxaliplatin-based chemotherapy for colorectal liver metastases: correlation with post-hepatectomy outcome.

    Science.gov (United States)

    Soubrane, Olivier; Brouquet, Antoine; Zalinski, Stéphane; Terris, Benoît; Brézault, Catherine; Mallet, Vincent; Goldwasser, François; Scatton, Olivier

    2010-03-01

    Oxaliplatin-based chemotherapy induces sinusoidal obstruction syndrome (SOS) lesions in the nontumorous liver parenchyma, which may increase the risk of liver resection for colorectal liver metastases. The objective of this study was to evaluate the accuracy of aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 scoring systems to predict chemotherapy-associated liver injury and to correlate the severity of sinusoidal injury with postoperative outcome. Between 1998 and 2007, 78 patients were operated for colorectal liver metastases after preoperative oxaliplatin-based chemotherapy. Grading of steatosis and SOS in the nontumorous liver parenchyma was obtained in these patients. Univariate analysis of 18 preoperative factors to predict SOS occurrence was performed as well as multivariate analysis. Relevance of preoperative platelet count level, transaminase levels, and fibrosis scoring systems were evaluated to predict high grade lesions of SOS using a receiving operative curve analysis. Ninety-day mortality and morbidity were studied according to SOS severity in 51 patients who underwent major liver resection. Overall, pathologic examination showed high-grade lesions of SOS (SOS 2/3) in 46 (59%) patients. Univariate analysis showed that a low preoperative platelet count, elevated preoperative aspartate aminotransferase, short interval between chemotherapy and surgery were significant factors associated with high-grade lesions of SOS. Multivariate analysis showed that only the APRI score was an independent predictive factor for severe SOS. Receiving operative curve analysis revealed that the cut-off value predicting high-grade lesions of SOS with the best accuracy was an APRI score of 0.36 (area under the curve, 0.85; sensitivity, 87%; specificity, 69%). After major liver resection (n = 51), SOS 2/3 (n = 38) was associated with postoperative hepatic dysfunction (26/38 in SOS 2/3 vs. 3/13 in SOS 0/1; P = 0.004) and ascites (P = 0.03). A low

  18. Development and External Validation of the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer: Comparison with Two Western Risk Calculators in an Asian Cohort.

    Directory of Open Access Journals (Sweden)

    Jae Young Park

    Full Text Available We developed the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer (KPCRC-HG that predicts the probability of prostate cancer (PC of Gleason score 7 or higher at the initial prostate biopsy in a Korean cohort (http://acl.snu.ac.kr/PCRC/RISC/. In addition, KPCRC-HG was validated and compared with internet-based Western risk calculators in a validation cohort.Using a logistic regression model, KPCRC-HG was developed based on the data from 602 previously unscreened Korean men who underwent initial prostate biopsies. Using 2,313 cases in a validation cohort, KPCRC-HG was compared with the European Randomized Study of Screening for PC Risk Calculator for high-grade cancer (ERSPCRC-HG and the Prostate Cancer Prevention Trial Risk Calculator 2.0 for high-grade cancer (PCPTRC-HG. The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC and calibration plots.PC was detected in 172 (28.6% men, 120 (19.9% of whom had PC of Gleason score 7 or higher. Independent predictors included prostate-specific antigen levels, digital rectal examination findings, transrectal ultrasound findings, and prostate volume. The AUC of the KPCRC-HG (0.84 was higher than that of the PCPTRC-HG (0.79, p<0.001 but not different from that of the ERSPCRC-HG (0.83 on external validation. Calibration plots also revealed better performance of KPCRC-HG and ERSPCRC-HG than that of PCPTRC-HG on external validation. At a cut-off of 5% for KPCRC-HG, 253 of the 2,313 men (11% would not have been biopsied, and 14 of the 614 PC cases with Gleason score 7 or higher (2% would not have been diagnosed.KPCRC-HG is the first web-based high-grade prostate cancer prediction model in Korea. It had higher predictive accuracy than PCPTRC-HG in a Korean population and showed similar performance with ERSPCRC-HG in a Korean population. This prediction model could help avoid unnecessary biopsy and reduce overdiagnosis and overtreatment in

  19. Octagon to Square Wetting Area Transition of Water-Ethanol Droplets on a Micropyramid Substrate by Increasing Ethanol Concentration.

    Science.gov (United States)

    Feng, Huicheng; Chong, Karen Siew-Ling; Ong, Kian-Soo; Duan, Fei

    2017-02-07

    The wettability and evaporation of water-ethanol binary droplets on the substrate with micropyramid cavities are studied by controlling the initial ethanol concentrations. The droplets form octagonal initial wetting areas on the substrate. As the ethanol concentration increases, the side ratio of the initial wetting octagon increases from 1.5 at 0% ethanol concentration to 3.5 at 30% ethanol concentration. The increasing side ratio indicates that the wetting area transforms from an octagon to a square if we consider the octagon to be a square with its four corners cut. The droplets experience a pinning-depinning transition during evaporation. The pure water sessile droplet evaporation demonstrates three stages from the constant contact line (CCL) stage, and then the constant contact angle (CCA) stage, to the mixed stage. An additional mixed stage is found between the CCL and CCA stages in the evaporation of water-ethanol binary droplets due to the anisotropic depinning along the two different axes of symmetry of the octagonal wetting area. Droplet depinning occurs earlier on the patterned surface as the ethanol concentration increases.

  20. State of transition: Marijuana use among young adults in the San Francisco Bay Area.

    Science.gov (United States)

    Holmes, Louisa M; Popova, Lucy; Ling, Pamela M

    2016-09-01

    California may vote on marijuana legalization in 2016. Young adults have the highest rates of marijuana use, but little is known about the correlates of use in this age group, including factors that may be affected by policy change. We investigated whether there are differences in marijuana use by sociodemographic characteristics, psychological distress, loneliness and social support, controlling for risk factors such as alcohol and cigarette use as well as perceived harm of marijuana. Bivariate and multivariable analysis of past 30day marijuana use using the 2014 San Francisco Bay Area Young Adult Health Survey, a probabilistic multi-mode survey of (N=1324) young adults (aged 18-26years) residing in Alameda and San Francisco Counties, stratified by race/ethnicity. 291 (27%) sample participants reported current marijuana use. Compared to non-Hispanic Whites (referent) Asian/Pacific Islander respondents were less likely to use marijuana (AOR, 0.42; 95% CI, 0.22-0.80) while multiracial participants were twice as likely (AOR, 2.27; 95% CI, 1.06-4.85). Psychological distress was not related to marijuana use, but social support (AOR, 1.42; 95% CI, 1.08-1.88) and loneliness (AOR, 1.42; 95% CI, 1.09-1.86) were. Perceived harm of marijuana was inversely related to marijuana use (AOR, 0.60; 95% CI, 0.51-0.70), while smoking cigarettes (AOR, 3.95; 95% CI, 2.28-6.84) and binge drinking (AOR, 1.13; 95% CI, 1.03-1.24) were positively related. Legalization policies should include public education campaigns addressing potential harms of marijuana use particularly targeting multiracial young adults who also engage in other risk behaviors, such as cigarette smoking and binge drinking. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Finasteride Does Not Increase the Risk of High-grade Prostate Cancer: A Bias-adjusted Modeling Approach

    Science.gov (United States)

    Redman, Mary W.; Tangen, Catherine M.; Goodman, Phyllis J.; Parnes, Howard; Ford, Leslie G.; Lucia, M. Scott; Coltman, Charles A.; Thompson, Ian M.

    2010-01-01

    The Prostate Cancer Prevention Trial found that seven years of administration of finasteride reduced the risk of prostate cancer by 25% but with an apparent increased risk of high grade disease. Subsequent analyses found that finasteride affects cancer detection and improves accuracy of tumor grading at biopsy. We herein estimate the impact of finasteride on the risk of overall and high grade prostate cancer, accounting for these biases. Study endpoints (biopsy-proven cancer or a 7-year end-of-study biopsy) were available in 10,182 of 15,990 subjects assessable for 7-year status and grading information from 500 subjects diagnosed with cancer who underwent radical prostatectomy. Prostate cancer was observed in 22.9% (4.8% with high grade) in the placebo group versus 16.6% (5.8% with high grade) in the finasteride group. In this bias-adjusted analysis, the estimated rates are 21.1% (4.2%) and 14.7% (4.8%), respectively, a 30% risk reduction in prostate cancer (RR =0.70 (95% confidence interval (CI) =0.64-0.76, pfinasteride. Incorporating the prostatectomy data, estimated rates of high grade cancers are 8.2% (placebo) versus 6.0% (finasteride), a 27% risk reduction (RR = 0.73 (95% CI=0.56-0.96, p=0.02)) with finasteride. While the observed risk of high grade disease is greater with finasteride, this appears to be through facilitated diagnosis, primarily due to increased biopsy sensitivity. Men undergoing regular prostate cancer screening or who express an interest in cancer prevention should be informed of this prevention opportunity. PMID:19138953

  2. HPV 16 and cigarette smoking as risk factors for high-grade cervical intra-epithelial neoplasia.

    Science.gov (United States)

    Ho, G Y; Kadish, A S; Burk, R D; Basu, J; Palan, P R; Mikhail, M; Romney, S L

    1998-10-29

    Although genital human papillomavirus (HPV) infection is well established as the etiologic agent for cervical intraepithelial neoplasia (CIN), little is known about the cofactors involved in the development of high-grade lesions or the progression of low-grade to high-grade lesions. In our study of HPV-infected women with CIN (163 CIN I, 51 CIN II and 44 CIN III), women with CIN II or III were compared with those with CIN I for risk factors associated with high-grade lesions. After controlling for age, education, ethnicity and frequency of Pap smear screening, infection with HPV 16, but not high viral load or infection with multiple types, was associated with high-grade lesions (OR for CIN II = 11.96, OR for CIN III = 23.74). Risk of CIN III, but not CIN II, increased with number of cigarettes smoked per day (ORs = 1.49 and 3.35 for 10 cigarettes per day, respectively) and decreased with frequency of condom use during sex (ORs = 0.60 and 0.32 for women who used condoms occasionally/sometimes and most/all of the time, respectively). There were no associations between high-grade lesions and plasma levels of micronutrients (retinol, beta-carotene, alpha-tocopherol and reduced ascorbic acid). Our results indicate that infection with HPV 16 is associated with high-grade lesions. Additional cofactors, such as cigarette smoking, may be required as a carcinogen to advance HPV-infected cells toward neoplastic progression.

  3. A Review of the Role of Re-Irradiation in Recurrent High-Grade Glioma (HGG)

    Energy Technology Data Exchange (ETDEWEB)

    Amichetti, Maurizio, E-mail: amichett@atrep.it; Amelio, Dante, E-mail: amichett@atrep.it [ATreP, Agenzia Provinciale per la Protonterapia, via Perini 181, 38122 Trento (Italy)

    2011-10-28

    Despite the use of more effective multimodal treatments in high-grade glioma (HGG), the outcome of patients affected by this disease is still dismal and recurrence is a very common event. Many therapeutic approaches, alone or combined (surgery, drugs, targeted agents, immunotherapy, radiotherapy, supportive therapy), are available in the clinical armamentarium so far. The attitude of physicians is increasingly interventionist, but recurrent HGG still remains a very difficult scenario to be treated. Radiotherapy with different re-irradiation techniques is increasingly proposed as a therapeutic option with interesting results, even though the resulting duration of response is usually quite short. Most lesions re-recur locally, with inadequate identification and targeting of viable tumor being the most important cause of failure. Prognosis is affected by many patient-, tumor-, and treatment-associated prognostic factors. Radiotherapy is delivered with many advanced modalities: 3D-CRT, intensity-modulated radiation therapy, stereotactic fractionated radiotherapy, radiosurgery, and brachitherapy with or without chemotherapy administration. In order to evaluate the feasibility and efficacy of re-irradiation in this setting, we reviewed the PubMed and MEDLINE databases restricting the search to original reports published from January 1990 to June 2011. The search resulted in a total of 155 reports: 78 of them covering 2,688 patients treated with different irradiation modalities overall fulfilled the entry criteria. Radiation therapy demonstrated to be an acceptable option in recurrent HGG with good response rates and acceptable toxicity.

  4. High-grade myxofibrosarcoma presenting at the spermatic cord after radiotherapy for prostate cancer.

    Science.gov (United States)

    Tearada, Hiroshi; Nagata, Masao; Mugiya, Soichi; Ozono, Seiichiro

    2012-11-28

    A 72-year-old man with a history of prostate cancer presented 7 years postradiotherapy with a painless, egg-sized, rapidly growing nodule on the left groin at the radiation site. He underwent left high orchiectomy under a diagnosis of groin lymph node metastasis of prostate cancer. The tumour had penetrated deep into the internal inguinal ring and was resected as proximally as possible to the internal ring with a positive surgical margin. Macroscopically, the left testis was intact in the resected specimen. Immunohistochemical staining revealed that the tumour consisted of myxofibrosarcoma (MFS) with spindle cells; and was positive for vimentin, cytokeratin (AE1/AE3), MIB-1 and CD68, and negative for α-SMA, S-100, CD34 and myogenin. Thus, the tumour was diagnosed as high-grade MFS of the spermatic cord. Postoperative CT revealed a right renal tumour and adrenal tumour. Right radial nephrectomy was performed and the patient was doing well at 10-month follow-up.

  5. Pediatric high-grade astrocytomas: a distinct neuro-oncological paradigm.

    Science.gov (United States)

    Gerges, Noha; Fontebasso, Adam M; Albrecht, Steffen; Faury, Damien; Jabado, Nada

    2013-01-01

    Brain tumors are the leading cause of cancer-related death in children. High-grade astrocytomas (HGAs), in particular, are lethal in children across all ages. Integrative genome-wide analyses of the tumor's genome, transcriptome and epigenome, using next-generation sequencing technologies and genome-wide DNA methylation arrays, have provided valuable breakthroughs in our understanding of the pathogenesis of HGAs across all ages. Recent profiling studies have provided insight into the epigenetic nature of gliomas in young adults and HGAs in children, particularly with the identification of recurrent gain-of-function driver mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1/2) and the epigenetic influence of their oncometabolite 2-hydroxyglutarate, as well as mutations in the histone 3 variant 3 gene (H3F3A) and loss-of-function mutations in the histone 3 lysine 36 trimethyltransferase gene (SETD2). Mutations in H3F3A result in amino acid substitutions at residues thought to directly (K27M) or indirectly (G34R/V) affect histone post-translational modifications, suggesting they have the capacity to affect the epigenome in a profound manner. Here, we review recent genomic studies, and discuss evidence supporting the molecular characterization of pediatric HGAs to complement traditional approaches, such as histology of resected tumors. We also describe newly identified molecular mechanisms and discuss putative therapeutic approaches for HGAs specific to pediatrics, highlighting the necessity for the evolution of HGA disease management approaches.

  6. A Review of the Role of Re-Irradiation in Recurrent High-Grade Glioma (HGG

    Directory of Open Access Journals (Sweden)

    Maurizio Amichetti

    2011-10-01

    Full Text Available Despite the use of more effective multimodal treatments in high-grade glioma (HGG, the outcome of patients affected by this disease is still dismal and recurrence is a very common event. Many therapeutic approaches, alone or combined (surgery, drugs, targeted agents, immunotherapy, radiotherapy, supportive therapy, are available in the clinical armamentarium so far. The attitude of physicians is increasingly interventionist, but recurrent HGG still remains a very difficult scenario to be treated. Radiotherapy with different re-irradiation techniques is increasingly proposed as a therapeutic option with interesting results, even though the resulting duration of response is usually quite short. Most lesions re-recur locally, with inadequate identification and targeting of viable tumor being the most important cause of failure. Prognosis is affected by many patient-, tumor-, and treatment-associated prognostic factors. Radiotherapy is delivered with many advanced modalities: 3D-CRT, intensity-modulated radiation therapy, stereotactic fractionated radiotherapy, radiosurgery, and brachitherapy with or without chemotherapy administration. In order to evaluate the feasibility and efficacy of re-irradiation in this setting, we reviewed the PubMed and MEDLINE databases restricting the search to original reports published from January 1990 to June 2011. The search resulted in a total of 155 reports: 78 of them covering 2,688 patients treated with different irradiation modalities overall fulfilled the entry criteria. Radiation therapy demonstrated to be an acceptable option in recurrent HGG with good response rates and acceptable toxicity.

  7. Detection of high-grade atypia nuclei in breast cancer imaging

    Science.gov (United States)

    Noël, Henri; Roux, Ludovic; Lu, Shijian; Boudier, Thomas

    2015-03-01

    Along with mitotic count, nuclear pleomorphism or nuclear atypia is an important criterion for the grading of breast cancer in histopathology. Though some works have been done in mitosis detection (ICPR 2012,1 MICCAI 2013,2 and ICPR 2014), not much work has been dedicated to automated nuclear atypia grading, especially the most difficult task of detection of grade 3 nuclei. We propose the use of Convolutional Neural Networks for the automated detection of cell nuclei, using images from the three grades of breast cancer for training. The images were obtained from ICPR contests. Additional manual annotation was performed to classify pixels into five classes: stroma, nuclei, lymphocytes, mitosis and fat. At total of 3,000 thumbnail images of 101 × 101 pixels were used for training. By dividing this training set in an 80/20 ratio we could obtain good training results (around 90%). We tested our CNN on images of the three grades which were not in the training set. High grades nuclei were correctly classified. We then thresholded the classification map and performed basic analysis to keep only rounded objects. Our results show that mostly all atypical nuclei were correctly detected.

  8. Hemangioma of uterine cervix associated with high-grade squamous intraepithelial lesion

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    Đolai Matilda

    2015-01-01

    Full Text Available Introduction. Benign, especially polypoid, lesions of the cervix are common in everyday work. Rare tumors of this region are vascular ones, particularly capillary and/or cavernous hemangiomas. Cervical hemangiomas are especially rare, usually asymptomatic and only one third of the cases is clinically manifested as vaginal bleeding, polyps, etc. Case report. We reported a 54-year-old postmenopausal female patient who had undergone conization due to high-grade squamous intra-epithelial lesion (H-SIL. Microscopic analysis of slices confirmed the existence of dysplastic changes in the endocervical epithelium and in small part in the epithelium of the gland of H-SIL type. In 2 of 15 slices, within the walls of the cervix, dilated, amplified and abnormal blood vessels lined with endothelium were observed, vaguely limited by the surrounding connective tissue of lamina propria and smooth muscle wall of the cervix. According to the pathological characteristics, the change corresponded to the hemangioma. Both changes were completely removed. Conclusion. In comparison with the available literature data, the presented case is the first to describe the association of hemangioma and dysplastic changes in the endocervical epithelium. Hemangioma was incidentally discovered in the histological sections of the material after the conization in a postmenopausal women.

  9. Gene Expression Profiling of Chemokines and Their Receptors in Low and High Grade Astrocytoma

    Science.gov (United States)

    Sharma, Ira; Singh, Avninder; Sharma, Karam Chand; Saxena, Sunita

    2017-05-01

    Background: Despite intense interest in molecular characterization and searches for novel therapeutic targets, the glioblastoma remains a formidable clinical challenge. Among many contributors to gliomagenesis, chemokines have drawn special attention due to their involvement in a plethora of biological processes and pathological conditions. In the present study we aimed to elucidate any pro-gliomagenic chemokine axis and probable roles in development of glioblastoma multiforme (GBM). Method: An array of 84 chemokines, chemokine receptors and related genes were studied by real time PCR with comparison between low grade astrocytoma (diffuse astrocytoma – grade II) and high grade astrocytoma (glioblastoma multiforme – grade IV). Gene ontology analysis and database mining were performed to funnel down the important axis in GBM followed by validation at the protein level by immunohistochemistry on tissue microarrays. Results: Gene expression and gene ontology analysis identified CXCL8 as an important chemokine which was more frequently up-regulated in GBM as compared to diffuse astrocytoma. Further we demonstrated localization of CXCL8 and its receptors in glioblastoma possibly affecting autocrine and paracrine signalling that promotes tumor cell proliferation and neovascularisation with vascular mimicry. Conclusion: From these results CXCL8 appears to be an important gliomagenic chemokine which may be involved in GBM growth by promoting tumor cell proliferation and neovascularization via vascular mimicry. Further in vitro and in vivo investigations are required to explore its potential candidature in anti-GBM therapy. Creative Commons Attribution License

  10. Malignant phyllodes tumor of the breast with heterologous high-grade angiosarcoma

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    Ghassan Tranesh

    2017-03-01

    Full Text Available Phyllodes tumors (PTs account for <3% of fibroepithelial breast lesions and for 0.3% to 1.0% of primary breast tumors. They occur predominantly in middle-aged women (mean age range, 40–50 years. PTs can be categorized into benign, borderline, and malignant; the first 2 categories are distinguished only by degree of cellular atypia and mitotic activity. Malignant PTs are more frequent among persons of Hispanic ethnicity, especially those born in Central America or South America. Heterologous sarcomatous elements may be present in malignant PTs, predominantly liposarcoma and rarely fibrosarcoma, rhabdomyosarcoma, leiomyosarcoma, osteosarcoma, and chondrosarcoma. Breast angiosarcoma (BA is a rare heterologous, sarcomatous element that may arise secondary to malignant PT. We report a 47-year-old woman with no history of previous surgery or radiation therapy who presented to the emergency department with a painful right breast mass. She admittedly noticed the right breast mass for many years; however, recently it increased in size. Mammography and ultrasonography identified a partially cystic mass. Core needle biopsy showed dense hyalinized fibrous tissue with old blood clots, suggestive of infarcted fibroadenoma. The patient received antibiotics and analgesics; however, she reported intractable pain and a worsening skin rash of her right breast. Chest computed tomography and magnetic resonance imaging showed a doubling in mass size, with pectoralis major muscle involvement. Incisional biopsy showed malignant PT with heterologous high-grade angiosarcoma. The diagnosis of angiosarcoma was confirmed through immunoreactivity for CD31, FLI1, and ERG immunostains.

  11. Efficient molecular subtype classification of high-grade serous ovarian cancer.

    Science.gov (United States)

    Leong, Huei San; Galletta, Laura; Etemadmoghadam, Dariush; George, Joshy; Köbel, Martin; Ramus, Susan J; Bowtell, David

    2015-07-01

    High-grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost-effective and high-throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman-based (low-density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin-fixed, paraffin-embedded samples. All platforms achieved > 90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo-naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  12. Automated high-grade prostate cancer detection and ranking on whole slide images

    Science.gov (United States)

    Huang, Chao-Hui; Racoceanu, Daniel

    2017-03-01

    Recently, digital pathology (DP) has been largely improved due to the development of computer vision and machine learning. Automated detection of high-grade prostate carcinoma (HG-PCa) is an impactful medical use-case showing the paradigm of collaboration between DP and computer science: given a field of view (FOV) from a whole slide image (WSI), the computer-aided system is able to determine the grade by classifying the FOV. Various approaches have been reported based on this approach. However, there are two reasons supporting us to conduct this work: first, there is still room for improvement in terms of detection accuracy of HG-PCa; second, a clinical practice is more complex than the operation of simple image classification. FOV ranking is also an essential step. E.g., in clinical practice, a pathologist usually evaluates a case based on a few FOVs from the given WSI. Then, makes decision based on the most severe FOV. This important ranking scenario is not yet being well discussed. In this work, we introduce an automated detection and ranking system for PCa based on Gleason pattern discrimination. Our experiments suggested that the proposed system is able to perform high-accuracy detection ( 95:57% +/- 2:1%) and excellent performance of ranking. Hence, the proposed system has a great potential to support the daily tasks in the medical routine of clinical pathology.

  13. Differential proteomics analysis of low- and high-grade of astrocytoma using iTRAQ quantification

    Science.gov (United States)

    Ren, Tong; Lin, Shide; Wang, Zhongfeng; Shang, Aijia

    2016-01-01

    Astrocytoma is one of the most common types of brain tumor, which is histologically and clinically classified into four grades (I–IV): I (pilocytic astrocytoma), II (diffuse astrocytoma), III (anaplastic astrocytoma), and IV (glioblastoma multiforme). A higher grade astrocytoma represents a worse prognosis and is more aggressive. In this study, we compared the differential proteome profile of astrocytoma from grades I to IV. The protein samples from clinical specimens of grades I, II, III, and IV astrocytoma were analyzed by two-dimensional liquid chromatography–tandem mass spectrometry and isobaric tags for relative and absolute quantitation and quantification. A total of 2,190 proteins were identified. Compared to grade I astrocytoma, 173 (12.4%), 304 (14%), and 462 (21.2%) proteins were aberrantly expressed in grades II, III, and IV, respectively. By bioinformatics analysis, the cell proliferation, invasion, and angiogenesis-related pathways increase from low- to high-grade of astrocytoma. Five differentially expressed proteins were validated by Western blot. Within them, matrix metalloproteinase-9 and metalloproteinase inhibitor 1 were upregulated in glioblastoma multiforme group; whereas fibulin-2 and -5 were downregulated in grade II/III/IV astrocytoma, and the negative expression was significantly associated with advanced clinical stage. Functional analysis showed that both fibulin-2 and -5 may exert an antitumor effect by inhibiting cell proliferation, in vitro migration/invasion in glioma cells. New molecular biomarkers are likely to be used for accurate classification of astrocytoma and likely to be the target for drug development. PMID:27713642

  14. Gene Expression Profiling of Chemokines and Their Receptors in Low and High Grade Astrocytoma

    Science.gov (United States)

    Sharma, Ira; Singh, Avninder; Sharma, Karam Chand; Saxena, Sunita

    2017-01-01

    Background: Despite intense interest in molecular characterization and searches for novel therapeutic targets, the glioblastoma remains a formidable clinical challenge. Among many contributors to gliomagenesis, chemokines have drawn special attention due to their involvement in a plethora of biological processes and pathological conditions. In the present study we aimed to elucidate any pro-gliomagenic chemokine axis and probable roles in development of glioblastoma multiforme (GBM). Method: An array of 84 chemokines, chemokine receptors and related genes were studied by real time PCR with comparison between low grade astrocytoma (diffuse astrocytoma – grade II) and high grade astrocytoma (glioblastoma multiforme – grade IV). Gene ontology analysis and database mining were performed to funnel down the important axis in GBM followed by validation at the protein level by immunohistochemistry on tissue microarrays. Results: Gene expression and gene ontology analysis identified CXCL8 as an important chemokine which was more frequently up-regulated in GBM as compared to diffuse astrocytoma. Further we demonstrated localization of CXCL8 and its receptors in glioblastoma possibly affecting autocrine and paracrine signalling that promotes tumor cell proliferation and neovascularisation with vascular mimicry. Conclusion: From these results CXCL8 appears to be an important gliomagenic chemokine which may be involved in GBM growth by promoting tumor cell proliferation and neovascularization via vascular mimicry. Further in vitro and in vivo investigations are required to explore its potential candidature in anti-GBM therapy. PMID:28610419

  15. [(18F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for high-grade glioma

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    Ratib Osman

    2008-12-01

    Full Text Available Abstract Background To compare morphological gross tumor volumes (GTVs, defined as pre- and postoperative gadolinium enhancement on T1-weighted magnetic resonance imaging to biological tumor volumes (BTVs, defined by the uptake of 18F fluoroethyltyrosine (FET for the radiotherapy planning of high-grade glioma, using a dedicated positron emission tomography (PET-CT scanner equipped with three triangulation lasers for patient positioning. Methods Nineteen patients with malignant glioma were included into a prospective protocol using FET PET-CT for radiotherapy planning. To be eligible, patients had to present with residual disease after surgery. Planning was performed using the clinical target volume (CTV = GTV ∪ BTV and planning target volume (PTV = CTV + 20 mm. First, the interrater reliability for BTV delineation was assessed among three observers. Second, the BTV and GTV were quantified and compared. Finally, the geometrical relationships between GTV and BTV were assessed. Results Interrater agreement for BTV delineation was excellent (intraclass correlation coefficient 0.9. Although, BTVs and GTVs were not significantly different (p = 0.9, CTVs (mean 57.8 ± 30.4 cm3 were significantly larger than BTVs (mean 42.1 ± 24.4 cm3; p 3; p Conclusion Using FET, the interrater reliability had excellent agreement for BTV delineation. With FET PET-CT planning, the size and geometrical location of GTVs and BTVs differed in a majority of patients.

  16. Comparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ.

    LENUS (Irish Health Repository)

    Howley, R

    2012-10-15

    Developing targeted therapies for high grade gliomas (HGG), the most common primary brain tumor in adults, relies largely on glioma cultures. However, it is unclear if HGG tumorigenic signaling pathways are retained under in-vitro conditions. Using array comparative genomic hybridization and immunohistochemical profiling, we contrasted the epidermal and platelet-derived growth factor receptor (EGFR\\/PDGFR) in-vitro pathway status of twenty-six primary HGG cultures with the pathway status of their original HGG biopsies. Genomic gains or amplifications were lost during culturing while genomic losses were more likely to be retained. Loss of EGFR amplification was further verified immunohistochemically when EGFR over expression was decreased in the majority of cultures. Conversely, PDGFRα and PDGFRβ were more abundantly expressed in primary cultures than in the original tumor (p<0.05). Despite these genomic and proteomic differences, primary HGG cultures retained key aspects of dysregulated tumorigenic signaling. Both in-vivo and in-vitro the presence of EGFR resulted in downstream activation of P70s6K while reduced downstream activation was associated with the presence of PDGFR and the tumor suppressor, PTEN. The preserved pathway dysregulation make this glioma model suitable for further studies of glioma tumorigenesis, however individual culture related differences must be taken into consideration when testing responsiveness to chemotherapeutic agents.

  17. The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

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    Shunfei Yan

    2017-01-01

    Full Text Available Overall survival for patients with ovarian cancer (OC has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC. HGSOC is characterized by genomic structural variations with relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR and ribosome biogenesis has been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes. The poly (ADP-ribose polymerase (PARP inhibitor olaparib has been approved to treat women with defects in HR due to germline BRCA mutations. Recent evidence demonstrated the efficacy of targeting ribosome biogenesis with the specific inhibitor of ribosomal RNA synthesis, CX-5461 in v-myc avian myelocytomatosis viral oncogene homolog (MYC-driven haematological and prostate cancers. CX-5461 has now progressed to a phase I clinical trial in patients with haematological malignancies and phase I/II trial in breast cancer. Here we review the currently available targeted therapies for HGSOC and discuss the potential of targeting ribosome biogenesis as a novel therapeutic approach against HGSOC.

  18. Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma

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    Ruifen Dong

    2016-09-01

    Full Text Available Abstract Background Patient derived xenografts (PDX are generated by transplanting the original patient’s tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC is a deadly form of ovarian/fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient. Methods In this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged (from P0 to P4 and tumors were grafted orthotopically under the ovarian bursa or subcutaneously. Results Comparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted. Conclusion Our findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC.

  19. Uncovering the role of nuclear Lysyl oxidase (LOX) in advanced high grade serous ovarian cancer.

    Science.gov (United States)

    De Donato, Marta; Petrillo, Marco; Martinelli, Enrica; Filippetti, Flavia; Zannoni, Gian Franco; Scambia, Giovanni; Gallo, Daniela

    2017-07-01

    Lysyl oxidase (LOX) is an enzyme that catalyzes the cross-linking of collagen and elastin in the extracellular matrix, thus controlling the tensile strength of tissues. Along with this primary function, there are evidences supporting a role for LOX in many critical biological functions, including gene expression regulation, cell growth, adhesion and migration. Accordingly, recent studies have supported a pivotal role for LOX in cancer progression and metastasis. The current study aimed at investigating the prognostic significance and the functional role of intracellular LOX in ovarian cancer. To this end, we analyzed LOX expression by immunohistochemistry in archived tumor material from advanced high grade serous ovarian cancer (HGSOC) patients (n=70) and correlated data with clinicopathological parameters and with response to chemotherapy. In vitro experiments were also used to investigate the functional consequences of LOX expression on behavioral aspects of HGSOC cells. Our results showed that nuclear LOX expression is associated with unfavorable outcome in advanced HGSOC, being an independent prognostic factor for disease recurrence. Besides, high nuclear levels were seen to be associated with resistance to first-line chemotherapy. Through gene expression modulation experiments in HGSOC cell lines, we demonstrate that LOX positively regulates cell proliferation, migration and anchorage-independent growth. Collectively, our data suggest that LOX functions as a tumor promoter in HGSOC and positively regulates several aspects of the metastatic cascade. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. “Reverse Bohlman” technique for the treatment of high grade spondylolisthesis in an adult population

    Science.gov (United States)

    Macagno, Angel E.; Hasan, Saqib; Jalai, Cyrus M.; Worley, Nancy; de Moura, Alexandre B.; Spivak, Jeffrey; Bendo, John A.; Passias, Peter G.

    2016-01-01

    Background/aims Surgical techniques for effective high-grade spondylolisthesis (HGS) remain controversial. This study aims to evaluate radiographic/clinical outcomes in HGS patients treated using modified “Reverse Bohlman” (RB) technique. Methods Review of consecutive HGS patients undergoing RB at a single university-center from 2006 to 2013. Clinical, surgical, radiographic parameters collected. Results Six patients identified: five with L5-S1 HGS with L4-L5 instability and one had an L4-5 isthmic spondylolisthesis and grade 1 L5-S1 isthmic spondylolisthesis. Two interbody graft failures and one L5-S1 pseudoarthrosis. Postoperative improvement of anterolisthesis (62.3% vs. 49.6%, p = 0.003), slip angle (10 vs. 5°, p = 0.005), and lumbar lordosis (49 vs. 57.5°, p = 0.049). Conclusions RB technique for HGS recommended when addressing adjacent level instability/slip. PMID:26955227

  1. Decreased FOXD3 Expression Is Associated with Poor Prognosis in Patients with High-Grade Gliomas.

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    Wei Du

    Full Text Available The transcription factor forkhead box D3 (FOXD3 plays important roles in the development of neural crest and has been shown to suppress the development of various cancers. However, the expression and its potential biological roles of FOXD3 in high-grade gliomas (HGGs remain unknown.The mRNA and protein expression levels of FOXD3 were examined using real-time quantitative PCR and western blotting in 23 HGG and 13 normal brain samples, respectively. Immunohistochemistry was used to validate the expression FOXD3 protein in 184 HGG cases. The association between FOXD3 expression and the prognosis of HGG patients were analyzed using Kaplan-Meier survival curves and Cox proportional hazards regression models. In addition, we further examined the effects of FOXD3 on the proliferation and serum starvation-induced apoptosis of glioma cells.In comparison to normal brain tissues, FOXD3 expression was significantly decreased in HGG tissues at both mRNA and protein levels. Immunohistochemistry further validated the expression of FOXD3 in HGG tissues. Moreover, low FOXD3 expression was significantly associated with poor prognosis in HGG patients. Depletion of FOXD3 expression promoted glioma cell proliferation and inhibited serum starvation-induced apoptosis, whereas overexpression of FOXD3 inhibited glioma cell proliferation and promoted serum starvation-induced apoptosis.Our results indicated that FOXD3 might serve as an independent prognostic biomarker and a potential therapeutic target for HGGs, which warrant further investigation.

  2. High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk.

    Science.gov (United States)

    Huang, Bangxing; Cai, Jing; Xu, Xia; Guo, Shuang; Wang, Zehua

    2016-01-01

    This study investigated prognostic significance of tumor budding in early-stage cervical cancer (ESCC) following radical surgery and its contribution to improve the stratification of patients with recurrence risk. The archival medical records and H&E-stained slides of 643 patients with IA2-IIA stage cervical cancer who underwent radical surgery were retrospectively reviewed. Clinicopathological parameters were noted, and tumor buds were counted using immunohistochemistry for each case. The prognostic significance of tumor budding was analyzed. Prediction models that comprised tumor budding were established, and the performance was compared between the novel models and classic criteria via log-rank test and receiver operating characteristic analysis. Tumors with high-grade tumor budding (HTB) exhibited a substantially increased risk of recurrence (hazard ratio = 4.287, P tumor size ≥ 4 cm, deep stromal invasion of outer 1/3, and lymphovascular space invasion to stratify patients with an intermediate risk was most predictive of recurrence compared with the classic criteria. Tumor budding is an independent, unfavorable, prognostic factor for ESCC patients following radical surgery and holds promise for improved recurrence risk stratification.

  3. The Molecular Fingerprint of High Grade Serous Ovarian Cancer Reflects Its Fallopian Tube Origin

    Directory of Open Access Journals (Sweden)

    Thomas Meyer

    2013-03-01

    Full Text Available High grade serous ovarian cancer (HGSC, the most lethal and frequent type of epithelial ovarian cancer (EOC, has poor long term prognosis due to a combination of factors: late detection, great metastatic potential and the capacity to develop resistance to available therapeutic drugs. Furthermore, there has been considerable controversy concerning the etiology of this malignancy. New studies, both clinical and molecular, strongly suggest that HGSC originates not from the surface of the ovary, but from the epithelial layer of the neighboring fallopian tube fimbriae. In this paper we summarize data supporting the central role of fallopian tube epithelium in the development of HGSC. Specifically, we address cellular pathways and regulatory mechanisms which are modulated in the process of transformation, but also genetic changes which accumulate during disease progression. Similarities between fallopian tube mucosa and the malignant tissue of HGSC warrant a closer analysis of homeostatic mechanisms in healthy epithelium in order to elucidate key steps in disease development. Finally, we highlight the importance of the cancer stem cell (CSC identification and understanding of its niche regulation for improvement of therapeutic strategies.

  4. HPV DNA genotyping test in low and high grade intraephitelial lesions

    Directory of Open Access Journals (Sweden)

    Maria Gabriella Lepore

    2009-12-01

    Full Text Available The human papillomavirus (HPV is certainly one of the few viruses associated with cancer and is present in a significant number of cancers of the anus, penis, vagina, vulva and in almost all cervical cancers.The aim of our work is to evaluate the impact of genotypes high-risk oncogenic (HR in low-grade (LSIL and high grade (HSIL intraepithelial lesions. In it are also evaluated the impact of genotypes low oncogenic risk (LR and the percentage of non-detection (NR Papillomavirus DNA Between January 2008 and June 2009 we submitted for HPV DNA genotyping test 392 patients, seronegative for HIV1/2, of which 278 with LSIL and 114 with HSIL. In 250 patients tested positive for HPV DNA HR the type 16 is present in 102 patients (41%, the 18 in 62 (25%, the 31 in 37 patients (15%, the 33 in 13 patients (5%; also was limited the simultaneous presence of 16 and 18 (13 patients 5% The search for HPV DNA is a modern method of study of cervical pathology. Optimizes the follow-up of intraepithelial lesions and the therapeutic intervention, avoiding the dangers of over/ undertreatment and allows to monitor women treated for cervical pathology.

  5. Prognostically relevant gene signatures of high-grade serous ovarian carcinoma

    Science.gov (United States)

    Verhaak, Roel G.W.; Tamayo, Pablo; Yang, Ji-Yeon; Hubbard, Diana; Zhang, Hailei; Creighton, Chad J.; Fereday, Sian; Lawrence, Michael; Carter, Scott L.; Mermel, Craig H.; Kostic, Aleksandar D.; Etemadmoghadam, Dariush; Saksena, Gordon; Cibulskis, Kristian; Duraisamy, Sekhar; Levanon, Keren; Sougnez, Carrie; Tsherniak, Aviad; Gomez, Sebastian; Onofrio, Robert; Gabriel, Stacey; Chin, Lynda; Zhang, Nianxiang; Spellman, Paul T.; Zhang, Yiqun; Akbani, Rehan; Hoadley, Katherine A.; Kahn, Ari; Köbel, Martin; Huntsman, David; Soslow, Robert A.; Defazio, Anna; Birrer, Michael J.; Gray, Joe W.; Weinstein, John N.; Bowtell, David D.; Drapkin, Ronny; Mesirov, Jill P.; Getz, Gad; Levine, Douglas A.; Meyerson, Matthew

    2012-01-01

    Because of the high risk of recurrence in high-grade serous ovarian carcinoma (HGS-OvCa), the development of outcome predictors could be valuable for patient stratification. Using the catalog of The Cancer Genome Atlas (TCGA), we developed subtype and survival gene expression signatures, which, when combined, provide a prognostic model of HGS-OvCa classification, named “Classification of Ovarian Cancer” (CLOVAR). We validated CLOVAR on an independent dataset consisting of 879 HGS-OvCa expression profiles. The worst outcome group, accounting for 23% of all cases, was associated with a median survival of 23 months and a platinum resistance rate of 63%, versus a median survival of 46 months and platinum resistance rate of 23% in other cases. Associating the outcome prediction model with BRCA1/BRCA2 mutation status, residual disease after surgery, and disease stage further optimized outcome classification. Ovarian cancer is a disease in urgent need of more effective therapies. The spectrum of outcomes observed here and their association with CLOVAR signatures suggests variations in underlying tumor biology. Prospective validation of the CLOVAR model in the context of additional prognostic variables may provide a rationale for optimal combination of patient and treatment regimens. PMID:23257362

  6. Clonal lineage of high grade serous ovarian cancer in a patient with neurofibromatosis type 1

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    Eric J. Norris

    2018-02-01

    Full Text Available Neurofibromatosis type 1 (NF1 is caused by mutations in the NF1 gene encoding neurofibromin, which negatively regulates Ras signaling. NF1 patients have an increased risk of developing early onset breast cancer, however, the association between NF1 and high grade serous ovarian cancer (HGSOC is unclear. Since most NF1-related tumors exhibit early biallelic inactivation of NF1, we evaluated the evolution of genetic alterations in HGSOC in an NF1 patient. Somatic variation analysis of whole exome sequencing of tumor samples from both ovaries and a peritoneal metastasis showed a clonal lineage originating from an ancestral clone within the left adnexa, which exhibited copy number (CN loss of heterozygosity (LOH in the region of chromosome 17 containing TP53, NF1, and BRCA1 and mutation of the other TP53 allele. This event led to biallelic inactivation of NF1 and TP53 and LOH for the BRCA1 germline mutation. Subsequent CN alterations were found in the dominant tumor clone in the left ovary and nearly 100% of tumor at other sites. Neurofibromin modeling studies suggested that the germline NF1 mutation could potentially alter protein function. These results demonstrate early, biallelic inactivation of neurofibromin in HGSOC and highlight the potential of targeting RAS signaling in NF1 patients.

  7. 5-Aminolevulinic acid fluorescence in high grade glioma surgery: surgical outcome, intraoperative findings, and fluorescence patterns.

    Science.gov (United States)

    Della Puppa, Alessandro; Ciccarino, Pietro; Lombardi, Giuseppe; Rolma, Giuseppe; Cecchin, Diego; Rossetto, Marta

    2014-01-01

    5-Aminolevulinic acid (5-ALA) fluorescence is a validated technique for resection of high grade gliomas (HGG); the aim of this study was to evaluate the surgical outcome and the intraoperative findings in a consecutive series of patients. Clinical and surgical data from patients affected by HGG who underwent surgery guided by 5-ALA fluorescence at our Department between June 2011 and February 2014 were retrospectively evaluated. Surgical outcome was evaluated by assessing the resection rate as gross total resection (GTR) > 98% and GTR > 90%. We finally stratified data for recurrent surgery, tumor location, tumor size, and tumor grade (IV versus III grade sec. WHO). 94 patients were finally enrolled. Overall GTR > 98% and GTR > 90% was achieved in 93% and 100% of patients. Extent of resection (GTR > 98%) was dependent on tumor location, tumor grade (P < 0.05), and tumor size (P < 0.05). In 43% of patients the boundaries of fluorescent tissue exceeded those of tumoral tissue detected by neuronavigation, more frequently in larger (57%) (P < 0.01) and recurrent (60%) tumors. 5-ALA fluorescence in HGG surgery enables a GTR in 100% of cases even if selection of patients remains a main bias. Recurrent surgery, and location, size, and tumor grade can predict both the surgical outcome and the intraoperative findings.

  8. 5-Aminolevulinic Acid Fluorescence in High Grade Glioma Surgery: Surgical Outcome, Intraoperative Findings, and Fluorescence Patterns

    Directory of Open Access Journals (Sweden)

    Alessandro Della Puppa

    2014-01-01

    Full Text Available Background. 5-Aminolevulinic acid (5-ALA fluorescence is a validated technique for resection of high grade gliomas (HGG; the aim of this study was to evaluate the surgical outcome and the intraoperative findings in a consecutive series of patients. Methods. Clinical and surgical data from patients affected by HGG who underwent surgery guided by 5-ALA fluorescence at our Department between June 2011 and February 2014 were retrospectively evaluated. Surgical outcome was evaluated by assessing the resection rate as gross total resection (GTR>98% and GTR>90%. We finally stratified data for recurrent surgery, tumor location, tumor size, and tumor grade (IV versus III grade sec. WHO. Results. 94 patients were finally enrolled. Overall GTR>98% and GTR>90% was achieved in 93% and 100% of patients. Extent of resection (GTR>98% was dependent on tumor location, tumor grade (P<0.05, and tumor size (P<0.05. In 43% of patients the boundaries of fluorescent tissue exceeded those of tumoral tissue detected by neuronavigation, more frequently in larger (57% (P<0.01 and recurrent (60% tumors. Conclusions. 5-ALA fluorescence in HGG surgery enables a GTR in 100% of cases even if selection of patients remains a main bias. Recurrent surgery, and location, size, and tumor grade can predict both the surgical outcome and the intraoperative findings.

  9. Management of high-grade bone sarcomas over two decades: The Norwegian Radium Hospital experience

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    Hege Aksnes, Liv; Sundby Hall, Kirsten; Folleraas, Gunnar; Stenwig, Anna Elisabeth; Bjerkehagen, Bodil; Taksdal, Ingeborg; Winderen, Mette; Bruland, Oeyvind Sverre; Saeter, Gunnar [The Norwegian Radium Hospital, Montebello, Oslo (Norway)

    2006-02-15

    All cases of high-grade osteosarcoma (OS) (n=196) and Ewing's sarcoma of bone (ES) (n=56) treated at the Norwegian Radium Hospital in the period 1980-1999 were analyzed retrospectively. They were allocated to consecutive ten-year periods by their time of diagnosis. Patient and tumour characteristics have been relatively stable. Eighty percent of all patients received surgical treatment and the amputation rate decreased from 64% to 23%. The percentage of patients receiving chemotherapy has remained around 80%. The use of radiotherapy in primary treatment decreased gradually from 33% to 18%. Sarcoma specific survival (SSS) at five years for all patients increased significantly from 39% to 53%. Similar trends for improvement were seen for both OS and ES. In multivariate analysis, independent prognostic factors for improved SSS were non-metastatic disease at diagnosis, age under 40, extremity tumours, small tumours and treatment from 1995 onwards. No major new treatment options have emerged over these 20 years. The improved outcome appears partly to be due to refinements in the use of existing modalities and improved quality and integration of multidisciplinary approaches. Improved formalized organisation of the sarcoma group and annual audited reports of its patient and research activity may also have contributed to improved focus and performance.

  10. A New Technique for Preparation of High-Grade Titanium Slag from Titanomagnetite Concentrate by Reduction-Melting-Magnetic Separation Processing

    Science.gov (United States)

    Lv, Chao; Yang, Kun; Wen, Shu-ming; Bai, Shao-jun; Feng, Qi-cheng

    2017-10-01

    This paper proposes a new technique for preparation of high-grade titanium slag from Panzhihua vanadium titanomagnetite concentrate by reduction-melting-magnetic separation processing. Chemical analysis, x-ray diffraction, and scanning electron microscopy in conjunction with energy-dispersive spectroscopy were used to characterize the samples. The effective separation of iron and titanium slag could be realized by melting metallized pellets at 1550°C for 60 min with the addition of 1% CaO (basicity of 1.1) and 2% graphite powder. The small iron particles embedded in the slag could be removed by fine grinding and magnetic separation process. The grade of TiO2 in the obtained high-grade titanium slag reached 60.68% and the total recovery of TiO2 was 91.25%, which could be directly applied for producing titanium white by the sulfuric acid process. This technique provides an alternative method to use vanadium titanomagnetite concentrate of the Panzhihua area in China.

  11. Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume

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    Choi, Yoon Seong; Ahn, Sung Soo; Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, College of Medicine, Seoul (Korea, Republic of); Chang, Jong Hee; Kang, Seok-Gu [Yonsei University College of Medicine, Department of Neurosurgery, Seoul (Korea, Republic of); Kim, Se Hoon [Yonsei University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Zhou, Jinyuan [Johns Hopkins University School of Medicine, Division of MRI Research, Department of Radiology, Baltimore, MD (United States)

    2017-08-15

    To evaluate the added value of amide proton transfer (APT) imaging to the apparent diffusion coefficient (ADC) from diffusion tensor imaging (DTI) and the relative cerebral blood volume (rCBV) from perfusion magnetic resonance imaging (MRI) for discriminating between high- and low-grade gliomas. Forty-six consecutive adult patients with diffuse gliomas who underwent preoperative APT imaging, DTI and perfusion MRI were enrolled. APT signals were compared according to the World Health Organization grade. The diagnostic ability and added value of the APT signal to the ADC and rCBV for discriminating between low- and high-grade gliomas were evaluated using receiver operating characteristic (ROC) analyses and integrated discrimination improvement. The APT signal increased as the glioma grade increased. The discrimination abilities of the APT, ADC and rCBV values were not significantly different. Using both the APT signal and ADC significantly improved discrimination vs. the ADC alone (area under the ROC curve [AUC], 0.888 vs. 0.910; P = 0.007), whereas using both the APT signal and rCBV did not improve discrimination vs. the rCBV alone (AUC, 0.927 vs. 0.923; P = 0.222). APT imaging may be a useful imaging biomarker that adds value to the ADC for discriminating between low- and high-grade gliomas. (orig.)

  12. Spontaneous Remission of an Untreated, MYC and BCL2 Coexpressing, High-Grade B-Cell Lymphoma: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    D. Alan Potts

    2017-01-01

    Full Text Available Non-Hodgkin lymphomas (NHL are a heterogeneous group of hematologic malignancies typically treated with multiagent chemotherapy. Rarely, spontaneous remissions can be observed, particularly in more indolent subtypes. The prognosis of aggressive NHL can be predicted using clinical and histopathologic factors. In aggressive B-cell NHL, the importance of MYC and BCL2 proto-oncogene coexpression (as assessed by immunohistochemistry and high-grade histologic features are particularly noteworthy. We report a unique case of spontaneous remission in a patient with an aggressive B-cell NHL which harbored high-risk histopathologic features, including MYC protein expression at 70–80%, BCL2 protein expression, and morphologic features suggestive of high-grade B-cell lymphoma, NOS (formerly B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma [BCLU]. After undergoing a biopsy to confirm this diagnosis, he opted to forego curative-intent chemotherapy. The single, yet relatively large area of involvement noted on 18F-fluorodeoxyglucose positron emission tomography-computed tomography steadily resolved on subsequent follow-up studies. He remained without evidence of recurrence one year later, having never received treatment. This case emphasizes the potential for spontaneous remission in NHL and demonstrates that this phenomenon can be observed despite contemporary high-risk histopathologic features.

  13. Integrated approach to ecohydrology of semi-arid sites in areas of complex topography and biome transitions

    Science.gov (United States)

    Gutierrez, H. A.; Ivanov, V. Y.; Vivoni, E. R.; Bras, R. L.

    2005-05-01

    Vegetation constitutes an essential link in the hydrologic cycle at the land surface - atmosphere interface. Vegetation exerts a predominant control over the partition of rainfall into soil infiltration and evapotranspiration and determines to a great extent the water budget of entire regions. Conversely, water availability has a strong influence on the vegetation dynamics, including growth rates and overall health. In semiarid areas, changes in vegetation composition can follow slight variations in climate-derived moisture availability that, in turn, have a feedback effect on the surface water and energy balance. In this study, we present an integrated approach for studying the ecohydrology of semiarid regions characterized by complex topography and transitions between different vegetation life forms (grasses, shrubs, trees). We first present a set of hypotheses on the interaction between vegetation, landscape conditions, and climate variability in biome transitions zones. These hypotheses will be tested via the combination of numerical modeling and field data collection in the Sevilleta National Wildlife Refuge, central New Mexico. The field site is a first-order drainage basin consisting of two opposing hillslopes that differentially support a shrub-grass ecosystem and a conifer-grass community. Our modeling approaches consist of an ecohydrological module coupled to a 1-D vadose zone model as well as a more complex 3-D ecohydrological framework capable of simulating full vegetation dynamics at the watershed scale. The field instrumentation and model development efforts will be used synergistically to improve our understanding of the ecohydrology of semiarid complex watersheds. We then present an analysis of the ecohydrological model simulations driven by short- term meteorological data (~10 years) as well as by longer term, synthetically-generated climate scenarios. In particular, we will focus on the response of different vegetation communities to the

  14. Risk factors for anal high-grade squamous intraepithelial lesions in HIV-positive MSM: is targeted screening possible?

    NARCIS (Netherlands)

    Siegenbeek van Heukelom, Matthijs L.; Marra, Elske; de Vries, Henry J. C.; Schim van der Loeff, Maarten F.; Prins, Jan M.

    2017-01-01

    HIV-positive MSM are at increased risk for developing anal squamous cell carcinoma. Detection of precursor lesions of anal cancer [anal high-grade squamous intraepithelial lesions (HSIL)] is cumbersome and expensive. Our objective was to identify potential risk factors for anal HSIL in HIV-positive

  15. Treatment of High-Grade Anal Dysplasia in High Risk Patients: Outcome at an Urban Community Health Center

    Science.gov (United States)

    Assoumou, Sabrina Annick; Panther, Lori Ann; Feng, Yang; Gelman, Rebecca Sue; Fugelso, Dana Kailani; Mayer, Kenneth Hugh

    2013-01-01

    SUMMARY Human immunodeficiency (HIV)-infected patients and men who have sex with men (MSM) have a higher rate of high-grade anal intraepithelial neoplasia (HGAIN), a likely precursor to anal cancer. This retrospective study describes the outcome of treating MSM with incident biopsy-proven HGAIN in an urban community health setting with access to outpatient ablation or operative treatment. The main outcome was freedom from HGAIN at follow-up. 153 met inclusion criteria; 86 (56%) were HIV-infected. Eighty (52%) received outpatient ablation, 49(61%) had a follow-up within 9 months. Among those, 26 (53%) were free of high-grade disease, 19 (39%) had high-grade disease; and 4 (8%) had unknown grading. In a logistic regression model, a lower extent of anal disease (1 quadrant vs. 2,3, or 4 quadrants) was significantly associated with a lower probability of high-grade disease (p-value 0.04.) HGAIN could be managed in a community health setting; however, systems are needed to ensure follow-up care. PMID:23535356

  16. Degree of Student's Assimilation to the Meaning of the Term Citizenships in the Schools High Grade Basic Level in Jordan

    Science.gov (United States)

    Al-Zboon, Mohamed Saleem

    2014-01-01

    This study aimed at identifying the degree of the Assimilation of the meaning of the term "CITIZENSHIP" by the high grade basic level school students in Jordan. The research sample was composed of (1,116) male and female students during the scholastic year 2012/2013. To collect data and then measure results, the standard measurement tool…

  17. MEG network differences between low- and high-grade glioma related to epilepsy and cognition.

    Directory of Open Access Journals (Sweden)

    Edwin van Dellen

    Full Text Available OBJECTIVE: To reveal possible differences in whole brain topology of epileptic glioma patients, being low-grade glioma (LGG and high-grade glioma (HGG patients. We studied functional networks in these patients and compared them to those in epilepsy patients with non-glial lesions (NGL and healthy controls. Finally, we related network characteristics to seizure frequency and cognitive performance within patient groups. METHODS: We constructed functional networks from pre-surgical resting-state magnetoencephalography (MEG recordings of 13 LGG patients, 12 HGG patients, 10 NGL patients, and 36 healthy controls. Normalized clustering coefficient and average shortest path length as well as modular structure and network synchronizability were computed for each group. Cognitive performance was assessed in a subset of 11 LGG and 10 HGG patients. RESULTS: LGG patients showed decreased network synchronizability and decreased global integration compared to healthy controls in the theta frequency range (4-8 Hz, similar to NGL patients. HGG patients' networks did not significantly differ from those in controls. Network characteristics correlated with clinical presentation regarding seizure frequency in LGG patients, and with poorer cognitive performance in both LGG and HGG glioma patients. CONCLUSION: Lesion histology partly determines differences in functional networks in glioma patients suffering from epilepsy. We suggest that differences between LGG and HGG patients' networks are explained by differences in plasticity, guided by the particular lesional growth pattern. Interestingly, decreased synchronizability and decreased global integration in the theta band seem to make LGG and NGL patients more prone to the occurrence of seizures and cognitive decline.

  18. Identification of human papillomavirus type 16 integration sites in high-grade precancerous cervical lesions.

    Science.gov (United States)

    Matovina, Mihaela; Sabol, Ivan; Grubisić, Goran; Gasperov, Nina Milutin; Grce, Magdalena

    2009-04-01

    Infection with oncogenic human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. In many cases of cervical cancer and all cervical cancer derived cell lines oncogenic HPV DNA is found to be integrated, indicating the importance of integration in disease development. In this study, 176 HPV 16 positive precancerous cervical lesions were analyzed for the physical state of viral genome to determine the sites of integration into a host cell DNA and to evaluate the incidence of the integration in different stages of cervical lesions. The detection of integrated papillomavirus sequences (DIPS) method in combination with the amplification by polymerase chain reaction (PCR) of E1/E2 region was used to identify the physical state of HPV 16 genome. The site of integration within a host cell genome was determined by sequencing of unusual sized DIPS amplicons. The combined results of DIPS and E1/E2 PCR revealed the integration of HPV 16 DNA in 7.4% samples. The integration was found only in high grade cervical lesions indicating that it is a late event in disease progression. Sequencing of 11 DIPS amplicons revealed HPV DNA from 6 samples (54.5%) to be integrated in cellular genes (VMP1, PVRL1, CHERP, CEACAM5, AHR, MRF-2) and also 6 (54.5%) within the common fragile sites (CFS). Although, the HPV integration is known to be a random event, this study indicates that HPV 16 integrates more than by chance within or close to CFSs. As most of the genes affected by HPV 16 integration can be linked with some aspects of tumor formation, this indicates that the site of HPV DNA integration might play a role in the rate and the nature of tumor development.

  19. Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis.

    Science.gov (United States)

    Erson-Omay, E Zeynep; Çağlayan, Ahmet Okay; Schultz, Nikolaus; Weinhold, Nils; Omay, S Bülent; Özduman, Koray; Köksal, Yavuz; Li, Jie; Serin Harmancı, Akdes; Clark, Victoria; Carrión-Grant, Geneive; Baranoski, Jacob; Çağlar, Caner; Barak, Tanyeri; Coşkun, Süleyman; Baran, Burçin; Köse, Doğan; Sun, Jia; Bakırcıoğlu, Mehmet; Moliterno Günel, Jennifer; Pamir, M Necmettin; Mishra-Gorur, Ketu; Bilguvar, Kaya; Yasuno, Katsuhito; Vortmeyer, Alexander; Huttner, Anita J; Sander, Chris; Günel, Murat

    2015-10-01

    Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis. We analyzed and compared 720 exome-sequenced gliomas (136 from Yale, 584 from The Cancer Genome Atlas) based on their genomic, histological, and clinical features. We identified a subgroup of HGGs (6 total, 4 adults and 2 children) that harbored a statistically significantly increased number of somatic mutations (mean = 9257.3 vs 76.2, P = .002). All of these "ultramutated" tumors harbored somatic mutations in the exonuclease domain of the polymerase epsilon gene (POLE), displaying a distinctive genetic profile, characterized by genomic stability and increased C-to-A transversions. Histologically, they all harbored multinucleated giant or bizarre cells, some with predominant infiltrating immune cells. One adult and both pediatric patients carried homozygous germline mutations in the mutS homolog 6 (MSH6) gene. In adults, POLE mutations were observed in patients younger than 40 years and were associated with a longer progression-free survival. We identified a genomically, histologically, and clinically distinct subgroup of HGGs that harbored somatic POLE mutations and carried an improved prognosis. Identification of distinctive molecular and pathological HGG phenotypes has implications not only for improved classification but also for potential targeted treatments. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. The role of tandem duplicator phenotype in tumour evolution in high-grade serous ovarian cancer.

    Science.gov (United States)

    Ng, Charlotte K Y; Cooke, Susanna L; Howe, Kevin; Newman, Scott; Xian, Jian; Temple, Jillian; Batty, Elizabeth M; Pole, Jessica C M; Langdon, Simon P; Edwards, Paul A W; Brenton, James D

    2012-04-01

    High-grade serous ovarian carcinoma (HGSOC) is characterized by genomic instability, ubiquitous TP53 loss, and frequent development of platinum resistance. Loss of homologous recombination (HR) is a mutator phenotype present in 50% of HGSOCs and confers hypersensitivity to platinum treatment. We asked which other mutator phenotypes are present in HGSOC and how they drive the emergence of platinum resistance. We performed whole-genome paired-end sequencing on a model of two HGSOC cases, each consisting of a pair of cell lines established before and after clinical resistance emerged, to describe their structural variants (SVs) and to infer their ancestral genomes as the SVs present within each pair. The first case (PEO1/PEO4), with HR deficiency, acquired translocations and small deletions through its early evolution, but a revertant BRCA2 mutation restoring HR function in the resistant lineage re-stabilized its genome and reduced platinum sensitivity. The second case (PEO14/PEO23) had 216 tandem duplications and did not show evidence of HR or mismatch repair deficiency. By comparing the cell lines to the tissues from which they originated, we showed that the tandem duplicator mutator phenotype arose early in progression in vivo and persisted throughout evolution in vivo and in vitro, which may have enabled continual evolution. From the analysis of SNP array data from 454 HGSOC cases in The Cancer Genome Atlas series, we estimate that 12.8% of cases show patterns of aberrations similar to the tandem duplicator, and this phenotype is mutually exclusive with BRCA1/2 carrier mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  1. Prognostic impact of ReTURB in high grade T1 primary bladder cancer

    Directory of Open Access Journals (Sweden)

    Roberto Sanseverino

    2016-07-01

    Full Text Available Purpose: To evaluate whether pathological outcomes of ReTURB have a prognostic impact on recurrence and progression of primitive T1HG bladder cancer. Material and methods: Patients affected by primitive T1HG TCC of bladder underwent restaging TURB (ReTURB. Patients with muscle invasive disease at ReTURB underwent radical cystectomy; those with non-muscle invasive residual (NMI-RT and those with no residual tumour (NRT received an intravesical BCG therapy. We compared recurrence and progression in NMIRT patients and NRT patients at restaging TURB. Patients were followed every 3-6 months with cystoscopy and urine cytology. Results: 212 patients were enrolled in the study. At ReTURB, residual cancer was detected in 92 of 196 (46.9% valuable patients: 14.3% of these were upstaged to T2. At follow up of 26.3 ± 22.8 months, there were differences in recurrence and progression rates between NRT and NMIRT patients: 26.9% and 45.3% (p < 0.001, 10.6% and 23.4% (p 0.03, respectively. Recurrence-free and progression-free survivals were significantly higher in NRT compared to NMIRT patients: 73.1% and 54.7% (p < 0.001, 89.4% and 76.6 (p 0.03, respectively. Conclusions: ReTURB allows to identify a considerable number of residual and understaged cancer. Patients with NMIRT on ReTURB have worse prognosis than those with NRT in terms of recurrence and progression free survival. These outcomes seem to suggest a prognostic impact of findings on ReTURB that could be a valid tool in management of high grade T1 TCC.

  2. Differentiation of intracranial tuberculomas and high grade gliomas using proton MR spectroscopy and diffusion MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Juan, E-mail: pengjuan1209@126.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Ouyang, Yu, E-mail: 1957ouyangyu@sina.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Fang, Wei-Dong, E-mail: fwd9707@yahoo.com.cn [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Luo, Tian-You, E-mail: ltychy@sina.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Li, Yong-Mei, E-mail: lymzhang70@yahoo.com.cn [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Lv, Fa-Jin, E-mail: fajinlv@hotmail.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Zhang, Zhi-Wei, E-mail: jintianzzw@163.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Li, Xin-You, E-mail: lixinyou666@163.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China)

    2012-12-15

    Objective: The purpose of this study was to determine whether proton MR spectroscopy ({sup 1}H MRS) and diffusion-weighted (DW) imaging can be used to differentiate intracranial tuberculomas from high grade gliomas (HGGs). Materials and methods: A total of 41 patients (19 with intracranial tuberculomas and 22 with HGGs) were examined in our study. {sup 1}H MRS and DW imaging were performed at a 1.5T MR scanner before operation or treatment. Concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lipid and lactate (LL) in the contrast-enhancing rim of each lesion were expressed as metabolite ratios and were normalized to the contralateral hemisphere. The apparent diffusion coefficient (ADC) was also calculated. The metabolite ratios and ADC values in the enhancing rim of intracranial tuberculomas and HGGs were compared using the Wilcoxon rank sum test. Diagnostic accuracy was compared using receiver operating characteristic (ROC) analysis. Results: Significant differences were found in the maximum Cho/Cr (P = 0.015), Cho/NAA (P = 0.001) and Cho/Cho-n ratios (P = 0.002), and minimum ADC value (P < 0.001) between the intracranial tuberculomas and HGGs. Diagnostic accuracy was higher by minimum ADC value than maximum Cho/Cr, Cho/NAA and Cho/Cho-n ratios (93.8% versus 75.7%, 80.8% and 78.1%). Conclusion: These results suggest a promising role for {sup 1}H MRS and DW imaging in the differentiation between the intracranial tuberculomas and HGGs.

  3. The challenges of management of high-grade gliomas in Nigeria

    Directory of Open Access Journals (Sweden)

    Chika Anele Ndubuisi

    2017-01-01

    Full Text Available Background: High-grade gliomas (HGG are among the most challenging brain tumors despite many research efforts worldwide. Aim: The aim of this study was to evaluate the local challenges that may influence outcome of HGG managed in a neurosurgical center in Nigeria. Methodology: Retrospective analysis of prospectively recorded data of patients managed for intracranial HGG at Memfys Hospital for Neurosurgery, Enugu, Nigeria, between the year 2006 and 2015. Only cases with conclusive histology following surgery were analyzed. Results: Glioma was 60 (23.8% of 252 histology confirmed brain tumors. HGG represented 53.8% of gliomas with male:female ratio of 2.2:1.0 and peaked from fifth decade of life. Glioblastoma multiforme accounted for 69% of HGG. At 1-year postsurgery, 53% of HGGs were dead and 88% of these deaths were in the World Health Organization Grade IV group. Only 40% of cases could receive adjuvant treatment with only 15% mortality at 1 year in this subgroup that received adjuvant therapy. In addition, 19% of cases had surgery at Karnofsky score (Ks of ≥70%. However, 94% of mortality at 1 year was related to surgery at Ks of ≤60%. Only four patients had a tumor volume of ≤50 cm3, and among these cases, three patients were independent at 1 year. Patients with tumor volume above 50 cm3 accounted for 94% of mortality. Conclusion: The peak age incidence for HGG seems to be lower than in Caucasians. Most cases present late with poor Ks and big tumor volume. The proportion with access to adjuvant treatment is still poor. Preoperative Karnofsky, extent of resection, duration of hospital, and Intensive Care Unit stay have impact on outcome.

  4. Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling.

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    Bashashati, Ali; Ha, Gavin; Tone, Alicia; Ding, Jiarui; Prentice, Leah M; Roth, Andrew; Rosner, Jamie; Shumansky, Karey; Kalloger, Steve; Senz, Janine; Yang, Winnie; McConechy, Melissa; Melnyk, Nataliya; Anglesio, Michael; Luk, Margaret T Y; Tse, Kane; Zeng, Thomas; Moore, Richard; Zhao, Yongjun; Marra, Marco A; Gilks, Blake; Yip, Stephen; Huntsman, David G; McAlpine, Jessica N; Shah, Sohrab P

    2013-09-01

    High-grade serous ovarian cancer (HGSC) is characterized by poor outcome, often attributed to the emergence of treatment-resistant subclones. We sought to measure the degree of genomic diversity within primary, untreated HGSCs to examine the natural state of tumour evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on 31 spatially and temporally separated HGSC tumour specimens (six patients), including ovarian masses, distant metastases and fallopian tube lesions. We found widespread intratumoural variation in mutation, copy number and gene expression profiles, with key driver alterations in genes present in only a subset of samples (eg PIK3CA, CTNNB1, NF1). On average, only 51.5% of mutations were present in every sample of a given case (range 10.2-91.4%), with TP53 as the only somatic mutation consistently present in all samples. Complex segmental aneuploidies, such as whole-genome doubling, were present in a subset of samples from the same individual, with divergent copy number changes segregating independently of point mutation acquisition. Reconstruction of evolutionary histories showed one patient with mixed HGSC and endometrioid histology, with common aetiologic origin in the fallopian tube and subsequent selection of different driver mutations in the histologically distinct samples. In this patient, we observed mixed cell populations in the early fallopian tube lesion, indicating that diversity arises at early stages of tumourigenesis. Our results revealed that HGSCs exhibit highly individual evolutionary trajectories and diverse genomic tapestries prior to therapy, exposing an essential biological characteristic to inform future design of personalized therapeutic solutions and investigation of drug-resistance mechanisms. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  5. Genetic heterogeneity after first-line chemotherapy in high-grade serous ovarian cancer.

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    Lambrechts, Sandrina; Smeets, Dominiek; Moisse, Matthieu; Braicu, Elena Ioana; Vanderstichele, Adriaan; Zhao, Hui; Van Nieuwenhuysen, Els; Berns, Els; Sehouli, Jalid; Zeillinger, Robert; Darb-Esfahani, Silvia; Cacsire Castillo-Tong, Dan; Lambrechts, Diether; Vergote, Ignace

    2016-01-01

    Most high-grade serous ovarian carcinoma (HGSOC) patients benefit from first-line platinum-based chemotherapy, but progressively develop resistance during subsequent lines. Re-activating BRCA1 or MDR1 mutations can underlie platinum resistance in end-stage patients. However, little is known about resistance mechanisms occurring after a single line of platinum, when patients still qualify for other treatments. In 31 patients with primary platinum-sensitive HGSOC, we profiled tumours collected during debulking surgery before and after first-line chemotherapy using whole-exome sequencing and single nucleotide polymorphism profiling. Besides germline BRCA1/2 mutations, we observed frequent loss-of-heterozygosity in homologous recombination (HR) genes and mutation spectra characteristic of HR-deficiency in all tumours. At relapse, tumours differed considerably from their primary counterparts. There was, however, no evidence of events reactivating the HR pathway, also not in tumours resistant to second-line platinum. Instead, a platinum score of 13 copy number regions, among other genes including MECOM, CCNE1 and ERBB2, correlated with platinum-free interval (PFI) after first-line therapy, whereas an increase of this score in recurrent tumours predicted the change in PFI during subsequent therapy. Already after a single line of platinum, there is huge variability between primary and recurrent tumours, advocating that in HGSOC biopsies need to be collected at relapse to tailor treatment options to the underlying genetic profile. Nevertheless, all primary platinum-sensitive HGSOCs remained HR-deficient, irrespective of whether they became resistant to second-line platinum, further suggesting these tumours qualify for second-line Poly APD ribose polymerase (PARP) inhibitor treatment. Finally, chromosomal instability contributes to acquired resistance after a single line of platinum therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. The prognostic value of IDH mutations and MGMT promoter status in secondary high-grade gliomas.

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    Juratli, T A; Kirsch, M; Geiger, K; Klink, B; Leipnitz, E; Pinzer, T; Soucek, S; Schrock, E; Schrok, E; Schackert, G; Krex, D

    2012-12-01

    Reports about the prognostic value of IDH mutations and the promoter region of the O6-Methyl-guanyl-methyl-transferase gene in secondary high-grade gliomas (sHGG) are few in number. We investigated the prognostic value of IDH mutations and methylation of the promoter region of the MGMT gene in 99 patients with sHGG and analyzed the clinical course of those tumors. Patients with sHGG were screened for IDH mutations by direct sequencing, and, for promoter status of MGMT gene, by the methylation-specific polymerase chain reaction. A total of 48 of 99 patients (48.5 %) had secondary anaplastic gliomas (Group 1), while 51 patients had secondary glioblastomas (Group 2). The median survival time after malignant progression of all patients with sHGG and with an IDH mutation was 4 years, which is significantly longer than in patients with wild-type IDH (1.2 years, p = 0.009). Patients' survival was not significantly influenced by the tumors' MGMT promoter status, both in Group 1- 9.7 years vs. 6.1 years, methylated vs. unmethylated promoter (p = 0.330)-as well as in Group 2-1.5 years vs. 1.6 years, methylated versus unmethylated promoter (p = 0.829). In our population, the IDH mutation status was not associated with increased PFS or median survival time in sGBM patients. However, patients with secondary anaplastic glioma and IDH mutation had a significantly improved outcome. In addition, IDH mutations are a more powerful prognostic marker concerning both PFS and MS than the MGMT promoter status in those patients.

  7. Successful Management of Intraoperative Acute Bilateral Pulmonary Embolism in a High Grade Astrocytoma Patient.

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    Khraise, Wail N; Allouh, Mohammed Z; Hiasat, Mohammad Y; Said, Raed S

    2016-08-31

    BACKGROUND Intraoperative pulmonary embolism (PE) is a rare life-threatening complication in patients undergoing surgical intervention. Generally, cancer patients have a higher risk for developing this complication. Unfortunately, there is no standard procedure for its management. CASE REPORT We report the case of a 39-year-old woman with high-grade glioma in the right frontal lobe who was admitted to the surgical theater for craniotomy and excision of the tumor. During the general anesthesia procedure and just before inserting the central venous line, her end-tidal CO2 and O2 saturation dropped sharply. The anesthesiologist quickly responded with an aggressive resuscitation procedure that included aspiration through the central venous line, 100% O2, and IV administration of ephedrine 6 mg, colloid 500 mL, normal saline 500 mL, and heparin 5000 IU. The patient was extubated and remained in the supine position until she regained consciousness and her vital signs returned to normal. Subsequent radiological examination revealed a massive bilateral PE. A retrievable inferior vena cava (IVC) filter was inserted, and enoxaparin anticoagulant therapy was prescribed to stabilize the patient's condition. After 3 weeks, she underwent an uneventful craniotomy procedure and was discharged a week later under the enoxaparin therapy. CONCLUSIONS The successful management of intraoperative PE requires a quick, accurate diagnosis accompanied with an aggressive, fast response. Anesthesiologists are usually the ones who are held accountable for the diagnosis and early management of this complication. They must be aware of the possibility of such a complication and be ready to react properly and decisively in the operation theater.

  8. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation treatment of recurrent high-grade gliomas.

    Science.gov (United States)

    Clavo, Bernardino; Robaina, Francisco; Jorge, Ignacio J; Cabrera, Raquel; Ruiz-Egea, Eugenio; Szolna, Adam; Otermin, Emilio; Llontop, Pedro; Carames, Miguel A; Santana-Rodríguez, Norberto; Sminia, Peter

    2014-11-01

    Relapsed high-grade gliomas (HGGs) have poor prognoses and there is no standard treatment. HGGs have ischemia/hypoxia associated and, as such, drugs and oxygen have low access, with increased resistance to chemotherapy and radiotherapy. Tumor hypoxia modification can improve outcomes and overall survival in some patients with these tumors. In previous works, we have described that cervical spinal cord stimulation can modify tumor microenvironment in HGG by increasing tumor blood flow, oxygenation, and metabolism. The aim of this current, preliminary, nonrandomized, study was to assess the clinical effect of spinal cord stimulation during brain reirradiation and chemotherapy deployed for the treatment of recurrent HGG; the hypothesis being that an improvement in oxygenated blood supply would facilitate enhanced delivery of the scheduled therapy. Seven patients had spinal cord stimulation applied during the scheduled reirradiation and chemotherapy for the treatment of recurrent HGG (6 anaplastic gliomas and 1 glioblastoma). Median dose of previous irradiation was 60 Gy (range = 56-72 Gy) and median dose of reirradiation was 46 Gy (range = 40-46 Gy). Primary end point of the study was overall survival (OS) following confirmation of HGG relapse. From the time of diagnosis of last tumor relapse before reirradiation, median OS was 39 months (95% CI = 0-93) for the overall study group: 39 months (95% CI = 9-69) for those with anaplastic gliomas and 16 months for the patient with glioblastoma. Posttreatment, doses of corticosteroids was significantly decreased (P = .026) and performance status significantly improved (P = .046). Spinal cord stimulation during reirradiation and chemotherapy is feasible and well tolerated. In our study, spinal cord stimulation was associated with clinical improvement and longer survival than previously reported in recurrent anaplastic gliomas. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation in relapsed HGGs merits

  9. Digital PCR quantification of SERPINA1 predicts prognosis in high-grade glioma.

    Science.gov (United States)

    Ookawa, Satoshi; Wanibuchi, Masahiko; Kataoka-Sasaki, Yuko; Sasaki, Masanori; Oka, Shinichi; Ohtaki, Shunya; Noshiro, Shouhei; Komatsu, Katsuya; Akiyama, Yukinori; Mikami, Takeshi; Mikuni, Nobuhiro; Kocsis, Jeffery D; Honmou, Osamu

    2018-01-05

    SERPINA1 plays an anti-inflammatory role in protecting tissues from proteolytic mechanisms. SERPINA1 is positive in gliomas by immunohistochemical analysis; however, the role of SERPINA1 including the relationship with prognosis has been uncertain. In recent years, digital polymerase chain reaction (PCR) has provided ultra-sensitive assessment of mRNA expression from formalin fixed paraffin embedded (FFPE) tissues. In this study, we quantitatively determined the expression of SERPINA1 in high-grade gliomas (HGGs) using digital PCR and analyzed its relationship with prognosis. A total of 29 FFPE surgical samples from patients with HGGs (7 of World Health Organization [WHO] grade III and 22 of WHO grade IV), and human glioblastoma cell lines, U87 and U118, were used for analysis. A qualitative assessment using immunostaining and quantitative assessment using digital PCR were performed to assess the expression of SERPINA1. The expression of SERPINA1 was demonstrated in glioma tissues and GBM cell lines by immunostaining. Digital PCR analysis showed that SERPINA1 was expressed in 14.3% and 63.6% of the tissues from patients with grade III and grade IV HGG, respectively (p = 0.035). The median overall survival of 38.8 months in the low SERPINA1 expression group was longer than that of 15.3 months in the high expression group (p = 0.030). The frequency and the amount of SERPINA1 expression were higher in grade IV than in grade III HGGs. The high expression of SERPINA1 indicates a poor prognosis of HGGs. Copyright © 2018. Published by Elsevier Inc.

  10. Tumour and surgery effects on cognitive functioning in high-grade glioma patients.

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    Habets, Esther J J; Kloet, Alfred; Walchenbach, Rob; Vecht, Charles J; Klein, Martin; Taphoorn, Martin J B

    2014-08-01

    Many high-grade glioma (HGG) patients have cognitive impairments, which impact daily functioning. Cognitive impairments can be caused by tumour-, treatment-, and patient-related factors. The effect of the tumour and of surgical resection on cognition is, however, not well known. We investigated tumour and surgical effects on cognitive functioning in patients with HGG. At baseline, preceding surgery, 62 patients with HGG underwent neuropsychological testing concerning seven cognitive domains: verbal and working memory, attention, executive functioning, psychomotor function, information processing speed, and visuoconstructive abilities. Thirty-nine patients were included in follow-up testing after surgery, but before subsequent treatment. Tumour size and site, use of anti-epileptic drugs and corticosteroids, and extent of resection were recorded. Compared to healthy controls, cognitive functioning of patients was significantly impaired in all domains. Prior to surgery 79 % (49 of 62) of patients had cognitive impairment in at least one domain. At median follow-up of 5 weeks after surgery, 59 % (23 of 39) of patients were cognitively impaired in at least one domain. At follow-up, 49 % showed improvement, while 23 % declined. Left hemisphere tumour localization was associated with worse verbal memory (P=0.004), and larger tumours in this hemisphere with poorer executive functioning (P < 0.001). Changes in cognitive performance at follow-up relative to baseline were not related to tumour characteristics or extent of resection. Tumour-related cognitive deficits are present in a majority of HGG patients preceding surgery. Surgery does not result in cognitive deterioration in the short term in most patients.

  11. Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread.

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    Bachmayr-Heyda, Anna; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Deycmar, Simon; Reiner, Agnes T; Polterauer, Stephan; Dekan, Sabine; Pils, Dietmar

    2016-06-28

    High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors.23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed.Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer.

  12. Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors.

    Science.gov (United States)

    Sharma, Vikas; Purkait, Suvendu; Takkar, Sonam; Malgulwar, Prit Benny; Kumar, Anupam; Pathak, Pankaj; Suri, Vaishali; Sharma, Mehar C; Suri, Ashish; Kale, Shashank Sharad; Kulshreshtha, Ritu; Sarkar, Chitra

    2016-04-01

    Enhancer of Zeste homologue2 (EZH2) is an epigenetic regulator that functions as oncogene in astrocytic tumors, however, EZH2 regulation remains little studied. In this study, we measured EZH2 levels in low (Gr-II,DA) and high grade (Gr-IV,GBM) astrocytic tumors and found significant increased EZH2 transcript level with grade(median DA-8.5, GBM-28.9).However, a different trend was reflected in protein levels, with GBMs showing high EZH2 LI(median-26.5) compared to DA (median 0.3). This difference in correlation of EZH2 protein and RNA levels suggested post-transcriptional regulation of EZH2, likely mediated by miRNAs. We selected eleven miRNAs that strongly predicted to target EZH2 and measured their expression. Three miRNAs (miR-26a-5p,miR27a-3p and miR-498) showed significant correlation with EZH2 protein, suggesting them as regulators of EZH2, however miR-26a-5p levels decreased with grade. ChIP analyses revealed H3K27me3 modifications in miR-26a promoter suggesting feedback loop between EZH2 and miR26a. We further measured six downstream miRNA targets of EZH2 and found significant downregulation of four (miR-181a/b and 200b/c) in GBM. Interestingly, EZH2 associated miRNAs were predicted to target 25 genes in glioma-pathway, suggesting their role in tumor formation or progression. Collectively, our work suggests EZH2 and its miRNA interactors may serve as promising biomarkers for progression of astrocytic tumors and may offer novel therapeutic strategies.

  13. Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

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    Zhang, Hui; Liu, Tao; Zhang, Zhen; Payne, Samuel H.; Zhang, Bai; McDermott, Jason E.; Zhou, Jian-Ying; Petyuk, Vladislav A.; Chen, Li; Ray, Debjit; Sun, Shisheng; Yang, Feng; Chen, Lijun; Wang, Jing; Shah, Punit; Cha, Seong Won; Aiyetan, Paul; Woo, Sunghee; Tian, Yuan; Gritsenko, Marina A.; Clauss, Therese R.; Choi, Caitlin; Monroe, Matthew E.; Thomas, Stefani; Nie, Song; Wu, Chaochao; Moore, Ronald J.; Yu, Kun-Hsing; Tabb, David L.; Fenyö, David; Bafna, Vineet; Wang, Yue; Rodriguez, Henry; Boja, Emily S.; Hiltke, Tara; Rivers, Robert C.; Sokoll, Lori; Zhu, Heng; Shih, Ie-Ming; Cope, Leslie; Pandey, Akhilesh; Zhang, Bing; Snyder, Michael P.; Levine, Douglas A.; Smith, Richard D.; Chan, Daniel W.; Rodland, Karin D.

    2016-07-01

    Ovarian cancer remains the most lethal gynecological malignancy in the developed world, despite recent advances in genomic information and treatment. To better understand this disease, define an integrated proteogenomic landscape, and identify factors associated with homologous repair deficiency (HRD) and overall survival, we performed a comprehensive proteomic characterization of ovarian high-grade serous carcinomas (HGSC) previously characterized by The Cancer Genome Atlas (TCGA). We observed that messenger RNA transcript abundance did not reliably predict abundance for 10,030 proteins across 174 tumors. Clustering of tumors based on protein abundance identified five subtypes, two of which correlated robustly with mesenchymal and proliferative subtypes, while tumors characterized as immunoreactive or differentiated at the transcript level were intermixed at the protein level. At the genome level, HGSC is characterized by a complex landscape of somatic copy number alterations (CNA), which individually do not correlate significantly with survival. Correlation of CNAs with protein abundances identified loci with significant trans regulatory effects mapping to pathways associated with proliferation, cell motility/invasion, and immune regulation, three known hallmarks of cancer. Using the trans regulated proteins we also created models significantly correlated with patient survival by multivariate analysis. Integrating protein abundance with specific post-translational modification data identified subnetworks correlated with HRD status; specifically, acetylation of Lys12 and Lys16 on histone H4 was associated with HRD status. Using quantitative phosphoproteomics data covering 4,420 proteins as reflective of pathway activity, we identified the PDGFR and VEGFR signaling pathways as significantly up-regulated in patients with short overall survival, independent of PDGFR and VEGFR protein levels, potentially informing the use of anti-angiogenic therapies. Components of

  14. Transcriptional consequence and impaired gametogenesis with high-grade aneuploidy in Arabidopsis thaliana.

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    Kuan-Lin Lo

    Full Text Available Aneuploidy features a numerical chromosome variant that the number of chromosomes in the nucleus of a cell is not an exact multiple of the haploid number, which may have an impact on morphology and gene expression. Here we report a tertiary trisomy uncovered by characterizing a T-DNA insertion mutant (aur2-1/+ in the Arabidopsis (Arabidopsis thaliana AURORA2 locus. Whole-genome analysis with DNA tiling arrays revealed a chromosomal translocation linked to the aur2-1 allele, which collectively accounted for a tertiary trisomy 2. Morphologic, cytogenetic and genetic analyses of aur2-1 progeny showed impaired male and female gametogenesis to various degrees and a tight association of the aur2-1 allele with the tertiary trisomy that was preferentially inherited. Transcriptome analysis showed overlapping and distinct gene expression profiles between primary and tertiary trisomy 2 plants, particularly genes involved in response to stress and various types of external and internal stimuli. Additionally, transcriptome and gene ontology analyses revealed an overrepresentation of nuclear-encoded organelle-related genes functionally involved in plastids, mitochondria and peroxisomes that were differentially expressed in at least three if not all Arabidopsis trisomics. These observations support a previous hypothesis that aneuploid cells have higher energy requirement to overcome the detrimental effects of an unbalanced genome. Moreover, our findings extend the knowledge of the complex nature of the T-DNA insertion event influencing plant genomic integrity by creating high-grade trisomy. Finally, gene expression profiling results provide useful information for future research to compare primary and tertiary trisomics for the effects of aneuploidy on plant cell physiology.

  15. Low-Dose-Rate Definitive Brachytherapy for High-Grade Vaginal Intraepithelial Neoplasia

    Science.gov (United States)

    Monnier, Laurie; Dumas, Isabelle; Morice, Philippe; Pautier, Patricia; Duvillard, Pierre; Azoury, Fares; Mazeron, Renaud; Haie-Meder, Christine

    2011-01-01

    Background. Treatment of high-grade vaginal intraepithelial neoplasia (VAIN) is controversial and could include surgical excision, topical medication, brachytherapy, or other treatments. We report the results of low-dose-rate (LDR) vaginal brachytherapy for grade 3 VAIN (VAIN-3) over a 25-year period at Gustave Roussy Institute. Patients and Methods. We retrospectively reviewed the files of all patients treated at Gustave Roussy Institute for VAIN-3 since 1985. The treatment consisted of LDR brachytherapy using a personalized vaginal mold and delivered 60 Gy to 5 mm below the vaginal mucosa. All patients had at least an annual gynecological examination, including a vaginal smear. Results. Twenty-eight patients were eligible. The median follow-up was 41 months. Seven patients had a follow-up brachytherapy was 63 years (range, 38–80 years). Twenty-six patients had a history of VAIN recurring after cervical intraepithelial neoplasia and 24 had a previous hysterectomy. The median brachytherapy duration was 4.5 days. Median doses to the International Commission of Radiation Units and Measurements rectum and bladder points were 68 Gy and 45 Gy, respectively. The median prescription volume (60 Gy) was 74 cm3. Only one “in field” recurrence occurred, corresponding to a 5- and 10-year local control rate of 93% (95% confidence interval, 70%–99%). The treatment was well tolerated, with no grade 3 or 4 late toxicity and only one grade 2 digestive toxicity. No second cancers were reported. Conclusion. LDR brachytherapy is an effective and safe treatment for vaginal intraepithelial neoplasia. PMID:21262875

  16. Surgery of high grade gliomas - pros in favor of maximal cytoreductive surgery

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    C. Abrudan

    2011-03-01

    Full Text Available Background: Malignant glioma is themost common primary brain tumour inadults. More and more studies are focusedon the role of surgery in prolonged medianof survival and survival at two years. Thepurpose of this study is to add somearguments in favour of radical surgery inmalignant glioma.Material and Methods: The study is based433 cases of high grade cerebral gliomaoperated between 01.01.2000-31.12.2009 atthe Department of Neurosurgery, ClujCounty Emergency Hospital. We analyzedage, gender, type and duration ofsymptoms, type of surgery, pathologicaldiagnosis and the correlation of thesefactors with overall survival. Data for longterm follow up were available for 266patients.Results: The results shows, according totheir histological features, the fallowingdispersions: astrocitomas grade III (28%,glioblastoma multiforme (64%, high gradeoligodendrogliomas (5% and high gradeependimomas (3%. The global survivalrate was 47 % at 12 months, 26,3% at 18months and 16,7% at 24 months. The ageand type of surgery are prognostic factorsthat significantly influenced the survival at12, 18 and 24 months (9,3 months age 65 years; 9,2months GTR versus 6,4 months STR-at 12months monitoring; 11,7 months age 65; 11,5 monthsGTR versus 7,1 months STR-at 18 monthsmonitoring; 12,8 months age 65; 12,6 months GTR versus7,5 months STR –at 24 monthsmonitoring.Conclusions: Our study shows that longterm postoperative outcome after radicalsurgical resection are better than the resultsof either partial resection or simple biopsy;in terms of duration of survival (thedifference of mean survival at 12, 18 and 24months monitoring was 2,8 months, 4,4months and 5,1 months respectively infavour of patients with gross total removal .

  17. Cytology and human papillomavirus co-test results preceding incident high-grade cervical intraepithelial neoplasia.

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    Ina U Park

    Full Text Available High-risk HPV (hrHPV and cytology co-testing is utilized for primary cervical cancer screening and for enhanced follow-up of women who are hrHPV-positive, cytology negative. However, data are lacking on the utility of this method to detect pre-cancer or cancer in community-based clinical practice. This study describes cytology and hrHPV results preceding high-grade cervical intraepithelial neoplasia, adenocarcinoma in situ, or cervical cancer (i.e., CIN2+ in an integrated health system employing routine co-testing among women aged 30 years and older.We conducted a cross-sectional analysis of adult female members of Kaiser Permanente Northern California (KPNC with incident CIN2+ between July 2008 and June 2009. The primary outcome was the proportions of cytologic diagnoses and hrHPV co-test results preceding a diagnosis of CIN2+. Cervical cytology and hrHPV testing results were abstracted from electronic medical records.Of 1283 CIN2+ cases among adult women, 880 (68.5% were among women aged 30 years and older and 145/880 (16.5%, 95% CI 14.1-19.1 had only normal cytology during the 12 months prior to diagnosis. Furthermore, 133/880 (15.1%, 95% 12.9-17.7 were preceded by only normal cytology and persistent hrHPV infection (at least 2 positive hrHPV tests during the 6-36 months preceding CIN2+ diagnosis.Incident CIN2+ is frequently preceded by normal cytology and persistent hrHPV infection among women aged 30 years and older; screening strategies that employ HPV testing and cytology may improve the detection of CIN2+ compared with cytology alone.

  18. Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis.

    Science.gov (United States)

    Figarella-Branger, Dominique; Mokhtari, Karima; Colin, Carole; Uro-Coste, Emmanuelle; Jouvet, Anne; Dehais, Caroline; Carpentier, Catherine; Villa, Chiara; Maurage, Claude-Alain; Eimer, Sandrine; Polivka, Marc; Vignaud, Jean-Michel; Laquerriere, Annie; Sevestre, Henri; Lechapt-Zalcman, Emmanuelle; Quintin-Roué, Isabelle; Aubriot-Lorton, Marie-Hélène; Diebold, Marie-Danièle; Viennet, Gabriel; Adam, Clovis; Loussouarn, Delphine; Michalak, Sophie; Rigau, Valérie; Heitzmann, Anne; Vandenbos, Fanny; Forest, Fabien; Chiforeanu, Danchristian; Tortel, Marie-Claire; Labrousse, François; Chenard, Marie-Pierre; Nguyen, Anh Tuan; Varlet, Pascale; Kemeny, Jean Louis; Levillain, Pierre-Marie; Cazals-Hatem, Dominique; Richard, Pomone; Delattre, Jean-Yves

    2015-07-01

    Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO. © 2014 International Society of Neuropathology.

  19. Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma

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    Karunamuni, Roshan [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Bartsch, Hauke; White, Nathan S. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Moiseenko, Vitali; Carmona, Ruben; Marshall, Deborah C.; Seibert, Tyler M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McDonald, Carrie R. [Department of Psychiatry, University of California San Diego, La Jolla, California (United States); Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua [Department of Radiology, University of California San Diego, La Jolla, California (United States); Mell, Loren [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Brewer, James B.; Dale, Anders M. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2016-02-01

    Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thickness between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.

  20. Microstructures, textures and geothermometry of graphitic carbon in low- to high-grade mylonites

    Science.gov (United States)

    Cao, Shuyun; Neubauer, Franz; Lv, Meixia; Li, Junyu; Dong, Yanlong

    2017-04-01

    Graphitization differs from most mineral transformations occurring during diagenesis and metamorphism in that is an irreversible process. Graphitic carbon exhibits a large range of structures and chemical compositions, ranging from amorphous-like compounds (e.g. soot, low-grade coal), through a myriad of turbostratic structures (e.g. carbonaceous materials in metamorphic rocks), to rather rare crystalline flaky graphite. Graphitic material has a number of properties and the most significant one is the structural change of the graphitic materials with increase of temperature in the fault zones as well as in very low-grade to high-grade metamorphic terrains. During metamorphic processes, organic matter is progressively transformed into graphite and the degree of maturation or graphitization of graphitic materials is a potential tool, therefore, considered as a reliable indicator of peak conditions of the metamorphic grade in metamorphic petrology. In mylonites and brittle fault zones, graphitic material is rheologically very weak, a phenomenon, which results in shear concentration along zones rich in graphitic material. The characteristics and metamorphic peak conditions of graphitic material-bearing mylonites from fault zones are studied using optical microscopy, SEM, Electron Back-Scattered Diffraction (EBSD) and Raman microspectroscopy and carbon isotopic analysis. The graphite grains are distributed parallel to the mylonitic foliation and present coarse to very fine-grained microstructures. The deformation includes dislocation glide. The deformed graphite lattice-preferred orientation by EBSD measured records presents intracrystalline slip system, which is easy in the direction of the -axes and, in fact, nearly in any direction within the basal planes. The thermometry of graphitic material by Raman spectroscopy was calibrated for the temperature range from 360 to 650 °C. These structural analyses of graphitic material in mylonitic rocks allow unraveling the

  1. Arthroscopically assisted stabilization of acute high-grade acromioclavicular joint separations.

    Science.gov (United States)

    Scheibel, Markus; Dröschel, Silvia; Gerhardt, Christian; Kraus, Natascha

    2011-07-01

    The purpose of this study was to evaluate the clinical and radiological results after arthroscopically assisted and image intensifier--controlled stabilization of high-grade acromioclavicular (AC) joint separations using the double TightRope technique with the first-generation implant. The double TightRope technique using the first-generation implant leads to good clinical and radiological results by re-creating the anatomy of the AC joint. Case series; Level of evidence, 4. Thirty-seven consecutive patients (4 women and 33 men; mean age, 38.6 years) who sustained an acute AC joint dislocation grade V according to Rockwood were included in this prospective study. The Subjective Shoulder Value (SSV), the Constant Score (CS), the Taft Score (TS), and a newly developed Acromioclavicular Joint Instability Score (ACJI) were used for final follow-up. Bilateral stress views and bilateral Alexander views were taken to evaluate radiographic signs of recurrent vertical and horizontal AC joint instability. Twenty-eight patients (2 women and 26 men; mean age, 38.8 years [range, 18-66 years]) could be evaluated after a mean follow-up of 26.5 months (range, 20.1-32.8 months). The interval from trauma to surgery averaged 7.3 days (range, 0-18 days). The mean SSV reached 95.1% (range, 85%-100%), the mean CS was 91.5 points (range, 84-100) (contralateral side: mean, 92.6 points), the mean TS was 10.5 points (range, 7-12), and the ACJI averaged 79.9 points (range, 45-100). The final coracoclavicular distance was 13.6 mm (range, 5-27 mm) on the operated versus 9.4 mm (range, 4-15 mm) on the contralateral side (P partial recurrent vertical and horizontal AC joint instability.

  2. A survival analysis comparing women with ovarian low-grade serous carcinoma to those with high-grade histology

    Directory of Open Access Journals (Sweden)

    Chen M

    2014-10-01

    Full Text Available Ming Chen,1 Ying Jin,1 Yalan Bi,2 Jie Yin,1 Yongxue Wang,1 Lingya Pan1 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; 2Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China Abstract: Ovarian low-grade serous carcinoma (LGSC and high-grade serous carcinoma have distinct molecular profiles, clinical behaviors, and treatment responses. The survival advantage for patients with low-grade carcinoma compared with patients with high-grade histology remains controversial. We retrospectively reviewed the medical charts of 381 patients with ovarian serous carcinoma at Peking Union Medical College Hospital from 2007 to 2010. Patients were classified into two groups according to MD Anderson two-tier system: 35 (9.2% cases with LGSC and 346 with high-grade serous carcinoma. Patients with low-grade serous ovarian cancer had a significantly younger age at diagnosis (46 versus 56 years, P=0.046, and their median progression-free survival (PFS and overall survival values were 35.0 and 54.0 months, respectively. A multivariate analysis showed that, for serous ovarian cancer, the histological grade was a significant prognostic factor for PFS but not for overall survival (P=0.022 and P=0.0566, respectively. When stratified by the existence of a residual disease, patients with low-grade disease who underwent cytoreductive surgery without macroscopic residual disease (>1 cm had a significantly improved median PFS time (36.0 months compared with that of patients with high-grade carcinoma who received optimal cytoreductive surgery (16.0 months, P=0.017. Conversely, patients with low-grade and high-grade carcinoma who were left with macroscopic residue (>1 cm experienced a similarly shorter median PFS (10.0 and 13

  3. A novel minimally invasive technique for the treatment of high-grade isthmic spondylolisthesis using a posterior transsacral rod.

    Science.gov (United States)

    Shedid, Daniel; Weil, Alexander G; Lieberman, Isidore

    2014-04-01

    Case report of 3 patients with high-grade isthmic spondylolisthesis treated using a novel minimally invasive technique using a posterior transsacral rod. To assess the efficacy, safety, and advantages of this approach in the treatment of high-grade L5-S1 spondylolisthesis. Surgical treatment of high-grade isthmic spondylolisthesis at the L5-S1 level is technically demanding. The most commonly used procedure is posterior spinal fusion. In this report, we present a new minimally invasive technique for the treatment high-grade isthmic spondylolisthesis in 3 patients with sagittally balanced spines. Three patients with high-grade L5-S1 spondylolisthesis underwent L4-S1 fusion with percutaneous pedicle screw fixation supplemented with a transsacral rod implanted through a tubular retractor. We report technical details, clinical, and radiologic results at follow-up. All 3 patients suffered from grade 3 or 4 L5-S1 spondylolisthesis. All patients had neutral sagittal balance on preoperative imaging. There were no postoperative complications and all 3 patients were discharged within 48 hours. At final follow-up (range, 13-18 mo), all patients were pain free off all narcotic pain medication and fusion was observed in all 3 patients. We have shown the technical feasibility of anterior and posterior fusion for severe L5-S1 spondylolisthesis using a minimally invasive percutaneous technique through a transsacral approach. The main advantage of a posterior transsacral axial rod fixation is that it creates a structurally sound anterior column support, thus eliminating the problems related to bone grafts and eliminating the complications associated with an anterior approach. Our preliminary results suggest that this technique is feasible and seems to be associated with favorable outcome, although larger studies are warranted to verify these findings.

  4. Laser CO2 vaporization for high-grade cervical intraepithelial neoplasia: a long-term follow-up series.

    Science.gov (United States)

    Fallani, Maria Grazia; Penna, Carlo; Fambrini, Massimiliano; Marchionni, Mauro

    2003-10-01

    The goal of this study was to evaluate the effectiveness of laser CO(2) vaporization for conservative treatment of ectocervical high-grade cervical intraepithelial neoplasia (CIN) particularly by the evaluation of the reappearance risk of disease in long-term follow-up. One hundred fifty-nine patients were submitted to CO(2) laser vaporization for high-grade CIN and followed up for a minimum of 5 years. Selection of cases, depth of ablation, complications, and cure rate (percentage of treated patients in whom there was no recurrent/persistent high-grade CIN at the 5-year follow-up examination) were retrospectively evaluated. Selected cases for colposcopy were submitted to a 6-mm mean depth of vaporization without intra- or postoperative complications. The cure rate for a single treatment was 97.5% and a satisfactory colposcopic follow-up was possible in 99.4% of treated patients. No case of invasive carcinoma occurred after a mean follow-up of 7.1 years. Four cases (2.5%) were high-grade CIN persistence observed after a mean time of 3.75 months, suggesting incomplete destruction of the deepest part of the lesion involving the glandular crypt base. Long-term follow-up proves that laser CO(2) vaporization still has a place in the treatment of CIN. In selected cases it represents a safe alternative for conization in the treatment of high-grade CIN, but colposcopic expertise is essential for adequate preoperative selection of cases.

  5. Therapeutically blocking Interleukin-11 Receptor-α enhances doxorubicin cytotoxicity in high grade type I endometrioid tumours.

    Science.gov (United States)

    Winship, Amy; Van Sinderen, Michelle; Rainczuk, Katarzyna; Dimitriadis, Evdokia

    2017-04-04

    High grade type I endometrial cancers have poor prognosis. Interleukin (IL)11 is elevated in tumours and uterine lavage with increasing tumour grade in women. IL11 regulates cell cycle, invasion and migration and we recently demonstrated that IL11 receptor (R)α inhibition impaired low and moderate grade endometrial tumourigenesis in vivo. In this report, we hypothesized that micro-RNA(miR)-1 regulates IL11 and that IL11 promotes high grade endometrial tumour growth. We aimed to determine whether combination treatment using an anti-human IL11Rα blocking antibody (Ab) and doxorubicin chemotherapeutic impairs high grade tumour growth. MiR-1 was absent in human endometrial tumours versus human benign endometrium (n = 10/group). Transfection with miR-1 mimic restored miR-1 expression, down-regulated IL11 mRNA and impaired cell viability in grade 3-derived AN3CA human endometrial epithelial cancer cells. AN3CA cell proliferation was reduced in response to Ab and doxorubicin combination treatment versus Ab, IgG control, or doxorubicin alone. Subcutaneous xenograft tumours were established in female Balb/c athymic nude mice using AN3CA cells expressing IL11 and IL11Rα. Administration of recombinant human IL11 to mice (n = 4/group) activated IL11 downstream target, signal transducers and activators of transcription (STAT3) and significantly increased tumour growth (p < 0.05), suggesting that IL11 promotes high grade tumour growth. IL11Rα blocking Ab reduced STAT3 phosphorylation and combination treatment with doxorubicin resulted in a significant reduction in tumour growth (p < 0.05) compared to Ab, doxorubicin, or IgG control. Our data suggest that therapeutically targeting IL11Rα in combination with doxorubicin chemotherapy could inhibit high grade type I endometrioid cancer growth.

  6. Sequential proton boost after standard chemoradiation for high-grade glioma.

    Science.gov (United States)

    Adeberg, Sebastian; Bernhardt, Denise; Harrabi, Semi Ben; Uhl, Matthias; Paul, Angela; Bougatf, Nina; Verma, Vivek; Unterberg, Andreas; Wick, Wolfgang; Haberer, Thomas; Combs, Stephanie E; Herfarth, Klaus; Debus, Juergen; Rieken, Stefan

    2017-11-01

    To retrospectively assess the feasibility and safety of a sequential proton boost following conventional chemoradiation in high-grade glioma (HGG). Sixty-six consecutive patients with HGG were treated with 50.0 Gy photons (50.0-50.4 Gy) in 2.0 Gy (1.8-2.0 Gy) fractions, followed by a proton boost with 10 Gy equivalent (Gy(RBE)) in 2.0 Gy(RBE) fractions. Patients were matched one to one with 66 patients with HGG undergoing conventional radiation therapy (RT) with 60.0 Gy photons (59.4-60.0 Gy) in 2.0 Gy fractions (1.8-2.0 Gy). Matching criteria were age, WHO grade, Karnofsky's performance status, PTV size, temozolomide therapy (each p > 0.1). The study assessed progression-free survival (PFS), overall survival (OS), acute treatment-related toxicity (CTCAE v.4.03) and pseudoprogression (RANO criteria). Median PFS and OS were similar in both treatment groups (bimodality RT, PFS: 8.8 months [2-32 months], OS 19.1 months [4-41 months]; photon-only RT, PFS: 7.2 months [2-39 months], 20.9 months [3-53 months]; p = 0.430 and p = 0.125). The median PTV of the proton boost was significantly smaller than the photon plan PTVs (each p compared to photon-only plans, yielded comparable progression and survival rates at lower CTCAE grade 3 acute toxicity rates. Pseudoprogression occurred rarely and evenly distributed in both treatment groups. Thus, bimodality RT was at least equivalent regarding outcome and potentially superior with respect to toxicity in patients with HGG. Treating patients with HGG with 50.0 Gy photons in 2.0 Gy fractions, followed by a proton boost with 10 Gy(RBE) in 2.0 Gy(RBE) fractions, is safe and feasible. Severe radiation-induced acute toxicity and pseudoprogression were rare in both treatment groups. Therefore, in this clinical setting, combined proton radiotherapy might be beneficial in terms of further risk reduction for treatment-related side effects. Interestingly, treatment volume reduction

  7. Local delivery of cancer-cell glycolytic inhibitors in high-grade glioma.

    Science.gov (United States)

    Wicks, Robert T; Azadi, Javad; Mangraviti, Antonella; Zhang, Irma; Hwang, Lee; Joshi, Avadhut; Bow, Hansen; Hutt-Cabezas, Marianne; Martin, Kristin L; Rudek, Michelle A; Zhao, Ming; Brem, Henry; Tyler, Betty M

    2015-01-01

    3-bromopyruvate (3-BrPA) and dichloroacetate (DCA) are inhibitors of cancer-cell specific aerobic glycolysis. Their application in glioma is limited by 3-BrPA's inability to cross the blood-brain-barrier and DCA's dose-limiting toxicity. The safety and efficacy of intracranial delivery of these compounds were assessed. Cytotoxicity of 3-BrPA and DCA were analyzed in U87, 9L, and F98 glioma cell lines. 3-BrPA and DCA were incorporated into biodegradable pCPP:SA wafers, and the maximally tolerated dose was determined in F344 rats. Efficacies of the intracranial 3-BrPA wafer and DCA wafer were assessed in a rodent allograft model of high-grade glioma, both as a monotherapy and in combination with temozolomide (TMZ) and radiation therapy (XRT). 3-BrPA and DCA were found to have similar IC50 values across the 3 glioma cell lines. 5% 3-BrPA wafer-treated animals had significantly increased survival compared with controls (P = .0027). The median survival of rats with the 50% DCA wafer increased significantly compared with both the oral DCA group (P = .050) and the controls (P = .02). Rats implanted on day 0 with a 5% 3-BrPA wafer in combination with TMZ had significantly increased survival over either therapy alone. No statistical difference in survival was noted when the wafers were added to the combination therapy of TMZ and XRT, but the 5% 3-BrPA wafer given on day 0 in combination with TMZ and XRT resulted in long-term survivorship of 30%. Intracranial delivery of 3-BrPA and DCA polymer was safe and significantly increased survival in an animal model of glioma, a potential novel therapeutic approach. The combination of intracranial 3-BrPA and TMZ provided a synergistic effect. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Recognition and characterisation of high-grade ignimbrites from the Neoproterozoic rhyolitic volcanism in southernmost Brazil

    Science.gov (United States)

    Sommer, Carlos Augusto; Lima, Evandro Fernandes; Machado, Adriane; Rossetti, Lucas de Magalhães May; Pierosan, Ronaldo

    2013-11-01

    Neoproterozoic magmatism in southern Brazil is associated with translithospheric shear belts and strike-slip basins in a post-collisional setting related to the last stages of the Brasilian-Pan African Orogenic Cycle. It evolved from an association of high-K calc-alkaline, leucocratic-peraluminous and continental tholeiitic magmas, to an association with shoshonitic magmas and, eventually, to an association with magmas of the sodic mildly alkaline series. This magmatism varies from metaluminous to peralkaline and exhibits alkaline sodic affinity. A large volcanism is related to this alkaline sodic magmatism and is named the Acampamento Velho Formation. This unit was coeval with subaerial siliciclastic sedimentation in post-collisional basins preserved in the region. The Acampamento Velho Formation consists of pyroclastic and effusive volcanic deposits, which are mainly silicic, emplaced under subaerial conditions. The best exposures of this volcanism occur on the Ramada and Taquarembó plateaus, located southwest of Rio Grande do Sul in southernmost Brazil. The pyroclastic flow deposits are composed mainly of juvenile fragments such as pumices, shards and crystal fragments. Welding is very effective in these units. High-grade ignimbrites occur at the base and intermediate portions of the deposits and rheoignimbrites are observed at the top. The pre-eruptive temperature calculations, which were obtained at the saturation of zircon, revealed values between 870 °C and 978 °C for Taquarembó Plateau and 850 °C-946 °C for Ramada Plateau. The calculated viscosity values vary from 6.946 to 8.453 log η (Pas) for the rheoignimbrites and 7.818 to 10.588 log η (Pas) for the ignimbrites. Zr contents increase toward the top of the pyroclastic sequence, which indicates an increase in peralkalinity and determines the reduction in viscosity for clasts at the upper portions of the flows. The patterns of the structures of the ignimbrites and rheoignimbrites in the Taquaremb

  9. Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a phylogenetic analysis.

    Directory of Open Access Journals (Sweden)

    Roland F Schwarz

    2015-02-01

    Full Text Available The major clinical challenge in the treatment of high-grade serous ovarian cancer (HGSOC is the development of progressive resistance to platinum-based chemotherapy. The objective of this study was to determine whether intra-tumour genetic heterogeneity resulting from clonal evolution and the emergence of subclonal tumour populations in HGSOC was associated with the development of resistant disease.Evolutionary inference and phylogenetic quantification of heterogeneity was performed using the MEDICC algorithm on high-resolution whole genome copy number profiles and selected genome-wide sequencing of 135 spatially and temporally separated samples from 14 patients with HGSOC who received platinum-based chemotherapy. Samples were obtained from the clinical CTCR-OV03/04 studies, and patients were enrolled between 20 July 2007 and 22 October 2009. Median follow-up of the cohort was 31 mo (interquartile range 22-46 mo, censored after 26 October 2013. Outcome measures were overall survival (OS and progression-free survival (PFS. There were marked differences in the degree of clonal expansion (CE between patients (median 0.74, interquartile range 0.66-1.15, and dichotimization by median CE showed worse survival in CE-high cases (PFS 12.7 versus 10.1 mo, p = 0.009; OS 42.6 versus 23.5 mo, p = 0.003. Bootstrap analysis with resampling showed that the 95% confidence intervals for the hazard ratios for PFS and OS in the CE-high group were greater than 1.0. These data support a relationship between heterogeneity and survival but do not precisely determine its effect size. Relapsed tissue was available for two patients in the CE-high group, and phylogenetic analysis showed that the prevalent clonal population at clinical recurrence arose from early divergence events. A subclonal population marked by a NF1 deletion showed a progressive increase in tumour allele fraction during chemotherapy.This study demonstrates that quantitative measures of intra

  10. CN-07PREDICTORS OF ACUTE SEVERE LYMPHOPENIA DURING RADIOTHERAPY AND TEMOZOLOMIDE FOR HIGH-GRADE GLIOMA

    Science.gov (United States)

    Huang, Jiayi; Robinson, Clifford; DeWees, Todd; Campian, Jian; Mullen, Daniel; Fergus, Sandra; Kim, Albert; Dunn, Gavin; Tran, David; Simpson, Joseph

    2014-01-01

    BACKGROUND: Acute severe lymphopenia (ASL) frequently develops during radiotherapy and temozolomide (RT + TMZ) for high-grade glioma (HGG) and has been shown to be correlated with survival. This study is designed to identify potential predictors of ASL, especially RT-specific parameters that can be modified. METHODS: From January 2007 to December 2012, 194 patients with HGG were treated RT + TMZ and had available data including lymphocyte count and radiation dose-volume histogram (DVH) parameters. RT was delivered to 2 planning target volumes (PTV1) over a median of 43 days (range 19-75): 60Gy (40.05-66) to PTV 1 and 51Gy (30-54) to PTV2. Concurrent TMZ was given daily at a dose of 75 mg/m2 for the duration of RT. ASL was defined as less than 500/ul (Common Toxicity Criteria version 4.0, grade 3-4) within the first two months from the start of RT. Peripheral blood including lymphocyte count was typically assessed weekly during RT and then monthly thereafter. DVH parameters were determined for brain, brainstem and PTV from the original RT plan. The stepwise logistic regression analysis (SLRA) was used to determine the most important predictors of ASL. RESULTS: Forty-five patients (23%) developed ASL. Patients with ASL had significantly worse OS than those without (median 11.2 vs 18.3 months, respectively, p < 0.001). The SLRA showed that female gender (odd ratio [OR], 5.21; 95% confidence interval [CI], 2.34-11.63), elder age (1.05; 1.01-1.08), higher V25Gy (volume receiving 25Gy) of brain (1.04; 1.01-1.06), lower pretreatment lymphocyte count (1.001; 1.00-1.002) were the most significant predictors for ASL. ASL rate was 40% for patients with V25Gy ≥ 66% and 15% for V25Gy < 66%. CONCLUSIONS: Female gender, elder age, increased V25Gy of brain, and low pretreatment lymphocyte count are significant predictors of ASL during treatment of HGG. Maintaining V25Gy of brain below 66% may reduce the rate of ASL.

  11. P13.11USAGE OF CYBER KNIFE HYPOFRACTIONATED RADIOSURGERY IN HIGH GRADE GLIOMAS COMPLEX TREATMENT

    Science.gov (United States)

    Glavatskyi, O.; Buryk, V.M.; Kardash, K.A.; Pylypas, O.P.; Chebotaryova, T.I.

    2014-01-01

    respectively. CONCLUSIONS: Hypofractionated stereotactic radiosurgery is one of possible treatment options for high-grade gliomas which leads to a decrease in tumor volume and improves clinical status of patients even in cases of re-irradiation. Surgical treatment after radiosurgery doesn't worsen median overall survival and progression free survival prognosis.

  12. IGF-1 gene polymorphisms in Polish families with high-grade myopia

    Science.gov (United States)

    Rydzanicz, Malgorzata; Nowak, Dorota M.; Karolak, Justyna A.; Frajdenberg, Agata; Podfigurna-Musielak, Monika; Mrugacz, Malgorzata

    2011-01-01

    Purpose Recent work has suggested that insulin-like growth factor 1 (IGF-1) gene polymorphisms are genetically linked with high-grade myopia (HM), which is a complex-trait eye disorder in which numerous candidate loci and genes are thought to play a role. We investigated whether the IGF-1 single nucleotide polymorphisms (SNPs) rs6214, rs10860860, and rs2946834 are associated with HM (≤-6.0 diopters [D]) and any myopia (≤-0.5 D) phenotype in Polish families. Methods Forty-two multiplex HM Polish families, of whom 127 had HM, participated in the study. All of the family members (n=306) underwent a detailed ophthalmic examination, including axial length measurements. The IGF-1 SNPs rs6214, rs10860860, and rs2946834 were evaluated by PCR-RFLP and direct sequencing methods. Both Family-Based Association Test (FBAT) and family-based Pedigree Disequilibrium Test (PDT) were used to examine the potential association of the IGF-1 SNPs rs6214, rs10860860, and rs2946834 with HM or any myopia. To determine the distribution of the HM-associated SNPs rs6214 and rs10860860, 543 unrelated individuals from the general Polish population were also analyzed. Results We found no significant association between the IGF-1 SNPs rs6214, rs10860860, and rs2946834 and HM or any myopia phenotype in Polish HM families. In the general Polish population, the minor allele frequencies of the SNPs rs6214 and rs10860860 did not deviate significantly from the distribution reported for European populations (p=0.629). In the FBAT analysis under the dominant model, the haplotype consisted of T allele of rs10860860, with C allele of rs2946834 of IGF-1 was found less frequently transmitted to HM individuals (p=0.0065), pointing to a nonassociated or protective haplotype. Conclusions Our results do not support recent studies reporting an association of the SNPs rs6214, rs10860860, and rs2946834 in the IGF-1 gene with HM and any myopia phenotypes. Further replication studies involving other populations

  13. Simultaneous integrated vs. sequential boost in VMAT radiotherapy of high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Farzin, Mostafa [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Radiation Oncology, Munich (Germany); Tehran University of Medical Science, Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran (Iran, Islamic Republic of); Molls, Michael; Astner, Sabrina; Oechsner, Markus [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Radiation Oncology, Munich (Germany); Rondak, Ina-Christine [Klinikum rechts der Isar, Technische Universitaet Muenchen, Institut fuer Medizinische Statistik und Epidemiologie, Munich (Germany)

    2015-12-15

    In 20 patients with high-grade gliomas, we compared two methods of planning for volumetric-modulated arc therapy (VMAT): simultaneous integrated boost (SIB) vs. sequential boost (SEB). The investigation focused on the analysis of dose distributions in the target volumes and the organs at risk (OARs). After contouring the target volumes [planning target volumes (PTVs) and boost volumes (BVs)] and OARs, SIB planning and SEB planning were performed. The SEB method consisted of two plans: in the first plan the PTV received 50 Gy in 25 fractions with a 2-Gy dose per fraction. In the second plan the BV received 10 Gy in 5 fractions with a dose per fraction of 2 Gy. The doses of both plans were summed up to show the total doses delivered. In the SIB method the PTV received 54 Gy in 30 fractions with a dose per fraction of 1.8 Gy, while the BV received 60 Gy in the same fraction number but with a dose per fraction of 2 Gy. All of the OARs showed higher doses (D{sub max} and D{sub mean}) in the SEB method when compared with the SIB technique. The differences between the two methods were statistically significant in almost all of the OARs. Analysing the total doses of the target volumes we found dose distributions with similar homogeneities and comparable total doses. Our analysis shows that the SIB method offers advantages over the SEB method in terms of sparing OARs. (orig.) [German] Es wurden 2 Arten der Planung fuer die volumetrisch modulierte Rotationsbestrahlung (VMAT) bei 20 Patienten mit hochgradigen Gliomen verglichen: simultan integrierter Boost (SIB) und sequenzieller Boost (SEB). Dazu wurde die Dosisverteilung in den Zielvolumina und den Risikoorganen analysiert. Es wurden Planungsvolumina (PTV), Boostvolumina (BV) und Risikoorgane konturiert sowie SIB- und SEB-Plaene erstellt. Der SEB besteht aus 2 Plaenen. Im ersten Plan erhaelt das PTV 50 Gy in 25 Fraktionen. Im zweiten Plan erhaelt das Boostvolumen 10 Gy in 5 Fraktionen (Einzeldosis jeweils 2 Gy). Die Dosis

  14. DNA copy number changes in high-grade malignant peripheral nerve sheath tumors by array CGH

    Directory of Open Access Journals (Sweden)

    Bjerkehagen Bodil

    2008-06-01

    Full Text Available Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs are rare and highly aggressive soft tissue tumors showing complex chromosomal aberrations. In order to identify recurrent chromosomal regions of gain and loss, and thereby novel gene targets of potential importance for MPNST development and/or progression, we have analyzed DNA copy number changes in seven high-grade MPNSTs using microarray-based comparative genomic hybridization (array CGH. Results Considerable more gains than losses were observed, and the most frequent minimal recurrent regions of gain included 1q24.1-q24.2, 1q24.3-q25.1, 8p23.1-p12, 9q34.11-q34.13 and 17q23.2-q25.3, all gained in five of seven samples. The 17q23.2-q25.3 region was gained in all five patients with poor outcome and not in the two patients with disease-free survival. cDNA microarray analysis and quantitative real-time reverse transcription PCR were used to investigate expression of genes located within these regions. The gene lysyl oxidase-like 2 (LOXL2 was identified as a candidate target for the 8p23.1-p12 gain. Within 17q, the genes topoisomerase II-α (TOP2A, ets variant gene 4 (E1A enhancer binding protein, E1AF (ETV4 and baculoviral IAP repeat-containing 5 (survivin (BIRC5 showed increased expression in all samples compared to two benign tumors. Increased expression of these genes has previously been associated with poor survival in other malignancies, and for TOP2A, in MPNSTs as well. In addition, we have analyzed the expression of five micro RNAs located within the 17q23.2-q25.3 region, but none of them showed high expression levels compared to the benign tumors. Conclusion Our study shows the potential of using DNA copy number changes obtained by array CGH to predict the prognosis of MPNST patients. Although no clear correlations between the expression level and patient outcome were observed, the genes TOP2A, ETV4 and BIRC5 are interesting candidate targets for the 17q gain associated

  15. [Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].

    Science.gov (United States)

    Liu, W L; Wang, Z Z; Zhao, J Z; Hou, Y Y; Wu, X X; Li, W; Dong, B; Tong, T T; Guo, Y J

    2017-01-25

    Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t-tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found (P>0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls (t=-3.536, P=0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group (r=0.494, P0.05), while significant differences were found in CA(125) and sensitivity to platinum-based chemotherapy between the patients with BRCA mutation and wild type (Pmutations in sporadic HGSOC (P=0.007). Conclusion: The combination of CA(125) with BRCA have

  16. High grade squamous intraepithelial lesion in inmates from Ohio: cervical screening and biopsy follow-up

    Directory of Open Access Journals (Sweden)

    Rofagha Soraya

    2006-01-01

    Full Text Available Abstract Background Cervical carcinoma remains the second leading cause of cancer death in women worldwide and sexual behavior is regarded as the main contributing factor. We studied cervical cytology screening with surgical biopsy follow-up in women prisoners and compared the findings to those in the general population. Methods We reviewed 1024 conventional cervical smears, 73 cervical biopsies and 2 loop electrosurgical excision procedure (LEEP specimens referred to us from the Correctional Center in Columbus, Ohio during a 12-month period. The results were compared to 40,993 Pap smears from the general population for the same 12-month period. Results High grade squamous intraepithelial lesion (HGSIL was diagnosed in 1.3% of the cervical smears from the inmate population versus 0.6% in the general population (p < 0.01. The unsatisfactory rate was 1.6% compared to 0.3% in the general population (p < 0.01. Among the study population, follow-up tissue diagnosis was obtained in 24.3% of the abnormal cytology results (ASCUS, LGSIL, and HGSIL. Of the HGSIL Pap smears, 61.5% had a subsequent tissue diagnosis. Thirty-nine biopsies (52% of the all inmate biopsies and LEEP showed CIN II/III (cervical intraepithelial neoplasia II/III. Eight of these thirty-nine follow-up biopsies diagnosed as CIN II/III had a previous cervical cytology diagnosis of ASCUS. The average age for HGSIL was 30.5 years (S.D. = 5.7 and for low grade squamous intraepithelial lesion (LGSIL was 27.2 years (S.D. = 6.1. Conclusion A significantly higher prevalence of HGSIL cervical cytology and unsatisfactory smears was encountered in female inmates, with tissue follow-up performed in less than two thirds of the patients with HGSIL. These results are in keeping with data available in the literature suggesting that the inmate population is high-risk and may be subject to less screening and tissue follow-up than the general population. Clinicians should proceed with urgency to improve

  17. Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial*

    Science.gov (United States)

    Gurel, Bora; Lucia, M. Scott; Thompson, Ian M.; Goodman, Phyllis J.; Tangen, Catherine M.; Kristal, Alan R.; Parnes, Howard L.; Hoque, Ashraful; Lippman, Scott M.; Sutcliffe, Siobhan; Peskoe, Sarah B.; Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.

    2014-01-01

    Background Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established. Methods Prostate cancer cases (N=191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N=209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of H&E stained sections. Logistic regression was used to estimate associations. Results 86.2% of cases and 78.2% of controls had at least one biopsy core (of 3 assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 (95% CI 1.04–3.06) times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7–10, N=94; odds ratio [OR]=2.24, 95% CI 1.06–4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their PSA was low (Inflammation, most of which was chronic, was common in benign prostate tissue, and was positively associated with prostate cancer, especially high-grade. The association did not appear to be due to detection bias. Impact This study supports an etiologic link between inflammation and prostate carcinogenesis, and suggests an avenue for prevention by mitigating intraprostatic inflammation. PMID:24748218

  18. Geochemical compositional changes at the pliocene-pleistocene transition in fluviodeltaic deposits in the Tegelen-Reuver area (south-eastern Netherlands)

    NARCIS (Netherlands)

    Huisman, D.J.; Klaver, G.T.; Veldkamp, A.; Os, van B.J.H.

    2000-01-01

    At the Pliocene-Pleistocene transition, major changes occurred in the Rhine system: Climatic cooling, extension of the drainage area into the Alps and a marine regression. We studied the geochemistry, clay mineralogy and micromorphology of several sections with Pliocene and Early Pleistocene Rhine

  19. Systematic review of guidelines for the assessment and management of high-grade anal intraepithelial neoplasia (AIN II/III).

    Science.gov (United States)

    Alam, N N; White, D A; Narang, S K; Daniels, I R; Smart, N J

    2016-02-01

    There is ambiguity with regard to the optimal management of anal intraepithelial neoplasia (AIN) III. The aim of this review was to assess and compare international/national society guidelines currently available in the literature on the management, treatment and surveillance of AIN III. We also aimed to assess the quality of the studies used to compile the guidelines and to clarify the terminology used in histological assessment. An electronic search of PubMed and Embase was performed using the search terms 'anal intraepithelial neoplasia', 'AIN', 'anal cancer', 'guidelines', 'surveillance' and 'management'. Literature reviews and guidelines or practice guidelines in peer reviewed journals from 1 January 2000 to 31 December 2014 assessing the treatment, surveillance or management of patients with AIN related to human papilloma virus were included. The guidelines identified by the search were assessed for the quality of evidence behind them using the Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence. The database search identified 5159 articles and two further guidelines were sourced from official body guidelines. After inclusion criteria were applied, 28 full-text papers were reviewed. Twenty-five of these were excluded, leaving three guidelines for inclusion in the systematic review: those published by the Association of Coloproctology of Great Britain and Ireland, the American Society of Colon and Rectal Surgeons and the Italian Society of Colorectal Surgery. No guidelines were identified on the management of AIN III from human papilloma virus associations and societies. All three guidelines agree that a high index of clinical suspicion is essential for diagnosing AIN with a disease-specific history, physical examination, digital rectal examination and anal cytology. There is interchange of terminology from high-grade AIN (HGAIN) (which incorporates AIN II/III) and AIN III in the literature leading to confusion in therapy use. Treatment varies

  20. Transsacral transdiscal L5-S1 screws for the management of high-grade spondylolisthesis in an adolescent.

    Science.gov (United States)

    Palejwala, Ali; Fridley, Jared; Jea, Andrew

    2016-06-01

    The surgical management of high-grade spondylolisthesis in adolescents remains a controversial issue. Because the basic procedure, posterolateral fusion, is associated with a significant rate of pseudarthrosis and listhesis progression, there is a pressing need for alternative surgical techniques. In the present report, the authors describe the case of an adolescent patient with significant low-back pain who was found to have Grade IV spondylolisthesis at L5-S1 that was treated with transsacral transdiscal screw fixation. Bilateral pedicle screws were placed starting from the top of the S-1 pedicle, across the L5-S1 intervertebral disc space, and into the L-5 body. At 14 months after surgery, the patient had considerable improvement in his pain and radiographic fusion across L5-S1. The authors conclude that transsacral transdiscal pedicle screws may serve as an efficacious and safe option for the correction of high-grade spondylolisthesis in adolescent patients.

  1. Surface sediments in the marsh-sandy land transitional area: sandification in the western Songnen Plain, China.

    Science.gov (United States)

    Yu, Xiaofei; Grace, Michael; Zou, Yuanchun; Yu, Xuefeng; Lu, Xianguo; Wang, Guoping

    2014-01-01

    The development of sandification process was studied, by monitoring the changes of sediment characteristics, at marsh-sandy land intersections in China's Songnen region. A series of sediment collection plates were deployed in the region; after one year, sediments in these plates were analyzed for changes of mass and chemical characteristics. The sediment flux and the sand content of the sediments decreased with the increasing longitudinal distance between the sampling site and the centre line of a sand dune. The mean sediment flux was 29 ± 14 kg m(-2) yr(-1) and 0.6 ± 0.3 kg m(-2) yr(-1) in the sandy land and marsh, respectively. Strong, positive correlations were found between the concentrations of organic matter, total nitrogen, P, Fe, Ti, V and Zr, all of which were also negatively correlated with the sand content. The concentrations of organic matter, total nitrogen, P, Fe, Ti, V and Zr in the marsh sediment samples were all significantly greater than the corresponding concentrations of the sandy land (pmarsh could be divided into three distinct zones. Sand expansion extended about 88 m into the marsh. The mean sand content in the sediments of the sandy land was 91% and then 64% in the marsh, which in turn was higher than that of marshes outside the influence of sandification, suggesting that the marsh in the marsh-sandy land transitional area has already undergone extensive sandification in the past. The study results provide information on the wetland's function of indicating and buffering the sandification process.

  2. Prevalence of high-grade squamous intraepithelial lesions and cervical cancer among patients with unsatisfactory colposcopic examination, without visible lesion

    OpenAIRE

    Veiga, Fernanda Rangel da; Russomano, Fábio Bastos; Camargo, Maria José de; Monteiro, Aparecida Cristina Sampaio; Tristão, Aparecida; Silva, Gabriela Villar e

    2009-01-01

    CONTEXT AND OBJECTIVE: Cervical cancer is a serious public health problem in Brazil. For patients with unsatisfactory colposcopic examinations without visible lesions, but with cervical cytological tests suggesting high-grade squamous intraepithelial lesion (HSIL), the national recommendation is to repeat cervical cytological tests after three months. Our aim was to assess the prevalence of HSIL and cancer among patients with initial cervical cytological tests suggestive of HSIL but with unsa...

  3. Long-Term Risk for Noncervical Anogenital Cancer in Women with Previously Diagnosed High-Grade Cervical Intraepithelial Neoplasia

    DEFF Research Database (Denmark)

    Sand, Freja Lærke; Munk, Christian; Jensen, Signe Marie

    2016-01-01

    Background: High-risk human papillomavirus (HPV) is essential for developing high-grade cervical intraepithelial neoplasia (CIN2 and CIN3) and has also been associated with noncervical anogenital cancers. However, limited knowledge exists about the long-term risk for anal, vulvar, and vaginal...... ability to control a persistent HPV infection. Impact: This finding adds to our understanding of the relation between HPV infection and noncervical anogenital cancer....

  4. Urinary cytology with acridine orange fluorescence is highly valuable for predicting high-grade upper urinary tract urothelial carcinoma.

    Science.gov (United States)

    Li, Jing; Zhang, Zhihong; Wang, Jin; Zhang, Changwen; Li, Haibo; Xu, Yong

    2014-01-01

    To evaluate the clinical value of acridine orange fluorescent staining in urinary cytology for the diagnosis of upper urinary tract urothelial carcinoma. A retrospective analysis was conducted with 510 cases of upper urinary tract urothelial carcinoma (UTUC) in terms of the results of acridine orange fluorescence (AO-F) staining of the exfoliated cells in urine. The percentage of positive AO-F result and the positive predictive value of AO-F for high-grade and muscle invasive urothelial carcinoma were calculated and analyzed in terms of clinical characteristics. The overall percentage of positive AO-F result was 49% in the 510 patients, 54.1% for males and 40.6% for females. AO-F was positive in 51.9% of the patients with hematuria and 36.2% of the patients without hematuria. AO-F was positive in 56.4% of the patients with renal pelvis carcinoma and 42.8% of the patients with ureteral cancer; in 44.6% of the patients with non-muscle invasive carcinoma and 53.5% of the patients with muscle-invasive carcinoma. AO-F was positive in 26.8% of the cases with low-grade carcinoma and 55.3% of the patients with high-grade carcinoma. The positive predictive value of AO-F was 88% for high-grade cancer, and only 53.6% for muscle invasive carcinoma. Acridine orange fluorescence microscopy cannot increase the sensitivity of urine exfoliative cytology in the diagnosis of UTUC. It may be used as a predictor of high-grade UTUC. Acridine orange fluorescence microscopy in urinary cytodiagnosis does not show high value in predicting muscle invasive UTUC.

  5. Structural Evolution of Nonoperatively Treated High-Grade Partial-Thickness Tears of the Supraspinatus Tendon.

    Science.gov (United States)

    Kong, Bong Young; Cho, Minjoon; Lee, Hwa Ryeong; Choi, Young Eun; Kim, Sae Hoon

    2018-01-01

    High-grade partial-thickness rotator cuff tears (hPTRCTs) are frequently encountered in the shoulder. However, little information is available on the prevalence or timing of tear progression. Purpose/Hypothesis: The purpose was to prospectively evaluate the structural progression of hPTRCTs with a minimum follow-up of 1 year using magnetic resonance imaging (MRI). The hypothesis was that a substantial portion of hPTRCT patients would experience tear progression or evolution to a full-thickness rotator cuff tear. Case series; Level of evidence, 4. Between May 2010 and December 2015, 362 patients were diagnosed with hPTRCT (tear involvement >50% of the mediolateral length of the footprint) of the supraspinatus and were treated nonoperatively. Among these patients, 81 underwent follow-up MRI at least 1 year after initial presentation, and these patients were included in the final analysis. Initial and follow-up MRIs were used to determine whether tears had improved, had not changed, or had progressed. A change in tear involvement of >20% was defined as a significant change. Patients were categorized as follows: (1) a decrease in tear involvement of >20% (improved), (2) an increase or decrease of ≤20% (no change), or (3) an increase in tear involvement of >20% (progressed). Demographic data and morphologic data were analyzed to identify variables related to tear progression. Among them, severity of tendinosis was graded using MRIs: grade 1 (mild tendinosis), mild focal increase in tendon signal; grade 2 (moderate tendinosis), moderate focal increase in tendon signal; and grade 3 (marked tendinosis), marked generalized increase in tendon signal. At initial diagnosis, 23 were articular-side (28%) and 58 were bursal-side (72%) hPTRCTs. The study cohort was composed of 51 women and 30 men, and the mean patient age was 62.3 years (range, 41-77 years). Follow-up MRI was performed at a mean 19.9 ± 10.9 months (range, 12-52 months). A significant change in tear involvement

  6. Hypoxia-inducible factor 1α predicts recurrence in high-grade soft tissue sarcoma of extremities and trunk wall

    DEFF Research Database (Denmark)

    Nyström, Harriet; Jönsson, M; Werner-Hartman, L

    2017-01-01

    BACKGROUND AND AIM: Sarcomas are of mesenchymal origin and typically show abundant tumour stroma and presence of necrosis. In search for novel biomarkers for personalised therapy, we determined the prognostic impact of stromal markers, hypoxia and neovascularity in high-grade soft tissue leiomyos......BACKGROUND AND AIM: Sarcomas are of mesenchymal origin and typically show abundant tumour stroma and presence of necrosis. In search for novel biomarkers for personalised therapy, we determined the prognostic impact of stromal markers, hypoxia and neovascularity in high-grade soft tissue...... leiomyosarcoma and pleomorphic undifferentiated sarcoma. METHOD: We evaluated CD163, colony-stimulating factor (CSF)-1, CD16 and hypoxia-inducible factor 1 (HIF-1)α using immunohistochemical staining and assessed microvessel density using CD31 in 73 high-grade leiomyosarcomas and undifferentiated pleomorphic...... sarcomas of the extremities and the trunk wall. The results were correlated to metastasis-free and overall survival. RESULTS: Expression of HIF-1α was associated with the presence of necrosis and independently predicted shorter metastasis-free survival (HR 3.2, CI 1.4 to 7.0, p=0.004), whereas neither...

  7. Operative Versus Nonoperative Management of Acute High-Grade Acromioclavicular Dislocations: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Chang, Nicholas; Furey, Andrew; Kurdin, Anton

    2018-01-01

    Management of high-grade acromioclavicular (AC) joint dislocations has been controversial. Recent studies suggest no difference in outcomes between operative and nonoperative management of Rockwood types III-V injuries. The objective of this meta-analysis is to compare outcomes between operative and nonoperative management of high-grade AC joint dislocations. Search was conducted using PubMed, Embase, and Cochrane databases through October 2016. A broad search strategy was used to identify English, comparative studies of AC joint dislocations. Inclusion criteria included comparative studies of AC joint dislocations in adult patients with acute, high-grade AC dislocations. Two authors independently reviewed and assessed for bias according to the U.S. Preventative Task Force Quality Rating Criteria. Data were extracted for validated functional scores, clinical and radiographic outcomes, and complications. Nineteen studies (n = 954) were included in the meta-analysis. Operative group had better cosmetic outcome (odds ratio [OR] = 0.05; P dislocations. Patients in the nonoperative cohort had a more rapid return to work, but were associated with a poorer cosmetic outcome. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

  8. The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice.

    Science.gov (United States)

    Kim, Jaeyeon; Coffey, Donna M; Ma, Lang; Matzuk, Martin M

    2015-06-01

    Although named "ovarian cancer," it has been unclear whether the cancer actually arises from the ovary, especially for high-grade serous carcinoma (HGSC), also known as high-grade serous ovarian cancer, the most common and deadliest ovarian cancer. In addition, the tumor suppressor p53 is the most frequently mutated gene in HGSC. However, whether mutated p53 can cause HGSC remains unknown. In this study, we bred a p53 mutation, p53(R172H), into conditional Dicer-Pten double-knockout (DKO) mice, a mouse model duplicating human HGSC, to generate triple-mutant (TKO) mice. Like DKO mice, these TKO mice develop metastatic HGSCs originating from the fallopian tube. Unlike DKO mice, however, even after fallopian tubes are removed in TKO mice, ovaries alone can develop metastatic HGSCs, indicating that a p53 mutation can drive HGSC arising from the ovary. To confirm this, we generated p53(R172H)-Pten double-mutant mice, one of the genetic control lines for TKO mice. As anticipated, these double-mutant mice also develop metastatic HGSCs from the ovary, verifying the HGSC-forming ability of ovaries with a p53 mutation. Our study therefore shows that ovaries harboring a p53 mutation, as well as fallopian tubes, can be a distinct tissue source of high-grade serous ovarian cancer in mice.

  9. Reversibility of High-Grade Atrioventricular Block with Revascularization in Coronary Artery Disease without Infarction: A Literature Review

    Directory of Open Access Journals (Sweden)

    Rhanderson Cardoso

    2016-01-01

    Full Text Available Complete atrioventricular (AV block is known to be reversible in some cases of acute inferior wall myocardial infarction (MI. The reversibility of high-grade AV block in non-MI coronary artery disease (CAD, however, is rarely described in the literature. Herein we perform a literature review to assess what is known about the reversibility of high-grade AV block after right coronary artery revascularization in CAD patients who present without an acute MI. To illustrate this phenomenon we describe a case of 2 : 1 AV block associated with unstable angina, in which revascularization resulted in immediate and durable restoration of 1 : 1 AV conduction, thereby obviating the need for permanent pacemaker implantation. The literature review suggests two possible explanations: a vagally mediated response or a mechanism dependent on conduction system ischemia. Due to the limited understanding of AV block reversibility following revascularization in non-acute MI presentations, it remains difficult to reliably predict which patients presenting with high-grade AV block in the absence of MI may have the potential to avoid permanent pacemaker implantation via coronary revascularization. We thus offer this review as a potential starting point for the approach to such patients.

  10. Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume.

    Science.gov (United States)

    Choi, Yoon Seong; Ahn, Sung Soo; Lee, Seung-Koo; Chang, Jong Hee; Kang, Seok-Gu; Kim, Se Hoon; Zhou, Jinyuan

    2017-08-01

    To evaluate the added value of amide proton transfer (APT) imaging to the apparent diffusion coefficient (ADC) from diffusion tensor imaging (DTI) and the relative cerebral blood volume (rCBV) from perfusion magnetic resonance imaging (MRI) for discriminating between high- and low-grade gliomas. Forty-six consecutive adult patients with diffuse gliomas who underwent preoperative APT imaging, DTI and perfusion MRI were enrolled. APT signals were compared according to the World Health Organization grade. The diagnostic ability and added value of the APT signal to the ADC and rCBV for discriminating between low- and high-grade gliomas were evaluated using receiver operating characteristic (ROC) analyses and integrated discrimination improvement. The APT signal increased as the glioma grade increased. The discrimination abilities of the APT, ADC and rCBV values were not significantly different. Using both the APT signal and ADC significantly improved discrimination vs. the ADC alone (area under the ROC curve [AUC], 0.888 vs. 0.910; P = 0.007), whereas using both the APT signal and rCBV did not improve discrimination vs. the rCBV alone (AUC, 0.927 vs. 0.923; P = 0.222). APT imaging may be a useful imaging biomarker that adds value to the ADC for discriminating between low- and high-grade gliomas. • Higher APT values were correlated with higher glioma grades. • Adding the APT signal to the ADC improved glioma grading. • Adding the APT signal to rCBV did not improve glioma grading. • APT is a useful adjunct to the ADC for glioma grading.

  11. Relative accuracy of cervical and anal cytology for detection of high grade lesions by colposcope guided biopsy: a cut-point meta-analytic comparison.

    Directory of Open Access Journals (Sweden)

    Edward R Cachay

    Full Text Available BACKGROUND: We recently reported, using a receiver operating characteristic area metric, the first meta-analytic comparison of the relative accuracy of cervical and anal cytology in detecting moderate or severe histopathologic lesions by magnification directed punch biopsy. The aim of the present research was to meta-analytically examine cut-point specific operating characteristics (sensitivity, specificity of cervical and anal cytology in detecting high grade squamous intraepithelial lesion (HSIL histopathology by colposcope directed punch biopsy. METHODOLOGY/PRINCIPAL FINDINGS: The primary eligibility requirement was availability of tabulated cytology (normal, atypical cells of unclear significance [ASCUS], low grade squamous intraepithelial lesion, HSIL or atypical squamous cells cannot rule out high grade [ASC-H] and biopsy (

  12. On thrusting, regional unconformities and exhumation of high-grade greenstones in Neoarchean orogens. The case of the Waroonga Shear Zone, Yilgarn Craton

    Science.gov (United States)

    Zibra, I.; Korhonen, F. J.; Peternell, M.; Weinberg, R. F.; Romano, S. S.; Braga, R.; De Paoli, M. C.; Roberts, M.

    2017-08-01

    During the Neoarchean, the dominant tectonic style progressively changed from an episodic-overturn/stagnant-lid regime to modern-style plate tectonics. The Neoarchean strengthening of continental lithosphere changed the style of deformation of orogenic belts. The case study presented here provides insights into how such transition in tectonic style occurred, a matter that is generally controversial. We present structural and metamorphic data from the c. 2660 Ma Waroonga Shear Zone (WSZ) in the Neoarchean Yilgarn orogen (Western Australia). The WSZ contains a syntectonic pluton and older, high-grade greenstones. The tectonic fabric in the pluton developed during melt-present thrusting, followed by syn-cooling wrench-dominated transpression. Mafic greenstones preserve three metamorphic assemblages. The M1 assemblage (Grt-Cpx-Qtz) records peak P-T conditions of 12 ± 1 kbar and 800 ± 50 °C, followed by isothermal decompression to 9 kbar (M2). These anhydrous assemblages might predate the WSZ. Greenstones then underwent decompression at c. 2660 Ma (3-4 kbar; 600-650 °C), defined by the amphibole-rich M3 assemblage, synkinematic with the tectonic fabric in the WSZ. We show that shearing along the WSZ exhumed these greenstones by at least 10 km, inducing major uplift and erosion. Archean accretionary orogens developed on weak lithosphere, where deformation suppressed crustal thickening, orogenic relief and synorogenic exhumation of orogenic roots. However, our study indicates a genetic link between (i) strain localization along contractional structures, inducing large-scale uplift; (ii) exhumation of high-grade greenstones; (iii) development of inverse metamorphic gradients; (iv) establishment of a regional unconformity, with clastic sediments fed by the uplifted terrane; (v) incorporation of portions of the newly-formed orogenic basins into the footwall of the WSZ. These features imply that the Yilgarn orogenic lithosphere at c. 2660 Ma was stiff enough to allow

  13. Magnetic resonance perfusion for differentiating low-grade from high-grade gliomas at first presentation.

    Science.gov (United States)

    Abrigo, Jill M; Fountain, Daniel M; Provenzale, James M; Law, Eric K; Kwong, Joey Sw; Hart, Michael G; Tam, Wilson Wai San

    2018-01-22

    Gliomas are the most common primary brain tumour. They are graded using the WHO classification system, with Grade II-IV astrocytomas, oligodendrogliomas and oligoastrocytomas. Low-grade gliomas (LGGs) are WHO Grade II infiltrative brain tumours that typically appear solid and non-enhancing on magnetic resonance imaging (MRI) scans. People with LGG often have little or no neurologic deficit, so may opt for a watch-and-wait-approach over surgical resection, radiotherapy or both, as surgery can result in early neurologic disability. Occasionally, high-grade gliomas (HGGs, WHO Grade III and IV) may have the same MRI appearance as LGGs. Taking a watch-and-wait approach could be detrimental for the patient if the tumour progresses quickly. Advanced imaging techniques are increasingly used in clinical practice to predict the grade of the tumour and to aid clinical decision of when to intervene surgically. One such advanced imaging technique is magnetic resonance (MR) perfusion, which detects abnormal haemodynamic changes related to increased angiogenesis and vascular permeability, or "leakiness" that occur with aggressive tumour histology. These are reflected by changes in cerebral blood volume (CBV) expressed as rCBV (ratio of tumoural CBV to normal appearing white matter CBV) and permeability, measured by K trans . To determine the diagnostic test accuracy of MR perfusion for identifying patients with primary solid and non-enhancing LGGs (WHO Grade II) at first presentation in children and adults. In performing the quantitative analysis for this review, patients with LGGs were considered disease positive while patients with HGGs were considered disease negative.To determine what clinical features and methodological features affect the accuracy of MR perfusion. Our search strategy used two concepts: (1) glioma and the various histologies of interest, and (2) MR perfusion. We used structured search strategies appropriate for each database searched, which included: MEDLINE

  14. Low testosterone level is an independent risk factor for high-grade prostate cancer detection at biopsy.

    Science.gov (United States)

    Park, Juhyun; Cho, Sung Yong; Jeong, Seung-Hwan; Lee, Seung Bae; Son, Hwancheol; Jeong, Hyeon

    2016-08-01

    To investigate the relationship between low testosterone levels and prostate cancer detection risk in a biopsy population. In all, 681 men who underwent initial 12-core transrectal prostate biopsy at our institution were included in this retrospective study. Patients were divided into groups with low (levels (≥300 ng/dL). Clinical and pathological data were analysed. Among 681 men, 86 men (12.6%) had low testosterone levels, 143 (32.7%) had a positive biopsy, and 99 (14.5%) had high-grade prostate cancer. The mean age, prostate-specific antigen (PSA) level, PSA density, body mass index (BMI), number of abnormal digital rectal examination (DRE) findings, and diabetes mellitus (DM) history were significantly different between the low and normal level testosterone groups. A low testosterone level was significantly associated with a higher risk of detection of overall prostate cancer than a normal testosterone level in univariate analysis (odds ratio [OR] 2.545, P = 0.001), but not in multivariate analysis adjusting for parameters such as age, PSA, prostate volume, BMI, abnormal DRE findings and DM (OR 1.583, P = 0.277). Meanwhile, a low testosterone level was significantly related to a higher rate of high-grade prostate cancer compared with a normal testosterone level in univariate (OR 3.324, P level is an independent risk factor for high-grade prostate cancer detection at biopsy. Therefore, checking testosterone levels could help to determine whether prostate biopsy should be carried out. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

  15. Cytokeratin 5/6 expression, prognosis, and association with estrogen receptor α in high-grade serous ovarian carcinoma.

    Science.gov (United States)

    Taube, Eliane Tabea; Denkert, Carsten; Sehouli, Jalid; Unger, Ulrike; Kunze, Catarina Alisa; Budczies, Jan; Dietel, Manfred; Braicu, Elena; Darb-Esfahani, Silvia

    2017-09-01

    High-grade serous ovarian carcinoma remains one of the most lethal malignancies in women. For histopathologic differentiation from mesothelioma cytokeratin, 5/6 immunohistochemistry is widely used. Another preferred marker for differential diagnosis to mesothelioma is estrogen receptor α (ER-α). In this study, we determined the rate of cytokeratin 5/6-positive cells in primary high-grade serous carcinoma. A cohort of 215 patients with high-grade serous ovarian carcinoma was evaluated immunohistochemically for the protein expression of cytokeratin 5/6. Most tumors demonstrated at least partly positive for cytokeratin 5/6 (n=148; 68.3%), showing different staining patterns from scattered stained cells to a diffuse staining, at times with a distinctive tumor-stroma border motif. Sixty-seven (31%) were entirely negative. No correlation of cytokeratin immunoreactivity score (IRS) with conventional staging parameters could be demonstrated. From the different IRS values for cytokeratin 5/6, IRS=12 (n=6; 2.9%) seemed to indicate a worse prognosis, albeit not statistically significant. An association with ER-α expression could not be detected but the combination of cytokeratin 5/6 IRS=12 and ER-α negativity resulted in a significant negative prognostic marker (overall survival: P=.003 and progression-free survival: Pcarcinoma with various staining patterns, an important fact for the routine differential diagnosis with mesothelioma. Furthermore, cytokeratin 5/6 in combination with ER-α proved to be a negative prognostic marker, wherefore we suggest further investigation of its biological significance and possible manifestation of a basal differentiation. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells.

    Science.gov (United States)

    Thériault, Brigitte L; Cybulska, Paulina; Shaw, Patricia A; Gallie, Brenda L; Bernardini, Marcus Q

    2014-12-21

    Previously, it has been shown that KIF14 mRNA is overexpressed in ovarian cancer (OvCa), regardless of histological subtype. KIF14 levels are independently predictive of poor outcome and increased rates of recurrence in serous OvCa patients. Furthermore, it has been shown that KIF14 also controls the in vivo tumorigenicity of OvCa cell lines. In this study, we evaluate the potential of KIF14 as a therapeutic target through selective inhibition of KIF14 in primary high-grade serous patient-derived OvCa cells. To assess the dependence of primary serous OvCa cultures on KIF14, protein levels in 11 prospective high grade serous ovarian cancer samples were increased (KIF14 overexpression by transfection) or decreased (anti-KIF14 shRNA) in vitro, and proliferative capacity, anchorage independence and xenograft growth were assessed. Seven of eleven samples demonstrated increased/decreased in vitro proliferation in response to KIF14 overexpression/knockdown, respectively. When examining in vitro tumorigenicity (colony formation) and in vivo growth (subcutaneous xenografts) in response to KIF14 manipulation, none of the samples demonstrated growth in soft agar (11 samples), or xenograft growth (4 samples). Although primary high-grade serous OvCa cells may depend on KIF14 for in vitro proliferation we were unable to demonstrate a role for KIF14 on tumorigenicity or develop an in vivo model for assessment. We have, however developed an effective in vitro method to evaluate the effect of target gene manipulation on the proliferative capacity of primary OvCa cultures.

  17. BMP and TGFbeta pathways in human central chondrosarcoma: enhanced endoglin and Smad 1 signaling in high grade tumors

    Science.gov (United States)

    2012-01-01

    Background As major regulators of normal chondrogenesis, the bone morphogenic protein (BMP) and transforming growth factor β (TGFB) signaling pathways may be involved in the development and progression of central chondrosarcoma. In order to uncover their possible implication, the aim of this study was to perform a systematic quantitative study of the expression of BMPs, TGFBs and their receptors and to assess activity of the corresponding pathways in central chondrosarcoma. Methods Gene expression analysis was performed by quantitative RT-PCR in 26 central chondrosarcoma and 6 healthy articular cartilage samples. Expression of endoglin and nuclear localization of phosphorylated Smad1/5/8 and Smad2 was assessed by immunohistochemical analysis. Results The expression of TGFB3 and of the activin receptor-like kinase ALK2 was found to be significantly higher in grade III compared to grade I chondrosarcoma. Nuclear phosphorylated Smad1/5/8 and Smad2 were found in all tumors analyzed and the activity of both signaling pathways was confirmed by functional reporter assays in 2 chondrosarcoma cell lines. Immunohistochemical analysis furthermore revealed that phosphorylated Smad1/5/8 and endoglin expression were significantly higher in high-grade compared to low-grade chondrosarcoma and correlated to each other. Conclusions The BMP and TGFβ signaling pathways were found to be active in central chondrosarcoma cells. The correlation of Smad1/5/8 activity to endoglin expression suggests that, as described in other cell types, endoglin could enhance Smad1/5/8 signaling in high-grade chondrosarcoma cells. Endoglin expression coupled to Smad1/5/8 activation could thus represent a functionally important signaling axis for the progression of chondrosarcoma and a regulator of the undifferentiated phenotype of high-grade tumor cells. PMID:23088614

  18. Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

    Science.gov (United States)

    Feldman, C H; Liu, J; Feldman, S; Solomon, D H; Kim, S C

    2017-06-01

    Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving

  19. Phase transitions in diglyceride monolayers studied by computer simulations, pressure-area isotherms and x-ray diffraction

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Toxværd, S.; Larsen, N.B.

    1994-01-01

    1,2-sn-diglyceride monolayers exhibit unique and complex phase transitions as a function of surface pressure. The dynamical response of the layer on expanding the film has been investigated by computer simulations, (π-A) isotherms and grazing-incidence X-ray diffraction. Good agreement is found b...

  20. MFH Mimic in Breast: A High-Grade Malignant Phyllodes Tumor

    OpenAIRE

    Hemalatha, A. L.; Sindhuram, V. Sumana; Asha, U.

    2012-01-01

    Malignant phyllodes tumor is usually diagnosed by the presence of benign duct-like epithelium and malignant mesenchymal tissue. In addition to the usual fibrosarcomatous features, the mesenchymal component may show areas resembling osteogenic sarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, malignant mesenchymoma, and, very rarely, malignant fibrous histiocytoma. We present one such rare case of malignant phyllodes tumor with malignant fibrous histiocytoma-like stromal ...

  1. Cytohistological correlation of endocervical gland involvement with high-grade squamous intraepithelial lesions

    Directory of Open Access Journals (Sweden)

    G Kir

    2012-01-01

    Conclusion: Diagnosis of HSIL-EGI may be possible on Pap smears with a high positive predictive value and specificity but low sensitivity, possibly due to cytological sampling limitations. To clarify the results of the present study, more extensive studies with a particular emphasis on the sampling of the endocervical glandular area for cytological evaluation of the cervix are needed.

  2. Controlled rehabilitative and supportive care intervention trials in patients with high-grade gliomas and their caregivers

    DEFF Research Database (Denmark)

    Piil, K; Juhler, M; Jakobsen, J

    2016-01-01

    training improves functional outcome and massage therapy reduces stress. Patients and caregivers found that telephone follow-up and a specialist nurse function was an effective and useful way to achieve information and support. Finally, psycho-education increased feelings of mastery among caregivers......, quantitative and mixed methods primary studies in mixed study reviews. RESULTS: The search yielded 914 unique publications, of which 9 were classified eligible for this review. There is preliminary evidence that cognitive group therapy improves memory skills in patients with high-grade gliomas, early physical...

  3. The effect of out-of-furnace treatment on the properties of high-grade medium-carbon structural steel

    Directory of Open Access Journals (Sweden)

    T. Lipiński

    2010-01-01

    Full Text Available The experimental material consisted of high-grade, medium-carbon, semi-finished structural steel. The production process involved two melting technologies: in a 140-ton basic arc furnace with desulphurisation and argon refining variants, and in a 100-ton oxygen converter. Following heat treatment, rolled samples with a diameter of 10 mm were subjected to fatigue tests. Heat treatment involved quenching from a temperature of 1153 K and tempering at a temperature of 473, 673 and 783 K. Fatigue tests were performed with the use of a rotary bending machine at a frequency of 6000 cpm. The results were processed and presented in graphic form.

  4. Radiographic and clinical outcomes after instrumented reduction and transforaminal lumbar interbody fusion of mid and high-grade isthmic spondylolisthesis.

    Science.gov (United States)

    Goyal, Nitin; Wimberley, David W; Hyatt, Adam; Zeiller, Steve; Vaccaro, Alexander R; Hilibrand, Alan S; Albert, Todd J

    2009-07-01

    Retrospective cohort study. The objective of this study is to document and review the surgical technique and the clinical and radiographic outcomes after instrumented reduction and transforaminal lumbar interbody fusion of mid and high-grade adult isthmic spondylolisthesis. Although high-grade slips make up a distinct minority of all patients afflicted with spondylolisthesis, approximately 2% in most series, the treatment of this small cohort of patients has been the topic of on going, and often heated debate. Recently, there has been a trend in the literature toward the combination of instrumented posterior spinal fusion (PSF) and interbody fusion with or without reduction. Although spine surgeons have used this procedure as a tool to treat patient's with spondylolisthesis of any cause, there is no report in the literature describing the results of neural element decompression, transforaminal interbody fusion (TLIF) reduction, and instrumented PSF of the listhetic vertebrae in the treatment of high and mid-grade isthmic spondylolisthesis. From 1999 to 2003, 13 patients with mid and high-grade isthmic spondylolisthesis (Meyerding grades II, III, or IV) who failed conservative treatment were treated by posterior lumbar decompression, TLIF at the disk space of the level of the slip, instrumented PSF, and reduction of the listhetic vertebrae. Standing lumbar radiographs were taken preoperatively, at the time of the initial postoperative visit and at regular intervals thereafter. Several radiographic parameters were noted including degree of anterolisthesis, slip angle, sacral inclination, and disk height. Statistical comparisons were made with 2-tailed paired t tests. The average anterolisthesis, normalized to the superior endplate diameter, was 51.0%+/-16.6% preoperatively, 13.2%+/-11.8% immediately postoperative, and 17.0%+/-12.6% at final follow-up (Table 1). Of the 10 patients with sufficient radiographic follow-up, all but one had radiographic evidence of solid

  5. Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study

    OpenAIRE

    Del Mistro, Annarosa; Matteucci, Mario; Insacco, Egle Alba; Onnis, GianLibero; Da Re, Filippo; Baboci, Lorena; Zorzi, Manuel; Minucci, Daria

    2015-01-01

    Background. The aim of this retrospective observational study of women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was to assess the long-term risk of residual/recurrent high-grade CIN. Materials and Methods. We evaluated 760 women treated by loop electrosurgical excision procedure (684) or conization (76) between 2000 and 2009, and followed up to June 30, 2014 (median follow-up 6.7 years, range 4–14). Visits every 6 months for the first year after treatment and y...

  6. The PET-F.D.G. predicts the high grade recurrent gliomas survival treated by the association of bevacizumab-irinotecan; La TEP-FDG predit la survie des gliomes de haut grade recidivants traites par l'association bevacizumab-irinotecan

    Energy Technology Data Exchange (ETDEWEB)

    Colavolpe, C.; Guedj, E.; Mancini, J.; Bequet-Boucard, C.; Metellus, P.; Barrie, M.; Figarella-Branger, D.; Chinot, O.; Mundler, O. [CHU La Timone, Marseille, (France)

    2009-05-15

    The objective is to evaluate the prognosis value independent of the PET-F.D.G. on the global survival and without progression of recurred high grade gliomas treated by bevacizumab and irinotecan, in comparison with the others prognosis factors of the recurrence. In conclusions, the comparison of the F.D.G. fixation between the tumor area and contralateral one before anti-angiogenic treatment has a prognosis value independent on the global survival and without progression of recurred high grade gliomas treated by bevacizumab/irinotecan. (N.C.)

  7. Coexisting High-grade Vulvar Intraepithelial Neoplasia (VIN) and Condyloma Acuminatum - Independent Lesions Due to Different HPV Types Occurring in Immunocompromised Patients

    Science.gov (United States)

    Maniar, Kruti P.; Ronnett, Brigitte M.; Vang, Russell; Yemelyanova, Anna

    2012-01-01

    The majority of vulvar intraepithelial neoplasia (VIN) is high-grade and is related to high-risk human papillomavirus (HRHPV) (most commonly HPV16). It is considered to be the precursor of HRHPV-related vulvar squamous cell carcinoma. Vulvar condyloma acuminatum is low-risk HPV (LRHPV)-related (most commonly types 6 and 11) and has virtually no risk of neoplastic progression. While infection with multiple LR- and HRHPV types has been reported for cervical squamous intraepithelial lesions, coexisting vulvar condyloma and adjacent high-grade VIN have not been well characterized. Eleven cases of concurrent condyloma acuminatum and adjacent flat high-grade VIN and three cases of high-grade VIN with prominent condylomatous architecture were analyzed using immunohistochemical (IHC) analysis of p16 expression, in situ hybridization (ISH) for HPV detection (HPV6/11, HPV16, HPV 18, and HPV WS [types 6,11,16,18,31,33,35,45,51,52] probes), and HPV typing by PCR-based method (in select cases). All patients had underlying immunosuppressive conditions (human immunodeficiency virus infection or post-transplant therapy). Among the 11 cases of concurrent high-grade VIN and condyloma, the lesions were directly adjacent to one another in 5 cases (with 2 of these demonstrating an intimate admixture of lesions), and in 6 cases were found in separate tissue sections from the same specimen. Diffuse/strong p16 expression was seen in all high-grade VIN lesions, whereas patchy/weak staining was found in all condylomata. All condylomata contained HPV 6 or 11 as detected by ISH. All of the accompanying high-grade VIN lesions had HRHPV detected. Ten contained HPV 16 (9 by ISH, 1 by PCR), with the remaining case containing multiple HPV types by PCR. All condylomatous high-grade VIN lesions demonstrated diffuse/strong p16 expression and had evidence of HRHPV (one with HPV 16 by ISH, one with HPV 18 by ISH, and one with multiple HPV types by PCR), with no detection of HPV 6 or 11 by ISH. The

  8. Coexisting high-grade vulvar intraepithelial neoplasia (VIN) and condyloma acuminatum: independent lesions due to different HPV types occurring in immunocompromised patients.

    Science.gov (United States)

    Maniar, Kruti P; Ronnett, Brigitte M; Vang, Russell; Yemelyanova, Anna

    2013-01-01

    The majority of vulvar intraepithelial neoplasia (VIN) is high-grade and is related to high-risk human papillomavirus (HRHPV) (most commonly HPV 16). It is considered to be the precursor of HRHPV-related vulvar squamous cell carcinoma. Vulvar condyloma acuminatum is low-risk HPV (LRHPV)-related (most commonly types 6 and 11) and has virtually no risk of neoplastic progression. While infection with multiple LRHPV and HRHPV types has been reported for cervical squamous intraepithelial lesions, coexisting vulvar condyloma and adjacent high-grade VIN have not been well characterized. Eleven cases of concurrent condyloma acuminatum and adjacent flat high-grade VIN and 3 cases of high-grade VIN with prominent condylomatous architecture were analyzed using immunohistochemical analysis of p16 expression, in situ hybridization (ISH) for HPV detection [HPV 6/11, HPV 16, HPV 18, and HPV wide spectrum (types 6, 11, 16, 18, 31, 33, 35, 45, 51, 52) probes], and HPV typing by a polymerase chain reaction (PCR)-based method (in select cases). All patients had underlying immunosuppressive conditions (human immunodeficiency virus infection or posttransplant therapy). Among the 11 cases of concurrent high-grade VIN and condyloma, the lesions were directly adjacent to one another in 5 cases (with 2 of these demonstrating an intimate admixture of lesions), and in 6 cases the lesions were found in separate tissue sections from the same specimen. Diffuse/strong p16 expression was seen in all high-grade VIN lesions, whereas patchy/weak staining was found in all condylomata. All condylomata contained HPV 6 or 11 as detected by ISH. HRHPV was detected in all of the accompanying high-grade VIN lesions. Ten contained HPV 16 (9 by ISH, 1 by PCR), with the remaining case containing multiple HPV types by PCR. All condylomatous high-grade VIN lesions demonstrated diffuse/strong p16 expression and had evidence of HRHPV (1 with HPV 16 by ISH, 1 with HPV 18 by ISH, and 1 with multiple HPV types by

  9. Effect of Thin Prep® imaging system on laboratory rate and relative sensitivity of atypical squamous cells, high-grade squamous intraepithelial lesion not excluded and high-grade squamous intraepithelial lesion interpretations

    Directory of Open Access Journals (Sweden)

    Brooke R Koltz

    2013-01-01

    Full Text Available Introduction: Automated screening of Thin Prep ® Papanicolaou Tests has become increasingly common in clinical practice. Increased productivity has initiated laboratory use of the Thin Prep ® Imaging System (TIS. Increased sensitivity is a potential additional benefit of TIS. Published studies have shown an increase in discovery of dysplastic cells. This study evaluates the effect of TIS on the incidence of atypical squamous cells high-grade squamous intraepithelial lesion not excluded (ASC-H and high-grade squamous intraepithelial lesion (HGSIL results on Thin Prep ® Pap Tests by comparing TIS-assisted and manual screening findings and the diagnoses on subsequent follow-up in a screening population over a 1-year time period. Materials and Methods: A compilation of all ASC-H and HGSIL cases was prepared by conducting a computerized search over a 1-year period (7/06-6/07. The accumulated cases include Thin Prep Pap tests that were both TIS and manually screened. Follow-up results of cytologic and histologic cervical specimens were obtained for a time period extending to 2010. Interpretation utilizing TIS was in place 10 months prior to the study′s initiation. Results: During the study period 70,522 Pap tests were performed in our laboratory. One third (33% of Pap tests were screened with assistance of TIS. Manual screening was performed on 47,380 Pap tests of which 153 (0.32% were interpreted as ASC-H and 164 (0.35% were interpreted as HGSIL. During the same time period automated screening (TIS was performed on 23,111 Pap tests. Interpretation of 62 (0.27% cases provided an ASC-H result, while 71 (0.31% were HGSIL. Follow-up cervical dysplasia by colposcopic biopsy and cone biopsy was distributed proportionally between TIS and manual screening for both ASC-H and HGSIL categories. Cervical intraepithelial neoplasia (CIN II/III was identified on follow-up biopsy of 41% TIS cases and 45% manually screened cases for ASC-H. In the HGSIL subset 71

  10. Tipping Points towards Regional Forest or Urban Transition in Stressed Rural Areas: An Agent-based Modelling Application of Socio-Economic Shifts in Rural Vermont US

    Science.gov (United States)

    Tsai, Y.; Turnbull, S.; Zia, A.

    2015-12-01

    In rural areas where farming competes with urban development and environmental amenities, urban and forest transitions occur simultaneously at different locales with different rates due to the underlying socio-economic shifts. Here we develop an interactive land use transition agent-based model (ILUTABM) in which farmers' land use decisions are made contingent on expansion and location choices of urban businesses and urban residences, as well as farmers' perceived ecosystem services produced by their land holdings. The ILUTABM simulates heterogeneity in land use decisions at parcel levels by differentiating decision making processes for agricultural and urban landowners. Landowners are simulated to make land-use transition decisions as bounded rational agents that maximize their partial expected utility functions under different underlying socio-economic conditions given the category of a landowner and the spatial characteristics of the landowner's landholdings. The ILUTABM is parameterized by spatial data sets such as National Land Cover Database (NLCD), zoning, parcels, property prices, US census, farmers surveys, building/facility characteristics, soil, slope and elevation. We then apply the ILUTABM to the rural Vermont landscape, located in the Northeast Arm District of Lake Champlain and the downstream sub-watersheds of Missisquoi River, to generate phase transitions of rural land towards urban land near peri-urban areas and towards forest land near financially stressed farmlands during 2001-2051. Possible tipping point trajectories of rural land towards regional forest or urban transition are simulated under three socio-economic scenarios: business as usual (ILUTABM calibrated to 2011 NLCD), increased incentives for conservation easements, and increased incentives for attracting urban residences and businesses.

  11. Application of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2): Interobserver Agreement and Positive Predictive Value for Localization of Intermediate- and High-Grade Prostate Cancers on Multiparametric Magnetic Resonance Imaging.

    Science.gov (United States)

    Chen, Frank; Cen, Steven; Palmer, Suzanne

    2017-09-01

    To evaluate interobserver agreement with the use of and the positive predictive value (PPV) of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) for the localization of intermediate- and high-grade prostate cancers on multiparametric magnetic resonance imaging (mpMRI). In this retrospective, institutional review board-approved study, 131 consecutive patients who had mpMRI followed by transrectal ultrasound-MR imaging fusion-guided biopsy of the prostate were included. Two readers who were blinded to initial mpMRI reports, clinical data, and pathologic outcomes reviewed the MR images, identified all prostate lesions, and scored each lesion based on the PI-RADS v2. Interobserver agreement was assessed by intraclass correlation coefficient (ICC), and PPV was calculated for each PI-RADS category. PI-RADS v2 was found to have a moderate level of interobserver agreement between two readers of varying experience, with ICC of 0.74, 0.72, and 0.67 for all lesions, peripheral zone lesions, and transitional zone lesions, respectively. Despite only moderate interobserver agreement, the calculated PPV in the detection of intermediate- and high-grade prostate cancers for each PI-RADS category was very similar between the two readers, with approximate PPV of 0%, 12%, 64%, and 87% for PI-RADS categories 2, 3, 4, and 5, respectively. In our study, PI-RADS v2 has only moderate interobserver agreement, a similar finding in studies of the original PI-RADS and in initial studies of PI-RADS v2. Despite this, PI-RADS v2 appears to be a useful system to predict significant prostate cancer, with PI-RADS scores correlating well with the likelihood of intermediate- and high-grade cancers. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  12. MFH Mimic in Breast: A High-Grade Malignant Phyllodes Tumor

    Directory of Open Access Journals (Sweden)

    A. L. Hemalatha

    2012-01-01

    Full Text Available Malignant phyllodes tumor is usually diagnosed by the presence of benign duct-like epithelium and malignant mesenchymal tissue. In addition to the usual fibrosarcomatous features, the mesenchymal component may show areas resembling osteogenic sarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, malignant mesenchymoma, and, very rarely, malignant fibrous histiocytoma. We present one such rare case of malignant phyllodes tumor with malignant fibrous histiocytoma-like stromal differentiation.

  13. Differential proteomics analysis of low- and high-grade of astrocytoma using iTRAQ quantification

    OpenAIRE

    Ren T; Lin SD; Wang ZF; Shang AJ

    2016-01-01

    Tong Ren,1,* Shide Lin,2,* Zhongfeng Wang,3 Aijia Shang4 1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 2Department of Spinal Cord Injury, Institute of Orthopedics and Traumatology of Chinese PLA, General Hospital of Jinan Military Area Command, Jinan, 3State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, 4Department of Neurosurgery, General Hospital of Chinese People’s Lib...

  14. Tumour volume and high grade tumour volume are the best predictors of pathologic stage and biochemical recurrence after radical prostatectomy.

    Science.gov (United States)

    Chun, Felix K-H; Briganti, Alberto; Jeldres, Claudio; Gallina, Andrea; Erbersdobler, Andreas; Schlomm, Thorsten; Walz, Jochen; Eichelberg, Christian; Salomon, Georg; Haese, Alexander; Currlin, Eike; Ahyai, Sascha A; Bénard, François; Huland, Hartwig; Graefen, Markus; Karakiewicz, Pierre I

    2007-02-01

    Our goal was to examine to what extent tumour volume (TV) and percentage of high grade tumour volume (%HGTV) affect the rate of positive surgical margins and the rate of biochemical recurrence after radical prostatectomy. TV and %HGTV were routinely planimetrically quantified in a cohort of 780 consecutive patients. Mean follow-up was 46.7 months. Multivariable regression models addressed two separate endpoints: positive surgical margins and biochemical recurrence. The increase in model predictive accuracy related to the addition of TV and %HGTV to radical prostatectomy stage and grade was assessed, after 200 bootstrap resamples to reduce overfit bias. In multivariable logistic regression models addressing positive surgical margins rate, predictive accuracy increased by 1.9% (p<0.001) when TV was added to other covariates. No further increment was noted when %HGTV was added (p=0.3). In multivariable Cox regression models addressing biochemical recurrence, accuracy increased by 0.6% (p=0.002) when TV was added and an additional increase of 0.7% was recorded when %HGTV (p<0.001) was added. Tumour bulk reflected by TV affects local cancer control rate, which is reflected in the rate of positive surgical margins. Conversely, high grade cancer determines the rate of biochemical recurrence. These two variables represent the most powerful predictors of cancer control in men treated for localised prostate cancer. Moreover, they increase the ability of established predictors to predict the outcomes of interest. In consequence, they warrant consideration in future predictive and prognostic tools.

  15. The Impact of Seat belts and Airbags on High Grade Renal Injuries and Nephrectomy Rates in Motor Vehicle Collisions

    Science.gov (United States)

    Bjurlin, Marc A; Fantus, Richard J.; Mellett, Michele M.; Fantus, Richard J.; Villines, Dana

    2015-01-01

    Purpose Motor vehicle collisions (MVCs) are the most common cause of blunt genitourinary trauma. We compared renal injuries with no protective device to those with seat belts and/or airbags utilizing the National Trauma Data Bank (NTDB). Our primary endpoint was a reduction in high-grade renal injuries (grades III-V) with a secondary endpoint of reduction in nephrectomy rate. Materials and Methods The NTDB research datasets, admission year 2010, 2011, and 2012, were queried for MVC occupants with renal injury. Subjects were stratified by protective device and airbag deployment. Abbreviated Injury Score was converted to American Association for the Surgery of Trauma renal injury grade and nephrectomy rates were evaluated. Intergroup comparisons were analyzed for renal injury grades, nephrectomy, length of stay, and mortality with chi-square or one-way ANOVA. Protective device relative risk reduction was determined. Results A review of 466,028 MVCs revealed 3,846 renal injuries. Injured occupants without a protective device had a higher rate of high grade renal injury (45.1%) compared to those with seat belts (39.9%, p=0.008), airbags (42.3%, p=0.317), and seat belts with airbags (34.7%, pbelts (20.0%, pbelts with airbags (13.3%, pbelts and airbags. PMID:24846798

  16. The impact of seat belts and airbags on high grade renal injuries and nephrectomy rate in motor vehicle collisions.

    Science.gov (United States)

    Bjurlin, Marc A; Fantus, Richard Jacob; Fantus, Richard Joseph; Mellett, Michele M; Villines, Dana

    2014-10-01

    Motor vehicle collisions are the most common cause of blunt genitourinary trauma. We compared renal injuries with no protective device to those with seat belts and/or airbags using NTDB. Our primary end point was a decrease in high grade (grades III-V) renal injuries with a secondary end point of a nephrectomy rate reduction. The NTDB research data sets for hospital admission years 2010, 2011 and 2012 were queried for motor vehicle collision occupants with renal injury. Subjects were stratified by protective device and airbag deployment. The AIS was converted to AAST renal injury grade and nephrectomy rates were evaluated. Intergroup comparisons were analyzed for renal injury grades, nephrectomy, length of stay and mortality using the chi-square test or 1-way ANOVA. The relative risk reduction of protective devices was determined. A review of 466,028 motor vehicle collisions revealed a total of 3,846 renal injuries. Injured occupants without a protective device had a higher rate of high grade renal injuries (45.1%) than those with seat belts (39.9%, p = 0.008), airbags (42.3%, p = 0.317) and seat belts plus airbags (34.7%, p belts (20.0%), airbags (10.5%) and seat belts plus airbags (13.3%, each p belts and airbags. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  17. Acute kidney injury in patients with newly diagnosed high-grade hematological malignancies: impact on remission and survival.

    Directory of Open Access Journals (Sweden)

    Emmanuel Canet

    Full Text Available BACKGROUND: Optimal chemotherapy with minimal toxicity is the main determinant of complete remission in patients with newly diagnosed hematological malignancies. Acute organ dysfunctions may impair the patient's ability to receive optimal chemotherapy. DESIGN AND METHODS: To compare 6-month complete remission rates in patients with and without acute kidney injury (AKI, we collected prospective data on 200 patients with newly diagnosed high-grade malignancies (non-Hodgkin lymphoma, 53.5%; acute myeloid leukemia, 29%; acute lymphoblastic leukemia, 11.5%; and Hodgkin disease, 6%. RESULTS: According to RIFLE criteria, 137 (68.5% patients had AKI. Five causes of AKI accounted for 91.4% of cases: hypoperfusion, tumor lysis syndrome, tubular necrosis, nephrotoxic agents, and hemophagocytic lymphohistiocytosis. Half of the AKI patients received renal replacement therapy and 14.6% received suboptimal chemotherapy. AKI was associated with a lower 6-month complete remission rate (39.4% vs. 68.3%, P<0.01 and a higher mortality rate (47.4% vs. 30.2%, P<0.01 than patients without AKI. By multivariate analysis, independent determinants of 6-month complete remission were older age, poor performance status, number of organ dysfunctions, and AKI. CONCLUSION: AKI is common in patients with newly diagnosed high-grade malignancies and is associated with lower complete remission rates and higher mortality.

  18. High-grade spondylolisthesis: gradual reduction using Magerl's external fixator followed by circumferential fusion technique and long-term results.

    Science.gov (United States)

    Karampalis, Christos; Grevitt, Michael; Shafafy, Masood; Webb, John

    2012-05-01

    To report the results of a cohort of patients treated with this technique high lighting radiological and functional outcomes, discussing also benefits arising from a gradual reduction procedure compared with other techniques. We evaluated nine patients who have undergone high-grade listhesis reduction and circumferential fusion at our institution from 1988 to 2006. Average length of follow-up was 11 years (5-19). Functional outcomes and radiological measurements were recorded and reported. Slip magnitude was reduced by an average of 2.9 grades (Meyerding classification). Slip angle improved by an average of 66% (p = 0.0001), lumbosacral angle by 47% (p = 0.0002), sacral rotation by 51% (p = 0.0068) and sacral inclination by 47% (p = 0.0055). At the latest follow-up 88.9% had achieved solid fusion. Post-operative 10-point Visual Analogue Score (VAS) for back pain had improved by 70% (p Average postoperative Oswestry Disability Index for all patients was 8% (range 0-16%) and that for Low Back Outcome Scores was 56.6 (range 44-70). All components of Short Form 36 Health Survey were greater than 80%. Overall patients' expectations were met in 100%. This is an effective and safe technique which addresses the lumbosacral kyphosis and cosmetic deformity without the neurological complications which accompany other reduction and fusion techniques for high-grade spondylolisthesis.

  19. Pancreatic Metastasis of High-Grade Papillary Serous Ovarian Carcinoma Mimicking Primary Pancreas Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Yusuf Gunay

    2012-01-01

    Full Text Available Introduction. Reports of epithelial ovarian carcinomas metastatic to the pancreas are very rare. We herein present a metastasis of high grade papillary serous ovarian cancer to mid portion of pancreas. Case. A 42-year-old patient was admitted with a non-specified malignant cystic lesion in midportion of pancreas. She had a history of surgical treatment for papillary serous ovarian adenocarcinoma. A cystic lesion was revealed by an abdominal computerized tomography (CT performed in her follow up . It was considered as primary mid portion of pancreatic cancer and a distal pancreatectomy was performed. The final pathology showed high-grade papillary serous adenocarcinoma morphologically similar to the previously diagnosed ovarian cancer. Discussion. Metastatic pancreatic cancers should be considered in patients who present with a solitary pancreatic mass and had a previous non-pancreatic malignancy. Differential diagnosis of primary pancreatic neoplasm from metastatic malignancy may be very difficult. A biopsy for tissue confirmation is required to differentiate primary and secondary pancreatic tumors. Although, the value of surgical resection is poorly documented, resection may be considered in selected patients. Conclusion. Pancreatic metastasis of ovarian papillary serous adenocarcinoma has to be kept in mind when a patient with pancreatic mass has a history of ovarian malignancy.

  20. Predictors of local recurrence in high-grade soft tissue sarcomas: hydrogen peroxide as a local adjuvant.

    Science.gov (United States)

    Wooldridge, Adam N; Kolovich, Gregory P; Crist, Martha K; Mayerson, Joel L; Scharschmidt, Thomas J

    2013-02-01

    Soft tissue sarcomas have a mortality rate of 40% to 60%, with local recurrence being a poor prognostic factor for overall survival. Three-percent nondiluted hydrogen peroxide is hypothesized to be an effective local adjuvant. The purpose of this study was to identify risk factors for local recurrence in high-grade soft tissue sarcomas and to determine whether using hydrogen peroxide as a local adjuvant reduced the risks of local recurrence and surgical-site infection. Retrospective data were collected for 106 patients surgically treated for high-grade soft tissue sarcomas between 2002 and 2010. The primary endpoint was local recurrence. Eighteen (16.98%) cases of local recurrence occurred. Predictors of local recurrence were margin status, estimated blood loss, and histology (ie, malignant peripheral nerve sheath tumor), with hazard ratios of 4.44 (95% confidence interval [CI], 1.32-14.95), 1.19 (95% CI, 1.06-1.35), and 9.21 (95% CI, 2.11-40.16), respectively. Hydrogen peroxide yielded a statistically insignificant improvement in local recurrence, with a hazard ratio of 0.81 (95% CI, 0.27-2.48) and a reduced risk of surgical site infection, with a hazard ratio of 0.52 (95% CI, 0.15-1.81). Margin status, increased blood loss, and histologic subtype are associated with increased local recurrence risk. Using hydrogen peroxide improved local control and infection rates, but the difference was not statistically significant. Copyright 2013, SLACK Incorporated.

  1. Plasmin(ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer.

    Science.gov (United States)

    Zhao, Shuo; Dorn, Julia; Napieralski, Rudolf; Walch, Axel; Diersch, Sandra; Kotzsch, Matthias; Ahmed, Nancy; Hooper, John D; Kiechle, Marion; Schmitt, Manfred; Magdolen, Viktor

    2017-06-27

    In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed. In univariate Cox regression analysis, PLG staining was positively associated with prolonged overall survival (OS) [hazard ratio (HR)=0.59, p=0.026] of the patients. In multivariable analysis, PLG, together with residual tumor mass, remained a statistically significant independent prognostic marker (HR=0.49, p=0.009). In another small patient cohort (n=29), we assessed mRNA expression levels of PLG by quantitative PCR. Here, elevated PLG mRNA levels were also significantly associated with prolonged OS of patients (Kaplan-Meier analysis; p=0.001). This finding was validated by in silico analysis of a microarray data set (n=398) from The Cancer Genome Atlas (Kaplan-Meier analysis; p=0.031). In summary, these data indicate that elevated PLG expression represents a favorable prognostic biomarker in advanced (FIGO III/IV) high-grade serous ovarian cancer.

  2. Multivoxel magnetic resonance spectroscopy identifies enriched foci of cancer stem-like cells in high-grade gliomas

    Directory of Open Access Journals (Sweden)

    He T

    2017-01-01

    Full Text Available Tao He,1–3,* Tianming Qiu,4,* Xiaodong Wang,5 Hongxing Gui,6 Xilong Wang,2 Qikuan Hu,3,7 Hechun Xia,2 Gaoyang Qi,1,2 Jinsong Wu,4 Hui Ma2 1Clinical Medicine College, Ningxia Medical University, 2Department of Neurosurgery, General Hospital of Ningxia Medical University, 3Ningxia Key Laboratory of Cerebrocranial Diseases, The National Key Laboratory Incubation Base, Yinchuan, 4Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 5Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 6Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School of Rutgers University, Piscataway, NJ, USA; 7Department of Physiology, Ningxia Medical University, Yinchuan, People’s Republic of China *These authors contributed equally to this work Objective: This study investigated the correlation between choline/creatine (Cho/Cr ratios determined by multivoxel proton magnetic resonance spectroscopy (1H-MRS and the distribution of cancer stem-like cells (CSLCs in high-grade gliomas. Patients and methods: Sixteen patients with high-grade gliomas were recruited and underwent 1H-MRS examination before surgery to identify distinct tumor regions with variable Cho/Cr ratios. Using intraoperative neuronavigation, tumor tissues were accurately sampled from regions with high and low Cho/Cr ratios within each tumor. The distribution of CSLCs in samples from glioma tissue regions with different Cho/Cr ratios was quantified by neurosphere culture, immunohistochemistry, and Western blot. Results: The mean neurosphere formation rate in tissues with high Cho/Cr ratios was significantly increased compared with that in low Cho/Cr ratio tissues (13.94±5.94 per 100 cells vs 8.04±3.99 per 100 cells, P<0.001. Immunohistochemistry indicated that tissues with high Cho/Cr ratios had elevated expression of CD133, nestin, and CD15, relative to low Cho/Cr ratio tissue

  3. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia: A case-control study among Chinese adults

    National Research Council Canada - National Science Library

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-01-01

    Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully...

  4. A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

    Science.gov (United States)

    2017-11-07

    Adult Anaplastic Astrocytoma; Recurrent Grade III Glioma; Recurrent Grade IV Glioma; Adult Anaplastic Oligodendroglioma; Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Adult Anaplastic Oligoastrocytoma; Recurrent High Grade Glioma

  5. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  6. Human papillomavirus viral load in predicting high-grade CIN in women with cervical smears showing only atypical squamous cells or low-grade squamous intraepithelial lesion

    OpenAIRE

    Santos,André Luis Ferreira; Derchain,Sophie Françoise Mauricette; Martins,Marcos Roberto; Sarian,Luís Otávio Zanatta; Martinez,Edson Zangiacome; Syrjänen,Kari Juhani

    2003-01-01

    CONTEXT: Human papillomavirus (HPV) viral load may have an important role in predicting high-grade cervical intraepithelial neoplasia (CIN) in women with cervical smears showing atypical squamous cells or LSIL. OBJECTIVE: To determine whether the assessment of the viral load of high-risk HPV DNA is useful in predicting the detection of high-grade cervical intraepithelial neoplasia (CIN2 and 3) in women referred because of cervical smears showing only atypical squamous cells or LSIL. TYPE OF S...

  7. Zircon U-Pb ages and geochemistry of newly discovered Neoproterozoic orthogneisses in the Mishan region, NE China: Constraints on the high-grade metamorphism and tectonic affinity of the Jiamusi-Khanka Block

    Science.gov (United States)

    Yang, Hao; Ge, Wen-chun; Zhao, Guo-chun; Bi, Jun-hui; Wang, Zhi-hui; Dong, Yu; Xu, Wen-liang

    2017-01-01

    The Jiamusi-Khanka Block, located in the easternmost segment of the Central Asian Orogenic Belt (CAOB), is one of the least understood blocks in northeastern China. The age of its basement, the timing of the high-grade metamorphism, and the tectonic affinity of this block have all been subjects of controversy. Here we describe newly discovered Neoproterozoic orthogneisses from the Mishan region in the central Jiamusi-Khanka Block. SIMS and LA-ICP-MS U-Pb dating of the magmatic cores of zircons from three of these high-grade orthogneisses yielded weighted mean ages that range from 898 ± 4 to 891 ± 13 Ma, indicating that early Neoproterozoic magmatism did occur in the Jiamusi-Khanka Block. Twenty-two analyses of metamorphic zircons (rims as well as some grains) gave two groups of concordant ages, one at ca. 563 Ma, interpreted as the timing of the high-grade metamorphism, and the other around 518-496 Ma, interpreted as representing a subsequent retrograde metamorphism. The orthogneisses represent metamorphosed peraluminous syn-collisional syenogranites with SiO2 = 71.29-78.08 wt%, A/CNK = 1.06-1.99, and Na2O/K2O = 0.03-1.49, and they belong chemically to the high-potassium calc-alkaline series. They have low Sr (32-134 ppm) contents and Sr/Y ratios (1.6-16.9), and display strongly fractionated to nearly flat REE patterns with negative Eu anomalies (δEu = 0.22-0.95) and depletions in Nb-Ta. These geochemical characteristics suggest that the syenogranitic rocks were derived under low pressures from a crustal source with a high proportion of sedimentary rocks, perhaps in a subduction-related setting that was undergoing transition from compression to extension. In the context of the reconstruction of Gondwana, the ca. 898-891 Ma magmatic activity and the ca. 563 Ma high-grade metamorphism in the Mishan region provide constraints on the possible linkages between the Jiamusi-Khanka Block and East Gondwana during the Neoproterozoic to early Paleozoic.

  8. Diagnostic Values of DCE-MRI and DSC-MRI for Differentiation Between High-grade and Low-grade Gliomas: A Comprehensive Meta-analysis.

    Science.gov (United States)

    Liang, Jianye; Liu, Dexiang; Gao, Peng; Zhang, Dong; Chen, Hanwei; Shi, Changzheng; Luo, Liangping

    2018-03-01

    This study aimed to collect the studies on the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and dynamic susceptibility contrast MRI (DSC-MRI) in differentiating the grades of gliomas, and evaluate the diagnostic performances of relevant quantitative parameters in glioma grading. We systematically searched studies on the diagnosis of gliomas with DCE-MRI or DSC-MRI in Medline, PubMed, China National Knowledge Infrastructure database, Cochrane Library, and Embase published between January 2005 and December 2016. Standardized mean differences and 95% confidence intervals were calculated for volume transfer coefficient (K trans ), volume fraction of extravascular extracellular space (V e ), rate constant of backflux (K ep ), relative cerebral blood volume (rCBV), and relative cerebral blood flow (rCBF) using Review Manager 5.2 software. Sensitivity, specificity, area under the curve (AUC), and Begg test were calculated by Stata 12.0. Twenty-two studies with available outcome data were included in the analysis. The standardized mean difference of K trans values between high-grade glioma and low-grade glioma were 1.18 (0.91, 1.45); V e values were 1.43 (1.06, 1.80); K ep values were 0.65 (-0.05, 1.36); rCBV values were 1.44 (1.08, 1.81); and rCBF values were 1.17 (0.68, 1.67), respectively. The results were all significant statistically (P values (P = .07), and high-grade glioma had higher K trans , V e , rCBV, and rCBF values than low-grade glioma. AUC values of K trans , V e , rCBV, and rCBF were 0.90, 0.88, 0.93, and 0.73, respectively; rCBV had the largest AUC among the four parameters (P < .05). Both DCE-MRI and DSC-MRI are reliable techniques in differentiating the grades of gliomas, and rCBV was found to be the most sensitive one. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  9. Phase I Clinical Trial Assessing Temozolomide and Tamoxifen With Concomitant Radiotherapy for Treatment of High-Grade Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Shilpen, E-mail: Shilpenp@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, WA (United States); DiBiase, Steven [Robert Wood Johnson School of Medicine, Camden, NJ (United States); Meisenberg, Barry [DeCesaris Cancer Institute, Annapolis, MD (United States); Flannery, Todd [Princeton Radiation Oncology, Princeton, NJ (United States); Patel, Ashish [Division of Radiation Oncology, Abington Memorial Hospital, Abington, PA (United States); Dhople, Anil [MIMA Cancer Center, Melbourne, FL (Australia); Cheston, Sally; Amin, Pradip [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States)

    2012-02-01

    Purpose: The new standard treatment of glioblastoma multiforme is concurrent radiotherapy (RT) and temozolomide. The proliferation of high-grade gliomas might be partly dependent on protein kinase C-mediated pathways. Tamoxifen has been shown in vitro to inhibit protein kinase C through estrogen receptor-independent antineoplastic effects. This Phase I trial was designed to determine the maximal tolerated dose (MTD) of tamoxifen when given with temozolomide and concurrent RT to patients with high-grade gliomas. Methods and Materials: A total of 17 consecutive patients in four cohorts with World Health Organization Grade 3 (n = 2) and 4 (n = 15) gliomas were given tamoxifen twice daily during 6 weeks of concurrent RT and temozolomide. Eligibility included histologic diagnosis, age >18 years old, Karnofsky performance status {>=}60, and no previous brain RT or chemotherapy. The starting dose was 50 mg/m{sup 2} divided twice daily. If no dose-limiting toxicities (DLTs) occurred in 3 patients, the dose was escalated in 25-mg/m{sup 2} increments until the MTD was reached. When {>=}2 patients within a cohort experienced a DLT, the MTD had been exceeded. Temozolomide was given with RT at 75 mg/m{sup 2}. A dose of 60 Gy in 2 Gy/d fractions to a partial brain field was delivered. Results: A total of 6 patients in Cohort 4 had received tamoxifen at 125 mg/m{sup 2}. One patient was excluded, and the fourth patient developed Grade 4 thrombocytopenia (DLT). Thus, 3 more patients needed to be enrolled. A deep venous thrombosis (DLT) occurred in the sixth patient. Thus, the MTD was 100 mg/m{sup 2}. Conclusions: The MTD of tamoxifen was 100 mg/m{sup 2} when given concurrently with temozolomide 75 mg/m{sup 2} and RT. Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy.

  10. Is Nonoperative Management the Best First-line Option for High-grade Renal trauma? A Systematic Review.

    Science.gov (United States)

    Sujenthiran, Arunan; Elshout, Pieter Jan; Veskimae, Erik; MacLennan, Steven; Yuan, Yuhong; Serafetinidis, Efraim; Sharma, Davendra M; Kitrey, Noam D; Djakovic, Nenad; Lumen, Nicolaas; Kuehhas, Franklin E; Summerton, Duncan J

    2017-05-29

    The management of high-grade (Grade IV-V) renal injuries remains controversial. There has been an increase in the use of (NOM) but limited data exists comparing outcomes with open surgical exploration. To conduct a systematic review to determine if NOM is the best first-line option for high-grade renal trauma in terms of safety and effectiveness. Medline, Embase, and Cochrane Library were searched for all relevant publications, without time or language limitations. The primary harm outcome was overall mortality and the primary benefit outcome was renal preservation rate. Secondary outcomes included length of hospital stay and complication rate. Single-arm studies were included as there were few comparative studies. Only studies with more than 50 patients were included. Data were narratively synthesised in light of methodological and clinical heterogeneity. The risk of bias of each included study was assessed. Seven nonrandomised comparative and four single-arm studies were selected for data extraction. Seven hundred and eighty-seven patients were included from the comparative studies with 535 patients in the NOM group and 252 in the open surgical exploration group. A further 825 patients were included from single-arm studies. Results from comparative studies: overall mortality: NOM (0-3%), open surgical exploration (0-29%); renal preservation rate: NOM (84-100%), open surgical exploration (0-82%); complication rate: NOM (5-32%), open surgical exploration (10-76%). Overall mortality and renal preservation rate were significantly better in the NOM group whereas there was no statistical difference with regard to complication rate. Length of hospital stay was found be significantly reduced in the NOM group. Patients in the open surgical exploration group were more likely to have Grade V injuries, have a lower systolic blood pressure, and higher injury severity score on admission. No randomised controlled trials were identified and significant heterogeneity existed with

  11. Loss of Raf-1 kinase inhibitor protein (RKIP) is strongly associated with high-grade tumor budding and correlates with an aggressive phenotype in pancreatic ductal adenocarcinoma (PDAC)

    Science.gov (United States)

    2013-01-01

    Background Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor in a variety of human cancers and is known to inhibit Ras/Raf/MEK/ERK signaling. By suppressing the activation of the NFkB/SNAIL circuit, RKIP can regulate the induction of epithelial-mesenchymal transition (EMT). The aim of this study was to evaluate RKIP expression and to determine its association with clinicopathological features, including EMT in form of tumor budding in pancreatic ductal adenocarcinoma (PDAC). Methods Staining for RKIP was performed on a multipunch Tissue Microarray (TMA) of 114 well-characterized PDACs with clinico-pathological, follow-up and adjuvant therapy information. RKIP-expression was assessed separately in the main tumor body and in the tumor buds. Another 3 TMAs containing normal pancreatic tissue, precursor lesions (Pancreatic Intraepithelial Neoplasia, PanINs) and matched lymph node metastases were stained in parallel. Cut-off values were calculated by receiver operating characteristic (ROC) curve analysis. Results We found a significant progressive loss of RKIP expression between normal pancreatic ductal epithelia (average: 74%), precursor lesions (PanINs; average: 37%), PDAC (average 20%) and lymph node metastases (average 8%, p tumor buds (average: 6%) compared to the main tumor body (average 20%; p tumor body was marginally associated with advanced T-stage (p = 0.0599) as well as high-grade peritumoral (p = 0.0048) and intratumoral budding (p = 0.0373). RKIP loss in the buds showed a clear association with advanced T stage (p = 0.0089). Conclusions The progressive loss of RKIP seems to play a major role in the neoplastic transformation of pancreas, correlates with aggressive features in PDAC and is associated with the presence of EMT in form of tumor budding. PMID:24330423

  12. The demonstration of extension of high-grade glioma beyond magnetic resonance imaging defined edema by the use of 11 C-methionine positron emission tomography

    Directory of Open Access Journals (Sweden)

    Sridhar P Susheela

    2013-01-01

    Full Text Available The use of magnetic resonance imaging (MRI is the current standard for the delineation of target volumes for high-grade gliomas (HGG. While the peritumoral edema as per T2-weighted (T2W imaging is utilized as basis to delineate the initial borders of the clinical target volume (CTV, those areas enhancing on T1-weighted (T1W images with gadolinium contrast (T1-Gd are considered for treatment with further boost. However, recent data has emerged concerning the use of positron emission tomography (PET with 11 C-methionine, which seemingly provides additional information beyond MRI. We present the case of a gentleman with an inoperable HGG which was imaged with 11 C-methionine-PET ( 11 C-MET-PET/CT as well as MRI as part of the radiotherapy treatment planning (RTP process. The differences noted between the MRI and the PET defined volumes are presented. This being a patient who was not operated, the potentially confounding issue of surgery-induced PET-avidity is absent.

  13. Molecular MRI differentiation between primary central nervous system lymphomas and high-grade gliomas using endogenous protein-based amide proton transfer MR imaging at 3 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Shanshan [Southern Medical University, Department of Radiology, Zhujiang Hospital, Guangzhou, Guangdong (China); Johns Hopkins University School of Medicine, Department of Radiology, Baltimore, MD (United States); Yu, Hao; Wang, Xianlong; Lu, Shilong; Feng, Lyujin; Wen, Zhibo [Southern Medical University, Department of Radiology, Zhujiang Hospital, Guangzhou, Guangdong (China); Li, Yufa [Southern Medical University, Department of Pathology, Zhujiang Hospital, Guangzhou, Guangdong (China); Zhang, Yi; Heo, Hye-Young; Lee, Dong-Hoon; Zhou, Jinyuan [Johns Hopkins University School of Medicine, Department of Radiology, Baltimore, MD (United States)

    2016-01-15

    To show the ability of using the amide proton transfer-weighted (APTW) MRI signals as imaging biomarkers to differentiate primary central nervous system lymphomas (PCNSLs) from high-grade gliomas (HGGs). Eleven patients with lymphomas and 21 patients with HGGs were examined. Magnetization-transfer (MT) spectra over an offset range of ±6 ppm and the conventional MT ratio (MTR) at 15.6 ppm were acquired. The APTW signals, total chemical-exchange-saturation-transfer signal (integral between 0 and 5 ppm, CEST{sub total}), and MTR signal were obtained and compared between PCNSLs and HGGs. The diagnostic performance was assessed with the receiver operating characteristic (ROC) curve analysis. The PCNSLs usually showed more homogeneous APTW hyperintensity (spatially compared to normal brain tissue) than the HGGs. The APTW{sub max}, APTW{sub max-min} and CEST{sub total} signal intensities were significantly lower (P < 0.05, 0.001 and 0.05, respectively), while the APTW{sub min} and MTR were significantly higher (both P < 0.01) in PCNSL lesions than in HGG lesions. The APTW values in peritumoral oedema were significantly lower for PCNSLs than for HGGs (P < 0.01). APTW{sub max-min} had the highest area under the ROC curve (0.963) and accuracy (94.1 %) in differentiating PCNSLs from HGGs. The protein-based APTW signal would be a valuable MRI biomarker by which to identify PCNSLs and HGGs presurgically. (orig.)

  14. High-grade, compact spectrometers for Earth observation from SmallSats

    Science.gov (United States)

    van der Wal, L. F.; de Goeij, B. T. G.; Jansen, R.; Oosterling, J. A. J.; Snijders, B.

    2016-10-01

    Spectrolite breadboard will be presented and discussed. The design of Spectrolite offers the flexibility to tune its performance (spectral range, spectral resolution) to a specific application. Thus, based on the same basic system design, Spectrolite offers a range of applications to different clients. To illustrate this, we will present a mission concept to monitor NO2 concentrations over urban areas at high spatial resolution, based on a constellation of small satellites.

  15. Exploring the multidimensional nature of stock structure: a case study on herring dynamics in a transition area

    OpenAIRE

    Worsøe Clausen, Lotte; Mosegaard, Henrik; BEKKEVOLD Dorte

    2014-01-01

    Fish are not just fish. Differences within marine fish species in terms of morphology, behaviour, life history and certainly also genetic differentiation have been shown for an impressive number of species, including herring (Clupea harengus). These differences persist despite marine fish usually occupy areas without much environmental structuring and extensive mixing between populations occur. Many species of marine fishes have the capacity of dispersing over vast geographical areas, either ...

  16. Leaf Area Influence on Surface Layer in a Deciduous Forest. Part 2; Detecting Leaf Area and Surface Resistance During Transition Seasons

    Science.gov (United States)

    Sakai, Ricardo K.; Fitzjarrald, David R.; Moore, Kathleen E.; Sicker, John W.; Munger, Willian J.; Goulden, Michael L.; Wofsy, Steven C.

    1996-01-01

    Temperate deciduous forest exhibit dramatic seasonal changes in surface exchange properties following on the seasonal changes in leaf area index. The canopy resistance to water vapor transport r(sub c) decreased abruptly at leaf emergence in each year but then also continued to decrease slowly during the remaining growing season due to slowly increasing LAI. Canopy resistance and PAR-albedo (albedo from photosynthetically active radiation) began to increase about one month before leaf fall with the diminishment of CO2 gradient above the canopy as well. At this time evaporation begun to be controlled as if the canopy were leafless.

  17. Selective oxidation of lignocellulosic biomass to formic acid and high-grade cellulose using tailor-made polyoxometalate catalysts.

    Science.gov (United States)

    Albert, Jakob

    2017-09-21

    The main goal of this project was to identify and optimize tailor-made polyoxometalate catalysts for a fractionated oxidation of lignocellulosic biomass (i.e. wood and residues from sugar or paper industries) to produce formic acid (FA) and high-grade cellulose for further processing e.g. in white biotechnology to provide bio-ethanol. Homogeneous vanadium precursors like sodium metavanadate and vanadyl sulfate as well as Keggin-type polyoxometalates (POMs) and more exotic structures like Anderson-, Wells-Dawson- and Lindqvist-type POMs were screened for the desired catalytic performance. The most promising behaviour was found using the Lindqvist-type POM K5V3W3O19, showing for the first time in the literature a selective oxidation of only hemicellulose and lignin to formic acid, while the cellulose fraction was untrapped. However, this can only be a first step towards the project goal as low product yields were obtained.

  18. Modeling high-grade serous carcinoma: how converging insights into pathogenesis and genetics are driving better experimental platforms

    Directory of Open Access Journals (Sweden)

    Paul Michael Jones

    2013-08-01

    Full Text Available Recent developments in the study of epithelial ovarian cancer have called into question the traditional views regarding the site of tumor initiation. Histopathologic studies and genomic analyses suggest that extra-ovarian sites, like the fallopian tube, may harbor the coveted cell of origin and could therefore contribute significantly to the development of high-grade serous ovarian carcinoma (HG-SOC. Our ability to validate these emerging genomic and pathologic observations and characterize the early transformation events of HG-SOC hinges on the development of novel model systems. Currently, there are only a handful of new model systems that are addressing these concerns. This review will chronicle the convergent evolution of these ovarian cancer model systems in the context of the changing pathologic and genomic understanding of HG-SOC.

  19. Modeling High-Grade Serous Carcinoma: How Converging Insights into Pathogenesis and Genetics are Driving Better Experimental Platforms

    Science.gov (United States)

    Jones, Paul Michael; Drapkin, Ronny

    2013-01-01

    Recent developments in the study of epithelial ovarian cancer have called into question the traditional views regarding the site of tumor initiation. Histopathologic studies and genomic analyses suggest that extra-ovarian sites, like the fallopian tube, may harbor the coveted cell of origin and could therefore contribute significantly to the development of high-grade serous ovarian carcinoma (HG-SOC). Our ability to validate these emerging genomic and pathologic observations and characterize the early transformation events of HG-SOC hinges on the development of novel model systems. Currently, there are only a handful of new model systems that are addressing these concerns. This review will chronicle the convergent evolution of these ovarian cancer model systems in the context of the changing pathologic and genomic understanding of HG-SOC. PMID:23986883

  20. BRCA mutational status, initial disease presentation, and clinical outcome in high-grade serous advanced ovarian cancer: a multicenter study.

    Science.gov (United States)

    Petrillo, Marco; Marchetti, Claudia; De Leo, Rossella; Musella, Angela; Capoluongo, Ettore; Paris, Ida; Benedetti Panici, Pierluigi; Scambia, Giovanni; Fagotti, Anna

    2017-09-01

    In the last decades, there have been several efforts to clarify the role of BRCA mutational status in women with advanced ovarian cancer, demonstrating its role in cancer development, as well as the prognostic significance of BRCA genotype. Our aim is to evaluate the correlation between BRCA mutational status and disease presentation in a large series of advanced high-grade serous ovarian cancer patients. This is a retrospective multicenter study including a consecutive series of newly diagnosed high-grade serous ovarian cancer patients with International Federation of Gynecology and Obstetrics stage IIIC-IV disease, at least 18 months of follow-up time, and tested for BRCA 1/2 germline mutation status. Disease presentation was analyzed using the following variables: laparoscopic predictive index value, incidence of bulky lymph nodes, and ovarian masses. Progression-free survival was defined as the months elapsed from initial diagnosis (staging laparoscopy) and recurrent disease or last follow-up. In all, 324 high-grade serous ovarian cancer patients received BRCA testing, and 273 fulfilled inclusion criteria. BRCA1/2 germline mutations were observed in 107 women (39.2%). No differences were documented according to BRCA mutation status in terms of International Federation of Gynecology and Obstetrics stage, CA125 levels, or presence of ascites. In patients with BRCA1/2 mutations we observed a higher incidence of peritoneal spread without ovarian mass (25.2% vs 13.9%; P value = .018) and of bulky lymph nodes (30.8% vs 17.5%; P value = .010) compared with women showing BRCA1/2 wild type genotype. Furthermore, women with BRCA1/2 mutations showed high peritoneal tumor load (laparoscopic predictive index value ≥8; 42.1% vs 27.1%; P value = .016) more frequently. Focusing on survival, no differences in term of median progression-free survival were observed among women treated with primary debulking surgery and neoadjuvant chemotherapy in the group of patients with

  1. Gankyrin is frequently overexpressed in cervical high grade disease and is associated with cervical carcinogenesis and metastasis.

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    Full Text Available Our previous studies have showed that Gankyrin expression is correlated with a malignant phenotype in endometrial carcinoma. Here, we investigated the possible role of Gankyrin in cervical disease. The increasing protein level of Gankyrin was observed in high-grade cervical intraepithelial neoplasia and carcinoma compared with benign cervical tissues and low-grade cervical intraepithelial neoplasia. In para-carcinoma tissues, it was found interestingly that there was no lymph node metastasis when nuclei Gankyrin was positively expressed, but lymph node metastasis rate was 30% (6/20 when nuclei Gankyrin was negatively expressed. In vitro, the transfection of Gankyrin resulted in markedly up-regulating of Vimentin, β-catenin and Twist2, as well as down-regulating of E-cadherin in cervical carcinoma cells. Our results suggested that Gankyrin may be functional in cervical carcinogenesis and metastasis.

  2. Misdiagnosis of high-grade vulvar intraepithelial neoplasia (VIN III) as mild cervical intraepithelial neoplasia (CIN I) on Papanicolaou tests.

    Science.gov (United States)

    August, Carey Z; Ganji, Masoud; Froula, Evelyn

    2003-01-01

    Although high-grade vulvar intraepithelial neoplasia (VIN III) is a clinically significant lesion, it can be overlooked because of nonspecific clinical findings and the fact that its cytomorphologic features mimic those of mild cervical intraepithelial neoplasia (CIN I). To determine if there are cytomorphologic features on Papanicolaou tests that can reliably distinguish between VIN III and CIN I. Papanicolaou tests diagnosed as CIN I from patients with biopsy-proven CIN I were compared with Papanicolaou tests diagnosed as CIN I from patients with biopsy-proven VIN III but with no biopsy-proven CIN I. None of the cytomorphologic features evaluated could reliably distinguish CIN I from VIN III. Since the Papanicolaou test cannot be used to distinguish between CIN I and VIN III, the clinician must pay careful attention to the clinical and colposcopic findings. Further research evaluating the use of ancillary studies, such as human papillomavirus typing, may be useful.

  3. Adult high-grade B-cell lymphoma with Burkitt lymphoma signature: genomic features and potential therapeutic targets.

    Science.gov (United States)

    Bouska, Alyssa; Bi, Chengfeng; Lone, Waseem; Zhang, Weiwei; Kedwaii, Ambreen; Heavican, Tayla; Lachel, Cynthia M; Yu, Jiayu; Ferro, Roberto; Eldorghamy, Nanees; Greiner, Timothy C; Vose, Julie; Weisenburger, Dennis D; Gascoyne, Randy D; Rosenwald, Andreas; Ott, German; Campo, Elias; Rimsza, Lisa M; Jaffe, Elaine S; Braziel, Rita M; Siebert, Reiner; Miles, Rodney R; Dave, Sandeep; Reddy, Anupama; Delabie, Jan; Staudt, Louis M; Song, Joo Y; McKeithan, Timothy W; Fu, Kai; Green, Michael; Chan, Wing C; Iqbal, Javeed

    2017-10-19

    The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24, and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes. Mutations in genes promoting the tonic B-cell receptor (BCR)→PI3K pathway (TCF3 and ID3) did not differ by age, whereas effectors of chronic BCR→NF-κB signaling were associated with adult-mBL. A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation profile similar to mBL. These double-hit lymphomas may have arisen from a tumor precursor that acquired both BCL2 and MYC translocations and/or KMT2D (MLL2) mutation. Gain/amplification of MIR17HG and its paralogue loci was observed in 50% of adult-mBL. In vitro studies suggested miR-17∼92's role in constitutive activation of BCR signaling and sensitivity to ibrutinib. Overall integrative analysis identified an interrelated gene network affected by copy number and mutation, leading to disruption of the p53 pathway and the BCR→PI3K or NF-κB activation, which can be further exploited in vivo by small-molecule inhibitors for effective therapy in adult-mBL.

  4. Performance of Aptima and Cobas HPV testing platforms in detecting high-grade cervical dysplasia and cancer.

    Science.gov (United States)

    Ge, Yimin; Christensen, Paul; Luna, Eric; Armylagos, Donna; Schwartz, Mary R; Mody, Dina R

    2017-08-01

    Human papillomavirus (HPV) tests and genotyping have been used in clinical risk assessment. The purpose of this study was to analyze the performance of 2 common HPV testing platforms in detecting high-grade cervical lesions (high-grade squamous intraepithelial lesion [HSIL] or worse [≥HSIL]). Between January 1 and December 31, 2015, 2041 Papanicolaou (Pap) tests with biopsy confirmation were analyzed along with HPV tests performed on Cobas or Aptima platforms. A biopsy diagnosis of grade 2 cervical intraepithelial neoplasia was confirmed with p16/Ki-67 immunohistochemistry. In total, 1866 and 175 Pap cases were tested on Cobas and Aptima platforms, respectively. Both platforms were highly sensitive (97% for both) for biopsy-confirmed ≥HSIL. Cobas HPV testing had higher positive rates for the diagnosis of benign lesions (84% vs 51%) and low-grade squamous intraepithelial lesions (89% vs 63%) on biopsy compared with Aptima. Aptima testing had significantly higher specificity for ≥HSIL than Cobas (41% vs 13%; P cervical lesions, Aptima HPV testing demonstrated significantly higher specificity and positive predictive value than Cobas testing for biopsy-confirmed ≥HSIL. The considerable difference may be related to the significant increase in E6/E7 expression after HPV DNA integration. The significantly higher specificity and overall accuracy of Aptima testing for ≥HSIL, resulting in the identification of high-risk populations that require immediate treatment and close follow-up, may prove useful in clinical risk stratification. Cancer Cytopathol 2017;125:652-7. © 2017 American Cancer Society. © 2017 American Cancer Society.

  5. Residual disease and risk factors in patients with high-grade cervical intraepithelial neoplasia and positive margins after initial conization

    Directory of Open Access Journals (Sweden)

    Fu Y

    2015-05-01

    Full Text Available Yunfeng Fu,1,2,* Chen Chen,3,* Suwen Feng,2 Xiaodong Cheng,2 Xinyu Wang,1,2 Xing Xie,1,2 Weiguo Lü2 1Department of Gynecology, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, 2Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 3Second Hospital of Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background: The purpose of this study was to determine the clinicopathologic predictors of residual disease in patients with high-grade cervical intraepithelial neoplasia (CIN and margin involvement after initial conization.Methods: Data from 145 patients who underwent subsequent surgery for high-grade CIN with positive margins were retrospectively analyzed.Results: After subsequent surgery, residual disease was diagnosed in 47 (34.2% patients, of whom five had invasive cervical carcinoma, 31 had CIN 3, nine had CIN 2, and two had CIN 1. Multivariate analysis revealed that only age ≥35 years (P=0.033, major abnormal cytology (P=0.002, and pre-cone high-risk human papillomavirus load ≥300 relative light units (P=0.011 were significant factors associated with residual disease.Conclusion: Age ≥35 years, major abnormal cytology, and pre-cone high-risk human papillomavirus load ≥300 relative light units were the only significant factors predicting post-cone residual disease. Appropriate application of these predictive factors may avoid delayed treatment and overtreatment. Keywords: cervical intraepithelial neoplasia, residual disease, conization, positive margin, predictor

  6. Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder.

    Science.gov (United States)

    Hodgson, Anjelica; Xu, Bin; Satkunasivam, Raj; Downes, Michelle R

    2018-02-01

    Inflammation and necrosis have been associated with prognosis in multiple epithelial malignancies. Our objective was to evaluate inflammation and necrosis in a cohort of patients with high-grade urothelial carcinomas of the bladder to determine their association with pathological parameters and their prognostic effect on relapse-free and disease-specific survival. A retrospective cohort that underwent radical cystectomy for urothelial carcinomas (n=235) was evaluated for invasive front and central inflammation using the Klintrup-Makinen assessment method. Necrosis was scored using a four-point scale. The relationship of inflammation and necrosis with stage, nodal status, carcinoma in situ, tumour size, margin status and vascular space invasion and the impact on relapse-free and disease-specific survival were calculated using appropriate statistical tests. On multivariate analysis, invasive front inflammation (p=0.003) and necrosis (p=0.000) were independent predictors of relapse-free survival. Both invasive front inflammation (p=0.009) and necrosis (p=0.002) again were independent predictors of disease-specific survival. For pathological features, low invasive front inflammation was associated with lymphovascular space invasion (p=0.008), a positive soft tissue margin (p=0.028) and carcinoma in situ (p=0.042). Necrosis was statistically associated with tumours >3 cm in size (p=0.013) and carcinoma in situ (pinflammation are additional histological variables with independent prognostic relevance in high-grade urothelial carcinoma of the bladder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Combining limb-sparing surgery with radiation therapy in high-grade soft tissue sarcoma of extremities - Is it effective?

    Science.gov (United States)

    Müller, D A; Beltrami, G; Scoccianti, G; Frenos, F; Capanna, R

    2016-07-01

    Limb-sparing surgery in combination with radiation therapy is a well-established treatment for high-grade soft tissue sarcomas of the extremities. But selection of cases and optimal sequence of irradiation and surgery still remain controversial. 769 patients with a high-grade soft tissue sarcoma of the extremities, who underwent a limb-sparing surgery, were retrospectively reviewed. Group 1 (N = 89) was treated with neo-adjuvant radiation therapy, group 2 (N = 315) with adjuvant irradiation and group 3 (N = 365) with surgery alone. After a mean follow up of 45 months 95 local recurrences occurred resulting in a local recurrence-free survival of 83.2% after 5 years and 75.9% after 10 years. Contaminated surgical margins (Odds ratio: 2.42) and previous inadequate surgeries (Odds ratio: 1.89) were identified as risk factors for failed local control. Neo-adjuvant radiation therapy provides the best local recurrence-free rate for 5 years (90.0%), whereas after 10 years (78.3%) adjuvant irradiation showed better local control. The metastatic-free rate was independent from achieved surgical margins (p = 0.179). Group 1 showed the highest rate of revision surgery (9.0%), followed by group 3 (5.5%) and group 2 (4.4%) (p = 0.085). However, the rate of irradiation-correlated side effects was higher in group 2 (15.2%) than in group 1 (11.2%) (p = 0.221). Surgery has to be effective for successful local control and remains the mainstay of the treatment in combination with neo-adjuvant as well as adjuvant irradiation. In really wide or even radical resections the benefit of radiation therapy can be discussed as the irradiation induced side effects are not negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis.

    Science.gov (United States)

    Bregar, Amy J; Alejandro Rauh-Hain, J; Spencer, Ryan; Clemmer, Joel T; Schorge, John O; Rice, Laurel W; Del Carmen, Marcela G

    2017-04-01

    To examine patterns of care and survival for Hispanic women compared to white and African American women with high-grade endometrial cancer. We utilized the National Cancer Data Base (NCDB) to identify women diagnosed with uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma and papillary serous carcinoma between 2003 and 2011. The effect of treatment on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. 43,950 women were eligible. African American and Hispanic women had higher rates of stage III and IV disease compared to white women (36.5% vs. 36% vs. 33.5%, p<0.001). African American women were less likely to undergo surgical treatment for their cancer (85.2% vs. 89.8% vs. 87.5%, p<0.001) and were more likely to receive chemotherapy (36.8% vs. 32.4% vs. 32%, p<0.001) compared to white and Hispanic women. Over the entire study period, after adjusting for age, time period of diagnosis, region of the country, urban or rural setting, treating facility type, socioeconomic status, education, insurance, comorbidity index, pathologic stage, histology, lymphadenectomy and adjuvant treatment, African American women had lower overall survival compared to white women (Hazard Ratio 1.21, 95% CI 1.16-1.26). Conversely, Hispanic women had improved overall survival compared to white women after controlling for the aforementioned factors (HR 0.87, 95% CI 0.80-0.93). Among women with high-grade endometrial cancer, African American women have lower all-cause survival while Hispanic women have higher all-cause survival compared to white women after controlling for treatment, sociodemographic, comorbidity and histopathologic variables. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Surgical Versus Nonsurgical Treatment for High-Grade Spondylolisthesis in Children and Adolescents: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Xue, Xuhong; Wei, Xiaochun; Li, Li

    2016-03-01

    The optimal management of high-grade spondylolisthesis in children and adolescent is controversial. There is a paucity of literature regarding operatively or nonoperative management in this setting. To assessment of the current state of evidence regarding high-grade spondylolisthesis treatment with the goal of obtaining outcome comparisons in these patients managed either operatively or nonoperatively. We performed a systematic literature search up to November 2014, using Medline, Embase, and The Cochrane Library. The analysis and eligibility criteria were documented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-guidelines) and Cochrane Back Review Group editorial board. We used the Newcastle-Ottawa quality assessment scale (NOS-scale) to assess the quality. Five observational studies were considered eligible for analysis based on the evaluation of 1596 identified papers. The mean overall difference in the Scoliosis Research Society questionnaire 22 between the surgical and nonsurgical groups was not statistically significant (95% CI: -0.17 to 0.21, P = 0.84). The pooled mean difference in progression of slip between the surgical and nonsurgical groups was no significant difference (OR: 0.47, 95% CI: 0.12-1.81, P = 0.27, I = 0%). Because of the preponderance of uncontrolled case series, low-quality evidence indicates that the quality of life and progression of slips was no significant difference between surgery and nonoperation group. Nonoperative patients had no radiologic progression of their slip during the follow-up period.

  10. The antidiabetic drug ciglitazone induces high grade bladder cancer cells apoptosis through the up-regulation of TRAIL.

    Directory of Open Access Journals (Sweden)

    Marie-Laure Plissonnier

    Full Text Available Ciglitazone belongs to the thiazolidinediones class of antidiabetic drug family and is a high-affinity ligand for the Peroxisome Proliferator-Activated Receptor γ (PPARγ. Apart from its antidiabetic activity, this molecule shows antineoplastic effectiveness in numerous cancer cell lines.Using RT4 (derived from a well differentiated grade I papillary tumor and T24 (derived from an undifferentiated grade III carcinoma bladder cancer cells, we investigated the potential of ciglitazone to induce apoptotic cell death and characterized the molecular mechanisms involved. In RT4 cells, the drug induced G2/M cell cycle arrest characterized by an overexpression of p53, p21(waf1/CIP1 and p27(Kip1 in concomitance with a decrease of cyclin B1. On the contrary, in T24 cells, it triggered apoptosis via extrinsic and intrinsic pathways. Cell cycle arrest and induction of apoptosis occurred at high concentrations through PPARγ activation-independent pathways. We show that in vivo treatment of nude mice by ciglitazone inhibits high grade bladder cancer xenograft development. We identified a novel mechanism by which ciglitazone kills cancer cells. Ciglitazone up-regulated soluble and membrane-bound TRAIL and let TRAIL-resistant T24 cells to respond to TRAIL through caspase activation, death receptor signalling pathway and Bid cleavage. We provided evidence that TRAIL-induced apoptosis is partially driven by ciglitazone-mediated down-regulation of c-FLIP and survivin protein levels through a proteasome-dependent degradation mechanism.Therefore, ciglitazone could be clinically relevant as chemopreventive or therapeutic agent for the treatment of TRAIL-refractory high grade urothelial cancers.

  11. The antidiabetic drug ciglitazone induces high grade bladder cancer cells apoptosis through the up-regulation of TRAIL.

    Science.gov (United States)

    Plissonnier, Marie-Laure; Fauconnet, Sylvie; Bittard, Hugues; Lascombe, Isabelle

    2011-01-01

    Ciglitazone belongs to the thiazolidinediones class of antidiabetic drug family and is a high-affinity ligand for the Peroxisome Proliferator-Activated Receptor γ (PPARγ). Apart from its antidiabetic activity, this molecule shows antineoplastic effectiveness in numerous cancer cell lines. Using RT4 (derived from a well differentiated grade I papillary tumor) and T24 (derived from an undifferentiated grade III carcinoma) bladder cancer cells, we investigated the potential of ciglitazone to induce apoptotic cell death and characterized the molecular mechanisms involved. In RT4 cells, the drug induced G2/M cell cycle arrest characterized by an overexpression of p53, p21(waf1/CIP1) and p27(Kip1) in concomitance with a decrease of cyclin B1. On the contrary, in T24 cells, it triggered apoptosis via extrinsic and intrinsic pathways. Cell cycle arrest and induction of apoptosis occurred at high concentrations through PPARγ activation-independent pathways. We show that in vivo treatment of nude mice by ciglitazone inhibits high grade bladder cancer xenograft development. We identified a novel mechanism by which ciglitazone kills cancer cells. Ciglitazone up-regulated soluble and membrane-bound TRAIL and let TRAIL-resistant T24 cells to respond to TRAIL through caspase activation, death receptor signalling pathway and Bid cleavage. We provided evidence that TRAIL-induced apoptosis is partially driven by ciglitazone-mediated down-regulation of c-FLIP and survivin protein levels through a proteasome-dependent degradation mechanism. Therefore, ciglitazone could be clinically relevant as chemopreventive or therapeutic agent for the treatment of TRAIL-refractory high grade urothelial cancers.

  12. Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study.

    Science.gov (United States)

    Del Mistro, Annarosa; Matteucci, Mario; Insacco, Egle Alba; Onnis, GianLibero; Da Re, Filippo; Baboci, Lorena; Zorzi, Manuel; Minucci, Daria

    2015-01-01

    The aim of this retrospective observational study of women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was to assess the long-term risk of residual/recurrent high-grade CIN. We evaluated 760 women treated by loop electrosurgical excision procedure (684) or conization (76) between 2000 and 2009, and followed up to June 30, 2014 (median follow-up 6.7 years, range 4-14). Visits every 6 months for the first year after treatment and yearly for up to the following 10 years included cytology, colposcopy when indicated, and HPV testing (search and typing). CIN2+ or vaginal intraepithelial neoplasia grade 2 or worse (VAIN2+) was detected in 67 cases (8.8%), 39 at first follow-up and 28 after one/more negative visits. The risk of CIN2+ was higher in case of positive margins (odds ratio (OR) 8.04, 95% CI 4.31-15.0), type 3 transformation zone (OR for CIN3 27.7, 95% CI 2.07-36.9), CIN3+ excision (OR 6.02, 95% CI 1.73-20.9), and positive high-risk HPV test at first follow-up (OR for HPV16: 20.6, 95% CI 6.8-62.6; OR for other hrHPV types: 18.3, 95% CI 5.9-57.0). Residual/recurrent high-grade CIN occurred in lesion grade, margins status, and hrHPV test result at 6-12 months of follow-up.

  13. Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study

    Directory of Open Access Journals (Sweden)

    Annarosa Del Mistro

    2015-01-01

    Full Text Available Background. The aim of this retrospective observational study of women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+ was to assess the long-term risk of residual/recurrent high-grade CIN. Materials and Methods. We evaluated 760 women treated by loop electrosurgical excision procedure (684 or conization (76 between 2000 and 2009, and followed up to June 30, 2014 (median follow-up 6.7 years, range 4–14. Visits every 6 months for the first year after treatment and yearly for up to the following 10 years included cytology, colposcopy when indicated, and HPV testing (search and typing. Results. CIN2+ or vaginal intraepithelial neoplasia grade 2 or worse (VAIN2+ was detected in 67 cases (8.8%, 39 at first follow-up and 28 after one/more negative visits. The risk of CIN2+ was higher in case of positive margins (odds ratio (OR 8.04, 95% CI 4.31–15.0, type 3 transformation zone (OR for CIN3 27.7, 95% CI 2.07–36.9, CIN3+ excision (OR 6.02, 95% CI 1.73–20.9, and positive high-risk HPV test at first follow-up (OR for HPV16: 20.6, 95% CI 6.8–62.6; OR for other hrHPV types: 18.3, 95% CI 5.9–57.0. Conclusion. Residual/recurrent high-grade CIN occurred in <9% cases, and the risk was associated with transformation zone type, lesion grade, margins status, and hrHPV test result at 6–12 months of follow-up.

  14. Consensus document of the Neuroendocrinology area of the Spanish Society of Endocrinology and Nutrition on management of hypopituitarism during transition.

    Science.gov (United States)

    Alvarez-Escolá, Cristina; Fernández-Rodríguez, Eva; Recio-Córdova, José María; Bernabéu-Morón, Ignacio; Fajardo-Montañana, Carmen

    2014-02-01

    The transition period from child to adult represents a crucial phase in the growth process where multiple physical and psychosocial changes occur. It has been arbitrarily defined as the period extending from late puberty to full adult maturity (i.e., from mid to late teenage years until 6-7 years after achievement of final height). The aim of this guideline is to emphasize the importance of adequate hormone replacement during this period and to review reassessment of pituitary function. In patients with GH deficiency diagnosed in childhood, an attempt is made to answer when to retest GH secretion, when to treat and how they should be monitored. Thyroxine, glucocorticoid, and sex steroid replacement are also reviewed. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  15. Intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia is a risk factor for the subsequent development of pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Rezaee, Neda; Barbon, Carlotta; Zaki, Ahmed; He, Jin; Salman, Bulent; Hruban, Ralph H; Cameron, John L; Herman, Joseph M; Ahuja, Nita; Lennon, Anne Marie; Weiss, Matthew J; Wood, Laura D; Wolfgang, Christopher L

    2016-03-01

    Non-invasive intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia and IPMN-associated invasive pancreatic ductal adenocarcinoma (PDAC) are frequently included under the term "malignancy". The goal of this study is to clarify the difference between these two entities. From 1996 to 2013, data of 616 patients who underwent pancreatic resection for an IPMN were reviewed. The median overall survival for patients with IPMN with high-grade dysplasia (92 months) was similar to survival for patients with IPMN with low/intermediate-grade dysplasia (118 months, p = 0.081), and superior to that of patients with IPMN-associated PDAC (29 months, p < 0.001). IPMN-associated PDAC had lymph node metastasis in 53%, perineural invasion in 58%, and vascular invasion in 33%. In contrast, no lymph node metastasis, perineural or vascular invasion was observed with high-grade dysplasia. None of the patients with IPMN with high-grade dysplasia developed recurrence outside the remnant pancreas. In stark contrast 58% of patients with IPMN-associated PDAC recurred outside the remnant pancreas. The rate of progression within the remnant pancreas was significant in patients with IPMN with high-grade (24%) and with low/intermediate dysplasia (22%, p = 0.816). Non-invasive IPMN with high-grade dysplasia should not be considered a malignant entity. Compared to patients with IPMN with low/intermediate-grade dysplasia, those with high-grade dysplasia have an increased risk of subsequent development of PDAC in the remnant pancreas. Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  16. 75 FR 61553 - National Transit Database: Amendments to the Urbanized Area Annual Reporting Manual and to the...

    Science.gov (United States)

    2010-10-05

    ... Reporting Manual and Announcement of Immediate Suspension of Collecting Security Data on the S&S-50 Form in... small rail modes, such as Inclined Plane. FTA also proposes combining the Monorail (MO) and Automated... apportionment of urbanized area formula grants. III. Announcement of Suspension of Personal Security Reporting...

  17. Traditional ecological knowledge trends in the transition to a market economy: empirical study in the Doñana natural areas.

    Science.gov (United States)

    Gómez-Baggethun, Erik; Mingorría, Sara; Reyes-García, Victoria; Calvet, Laura; Montes, Carlos

    2010-06-01

    Researchers and conservation managers largely agree on the relevance of traditional ecological knowledge for natural resource management in indigenous communities, but its prevalence and role as societies modernize are contested. We analyzed the transmission of traditional knowledge among rural local people in communities linked to protected areas in Doñana, southwestern Spain. We studied changes in knowledge related to local practices in agriculture and livestock farming among 198 informants from three generations that cover the period in which the area transited from an economy strongly dependent on local ecosystem services to a market economy with intensified production systems. Our results suggest an abrupt loss of traditional agricultural knowledge related to rapid transformations and intensification of agricultural systems, but maintenance of knowledge of traditional livestock farming, an activity allowed in the protected areas that maintains strong links with local cultural identity. Our results demonstrate the potential of protected areas in protecting remaining bodies of traditional ecological knowledge in developed country settings. Nevertheless, we note that strict protection in cultural-landscape-dominated areas can disrupt transmission of traditional knowledge if local resource users and related practices are excluded from ecosystem management.

  18. Differentiation of Primary Central Nervous System Lymphoma and High-Grade Glioma with Dynamic Susceptibility Contrast-Enhanced Perfusion Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Weihua Liao; Yunhai Liu; Xiaoyi Wang; Xinya Jiang; Beisha Tang; Jiasheng Fang; Changqing Chen; Zhongliang Hu (Dept.s of Radiology, Neurology, Neurosurgery, and Pathology, Xiangya Hospital, Central South Univ., Changsha, Hunan (China))

    2009-02-15

    Background: Preoperative differentiation of primary central nervous system lymphomas (PCNSLs) from other tumors is important for presurgical staging, intraoperative management, and postoperative treatment. Dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging (DSC perfusion MRI) can provide in vivo assessment of the microvasculature in intracranial mass lesions. Purpose: To determine the utility of DSC perfusion MRI in the differentiation of PCNSLs and high-grade gliomas, as well as their pathological and physiological differences. Material and Methods: Nine patients with pathologically proven PCNSLs and 11 patients with high-grade gliomas were examined using a 1.5T MRI scanner. DSC perfusion MRI was performed by gradient-echo echo-planar imaging (GE-EPI). The maximum rCBV ratio, the signal intensity-time curves, and the percentage of signal intensity recovery were obtained. The maximum relative cerebral blood volume (rCBV) ratio and the percentage of signal intensity recovery of PCNSLs were compared with those of high-grade gliomas by using Student's t test. Microvessel density (MVD) was evaluated using immunohistochemical staining of surgical specimens with anti-CD34, and MVDs of the two tumor groups were compared by using Student's t test. Results: The maximum rCBV ratio of primary intracranial lymphomas was 1.72+-0.59, while that of high-grade gliomas was 4.86+-2.18. PCNSLs tended to have relatively low perfusion compared to high-grade gliomas (P=0.001), and the MVD labeled by anti-CD34 of PCNSLs was much lower than that of gliomas (P<0.001). The signal intensity-time curve of primary intracranial lymphomas was different from that of high-grade gliomas. The percentage of signal intensity recovery was significantly greater in PCNSLs compared with that of high-grade gliomas (P<0.001). Conclusion: The difference in DSC perfusion MRI characteristics between PCNSLs and high-grade gliomas is determined by their different

  19. Specification for the vacuum chamber assemblies comprising flexible metal bellows, transition pieces, flanges, and vacuum tubes for the magnets in the Experimental Areas of the 450 GeV Proton Synchrotron

    CERN Document Server

    CERN. Geneva

    1982-01-01

    Specification for the vacuum chamber assemblies comprising flexible metal bellows, transition pieces, flanges, and vacuum tubes for the magnets in the Experimental Areas of the 450 GeV Proton Synchrotron

  20. Technical specification for the vacuum chamber assemblies comprising flexible metal bellows, transition pieces, flanges and vacuum tubes for the magnets MCA/MCB in the experimental areas of the 450 GeV proton synchrotron

    CERN Document Server

    CERN. Geneva

    1988-01-01

    Technical specification for the vacuum chamber assemblies comprising flexible metal bellows, transition pieces, flanges and vacuum tubes for the magnets MCA/MCB in the experimental areas of the 450 GeV proton synchrotron

  1. Food Insecurity in Urban and Rural Areas in Central Brazil: Transition from Locally Produced Foods to Processed Items.

    Science.gov (United States)

    Rodrigues, Livia Penna Firme; Carvalho, Raissa Costa; Maciel, Agatha; Otanasio, Polyanna Nunes; Garavello, Maria Elisa de Paula Eduardo; Nardoto, Gabriela Bielefeld

    2016-01-01

    Aiming to investigate the effect of diet and food consumption with regard to health, environment, and economy in light of nutrition ecology, we studied the dimensions of nutrition and food security in urban and rural settings in the region of Chapada dos Veadeiros, Central Brazil. We tracked diet and food consumption through carbon and nitrogen stable isotope ratios in fingernails of these inhabitants together with food intake data as a proxy for their diet patterns. We estimated household food insecurity by using the Brazilian Food Insecurity Scale. Nutrition and food insecurity was observed in both urban and rural areas, but was accentuated in rural settings. The diet pattern had high δ(13)C values in fingernails and low δ(15)N. Both urban and rural areas have diets with low diversity and relying on low-quality processed food staples at the same time that nutrition and food insecurity is quite high in the region.

  2. Deciphering polymetamorphic episodes in high-grade metamorphic orogens: Constraints from PbSL, Sm/Nd and Lu/Hf garnet dating of low- to high-grade metasedimentary rocks from the Kaoko belt (Namibia)

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    Seth, B.; Jung, S.; Gruner, B.

    2008-08-01

    Three dating techniques for metamorphic minerals using the Sm-Nd, Lu-Hf and Pb isotope systems are combined and interpreted in context with detailed petrologic data from crustal segments in NW Namibia. The combination of isochron ages using these different approaches is a valuable tool to testify for the validity of metamorphic mineral dating. Here, PbSL, Lu-Hf and Sm-Nd garnet ages obtained on low- to medium-grade metasedimentary rocks from the Central Kaoko Zone of the Neoproterozoic Kaoko belt (NW Namibia) indicate that these samples were metamorphosed at around 550-560 Ma. On the other hand, granulite facies metasedimentary rocks from the Western Kaoko Zone underwent two phases of high-grade metamorphism, one at ca. 660-625 Ma and another at ca. 550 Ma providing substantial evidence that the 660-625 Ma-event was indeed a major tectonothermal episode in the Kaoko belt. Our age data suggest that interpreting metamorphic ages by applying a single dating method only is not reliable enough when studying complex metamorphic systems. However, a combination of all three dating techniques used here provides a reliable basis for geochronological age interpretation.

  3. Quantified analysis of histological components and architectural patterns of gleason grades in apparent diffusion coefficient restricted areas upon diffusion weighted MRI for peripheral or transition zone cancer locations.

    Science.gov (United States)

    Helfrich, Olivier; Puech, Philippe; Betrouni, Nacim; Pinçon, Claire; Ouzzane, Adil; Rizk, Jérome; Marcq, Gauthier; Randazzo, Marco; Durand, Matthieu; Lakroum, Said; Leroy, Xavier; Villers, Arnauld

    2017-12-01

    To quantify and compare the histological components and architectural patterns of Gleason grades in cancerous areas with restriction on apparent diffusion coefficient (ADC) maps. Twelve consecutive cases with 14 separate ADC restriction areas, positive for cancer in the peripheral zone (PZ) and transition zone (TZ) were included. All had 3 Tesla MRI and radical prostatectomy. Ten regions of interest (ROIs) within and outside the 14 ADC restriction areas positive for cancer were selected. For each ROI, we performed quantitative analysis of (a) prostate benign and malignant histological component surface ratios, including stroma, glands, epithelium, lumen, cellular nuclei; (b) percent of Gleason grades and measures of ADC values. Means of histological components according to ADC restriction for cancerous area were compared with analyses of variance with repeated measures. Independent predictors of the probability of cancer were median epithelium/ROI ratio (P = 0.001) and nuclei/ROI ratio (P = 0.03). Independent predictors of the probability of ADC restriction were malignant glands/ROI and luminal space/ROI (P histological components for the comparison of true positive and false negative (P Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1786-1796. © 2017 International Society for Magnetic Resonance in Medicine.

  4. Low testosterone level predicts prostate cancer in re-biopsy in patients with high grade prostatic intraepithelial neoplasia.

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    García-Cruz, Eduard; Piqueras, Marta; Ribal, Maria José; Huguet, Jorge; Serapiao, Rodrigo; Peri, Lluis; Izquierdo, Laura; Alcaraz, Antonio

    2012-09-01

    What's known on the subject? and What does the study add? High grade prostatic intraepithelial neoplasia (HGPIN) is a risk factor for prostate cancer (PCa), but only multifocality is an indication for early rebiopsy. Other risk factors for PCa development from HGPIN remain unknown. PCa is related to testosterone. Testosterone has been proven to be linked to PCa detection and poor prognosis PCa. This study shows that low free and bioavailable testosterone levels are associated with an increased risk of PCa in a rebiopsy after HGPIN diagnosis. Men with low testosterone levels and HGPIN could therefore be considered a high-risk cohort for developing PCa. To determine the relevance of the hormonal profile of patients with high grade prostatic intraepithelial neoplasia (HGPIN) and its relationship to prostate cancer (PCa) in rebiopsy. We prospectively analysed 82 consecutive patients with a diagnosis of HGPIN without PCa in a prostate biopsy between September 2007 and December 2009. Of these 82 patients, 45 underwent rebiopsy and their hormonal profile was determined (testosterone and sex hormone-binding globulin [SHBG]) as part of our clinical protocol. Patient age, PSA level, prostate volume, PSA density, testosterone, free testosterone, bioavailable testosterone and SHBG were recorded prospectively. A comparative study between those patients with a positive rebiopsy and those with a negative rebiopsy was performed. We found that free testosterone (P = 0.04), bioavailable testosterone (P = 0.04) and SHBG (P = 0.02) were significantly associated with a positive rebiopsy. Other variables such as age (P = 0.745), PSA level (P = 0.630), prostate volume (P = 0.690), PSA density (P = 0.950), testosterone (P = 0.981) and prostatic intraepithelial neoplasia multifocality (P = 0.777) were not associated with the presence of adenocarcinoma in the rebiopsy. Patients with adenocarcinoma of the prostate after a diagnosis of HGPIN have higher SHBG levels and lower calculated free

  5. LINE-1 hypermethylation in white blood cell DNA is associated with high-grade cervical intraepithelial neoplasia.

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    Barchitta, Martina; Quattrocchi, Annalisa; Maugeri, Andrea; Canto, Carolina; La Rosa, Nadia; Cantarella, Maria Antonietta; Spampinato, Giuseppa; Scalisi, Aurora; Agodi, Antonella

    2017-08-30

    Long Interspersed Nuclear Elements-1 (LINEs-1) methylation from white blood cells (WBCs) DNA has been proposed as biomarker associated with different types of cancer. The aim of the present study was to investigate the degree of WBCs LINE-1 methylation, according to high-risk Human Papilloma Virus (hrHPV) status in a healthy population, and the association with high-grade Cervical Intraepithelial Neoplasia (CIN2+) in hrHPV positive women. Women with abnormal cervical cells were enrolled and classified by histological diagnosis and hrHPV infection. A structured questionnaire was used to obtain information on socio-demographic variables and lifestyle factors. LINE-1 methylation level in WBCs was measured by pyrosequencing-based methylation analysis after bisulfite conversion. Among 252 women diagnosed with normal cervical epithelium, with regard to LINE-1 methylation level no significant difference was observed between hrHPV positive and hrHPV negative women, also adjusting for known risk factors of infection. The association between WBCs LINE-1 methylation and CIN2+ status was analyzed in hrHPV positive women. The median value of LINE-1 methylation levels was higher in cases (CIN2+) than in controls (75.00% versus 73.17%; p = 0.002). For a one-unit increase in LINE-1 methylation level, the odds of being diagnosed with CIN2+ increased by 10%, adjusting for known factors related to LINE-1 methylation (adjOR: 1.10; 95% CI:1.01-1.20; p = 0.032). The Receiver-Operating Characteristic (ROC) curve analysis identified the cut-off value of 73.8% as the best threshold to separate cases from controls (sensitivity: 63.4% and specificity: 61.8%). LINE-1 methylation status in WBCs DNA may represent a cost-effective and tissue-accessible biomarker for high-grade CIN in hrHPV positive women. However, LINE-1 hypermethylation cannot be considered specific for cervical cancer (CC) and a model based solely on LINE-1 methylation levels has limited performance. Further investigations

  6. Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer

    Directory of Open Access Journals (Sweden)

    Barth Rolf F

    2012-08-01

    Full Text Available Abstract Boron neutron capture therapy (BNCT is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or “BPA”, and sodium borocaptate or “BSH” (Na2B12H11SH. In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger

  7. Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models.

    Science.gov (United States)

    Perets, Ruth; Wyant, Gregory A; Muto, Katherine W; Bijron, Jonathan G; Poole, Barish B; Chin, Kenneth T; Chen, Jin Yun H; Ohman, Anders W; Stepule, Corey D; Kwak, Soongu; Karst, Alison M; Hirsch, Michelle S; Setlur, Sunita R; Crum, Christopher P; Dinulescu, Daniela M; Drapkin, Ronny

    2013-12-09

    High-grade serous ovarian carcinoma presents significant clinical and therapeutic challenges. Although the traditional model of carcinogenesis has focused on the ovary as a tumor initiation site, recent studies suggest that there may be additional sites of origin outside the ovary, namely the secretory cells of the fallopian tube. Our study demonstrates that high-grade serous tumors can originate in fallopian tubal secretory epithelial cells and also establishes serous tubal intraepithelial carcinoma as the precursor lesion to high-grade serous ovarian and peritoneal carcinomas in animal models targeting the Brca, Tp53, and Pten genes. These findings offer an avenue to address clinically important questions that are critical for cancer prevention and early detection in women carrying BRCA1 and BRCA2 mutations. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Progression From Perianal High-Grade Anal Intraepithelial Neoplasia to Anal Cancer in HIV-Positive Men Who Have Sex With Men.

    Science.gov (United States)

    Tinmouth, Jill; Peeva, Valentina; Amare, Henok; Blitz, Sandra; Raboud, Janet; Sano, Marie; Steele, Leah; Salit, Irving E

    2016-09-01

    High-grade intraepithelial neoplasia is known to progress to invasive squamous-cell carcinoma of the anus. There are limited reports on the rate of progression from high-grade intraepithelial neoplasia to anal cancer in HIV-positive men who have sex with men. The purpose of this study was to describe in HIV-positive men who have sex with men with perianal high-grade intraepithelial neoplasia the rate of progression to anal cancer and the factors associated with that progression. This was a prospective cohort study. The study was conducted at an outpatient clinic at a tertiary care center in Toronto. Thirty-eight patients with perianal high-grade anal intraepithelial neoplasia were identified among 550 HIV-positive men who have sex with men. All of the patients had high-resolution anoscopy for symptoms, screening, or surveillance with follow-up monitoring/treatment. We measured the incidence of anal cancer per 100 person-years of follow-up. Seven (of 38) patients (18.4%) with perianal high-grade intraepithelial neoplasia developed anal cancer. The rate of progression was 6.9 (95% CI, 2.8-14.2) cases of anal cancer per 100 person-years of follow-up. A diagnosis of AIDS, previously treated anal cancer, and loss of integrity of the lesion were associated with progression. Anal bleeding was more than twice as common in patients who progressed to anal cancer. There was the potential for selection bias and patients were offered treatment, which may have affected incidence estimates. HIV-positive men who have sex with men should be monitored for perianal high-grade intraepithelial neoplasia. Those with high-risk features for the development of anal cancer may need more aggressive therapy.

  9. Fluorescence-Guided versus Conventional Surgical Resection of High Grade Glioma: A Single-Centre, 7-Year, Comparative Effectiveness Study.

    Science.gov (United States)

    Ng, Wei Ping; Liew, Boon Seng; Idris, Zamzuri; Rosman, Azmin Kass

    2017-03-01

    High grade gliomas (HGGs) are locally invasive brain tumours that carry a dismal prognosis. Although complete resection increases median survival, the difficulty in reliably demonstrating the tumour border intraoperatively is a norm. The Department of Neurosurgery, Hospital Sungai Buloh is the first public hospital in Malaysia to overcome this problem by adopting fluorescence-guided (FG) surgery using 5-aminolevulinic acid (5-ALA). A total of 74 patients with histologically proven HGGs treated between January 2008 and December 2014, who fulfilled the inclusion criteria, were enrolled. Kaplan-Meier survival estimates and Cox proportional hazard regression were used. Significant longer survival time (months) was observed in the FG group compared with the conventional group (12 months versus 8 months, P 80 (P = 0.010), histology (P < 0.001), surgical method (P < 0.001) and adjuvant therapy (P < 0.001). This study showed a significant clinical benefit for HGG patients in terms of overall survival using FG surgery as it did not result in worsening of post-operative function outcome when compared with the conventional surgical method. We advocate a further multicentered, randomised controlled trial to support these findings before FG surgery can be implemented as a standard surgical adjunct in local practice for the benefit of HGG patients.

  10. The Expression of the Zonula Adhaerens Protein PLEKHA7 Is Strongly Decreased in High Grade Ductal and Lobular Breast Carcinomas.

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Tille

    Full Text Available PLEKHA7 is a junctional protein, which participates in a complex that stabilizes E-cadherin at the zonula adhaerens. Since E-cadherin is involved in epithelial morphogenesis, signaling, and tumor progression, we explored PLEKHA7 expression in cancer. PLEKHA7 expression was assessed in invasive ductal and lobular carcinomas of the breast by immunohistochemistry, immunofluorescence and quantitative RT-PCR. PLEKHA7 was detected at epithelial junctions of normal mammary ducts and lobules, and of tubular and micropapillary structures within G1 and G2 ductal carcinomas. At these junctions, the localization of PLEKHA7 was along the circumferential belt (zonula adhaerens, and only partially overlapping with that of E-cadherin, p120ctn and ZO-1, as shown previously in rodent tissues. PLEKHA7 immunolabeling was strongly decreased in G3 ductal carcinomas and undetectable in lobular carcinomas. PLEKHA7 mRNA was detected in both ductal and lobular carcinomas, with no observed correlation between mRNA levels and tumor type or grade. In summary, PLEKHA7 is a junctional marker of epithelial cells within tubular structures both in normal breast tissue and ductal carcinomas, and since PLEKHA7 protein but not mRNA expression is strongly decreased or lost in high grade ductal carcinomas and in lobular carcinomas, loss of PLEKHA7 is a newly characterized feature of these carcinomas.

  11. Needs and preferences among patients with high-grade glioma and their caregivers - A longitudinal mixed methods study.

    Science.gov (United States)

    Piil, K; Jakobsen, J; Christensen, K B; Juhler, M; Guetterman, T C; Fetters, M D; Jarden, M

    2018-01-04

    Previous reports on the patient perspective of daily life during a 1-year high-grade glioma (HGG) trajectory from the time of diagnosis are sparse. The aim of this longitudinal mixed methods study is to identify the specific needs and preferences for rehabilitation and supportive care and how it links with physical activity, psychological measures and health quality longitudinally over the first year after diagnosis among patients with HGG and their caregivers by integrating qualitative and quantitative findings. Using a longitudinal mixed methods design, patients with malignant glioma (n = 30) and their caregivers (n = 33) were interviewed and completed questionnaires (patients only) about physical activity level, anxiety/depression and quality of life five times during the 1-year period. Their needs and preferences included interventions designed to re-define hope after diagnosis, health promoting physical activities initiated early, psychological symptom management strategies, and life planning. Caregivers are committed to their caregiving role, but their engagement is nonetheless challenged over time by enormous caregiver burdens. The identified specific needs and preferences favour supportive care, education, information and rehabilitation. Guidelines attentive to these needs and implemented in clinical practice have the potential to improve patients' health-related quality of life and support caregivers by involving them more actively in care and management. © 2018 The Authors. European Journal of Cancer Care Published by John Wiley & Sons Ltd.

  12. Multiple cancer/testis antigens are preferentially expressed in hormone-receptor negative and high-grade breast cancers.

    Directory of Open Access Journals (Sweden)

    Yao-Tseng Chen

    Full Text Available BACKGROUND: Cancer/testis (CT antigens are protein antigens normally expressed only in germ cells of testis, and yet are expressed in a proportion of a wide variety of human cancers. CT antigens can elicit spontaneous immune responses in cancer patients with CT-positive cancers, and CT antigen-based therapeutic cancer vaccine trials are ongoing for "CT-rich" tumors. Although some previous studies found breast cancer to be "CT-poor", our recent analysis identified increased CT mRNA transcripts in the ER-negative subset of breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we performed a comprehensive immunohistochemical study to investigate the protein expression of eight CT genes in 454 invasive ductal carcinomas, including 225 ER/PR/HER2-negative (triple-negative carcinomas. We found significantly more frequent expression of all eight CT antigens in ER-negative cancers, and five of them--MAGEA, CT7, NY-ESO-1, CT10 and CT45, were expressed in 12-24% of ER-negative cancers, versus 2-6% of ER-positive cancers (p2 cm. CONCLUSIONS/SIGNIFICANCE: CT antigens are preferentially expressed in hormone receptor-negative and high-grade breast cancer. Considering the limited treatment options for ER/PR/HER2 triple-negative breast cancer, the potential of CT-based immunotherapy should be explored.

  13. TP53 mutations, tetraploidy and homologous recombination repair defects in early stage high-grade serous ovarian cancer

    Science.gov (United States)

    Chien, Jeremy; Sicotte, Hugues; Fan, Jian-Bing; Humphray, Sean; Cunningham, Julie M.; Kalli, Kimberly R.; Oberg, Ann L.; Hart, Steven N.; Li, Ying; Davila, Jaime I.; Baheti, Saurabh; Wang, Chen; Dietmann, Sabine; Atkinson, Elizabeth J.; Asmann, Yan W.; Bell, Debra A.; Ota, Takayo; Tarabishy, Yaman; Kuang, Rui; Bibikova, Marina; Cheetham, R. Keira; Grocock, Russell J.; Swisher, Elizabeth M.; Peden, John; Bentley, David; Kocher, Jean-Pierre A.; Kaufmann, Scott H.; Hartmann, Lynn C.; Shridhar, Viji; Goode, Ellen L.

    2015-01-01

    To determine early somatic changes in high-grade serous ovarian cancer (HGSOC), we performed whole genome sequencing on a rare collection of 16 low stage HGSOCs. The majority showed extensive structural alterations (one had an ultramutated profile), exhibited high levels of p53 immunoreactivity, and harboured a TP53 mutation, deletion or inactivation. BRCA1 and BRCA2 mutations were observed in two tumors, with nine showing evidence of a homologous recombination (HR) defect. Combined Analysis with The Cancer Genome Atlas (TCGA) indicated that low and late stage HGSOCs have similar mutation and copy number profiles. We also found evidence that deleterious TP53 mutations are the earliest events, followed by deletions or loss of heterozygosity (LOH) of chromosomes carrying TP53, BRCA1 or BRCA2. Inactivation of HR appears to be an early event, as 62.5% of tumours showed a LOH pattern suggestive of HR defects. Three tumours with the highest ploidy had little genome-wide LOH, yet one of these had a homozygous somatic frame-shift BRCA2 mutation, suggesting that some carcinomas begin as tetraploid then descend into diploidy accompanied by genome-wide LOH. Lastly, we found evidence that structural variants (SV) cluster in HGSOC, but are absent in one ultramutated tumor, providing insights into the pathogenesis of low stage HGSOC. PMID:25916844

  14. Developing a new PI-RADS v2-based nomogram for forecasting high-grade prostate cancer.

    Science.gov (United States)

    Niu, X-K; He, W-F; Zhang, Y; Das, S K; Li, J; Xiong, Y; Wang, Y-H

    2017-06-01

    To establish a predictive nomogram for high-grade prostate cancer (HGPCa) in biopsy-naive patients based on the Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2), magnetic resonance imaging (MRI)-based prostate volume (PV), MRI-based PV-adjusted prostate-specific antigen density (PSAD), and other classical parameters. Between August 2014 and August 2015, 158 men who were eligible for analysis were included as the training cohort. A prediction model for HGPCa was built using backward logistic regression and was presented on a nomogram. The prediction model was evaluated by a validation cohort between September 2015 and March 2016 (n=89). Histology of all lesions was obtained with MRI-directed transrectal ultrasound (TRUS)-guided targeted and sectoral biopsy. The multivariate analysis revealed that patient age, PI-RADS v2 score, and adjusted PSAD were independent predictors for HGPCa. The most discriminative cut-off value for the logistic regression model was 0.33; the sensitivity, specificity, positive predictive value, and negative predictive value were 83.3%, 87.4%, 88.4%, and 81.2%, respectively. The diagnostic performance measures retained similar values in the validation cohort (AUC=0.83). The nomogram for forecasting HGPCa is effective and potentially reducing harm from unnecessary prostate biopsy and over-diagnosis. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  15. 5-aminolevulinic acid for quantitative seek-and-treat of high-grade dysplasia in Barrett's esophagus cellular models

    Science.gov (United States)

    Yeh, Shu-Chi Allison; Ling, Celine S. N.; Andrews, David W.; Patterson, Michael S.; Diamond, Kevin R.; Hayward, Joseph E.; Armstrong, David; Fang, Qiyin

    2015-02-01

    High-grade dysplasia (HGD) in Barrett's esophagus (BE) poses increased risk for developing esophageal adenocarcinoma. To date, early detection and treatment of HGD regions are still challenging due to the sampling error from tissue biopsy and relocation error during the treatment after histopathological analysis. In this study, CP-A (metaplasia) and CP-B (HGD) cell lines were used to investigate the "seek-and-treat" potential using 5-aminolevulinic acid-induced protoporphyrin IX (PpIX). The photodynamic therapy photosensitizer then provides both a phototoxic effect and additional image contrast for automatic detection and real-time laser treatment. Complementary to our studies on automatic classification, this work focused on characterizing subcellular irradiation and the potential phototoxicity on both metaplasia and HGD. The treatment results showed that the HGD cells are less viable than metaplastic cells due to more PpIX production at earlier times. Also, due to mitochondrial localization of PpIX, a better killing effect was achieved by involving mitochondria or whole cells compared with just nucleus irradiation in the detected region. With the additional toxicity given by PpIX and potential morphological/textural differences for pattern recognition, this cellular platform serves as a platform to further investigate real-time "seek-and-treat" strategies in three-dimensional models for improving early detection and treatment of BE.

  16. Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe

    DEFF Research Database (Denmark)

    Tjalma, Wiebren A; Fiander, Alison; Reich, Olaf

    2013-01-01

    Knowledge of differences in human papillomavirus (HPV)-type prevalence between high-grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV-infected cervical lesions and the potential impact of HPV vaccination...... on cervical cancer prevention. More than 6,000 women diagnosed with HG-CIN or ICC from 17 European countries were enrolled in two parallel cross-sectional studies (108288/108290). Centralised histopathology review and standardised HPV-DNA typing were applied to formalin-fixed paraffin-embedded cervical...... higher in ICC than in HG-CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/'other' (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/'other' (15/23/20/17 years). In Europe, HPV16 predominates in both...

  17. The influence of different classification standards of age groups on prognosis in high-grade hemispheric glioma patients.

    Science.gov (United States)

    Chen, Jian-Wu; Zhou, Chang-Fu; Lin, Zhi-Xiong

    2015-09-15

    Although age is thought to correlate with the prognosis of glioma patients, the most appropriate age-group classification standard to evaluate prognosis had not been fully studied. This study aimed to investigate the influence of age-group classification standards on the prognosis of patients with high-grade hemispheric glioma (HGG). This retrospective study of 125 HGG patients used three different classification standards of age-groups (≤ 50 and >50 years old, ≤ 60 and >60 years old, ≤ 45 and 45-65 and ≥ 65 years old) to evaluate the impact of age on prognosis. The primary end-point was overall survival (OS). The Kaplan-Meier method was applied for univariate analysis and Cox proportional hazards model for multivariate analysis. Univariate analysis showed a significant correlation between OS and all three classification standards of age-groups as well as between OS and pathological grade, gender, location of glioma, and regular chemotherapy and radiotherapy treatment. Multivariate analysis showed that the only independent predictors of OS were classification standard of age-groups ≤ 50 and > 50 years old, pathological grade and regular chemotherapy. In summary, the most appropriate classification standard of age-groups as an independent prognostic factor was ≤ 50 and > 50 years old. Pathological grade and chemotherapy were also independent predictors of OS in post-operative HGG patients. Copyright © 2015. Published by Elsevier B.V.

  18. Trends in incidence of anal cancer and high-grade anal intraepithelial neoplasia in Denmark, 1978-2008

    DEFF Research Database (Denmark)

    Nielsen, Ann; Plum, Christian Edinger Munk; Kjaer, Susanne K

    2012-01-01

    The aim of the study was to determine the incidences of anal cancer and high-grade anal intraepithelial neoplasia (AIN2/3) over time in Danish women and men. Describing the burden of anal cancer and AIN may be valuable in future evaluations of the human papillomavirus (HPV) vaccine. We included all...... anal cancers in the Danish Cancer Register in the period 1978-2008 and all cases of AIN2/3 in the Danish Registry of Pathology. Overall and age-, period- and histology-specific incidence rates were estimated. During the 30-year period, 2187 anal cancers were identified, two thirds of which were...... in women. Between 1978-1982 and 2003-2008, the age-standardized incidence rate of anal cancer increased from 0.68 to 1.48 per 100 000 person-years in women and from 0.45 to 0.80 per 100 000 person-years in men. Although there is no systematic screening for AIN in Denmark, we nevertheless identified 608...

  19. Triage for management of cervical high-grade squamous intraepithelial lesion patients with positive margin by conization: a retrospective analysis.

    Science.gov (United States)

    Dou, Yuya; Zhang, Xiaodan; Li, Yang; Wang, Fenfen; Xie, Xing; Wang, Xinyu

    2017-06-01

    The objective of this study is to guide a triage for the management of cervical high-grade squamous intraepithelial lesion (HSIL) patients with positive margin by conization. Clinico-pathological data of HSIL patients with positive margin by conization were retrospectively collected from January 2009 to December 2014. All patients underwent secondary conization or hysterectomy within 6 months. The rate of residual lesion was calculated, and the factors associated with residual lesion were analyzed by univariate and multivariate analyses. Among a total of 119 patients, 56 (47.06%) patients presented residual HSIL in their subsequent surgical specimens, including 4 cases of invasive cervical carcinoma (3 stage IA1 and 1 stage IA2 patients). Univariate analysis showed that patient age > 35 years (P = 0.005), menopausal period > 5 years (P = 0.0035), and multiple-quadrant involvement (P = 0.001) were significantly correlated with residual disease; however, multivariate analysis revealed that multiple-quadrant involvement (P = 0.001; OR, 3.701; 95%CI, 1.496-9.154) was an independent risk factor for residual disease. Nearly half of HSIL patients with positive margin by conization were disease-free in subsequent surgical specimens, and those with multiple positive margins may consider reconization or re-assessment.

  20. Serial changes in lymphocyte subsets in patients with newly diagnosed high grade astrocytomas treated with standard radiation and temozolomide.

    Science.gov (United States)

    Campian, Jian L; Piotrowski, Anna F; Ye, Xiaobu; Hakim, Frances T; Rose, Jeremy; Yan, Xiao-Yi; Lu, Yao; Gress, Ronald; Grossman, Stuart A

    2017-11-01

    The immune system plays a significant role in cancer prevention and outcome. In high grade astrocytomas (HGA), severe lymphopenia is associated with shortened survival due to tumor progression. This study was performed to quantify serial changes in lymphocyte subsets in HGA following standard radiation (RT) and temozolomide (TMZ). Adults (KPS >60, HIV negative) with newly diagnosed HGA scheduled to receive concurrent RT and TMZ and adjuvant TMZ were eligible. Blood was collected before beginning concurrent RT/TMZ and at weeks 6, 10, 18, and 26, and 3 months after completing adjuvant TMZ. Lymphocyte subsets were analyzed by flow cytometry. Twenty patients (70% glioblastoma, median age 53, 50% male, 80% Caucasian) who enrolled from January 2014 to August 2014 were followed until April 2016. Baseline dexamethasone dose was 0.5 mg/day and 15% had absolute lymphocyte counts (ALC) <1000 cells/mm3 before starting RT/TMZ. However, 75% developed lymphopenia with ALC <1000 cells/mm3 after completion of RT/TMZ. NK cells, B cells and all T lymphocytes subsets dropped significantly after concurrent RT/TMZ and remained depressed for the 48 weeks of observation. The CD4+/CD8+ ratio was not affected significantly during follow-up. Severe lymphopenia involving all subsets occurred early in treatment and remained present for nearly 1 year. To our knowledge, this is the first report of serial trends in lymphocyte subsets following standard RT and TMZ for HGA.

  1. PHASE ANALYSES OF URANIUM-BEARING MINERALS FROM THE HIGH GRADE ORE, NOPAL I, PENA BLANCA, MEXICO

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    M. Ren; P. Goodell; A. Kelts; E.Y. Anthony; M. Fayek; C. Fan; C. Beshears

    2005-07-11

    The Nopal I uranium deposit is located in the Pena Blanca district, approximately 40 miles north of Chihuahua City, Mexico. The deposit was formed by hydrothermal processes within the fracture zone of welded silicic volcanic tuff. The ages of volcanic formations are between 35 to 44 m.y. and there was secondary silicification of most of the formations. After the formation of at least part of the uranium deposit, the ore body was uplifted above the water table and is presently exposed at the surface. Detailed petrographic characterization, electron microprobe backscatter electron (BSE) imagery, and selected x-ray maps for the samples from Nopal I high-grade ore document different uranium phases in the ore. There are at least two stages of uranium precipitation. A small amount of uraninite is encapsulated in silica. Hexavalent uranium may also have been a primary precipitant. The uranium phases were precipitated along cleavages of feldspars, and along fractures in the tuff. Energy dispersive spectrometer data and x-ray maps suggest that the major uranium phases are uranophane and weeksite. Substitutions of Ca and K occur in both phases, implying that conditions were variable during the mineralization/alteration process, and that compositions of the original minerals have a major influence on later stage alteration. Continued study is needed to fully characterize uranium behavior in these semi-arid to arid conditions.

  2. Neuroendocrine Tumor, Well Differentiated, of the Breast: A Relatively High-Grade Case in the Histological Subtype

    Directory of Open Access Journals (Sweden)

    Shogo Tajima

    2013-01-01

    Full Text Available Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.

  3. Metabolomic serum profiling detects early-stage high-grade serous ovarian cancer in a mouse model.

    Science.gov (United States)

    Jones, Christina M; Monge, María Eugenia; Kim, Jaeyeon; Matzuk, Martin M; Fernández, Facundo M

    2015-02-06

    Ovarian cancer is a deadly disease killing more than any other gynecologic cancer. Nonspecific symptoms, combined with a lack of early detection methods, contribute to late diagnosis and low five-year survival rates. High-grade serous carcinoma (HGSC) is the most common and deadliest subtype that results in 90% of ovarian cancer deaths. To investigate metabolic patterns for early detection of this deadly ovarian cancer, Dicer-Pten double knockout (DKO) mice that phenocopy many of the features of metastatic HGSC observed in women were studied. Using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), serum samples from 14 early-stage tumor (ET) DKO mice and 11 controls were analyzed in depth to screen for metabolic signatures capable of differentiating early-stage HGSC from controls. Iterative multivariate classification selected 18 metabolites that, when considered as a panel, yielded 100% accuracy, sensitivity, and specificity for classification. Altered metabolic pathways reflected in that panel included those of fatty acids, bile acids, glycerophospholipids, peptides, and some dietary phytochemicals. These alterations revealed impacts to cellular energy storage and membrane stability, as well as changes in defenses against oxidative stress, shedding new light on the metabolic alterations associated with early ovarian cancer stages.

  4. Treatment of symptomatic high-grade intracranial stenoses with the balloon-expandable Pharos stent: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Kurre, W.; Berkefeld, J.; Mesnil de Rochemont, R. du [University of Frankfurt, Department of Neuroradiology, Frankfurt (Germany); Sitzer, M. [Klinikum Herford, Department of Neurology, Herford (Germany); Neumann-Haefelin, T. [University of Frankfurt, Department of Neurology, Frankfurt (Germany)

    2008-08-15

    We report our first clinical experience with a CE-marked flexible monorail balloon-expandable stent for treatment of high-grade intracranial stenoses. Between April 2006 and November 2007 21 patients with symptomatic intracranial stenoses (>70%) were treated with the PHAROS stent. In seven patients, the procedure was performed during acute stroke intervention. Procedural success, clinical complication rates and mid-term follow-up data were prospectively recorded. During a median follow-up period of 7.3 months one additional patient died of an unknown cause 3 months after the intervention. A patient with a significant residual stenosis presented with a new stroke after further progression of the residual stenosis. None of the successfully treated patients experienced ipsilateral stroke. Recanalization of intracranial stenoses with the balloon-expandable Pharos stent is technically feasible. The periprocedural complication rate and mid-term follow-up results were in the range of previously reported case series. This pilot study was limited by the small sample size and severe morbidity of the included patients. Final evaluation of the efficacy of Pharos stent treatment demands further investigation. (orig.)

  5. Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing.

    Science.gov (United States)

    Cole, Alexander J; Dwight, Trisha; Gill, Anthony J; Dickson, Kristie-Ann; Zhu, Ying; Clarkson, Adele; Gard, Gregory B; Maidens, Jayne; Valmadre, Susan; Clifton-Bligh, Roderick; Marsh, Deborah J

    2016-05-18

    The tumour suppressor p53 is mutated in cancer, including over 96% of high-grade serous ovarian cancer (HGSOC). Mutations cause loss of wild-type p53 function due to either gain of abnormal function of mutant p53 (mutp53), or absent to low mutp53. Massively parallel sequencing (MPS) enables increased accuracy of detection of somatic variants in heterogeneous tumours. We used MPS and immunohistochemistry (IHC) to characterise HGSOCs for TP53 mutation and p53 expression. TP53 mutation was identified in 94% (68/72) of HGSOCs, 62% of which were missense. Missense mutations demonstrated high p53 by IHC, as did 35% (9/26) of non-missense mutations. Low p53 was seen by IHC in 62% of HGSOC associated with non-missense mutations. Most wild-type TP53 tumours (75%, 6/8) displayed intermediate p53 levels. The overall sensitivity of detecting a TP53 mutation based on classification as 'Low', 'Intermediate' or 'High' for p53 IHC was 99%, with a specificity of 75%. We suggest p53 IHC can be used as a surrogate marker of TP53 mutation in HGSOC; however, this will result in misclassification of a proportion of TP53 wild-type and mutant tumours. Therapeutic targeting of mutp53 will require knowledge of both TP53 mutations and mutp53 expression.

  6. Analysis on Cooling Effect of Crushed-Rocks Embankment of Qinghai-Tibet High-Grade Road

    Directory of Open Access Journals (Sweden)

    Dongqing Li

    2015-01-01

    Full Text Available In order to study the cooling effect of the crushed-rocks embankment, the permeability and the inertial resistance coefficient were measured by the wind tunnel test of spheres with a diameter of 20 cm, and then the stabilities of the closed crushed-rocks embankment with the wide pavement, the closed crushed-rocks embankment with the narrow pavement, and the duct-ventilated and closed crushed-rocks embankment were calculated. In the next 50 years, assuming that the temperature in Qinghai-Tibet plateau will rise by 2.6°C condition, the cooling effects of these three special high-grade embankment structures were studied. The test results and the numerical calculation results show that the relationship between pressure gradient and seepage velocity in the spheres layer diverges completely from Darcy’s law, and it shows a nice quadratic nonlinear relationship. Stabilities of those two closed crushed-rock embankments without the duct-ventilated structure could be destroyed because of the high permafrost temperature under embankments. The duct-ventilated and closed crushed-rocks embankment can cool down the permafrost effectively and raise the permafrost table and ensure the long-term thermal stability of permafrost under road.

  7. Prevalence of High-Grade Intraepithelial Neoplasia in Patients with Cytology Presenting Atypical Squamous Cells of Undetermined Significance.

    Science.gov (United States)

    Marcos Lopes, Ana Cristina; Campaner, Adriana Bittencourt; Henrique, Laílca Quirino

    2016-01-01

    To evaluate the prevalence of histological high-grade lesions and cervical cancer in patients with ASCUS cytology. This is a cross-sectional prospective study involving 703 women with a uterus and atypical squamous cells of undetermined significance (ASCUS). The patients were submitted to a colposcopy and underwent a guided biopsy when changes on the colposcopy were detected. The findings revealed 456 (64.9%) women with a normal colposcopy and 247 (35.1%) with colposcopic abnormalities. The biopsy results were: cervical intraepithelial neoplasia grade 1 (CIN 1) in 51 (20.6%) patients, CIN 2 in 11 (4.5%) patients, CIN 3 in 8 (3.2%) patients, and a negative result in 177 (71.7%) patients; no cases of cancer were detected. Tallying of 456 normal colposcopies and 177 negative biopsies yielded a total of 90.04% negative exams. Furthermore, around 7.2% (51/703) of the patients exhibited CIN 1, a lesion associated with a high potential for regression. The biopsy results were not associated with patient age or menopausal status. We conclude that cytological surveillance of patients with ASCUS is feasible and safe given the low risk of CIN 2/3 or cervical cancer. © 2016 S. Karger AG, Basel.

  8. Cediranib, a pan-VEGFR inhibitor, and olaparib, a PARP inhibitor, in combination therapy for high grade serous ovarian cancer.

    Science.gov (United States)

    Ivy, S Percy; Liu, Joyce F; Lee, Jung-Min; Matulonis, Ursula A; Kohn, Elise C

    2016-01-01

    An estimated 22,000 women are diagnosed annually with ovarian cancer in the United States. Initially chemo-sensitive, recurrent disease ultimately becomes chemoresistant and may kill ~14,000 women annually. Molecularly targeted therapy with cediranib (AZD2171), a vascular endothelial growth factor receptor (VEGFR)-1, 2, and 3 signaling blocker, and olaparib (AZD2281), a poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, administered orally in combination has shown anti-tumor activity in the treatment of high grade serous ovarian cancer (HGSOC). This combination has the potential to change the treatment of HGSOC. Preclinical and clinical studies of single agent cediranib and olaparib or their combination are reviewed. Data are presented from peer-reviewed published manuscripts, completed and ongoing early phase clinical trials registered in ClinicalTrials.gov, National Cancer Institute-sponsored clinical trials, and related recent abstracts. Advances in the treatment of HGSOC that improve progression-free and overall survival have proven elusive despite examination of molecularly targeted therapy. HGSOC patients with deleterious germline or somatic mutations in BRCA1 or BRCA2 (BRCAm) are most responsive to PARP inhibitors (PARPi). PARPi combined with angiogenesis inhibition improved anti-cancer response and duration in both BRCAm and BRCA wild type HGSOC patients, compared to olaparib single agent treatment, demonstrating therapeutic chemical and contextual synthetic lethality.

  9. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib.

    LENUS (Irish Health Repository)

    Kinsella, Paula

    2012-03-10

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC(50)). Response for each culture was compared with the EGFR\\/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-α expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile.

  10. Potential impact of nonavalent HPV vaccine in the prevention of high-grade cervical lesions and cervical cancer in Portugal.

    Science.gov (United States)

    Pista, Angela; de Oliveira, Carlos Freire; Lopes, Carlos; Cunha, Maria J

    2017-10-01

    To estimate the potential impact of the nonavalent HPV vaccine for high-grade cervical lesions and invasive cervical cancer (ICC) in Portugal. The present secondary analysis used data collected in the CLEOPATRE II study on the prevalence of HPV 6/11/16/18/31/33/45/52/58 among female patients aged 20-88 years. The prevalence of HPV types in patients with cervical intraepithelial neoplasia (CIN) grades 2/3 and ICC was examined. Data were included from 582 patients. There were 177, 341, and 64 patients with CIN2, CIN3, and ICC, respectively, and 169 (95.5%), 339 (99.4%), and 62 (96.9) of them had HPV infections. Of patients with HPV infections, HPV 16, 18, 31, 33, 45, 52, and 58 infections were identified in 150 (88.8%), 329 (97.1%), and 60 (96.8%) patients with CIN2, CIN3, and ICC, respectively. HPV genotypes 6, 11, 16, 18, 31, 33, 45, 52, and 58 were identified in 540 (94.7%) of the patients with HPV infections. The addition of the five HPV genotypes included in the nonavalent HPV vaccine (HPV 31/33/45/52/58) could result in the new HPV vaccine preventing 94.7% of CIN2/3 and ICC occurrences. © 2017 International Federation of Gynecology and Obstetrics.

  11. Low-cost laser printable photomask: One-step, photoresist-free, fully solution processed high-grade photolithography mask

    Science.gov (United States)

    Yun, Jinho; Kim, Jongsu; Yang, Minyang; Kang, Bongchul

    2017-02-01

    Owing to the short life cycle of present-day microelectronics, conventional method of photomask fabrication should be replaced in order to improve the resultant agility and productivity of photolithography. To fulfill these requirements, we suggest a fully solution-based one-step fabrication method of a high-grade photomask, without the use of a photoresist, vacuum deposition, and etching process. The photomask is fabricated via the laser-induced instantaneous thermochemical metallization of an optically catalyzed hybrid complex synthesized in-situ from a low-cost particle-free organometallic solution. This reaction yields a masking layer whose high selectivity of less than 1 μm, self-generated retroreflective structure, and excellent optical surface are comparable to those of masks fabricated by vacuum depositions. In addition, the complexity of the process is minimized owing to the solution deposition of all the constituent layers. A series of evaluations and the application of this method to an actual photolithography process confirm that this approach constitute a next-generation photomask fabrication method by satisfying both improved agility and productivity of microelectronics manufacturing.

  12. Time to clinical investigation for Indigenous and non-Indigenous Queensland women after a high grade abnormal Pap smear, 2000-2009.

    Science.gov (United States)

    Whop, Lisa J; Baade, Peter D; Brotherton, Julia Ml; Canfell, Karen; Cunningham, Joan; Gertig, Dorota; Lokuge, Kamalini; Garvey, Gail; Moore, Suzanne P; Diaz, Abbey; O'Connell, Dianne L; Valery, Patricia; Roder, David M; Condon, John R

    2017-02-06

    To investigate time to follow-up (clinical investigation) for Indigenous and non-Indigenous women in Queensland after a high grade abnormality (HGA) being detected by Pap smear. Population-based retrospective cohort analysis of linked data from the Queensland Pap Smear Register (PSR), the Queensland Hospital Admitted Patient Data Collection, and the Queensland Cancer Registry. 34 980 women aged 20-68 years (including 1592 Indigenous women) with their first HGA Pap smear result recorded on the PSR (index smear) during 2000-2009 were included and followed to the end of 2010. Time from the index smear to clinical investigation (histology test or cancer diagnosis date), censored at 12 months. The proportion of women who had a clinical investigation within 2 months of a HGA finding was lower for Indigenous (34.1%; 95% CI, 31.8-36.4%) than for non-Indigenous women (46.5%; 95% CI, 46.0-47.0%; unadjusted incidence rate ratio [IRR], 0.65; 95% CI, 0.60-0.71). This difference remained after adjusting for place of residence, area-level disadvantage, and age group (adjusted IRR, 0.74; 95% CI, 0.68-0.81). However, Indigenous women who had not been followed up within 2 months were subsequently more likely to have a clinical investigation than non-Indigenous women (adjusted IRR for 2-4 month interval, 1.21; 95% CI, 1.08-1.36); by 6 months, a similar proportion of Indigenous (62.2%; 95% CI, 59.8-64.6%) and non-Indigenous women (62.8%; 95% CI, 62.2-63.3%) had been followed up. Prompt follow-up after a HGA Pap smear finding needs to improve for Indigenous women. Nevertheless, slow follow-up is a smaller contributor to their higher cervical cancer incidence and mortality than their lower participation in cervical screening.

  13. Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Piludu, Francesca; Vidiri, Antonello [Regina Elena National Cancer Institute, Radiology and Diagnostic Imaging Department, Rome (Italy); Marzi, Simona [Regina Elena National Cancer Institute, Medical Physics Laboratory, Rome (Italy); Pace, Andrea; Villani, Veronica [Regina Elena National Cancer Institute, Neurology Division, Rome (Italy); Fabi, Alessandra [Regina Elena National Cancer Institute, Oncology Department, Rome (Italy); Carapella, Carmine Maria [Regina Elena National Cancer Institute, Oncologic Surgery Department, Rome (Italy); Terrenato, Irene [Regina Elena National Cancer Institute, Biostatistics-Scientific Direction, Rome (Italy); Antenucci, Anna [Regina Elena National Cancer Institute, Clinical Pathology, Rome (Italy)

    2015-12-15

    The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas. Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V{sub tot}), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V{sub CE-T1} and V{sub NON-CE-T1}, respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K{sup trans} maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease. Responding patients showed a larger reduction in V{sub NON-CE-T1} after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K{sup trans}, after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V{sub tot} was predictive of overall survival (OS), while V{sub CE-T1} showed a tendency of correlation with OS. Tumor subvolumes with increased nIAUGC and K{sup trans} showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation. (orig.)

  14. Monitoring urban expansion and land use/land cover changes of Shanghai metropolitan area during the transitional economy (1979-2009) in China.

    Science.gov (United States)

    Yin, Jie; Yin, Zhane; Zhong, Haidong; Xu, Shiyuan; Hu, Xiaomeng; Wang, Jun; Wu, Jianping

    2011-06-01

    This study explored the spatio-temporal dynamics and evolution of land use/cover changes and urban expansion in Shanghai metropolitan area, China, during the transitional economy period (1979-2009) using multi-temporal satellite images and geographic information systems (GIS). A maximum likelihood supervised classification algorithm was employed to extract information from four landsat images, with the post-classification change detection technique and GIS-based spatial analysis methods used to detect land-use and land-cover (LULC) changes. The overall Kappa indices of land use/cover change maps ranged from 0.79 to 0.89. Results indicated that urbanization has accelerated at an unprecedented scale and rate during the study period, leading to a considerable reduction in the area of farmland and green land. Findings further revealed that water bodies and bare land increased, obviously due to large-scale coastal development after 2000. The direction of urban expansion was along a north-south axis from 1979 to 2000, but after 2000 this growth changed to spread from both the existing urban area and along transport routes in all directions. Urban expansion and subsequent LULC changes in Shanghai have largely been driven by policy reform, population growth, and economic development. Rapid urban expansion through clearing of vegetation has led to a wide range of eco-environmental degradation.

  15. Land has power. Energy transition an opportunity for rural areas. Documentation; Land unter Strom. Die Energiewende als Chance fuer den laendlichen Raum. Dokumentation

    Energy Technology Data Exchange (ETDEWEB)

    Bredenbeck, Martin; Gotzmann, Inge (comps.)

    2015-07-01

    The energy transition affects the rural areas of Germany in particular. Which Opportunities and risks this brings there shows a new release of Bund Heimat und Umwelt in Deutschland (German heritage and Environmental Foundation (BHU)). The Federation of heritage and civic associations devoted to the question of how to the conventional expansion of renewable energies innovative options can added. Thereby a diversified positioning of energy use, the advancement of historical forms of use and the spatial differentiation are important factors. [German] Die Energiewende betrifft die laendlichen Raeume Deutschlands in besonderem Masse. Welche Chancen und Risiken sie dort bringt, zeigt eine Neuerscheinung des Bund Heimat und Umwelt in Deutschland (BHU). Der Bundesverband der Heimatverbaende, Heimat- und Buergervereine widmet sich der Frage, wie zum konventionellen Ausbau erneuerbarer Energien innovative Optionen hinzutreten koennen. Eine breite Aufstellung von Energienutzungen, die Weiterentwicklung historischer Nutzungsformen und die raeumliche Differenzierung sind dabei wichtige Faktoren.

  16. AMMONOID SUCCESSION AT THE BAJOCIAN-BATHONIAN TRANSITION IN THE BAS AURAN AREA, DIGNE DISTRICT, SOUTH-EAST FRANCE

    Directory of Open Access Journals (Sweden)

    GIULIO PAVIA

    2008-07-01

    Full Text Available The uppermost Bajocian to lowermost Bathonian ammonoid succession has been studied in the Bas Auran area in view of choosing one of its sections as the Global Stratotype Section and Point (G.S.S.P. of the Bathonian Stage. The Bas Auran ammonite assemblages display exceptional values of record quality. The stratigraphic distribution of 629 specimens referred to 63 species and 35 genera, collected during the last forty years from three sections (Ravin du Bès, Ravin d'Auran, Ravin des Robines, is plotted and analyzed, bed by bed. Over 85 stratigraphic levels, through 9 m in thickness, have been studied at the top of the "Marno-calcaires à Cancellophycus" formation, ranging from the latest Bajocian (Parkinsoni Zone, Bomfordi Subzone to the earliest Bathonian (Zigzag Zone, Convergens Subzone and the base of the Macrescens Subzone. Ammonoid assemblages are composed of Northwest European and Mediterranean elements, associated with Sub-Mediterranean ones, allowing chronocorrelation between the Northwest European Convergens Subzone and the Sub-Mediterranean Parvum Subzone. The basal boundary of the Zigzag Zone and of the Bathonian Stage is placed at the base of Sturani's bed 23 in the Ravin du Bès section and is identified by the first occurrence of Gonolkites convergens, and coincides with the lowest occurrence of Morphoceras parvum. Features of the ammonoid succession indicate relatively homogeneous and good record quality, gradual biostratigraphic change and high degree of taxonomic similarity between the Bomfordi and Convergens subzones. Palaeontological criteria also indicate relatively high values of palaeontological and stratigraphic completeness at the base of levels RB070-RB071 (= level 23 in Sturani 1967 which corresponds to the Bajocian/Bathonian boundary. The Ravin du Bès Section, with forty-six successive ammonoid fossil-assemblages of the Convergens Subzone belonging to three biohorizons through five metres of thickness, shows maximum

  17. Five-year tracking of Plasmodium falciparum allele frequencies in a holoendemic area with indistinct seasonal transitions

    Directory of Open Access Journals (Sweden)

    Akala HM

    2014-11-01

    Full Text Available Hoseah M Akala, Angela O Achieng, Fredrick L Eyase, Dennis W Juma, Luiser Ingasia, Agnes C Cheruiyot, Charles Okello, Duke Omariba, Eunice A Owiti, Catherine Muriuki, Redemptah Yeda, Ben Andagalu, Jacob D Johnson, Edwin Kamau Global Emerging Infections Surveillance Program, United States Army Medical Research Unit-Kenya, Kenya Medical Research Institute, Walter Reed Project, Kisumu and Nairobi, Kenya Background: The renewed malaria eradication efforts require an understanding of the seasonal patterns of frequency of polymorphic variants in order to focus limited funds productively. Although cross-sectional studies in holoendemic areas spanning a single year could be useful in describing parasite genotype status at a given point, such information is inadequate in describing temporal trends in genotype polymorphisms. For Plasmodium falciparum isolates from Kisumu District Hospital, Plasmodium falciparum chloroquine-resistance transporter gene (Pfcrt-K76T and P. falciparum multidrug resistance gene 1 (PfMDR1-N86Y, were analyzed for polymorphisms and parasitemia changes in the 53 months from March 2008 to August 2012. Observations were compared with prevailing climatic factors, including humidity, rainfall, and temperature. Methods: Parasitemia (the percentage of infected red blood cells per total red blood cells was established by microscopy for P. falciparum malaria-positive samples. P. falciparum DNA was extracted from whole blood using a Qiagen DNA Blood Mini Kit. Single nucleotide polymorphism identification at positions Pfcrt-K76T and PfMDR1-N86Y was performed using real-time polymerase chain reaction and/or sequencing. Data on climatic variables were obtained from http://www.tutiempo.net/en/. Results: A total of 895 field isolates from 2008 (n=169, 2009 (n=161, 2010 (n=216, 2011 (n=223, and 2012 (n=126 showed large variations in monthly frequency of PfMDR1-N86Y and Pfcrt-K76T as the mutant genotypes decreased from 68.4%±15% and 38.1%±13% to

  18. An intra-individual comparison of MRI, [18F]-FET and [18F]-FLT PET in patients with high-grade gliomas.

    Directory of Open Access Journals (Sweden)

    Martha Nowosielski

    Full Text Available OBJECTIVES: Intra-individual spatial overlap analysis of tumor volumes assessed by MRI, the amino acid PET tracer [18F]-FET and the nucleoside PET tracer [18F]-FLT in high-grade gliomas (HGG. METHODS: MRI, [18F]-FET and [18F]-FLT PET data sets were retrospectively analyzed in 23 HGG patients. Morphologic tumor volumes on MRI (post-contrast T1 (cT1 and T2 images were calculated using a semi-automatic image segmentation method. Metabolic tumor volumes for [18F]-FET and [18F]-FLT PETs were determined by image segmentation using a threshold-based volume of interest analysis. After co-registration with MRI the morphologic and metabolic tumor volumes were compared on an intra-individual basis in order to estimate spatial overlaps using the Spearman's rank correlation coefficient and the Mann-Whitney U test. RESULTS: [18F]-FLT uptake was negative in tumors with no or only moderate contrast enhancement on MRI, detecting only 21 of 23 (91% HGG. In addition, [18F]-FLT uptake was mainly restricted to cT1 tumor areas on MRI and [18F]-FLT volumes strongly correlated with cT1 volumes (r = 0.841, p<0.001. In contrast, [18F]-FET PET detected 22 of 23 (96% HGG. [18F]-FET uptake beyond areas of cT1 was found in 61% of cases and [18F]-FET volumes showed only a moderate correlation with cT1 volumes (r = 0.573, p<0.001. Metabolic tumor volumes beyond cT1 tumor areas were significantly larger for [18F]-FET compared to [18F]-FLT tracer uptake (8.3 vs. 2.7 cm3, p<0.001. CONCLUSION: In HGG [18F]-FET but not [18F]-FLT PET was able to detect metabolic active tumor tissue beyond contrast enhancing tumor on MRI. In contrast to [18F]-FET, blood-brain barrier breakdown seems to be a prerequisite for [18F]-FLT tracer uptake.

  19. Association mapping of the high-grade myopia MYP3 locus reveals novel candidates UHRF1BP1L, PTPRR, and PPFIA2.

    Science.gov (United States)

    Hawthorne, Felicia; Feng, Sheng; Metlapally, Ravikanth; Li, Yi-Ju; Tran-Viet, Khanh-Nhat; Guggenheim, Jeremy A; Malecaze, Francois; Calvas, Patrick; Rosenberg, Thomas; Mackey, David A; Venturini, Cristina; Hysi, Pirro G; Hammond, Christopher J; Young, Terri L

    2013-03-21

    Myopia, or nearsightedness, is a common ocular genetic disease for which over 20 candidate genomic loci have been identified. The high-grade myopia locus, MYP3, has been reported on chromosome 12q21-23 by four independent linkage studies. We performed a genetic association study of the MYP3 locus in a family-based high-grade myopia cohort (n = 82) by genotyping 768 single-nucleotide polymorphisms (SNPs) within the linkage region. Qualitative testing for high-grade myopia (sphere ≤ -5 D affected, > -0.5 D unaffected) and quantitative testing on the average dioptric sphere were performed. Several genetic markers were nominally significantly associated with high-grade myopia in qualitative testing, including rs3803036, a missense mutation in PTPRR (P = 9.1 × 10(-4)) and rs4764971, an intronic SNP in UHRF1BP1L (P = 6.1 × 10(-4)). Quantitative testing determined statistically significant SNPs rs4764971, also found by qualitative testing (P = 3.1 × 10(-6)); rs7134216, in the 3' untranslated region (UTR) of DEPDC4 (P = 5.4 × 10(-7)); and rs17306116, an intronic SNP within PPFIA2 (P studied.

  20. Gastric low-grade MALT lymphoma, high-grade MALT lymphoma and diffuse large B cell lymphoma show different frequencies of trisomy

    NARCIS (Netherlands)

    Hoeve, M A; Gisbertz, I A; Schouten, H C; Schuuring, E; Bot, F J; Hermans, J; Hopman, A; Kluin, P M; Arends, J E; van Krieken, J H

    1999-01-01

    Gastric MALT lymphoma is a distinct entity related to Helicobacter pylori gastritis. Some studies suggest a role for trisomy 3 in the genesis of these lymphomas, but they mainly focused on low-grade MALT lymphoma. Gastric MALT lymphoma, however, comprises a spectrum from low- to high-grade cases.

  1. An Updated Critical Analysis of the Treatment Strategy for Newly Diagnosed High-grade T1 (Previously T1G3) Bladder Cancer

    NARCIS (Netherlands)

    Kulkarni, Girish S.; Hakenberg, Oliver W.; Gschwend, Juergen E.; Thalmann, George; Kassouf, Wassim; Kamat, Ashish; Zlotta, Alexandre

    Context: High-grade T1 (formerly T1G3) bladder cancer (BCa) has a high propensity to recur and progress. As a result, decisions pertaining to its treatment are difficult. Treatment with bacillus Calmette-Guerin (BCG) risks progression and metastases but may preserve the bladder. Cystectomy may offer

  2. Geodynamic evolution of the Pan-African lower crust in Sri Lanka : structural and petrological investigations into a high-grade gneiss terrain

    NARCIS (Netherlands)

    Kriegsman, L.

    1993-01-01

    Some main objectives of present-day geological research are to assess the role of the lower crust in collision and extensional tectonics and to unravel the mechanism and timing of crustal growth. Both objectives require input from the study of high-grade gneiss terrains, notably data concerning

  3. Methylation status as a predictor of intravesical Bacillus Calmette-Guérin (BCG) immunotherapy response of high grade non-muscle invasive bladder tumor.

    Science.gov (United States)

    Husek, Petr; Pacovsky, Jaroslav; Chmelarova, Marcela; Podhola, Miroslav; Brodak, Milos

    2017-06-01

    Genetic and epigenetic alterations play an important role in urothelial cancer pathogenesis. Deeper understanding of these processes could help us achieve better diagnosis and management of this life-threatening disease. The aim of this research was to evaluate the methylation status of selected tumor suppressor genes for predicting BCG response in patients with high grade non-muscle-invasive bladder tumor (NMIBC). We retrospectively evaluated 82 patients with high grade non-muscle-invasive bladder tumor (stage Ta, T1, CIS) who had undergone BCG instillation therapy. We compared epigenetic methylation status in BCG-responsive and BCG-failure groups. We used the MS-MLPA (Methylation-Specific Multiplex Ligation-Dependent Probe Amplification probe sets ME001 and ME004. The control group was 13 specimens of normal urotel (bladder tissue)). Newly identified methylations in high grade NMIBC were found in MUS81a, NTRK1 and PCCA. The methylation status of CDKN2B (P=0.00312 ** ) and MUS81a (P=0.0191 * ) is associated with clinical outcomes of BCG instillation therapy response. CDKN2B and MUS81a unmethylation was found in BCG failure patients. The results show that the methylation status of selected tumor suppressor genes (TSGs) has the potential for predicting BCG response in patients with NMIBC high grade tumors. Tumor suppressor genes such as CDKN2b, MUS81a, PFM-1, MSH6 and THBS1 are very promising for future research.

  4. Increased HIV-1 activity in anal high-grade squamous intraepithelial lesions compared with unaffected anal mucosa in men who have sex with men

    NARCIS (Netherlands)

    Pollakis, Georgios; Richel, Olivier; Vis, Joost D.; Prins, Jan M.; Paxton, William A.; de Vries, Henry J. C.

    2014-01-01

    We studied 3 patients with focal intra-anal tissue high-grade squamous intraepithelial lesions (HSILs). All had increased human immunodeficiency virus type 1 (HIV-1) RNA and DNA in lesions compared with that in healthy mucosa. HIV-1 RNA and HIV-1 episomal DNA were indicative of ongoing viral

  5. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Li, Qiyuan; Kar, Siddhartha

    2015-01-01

    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions assoc...

  6. Cryotherapy for Intra- and Perianal High-Grade Squamous Intraepithelial Lesions in HIV-Positive Men who have Sex with Men

    NARCIS (Netherlands)

    Siegenbeek van Heukelom, Matthijs L.; Gosens, Karien C. M.; Prins, Jan M.; de Vries, Henry J. C.

    2018-01-01

    Available treatment options for anal high-grade squamous intraepithelial lesions (HSIL) in HIV-positive men who have sex with men (MSM) are limited by low response rates and frequent recurrences. Cryotherapy is an established therapeutic option for several pre-malignant skin disorders. This

  7. Improved outcome of high grade, early 1 stage endometrioid endometrial carcinoma with adjuvant chemotherapy and radiotherapy : Comparison of 2 treatment strategies

    NARCIS (Netherlands)

    Reynaers, Eline Aem; Jutzi, Leah; Ezendam, N.P.M.; Kwon, Janice S.; Pijnenborg, Johanna M.a.

    2017-01-01

    Objective: patients with high grade endometrioid endometrial carcinoma have a high risk of recurrence, even in early stage. To determine the benefit of a more aggressive adjuvant treatment approach, different treatment strategies of 2 referral centers were compared. Materials and methods: outcome of

  8. Improved Outcome of High-Grade, Early 1-Stage Endometrioid Endometrial Carcinoma With Adjuvant Chemotherapy and Radiotherapy: Comparison of 2 Treatment Strategies

    NARCIS (Netherlands)

    Reynaers, E.A.; Jutzi, L.; Ezendam, N.P.; Kwon, J.S.; Pijnenborg, J.M.A.

    2017-01-01

    OBJECTIVE: Patients with high-grade endometrioid endometrial carcinoma have a high risk of recurrence, even in early stage. To determine the benefit of a more aggressive adjuvant treatment approach, different treatment strategies of 2 referral centers were compared. MATERIALS AND METHODS: Outcome of

  9. Columbia University: Computational Human High-grade Glioblastoma Multiforme Interactome - miRNA (Post-transcriptional) Layer | Office of Cancer Genomics

    Science.gov (United States)

    The Human High-Grade Glioma Interactome (HGi) contains a genome-wide complement of molecular interactions that are Glioblastoma Multiforme (GBM)-specific. HGi v3 contains the post-transcriptional layer of the HGi, which includes the miRNA-target (RNA-RNA) layer of the interactome. Read the Abstract

  10. Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

    NARCIS (Netherlands)

    Wouters, Maartje C. A.; Komdeur, Fenne L.; Workel, Hagma H.; Klip, Harry G.; Plat, Annechien; Kooi, Neeltje M.; Wisman, G. Bea A.; Mourits, Marian J. E.; Arts, Henriette J. G.; Oonk, Maaike H. M.; Yigit, Refika; de Jong, Steven; Melief, Cornelis J. M.; Hollema, Harry; Duiker, Evelien W.; Daemen, Toos; de Bruyn, Marco; Nijman, Hans W.

    2016-01-01

    Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address

  11. The role of smoking and alcohol intake in the development of high-grade squamous intraepithelial lesions among high-risk HPV-positive women

    DEFF Research Database (Denmark)

    Tolstrup, Janne; Munk, Christian; Thomsen, Birthe Lykke

    2006-01-01

    -risk human papillomavirus positive women with normal cytology, comparing 94 women who developed high-grade squamous intraepithelial lesions with 454 women who remained cytologically normal. Logistic regression was applied for statistical analysis. RESULTS: Compared with never smokers, the odds ratio for high...

  12. A longitudinal, qualitative and quantitative exploration of daily life and need for rehabilitation among patients with high-grade gliomas and their caregivers

    DEFF Research Database (Denmark)

    Piil, K; Jarden, Mary Ellen; Jakobsen, J

    2013-01-01

    High-grade gliomas (HGGs) are the most malignant type of brain tumours. The 5-year survival is 10% and a significant part of the ongoing research aims to increase survival through surgical and oncological treatments. Accordingly, there is an increasing need for investigating the HGG trajectory...

  13. 3D image of Brittle/Ductile transition in active volcanic area and its implication on seismicity: The Campi Flegrei caldera case study

    Science.gov (United States)

    Castaldo, Raffaele; Luca, D'auria; Susi, Pepe; Giuseppe, Solaro; Pietro, Tizzani

    2015-04-01

    The thermo-rheology of the rocks is a crucial aspect to understand the mechanical behavior of the crust in young and tectonically active area. As a consequence, several studies have been performed since last decades in order to understand the role of thermic state in the evolution of volcanic environments. In this context, we analyze the upper crust rheology of the Campi Flegrei active caldera (Southern Italy). Our target is the evaluation of the 3D geometry of the Brittle-Ductile transition beneath the resurgent caldera, by integrating the available geological, geochemical, and geophysical data. We first performed a numerical thermal model by using the a priori geological and geophysical information; than we employ the retrieved isothermal distribution to image the rheological stratification of the shallow crust beneath caldera. In particular, considering both the thermal proprieties and the mechanical heterogeneities of the upper crust, we performed, in a Finite Element environment, a 3D conductive time dependent thermal model through an numerical of solution of the Fourier equation. The dataset consist in temperature measurements recorded in several deep wells. More specifically, the geothermal gradients were measured in seven deep geothermal boreholes, located in three main distinct areas: Mofete, Licola, and San Vito. In addition, we take into account also the heat flow density map at the caldera surface calculated by considering the thermal measurements carried out in 30 shallow water wells. We estimate the isothermal distribution of the crust calibrating two model parameters: the heat production [W], associated to the magma injection episodes in the last 60 kyears within the magma chamber and the heat flow coefficient [W/m2*K] at the external surface. In particular, the optimization procedure has been performed using an exhaustive grid search, to minimize the differences between model and experimental measurements. The achieved results allowed us to

  14. Health-related quality of life in patients with high-grade gliomas: a quantitative longitudinal study.

    Science.gov (United States)

    Piil, K; Jakobsen, J; Christensen, K B; Juhler, M; Jarden, M

    2015-09-01

    The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity levels, prevalence and severity of anxiety and depressive symptoms and health-related quality of life among patients with a highgrade glioma. This paper is based on a longitudinal mixed methods study. Patients (n = 30) completed questionnaires at 5 time points from time of diagnosis until the final follow-up after 1 year. Scores of Karnofsky Performance Status (KPS), physical activity, anxiety and depression and health-related quality of life (FACT-Br) are obtained. Patients' physical activity level and KPS decrease during the disease- and treatment trajectory. The majority of patients did not report any depressive symptoms, eight individuals (26.7 %) being depressed at various time points. Among a sub-group of participants who completed all study requirements for the entire study period the level of anxiety decreased significantly during the study. The FACT-Br sub-scale of emotional well-being increased significant, indicating a better HRQOL attend of followup. The diagnosis of a HGG leads to an ongoing functional decline measured as a decline of the KPS and a reduced physical activity during leisure time. Supportive care combined with rehabilitative and palliative approaches might well be valuable along the trajectory especially during the post-surgery period when anxiety is at its highest peak.

  15. [Effectiveness of human papillomavirus genotyping for detection of high-grade anal intraepithelial neoplasia compared to anal cytology].

    Science.gov (United States)

    Padilla-España, Laura; Repiso-Jiménez, Juan Bosco; Fernández-Sánchez, Fernando; Pereda, Teresa; Rivas-Ruiz, Francisco; Fernández-Morano, Teresa; de la Torre-Lima, Javier; Palma, Fermín; Redondo, Maximino; de Troya-Martín, Magdalena

    2016-01-01

    The incidence of high-grade anal intraepithelial neoplasia (HGAIN) -with an aetiological based on high-risk types of human papillomavirus- is increasing in some high-risk groups. Screening for HGAIN includes routine anal cytology and, more recently, HPV genotyping. The main objective of this study was to determine the sensitivity and specificity of anal cytology and HPV genotyping for the detection of HGAIN. This is a study to determine the correlation of cytological and microbiological findings with anal biopsy findings in a cohort of patients at high risk of developing AIN referred to the department of sexually transmitted infections of the Hospital Costa del Sol, Spain, between January 2008 and December 2014. Of the 151 patients subjected to screening, a total of 92 patients, all of them with the result of three screening test (anal cytology, genotyping and biopsy) were included in the study. Just under two-thirds (62%) of them were HIV-positive. The sensitivity and specificity of anal cytology to detect HGAIN were 52.8 and 85.7%, respectively (k: 0.328), and 78 and 62.8% to detect two or more HPV oncogenic genotypes (k: 0.417). The detection of oncogenic HPV genotypes allowed the identification of 23 new cases of HGAIN that had been underdiagnosed with anal cytology, with 14 cases containing at least three high-risk genotypes. Anal cytology did not show enough sensitivity in HGAIN screening. HPV genotyping has shown to be a useful tool to detect HGAIN cases, although it could lead to an over-diagnosis as a solitary screening procedure. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  16. Prevalence of high-grade squamous intraepithelial lesions and cervical cancer among patients with unsatisfactory colposcopic examination, without visible lesion

    Directory of Open Access Journals (Sweden)

    Fernanda Rangel da Veiga

    Full Text Available CONTEXT AND OBJECTIVE: Cervical cancer is a serious public health problem in Brazil. For patients with unsatisfactory colposcopic examinations without visible lesions, but with cervical cytological tests suggesting high-grade squamous intraepithelial lesion (HSIL, the national recommendation is to repeat cervical cytological tests after three months. Our aim was to assess the prevalence of HSIL and cancer among patients with initial cervical cytological tests suggestive of HSIL but with unsatisfactory colposcopic examinations without visible lesions, in order to contribute towards the discussion regarding a more effective clinical approach that might diminish the likelihood of patient abandonment of follow-up before appropriate diagnosis and treatment. DESIGN AND SETTING: Cross-sectional study in Colposcopy Clinic of IFF/Fiocruz. METHOD: Patients admitted between December 1989 and April 2007 with cytological diagnoses of HSIL but with unsatisfactory colposcopic examinations without visible lesions underwent cervical cone biopsy. RESULTS: Sixty-five such patients were included, comprising 33.8% with HSIL and 4.6% with cancer, confirmed histologically. The other patients presented low-grade squamous intraepithelial lesion (26.1%, glandular dysplasia (1.5% and absence of disease (33.8%. CONCLUSION: The observed prevalence of cancer and HSIL does not seem to be enough to justify immediate referral for cone biopsies to investigate the cervical canal in these cases. The findings suggest that the recommendation of repeated cytological tests following an initial one with HSIL, among patients with unsatisfactory colposcopic examinations without visible lesions, is appropriate in our setting. Efforts are needed to ensure adherence to follow-up protocols in order to reduce the chances of losses.

  17. Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jiayi, E-mail: jhuang@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); DeWees, Todd A.; Badiyan, Shahed N.; Speirs, Christina K.; Mullen, Daniel F.; Fergus, Sandra [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Tran, David D.; Linette, Gerry; Campian, Jian L. [Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri (United States); Chicoine, Michael R.; Kim, Albert H.; Dunn, Gavin [Department of Neurosurgery, Washington University School of Medicine, St Louis, Missouri (United States); Simpson, Joseph R.; Robinson, Clifford G. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States)

    2015-08-01

    Purpose: Acute severe lymphopenia (ASL) frequently develops during radiation therapy (RT) and concurrent temozolomide (TMZ) for high-grade glioma (HGG) and is associated with decreased survival. The current study was designed to identify potential predictors of ASL, with a focus on actionable RT-specific dosimetric parameters. Methods and Materials: From January 2007 to December 2012, 183 patients with HGG were treated with RT+TMZ and had available data including total lymphocyte count (TLC) and radiation dose-volume histogram parameters. ASL was defined as TLC of <500/μL within the first 3 months from the start of RT. Stepwise logistic regression analysis was used to determine the most important predictors of ASL. Results: Fifty-three patients (29%) developed ASL. Patients with ASL had significantly worse overall survival than those without (median: 12.5 vs 20.2 months, respectively, P<.001). Stepwise logistic regression analysis identified female sex (odds ratio [OR]: 5.30; 95% confidence interval [CI]: 2.46-11.41), older age (OR: 1.05; 95% CI: 1.02-1.09), lower baseline TLC (OR: 0.92; 95% CI: 0.87-0.98), and higher brain volume receiving 25 Gy (V{sub 25Gy}) (OR: 1.03; 95% CI: 1.003-1.05) as the most significant predictors for ASL. Brain V{sub 25Gy} <56% appeared to be the optimal threshold (OR: 2.36; 95% CI: 1.11-5.01), with an ASL rate of 38% versus 20% above and below this threshold, respectively (P=.006). Conclusions: Female sex, older age, lower baseline TLC, and higher brain V{sub 25Gy} are significant predictors of ASL during RT+TMZ therapy for HGG. Maintaining the V{sub 25Gy} of brain below 56% may reduce the risk of ASL.

  18. Operative management of high-grade dysplastic L5 spondylolisthesis with the use of external transpedicular fixation: advantages and drawbacks.

    Science.gov (United States)

    Prudnikova, Oksana G; Shchurova, Elena N

    2016-06-01

    The aim of our study was to analyze clinical and radiographic outcomes of operative management of L5 high-grade dysplastic spondylolisthesis with the apparatus for external transpedicular fixation (AETF), and to compare the results of its use for reduction and spondylodesis. There were 13 patients with L5 dysplastic spondylolisthesis of grade 4 (Meyerding grading) and having a mean age of 25.0 ± 3.6 years. The management included two stages: gradual reduction with the AETF, followed by either isolated anterior spondylodesis with the same AETF (group 1, n = 8), or by spondylodesis using a combined method (internal transpedicular instrumentation and posterior lumbar interbody fusion [PLIF]) (group 2, n = 5). Clinical evaluation included pain (VAS scale) and functional status (Oswestry questionnaire [ODI]). Reduction and fusion completeness were assessed radiographically after treatment and at a mean follow-up of 2.1 ± 0.4 years. Initial slippage was reduced by 51.6 % with AETF and was of grade 1 or 2. Reduction made up 31.1 % at follow-ups (grade 2 or 3). Pain decreased by 57.6 % (p spondylolisthesis provides gradual controlled reduction of the slipped vertebra, decompression of cauda equine roots, and recovery of the local sagittal spinal column balance. It creates conditions for achieving stability of lumbosacral segments with combined spondylodesis (internal transpedicular instrumentation and PLIF). AETF is not suitable for spondylodesis due to a high rate of pseudarthrosis.

  19. Combined Immunoscore of CD103 and CD3 Identifies Long-Term Survivors in High-Grade Serous Ovarian Cancer.

    Science.gov (United States)

    Bösmüller, Hans-Christian; Wagner, Philipp; Peper, Janet Kerstin; Schuster, Heiko; Pham, Deborah Lam; Greif, Karen; Beschorner, Christine; Rammensee, Hans-Georg; Stevanović, Stefan; Fend, Falko; Staebler, Annette

    2016-05-01

    Increased numbers of tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSC) are associated with improved clinical outcome. Intraepithelial localization of TILs might be regulated by specific homing receptors, such as CD103, which is widely expressed by intraepithelial lymphocytes. Given the emerging role of CD103 TILs, we aimed to assess their contribution to the prognostic value of immunoscoring in HGSC. The density of intratumoral CD3 and CD103 lymphocytes was examined by immunohistochemistry on a tissue microarray of a series of 135 patients with advanced HGSC and correlated with CD4, CD8, CD56, FoxP3, and TCRγ T-cell counts, as well as E-cadherin staining and conventional prognostic parameters and clinical outcome. Both the presence of CD103 cells, as well as high numbers of intraepithelial CD3 lymphocytes (CD3E), showed a significant correlation with overall survival, in the complete series, as well as in patients with optimal debulking and/or platinum sensitivity. Combining CD3 and CD103 counts improved prognostication and identified 3 major subgroups with respect to overall survival. The most pronounced effect was demonstrated for patients with optimally resected and platinum-sensitive tumors. Patients with CD3/CD103 tumors showed a 5-year survival rate at 90%, CD3/CD103 at 63%, and CD3/CD103 at 0% (P CD3 counts improves the prognostic value of TIL counts in HGSC and might identify patients with early relapse or long-term survival based on the type and extent of the immune response.

  20. High-Grade Cervical Dysplasia following Radiation Therapy for Invasive Cervical Cancer: A Report of Four Cases

    Directory of Open Access Journals (Sweden)

    Mila Pontremoli Salcedo

    2015-05-01

    Full Text Available Introduction: The standard treatment for locally advanced cervical cancer is chemoradiation, with the majority of patients having a complete response to the therapy. The current surveillance recommendations from the Society of Gynecologic Oncology include annual cytology, with a small proportion of patients subsequently diagnosed with high-grade cervical dysplasia (CIN 2/3. To date, there is limited information regarding the optimal treatment and outcome for patients diagnosed with CIN 2/3. The current report describes the diagnosis, management and outcome of 4 patients diagnosed with CIN 2/3 following chemoradiation. Case Description: We describe 4 patients who developed CIN 2/3 seven months to 8 years following radiation therapy for locally advanced cervical cancer. All 4 patients were asymptomatic and the abnormalities were first detected by a Pap test. Three of the patients were managed conservatively with observation, and the CIN 2/3 resolved without intervention. One patient underwent 2 cervical conizations followed by a hysterectomy with no residual dysplasia noted on the hysterectomy specimen. Conclusion: The majority of patients with recurrent cervical cancer after chemoradiation are symptomatic, and most cases are detected by a physical examination. The role of cytology, colposcopy and biopsies may be of limited value. Furthermore, the significance of the diagnosis of CIN 2/3 in patients previously treated with radiation therapy was not associated with recurrent disease in the 4 patients described. Our results suggest that cytology may be of limited value in detecting recurrence in patients following radiation therapy, even when CIN 2/3 is detected.

  1. Long term efficacy of Photodynamic Therapy (PDT) as an ablative therapy of high grade dysplasia in Barrett's oesophagus.

    Science.gov (United States)

    Gray, J; Fullarton, G M

    2013-12-01

    Barrett's high grade dysplasia (HGD) is a pre-malignant condition which requires treatment with either oesophagectomy or ablative endoscopic therapy. Endoscopic ablative techniques have evolved through Photodynamic Therapy (PDT) to more recently radiofrequency ablation (RFA). Although RFA has superseded PDT due to improved efficacy and safety profile there remains a significant cohort of patients previously treated by PDT where the long term outcome is unclear. This study's aim was to assess the long term efficacy of PDT in patients with Barrett's HGD. Between June 2002 and 2007 21 patients (16 male, median age 70) underwent PDT for HGD in Barrett's oesophagus. Patients received intravenous photosensitiser Photofrin (Porfimer sodium) forty eight hours prior to endoscopic light activation by laser light at 630 nm. The patients returned at 6-12 weekly intervals for repeat endoscopy and biopsy. Sixteen patients remained free of HGD at median 62 (range 36-114) months. Three patients developed adenocarcinoma at 47, 48 and 54 months (15%). Two patients were treated endoscopically with RFA and YAG laser, while one patient had surgical resection. Four patients developed recurrent HGD treated with repeat PDT. There was a significant reduction in length of Barrett's segment (from 5 cm to 3 cm) post PDT. The stricture rate requiring endoscopic therapy was 37% and 10% of patients developed photosensitivity reactions. PDT successfully ablated HGD in 84% of patients and could therefore still be considered an effective salvage treatment for this condition in patients with co-morbidities precluding them for surgical resection. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Pre-radiation lymphocyte harvesting and post-radiation reinfusion in patients with newly diagnosed high grade gliomas.

    Science.gov (United States)

    Campian, Jian L; Ye, Xiaobu; Gladstone, Douglas E; Ambady, Prakash; Nirschl, Thomas R; Borrello, Ivan; Golightly, Marc; King, Karen E; Holdhoff, Matthias; Karp, Judith; Drake, Charles G; Grossman, Stuart A

    2015-09-01

    Radiation (RT), temozolomide (TMZ), and dexamethasone in newly diagnosed high grade gliomas (HGG) produces severe treatment-related lymphopenia (TRL) that is associated with early cancer-related deaths. This TRL may result from inadvertent radiation to circulating lymphocytes. This study reinfused lymphocytes, harvested before chemo-radiation, and assessed safety, feasibility, and trends in lymphocyte counts. Patients with newly diagnosed HGG and total lymphocyte counts (TLC) ≥ 1000 cells/mm(3) underwent apheresis. Cryopreserved autologous lymphocytes were reinfused once radiation was completed. Safety, feasibility, and trends in TLC, T cell subsets and cytokines were studied. Serial TLC were also compared with an unreinfused matched control group. Ten patients were harvested (median values: age 56 years, dexamethasone 3 mg/day, TLC/CD4 1980/772 cells/mm(3)). After 6 weeks of RT/TMZ, TLC fell 69 % (p < 0.0001) with similar reductions in CD4, CD8 and NK cells but not Tregs. Eight patients received lymphocyte reinfusions (median = 7.0 × 10(7) lymphocytes/kg) without adverse events. A post-reinfusion TLC rise of ≥300 cells/mm(3) was noted in 3/8 patients at 4 weeks and 7/8 at 14 weeks which was similar to 23 matched controls. The reduced CD4/CD8 ratio was not restored by lymphocyte reinfusion. Severe lymphopenia was not accompanied by elevated serum interleukin-7 (IL-7) levels. This study confirms that severe TRL is common in HGG and is not associated with high plasma IL-7 levels. Although lymphocyte harvesting/reinfusion is feasible and safe, serial lymphocyte counts are similar to unreinfused matched controls. Studies administering higher lymphocyte doses and/or IL-7 should be considered to restore severe treatment-related lymphopenia in HGG.

  3. Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma.

    Science.gov (United States)

    Huang, Jiayi; DeWees, Todd A; Badiyan, Shahed N; Speirs, Christina K; Mullen, Daniel F; Fergus, Sandra; Tran, David D; Linette, Gerry; Campian, Jian L; Chicoine, Michael R; Kim, Albert H; Dunn, Gavin; Simpson, Joseph R; Robinson, Clifford G

    2015-08-01

    Acute severe lymphopenia (ASL) frequently develops during radiation therapy (RT) and concurrent temozolomide (TMZ) for high-grade glioma (HGG) and is associated with decreased survival. The current study was designed to identify potential predictors of ASL, with a focus on actionable RT-specific dosimetric parameters. From January 2007 to December 2012, 183 patients with HGG were treated with RT+TMZ and had available data including total lymphocyte count (TLC) and radiation dose-volume histogram parameters. ASL was defined as TLC of <500/μL within the first 3 months from the start of RT. Stepwise logistic regression analysis was used to determine the most important predictors of ASL. Fifty-three patients (29%) developed ASL. Patients with ASL had significantly worse overall survival than those without (median: 12.5 vs 20.2 months, respectively, P<.001). Stepwise logistic regression analysis identified female sex (odds ratio [OR]: 5.30; 95% confidence interval [CI]: 2.46-11.41), older age (OR: 1.05; 95% CI: 1.02-1.09), lower baseline TLC (OR: 0.92; 95% CI: 0.87-0.98), and higher brain volume receiving 25 Gy (V25Gy) (OR: 1.03; 95% CI: 1.003-1.05) as the most significant predictors for ASL. Brain V25Gy <56% appeared to be the optimal threshold (OR: 2.36; 95% CI: 1.11-5.01), with an ASL rate of 38% versus 20% above and below this threshold, respectively (P=.006). Female sex, older age, lower baseline TLC, and higher brain V25Gy are significant predictors of ASL during RT+TMZ therapy for HGG. Maintaining the V25Gy of brain below 56% may reduce the risk of ASL. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Gene expression profiles of luteal phase fallopian tube epithelium from BRCA mutation carriers resemble high-grade serous carcinoma.

    Science.gov (United States)

    Tone, Alicia A; Begley, Heather; Sharma, Monika; Murphy, Joan; Rosen, Barry; Brown, Theodore J; Shaw, Patricia A

    2008-07-01

    To identify molecular alterations potentially involved in predisposition to adnexal serous carcinoma (SerCa) in the nonmalignant fallopian tube epithelium (FTE) of BRCA1/2 mutation carriers, given recent evidence implicating the distal FTE as a common source for SerCa. We obtained and compared gene expression profiles of laser capture microdissected nonmalignant distal FTE from 12 known BRCA1/2 mutation carriers (FTEb) and 12 control women (FTEn) during the luteal and follicular phase, as well as 13 high-grade tubal and ovarian SerCa. Gene expression profiles of tubal and ovarian SerCa specimens were indistinguishable by unsupervised cluster analysis and significance analysis of microarrays. FTEb samples as a group, and four individual FTEb samples from the luteal phase in particular, clustered closely with SerCa rather than normal control FTE. Differentially expressed genes from these four samples relative to other FTEb samples, as well as differentially expressed genes in all FTEb luteal samples relative to follicular samples, were mapped to the I2D protein-protein interaction database, revealing a complex network affecting signaling pathways previously implicated in tumorigenesis. Two candidates, disabled homolog 2 mitogen-responsive phosphoprotein (DAB2) and Ski-like (SKIL), were further validated by real-time reverse transcription-PCR and tissue arrays. FTEb luteal and SerCa samples expressed higher levels of oncogenic SKIL and decreased levels of tumor suppressor DAB2, relative to FTEb follicular samples. These findings support a common molecular pathway for adnexal SerCa and implicate factors associated with the luteal phase in predisposition to ovarian cancer in BRCA mutation carriers.

  5. Coding of Barrett's oesophagus with high-grade dysplasia in national administrative databases: a population-based cohort study.

    Science.gov (United States)

    Chadwick, Georgina; Varagunam, Mira; Brand, Christian; Riley, Stuart A; Maynard, Nick; Crosby, Tom; Michalowski, Julie; Cromwell, David A

    2017-06-09

    The International Classification of Diseases 10th Revision (ICD-10) system used in the English hospital administrative database (Hospital Episode Statistics (HES)) does not contain a specific code for oesophageal high-grade dysplasia (HGD). The aim of this paper was to examine how patients with HGD were coded in HES and whether it was done consistently. National population-based cohort study of patients with newly diagnosed with HGD in England. The study used data collected prospectively as part of the National Oesophago-Gastric Cancer Audit (NOGCA). These records were linked to HES to investigate the pattern of ICD-10 codes recorded for these patients at the time of diagnosis. All patients with a new diagnosis of HGD between 1 April 2013 and 31 March 2014 in England, who had data submitted to the NOGCA. The main outcome assessed was the pattern of primary and secondary ICD-10 diagnostic codes recorded in the HES records at endoscopy at the time of diagnosis of HGD. Among 452 patients with a new diagnosis of HGD between 1 April 2013 and 31 March 2014, Barrett's oesophagus was the only condition coded in 200 (44.2%) HES records. Records for 59 patients (13.1%) contained no oesophageal conditions. The remaining 193 patients had various diagnostic codes recorded, 93 included a diagnosis of Barrett's oesophagus and 57 included a diagnosis of oesophageal/gastric cardia cancer. HES is not suitable to support national studies looking at the management of HGD. This is one reason for the UK to adopt an extended ICD system (akin to ICD-10-CM). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High-Grade Gliomas

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    Ibrahim eQaddoumi

    2014-04-01

    Full Text Available Background. Epidermal growth factor receptor is overexpressed in most pediatric high-grade gliomas (HGG. Since erlotinib had shown activity in adults with HGG, we conducted a phase II trial of erlotinib and local radiotherapy in children with newly diagnosed HGG. Methods. Following maximum surgical resection, patients between 3 and 21 years with nonmetastatic HGG received local radiotherapy at 59.4 Gy (54 Gy for spinal tumors and those with ≥70% brain involvement. Erlotinib started on day 1 of radiotherapy (120 mg/m2 per day and continued for 2 years unless there was tumor progression or intolerable toxicities. The 2-year progression-free survival (PFS was estimated for patients with intracranial anaplastic astrocytoma (AA and glioblastoma.Results. Median age at diagnosis for 41 patients with intracranial tumors (21 with glioblastoma and 20 with AA was 10.9 years (range, 3.3 to 19 years. The 2-year PFS for patients with AA and glioblastoma was 15% ± 7% and 19% ± 8%, respectively. Only five patients remained alive without tumor progression. Twenty-six patients had at least one grade 3 or 4 toxicity irrespective of association with erlotinib; only four required dose modifications. The main toxicities were gastrointestinal (n=11, dermatologic (n=5, and metabolic (n=4. One patient with gliomatosis cerebri who required prolonged corticosteroids died of septic shock associated with pancreatitis. Conclusions. Although therapy with erlotinib was mostly well tolerated, it did not change the poor outcome of our patients. Our results showed that erlotinib is not a promising medication in the treatment of children with intracranial AA and glioblastoma.

  7. Convolutional neural networks for an automatic classification of prostate tissue slides with high-grade Gleason score

    Science.gov (United States)

    Jiménez del Toro, Oscar; Atzori, Manfredo; Otálora, Sebastian; Andersson, Mats; Eurén, Kristian; Hedlund, Martin; Rönnquist, Peter; Müller, Henning

    2017-03-01

    The Gleason grading system was developed for assessing prostate histopathology slides. It is correlated to the outcome and incidence of relapse in prostate cancer. Although this grading is part of a standard protocol performed by pathologists, visual inspection of whole slide images (WSIs) has an inherent subjectivity when evaluated by different pathologists. Computer aided pathology has been proposed to generate an objective and reproducible assessment that can help pathologists in their evaluation of new tissue samples. Deep convolutional neural networks are a promising approach for the automatic classification of histopathology images and can hierarchically learn subtle visual features from the data. However, a large number of manual annotations from pathologists are commonly required to obtain sufficient statistical generalization when training new models that can evaluate the daily generated large amounts of pathology data. A fully automatic approach that detects prostatectomy WSIs with high-grade Gleason score is proposed. We evaluate the performance of various deep learning architectures training them with patches extracted from automatically generated regions-of-interest rather than from manually segmented ones. Relevant parameters for training the deep learning model such as size and number of patches as well as the inclusion or not of data augmentation are compared between the tested deep learning architectures. 235 prostate tissue WSIs with their pathology report from the publicly available TCGA data set were used. An accuracy of 78% was obtained in a balanced set of 46 unseen test images with different Gleason grades in a 2-class decision: high vs. low Gleason grade. Grades 7-8, which represent the boundary decision of the proposed task, were particularly well classified. The method is scalable to larger data sets with straightforward re-training of the model to include data from multiple sources, scanners and acquisition techniques. Automatically

  8. Is central obesity, hyperinsulinemia and dyslipidemia associated with high-grade prostate cancer? A descriptive cross-sectional study

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    Pawni Prabhat

    2010-01-01

    Full Text Available Aim : The association of central obesity, hyperinsulinemia, and dyslipidemia with higher grade advanced prostate cancer as determined by Gleason grading is not well understood. We evaluated the effect of central obesity waist hip ratio (WHR ≥ 0.9 and biochemical parameters associated with central obesity on Gleason grading in North Indian patients of prostate cancer presenting at advanced stages. Materials and Methods : A cross-sectional study was conducted among 50 nondiabetic patients having clinical stages III and IV prostate cancer. Gleason grading on core biopsy samples by histopathology was done and patients were divided in two groups-group1, Gleason score ≥8; group 2, Gleason score <8. WHR along with serum levels of prostate-specific antigen (PSA, testosterone, insulin, and lipid profile was done in each patient. Results : The two groups are similar in Age (67.54 years; range (50-80 years. Group 1 men had statistically higher mean WHR (0.96 vs 0.90; P ≤ 0.001, higher mean triglyceride level (201.34 vs 150.52 mg/dL; P=0.0006, higher mean very low-density lipoprotein (VLDL (40.27 vs 30.10 mg/dL; P =0.0006, higher mean insulin (19.49 vs 15.04 μIU/mL; P = 0.0024, and lower mean high-density lipoprotein (HDL levels (32.39 vs 36.82 mg/dL; P = 0.034 than men in group 2. Serum levels of cholesterol, LDL, and testosterone did not show statistically significant differences between the two groups. Conclusions : This pilot study involving small number of patients indicates that central obesity, dyslipidemia, and hyperinsulinemia could be associated with high-grade prostate cancer.

  9. IGF2BP3 as a potential tissue marker for the diagnosis of esophageal high-grade intraepithelial neoplasia

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    Zhang JJ

    2017-08-01

    Full Text Available Jingjing Zhang,1,* Qing Ji,2,* Chunhua Jiao,3,* Lihua Ren,4 Ye Zhao,4 Yanfang Chen,4 Ruihua Shi,4 Yadong Feng4 1State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 2Department of Emergency, Jingjiang People’s Hospital, Jingjiang, 3Department of Gastroenterology, First Affiliated Hospital with Nanjing Medical University, 4Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: The clinical significance of insulin-like growth factor-II mRNA-binding protein-3 (IGF2BP3 in esophageal high-grade intraepithelial neoplasia (HGIN is not clear. This study was designed to characterize the expression of IGF2BP3 in HGIN. Patients and methods: IGF2BP3 expression was evaluated by Western blot analyses in 12 cases and by immunohistochemistry (IHC in 112 cases. The associations between IGF2BP3 expression in HGIN and the clinicopathological parameters were examined. Results: Moderate to strong IGF2BP3 expression was present in HGIN samples. Using IHC, it was found that IGF2BP3 was positive in 68 (60.71% cases. Intense IHC of IGF2BP3 in HGIN was associated with a deeper lesion depth, and the lesion depth was the only predictor of the positive expression of IGF2BP3. Conclusion: Our results suggested that IGF2BP3 may be a supplementary tissue marker for preoperative diagnosis of HGIN. Keywords: esophageal squamous cell carcinoma, precancerous lesion, immunohistochemistry detection, early diagnosis

  10. Pleomorphic lobular carcinoma: is it more similar to a classic lobular cancer or to a high-grade ductal cancer?

    Directory of Open Access Journals (Sweden)

    Costarelli L

    2017-12-01

    Full Text Available Leopoldo Costarelli, Domenico Campagna, Alessandra Ascarelli, Francesco Cavaliere, Maria Helena Colavito, Tatiana Ponzani, Laura Broglia, Massimo La Pinta, Elena Manna, Lucio Fortunato Breast Unit, San Giovanni-Addolorata Hospital, Rome, Italy Background: Pleomorphic invasive lobular carcinoma (P-ILC is an uncommon variety of invasive lobular carcinoma with aggressive clinical features. Little is described in the literature regarding this topic.Materials and methods: We reviewed our experiences from 2010 to 2015 and compared 40 patients with P-ILC, 126 patients with classic-ILC (C-ILC and 574 cases of high-grade invasive ductal carcinoma (HG-IDC. We studied the histologic and immunohistochemical features, clinical presentation and surgical treatment.Results: P-ILC is diagnosed at the same age and tumor diameter as those of the other two histologic types. It is associated more frequently with multiple lymph node metastases and high proliferative index, and HER2/neu is amplified in 10% of cases. In spite of sharing some histologic characteristics with C-ILC (same growth pattern, loss of E-cadherin expression, same genetic pathway, its clinical and pathologic features define an autonomous entity. Its surgical treatment is similar to those of C-ILC and HG-IDC.Conclusion: This is the first review comparing these three pathologic entities. Our findings may be useful in understanding this variety of invasive lobular carcinoma, and further studies are certainly needed in this field. Keywords: breast cancer, lobular cancer, pleomorphic, mastectomy

  11. High-Grade Squamous Intraepithelial Lesion Cytology With Negative High-Risk Human Papillomavirus Tests Rarely Diagnoses Endometrial Cancer.

    Science.gov (United States)

    Pretorius, Robert G; Peterson, Patricia

    2015-07-01

    We hypothesized that women with cervical cytologic results of high-grade squamous intraepithelial lesion (HSIL) and negative high-risk human papillomavirus (HR-HPV) test results would have a high risk of having endometrial cancer and would benefit from routine endometrial biopsy. Reports of women with cytologic results of HSIL and negative HR-HPV test results were found in an electronic colposcopy database; their charts were reviewed. Rates of endometrial cancer for cytologic results of HSIL and negative HR-HPV test results were compared to a historical series for cytologic results of HSIL with positive HR-HPV and cytologic results of atypical glandular cells (AGCs) and negative HR-HPV test results. Between August 10, 1998, and April 20, 2013, 56 women were evaluated in our colposcopy clinics for cytologic results of HSIL and negative HR-HPV test results; of these 56 women, 1 (1.8%) was diagnosed with endometrial cancer. No endometrial cancer was diagnosed during the follow-up (median = 63 mo) after colposcopy. The risk for endometrial cancer with cytologic results of HSIL and negative HR-HPV test results (1.8%, 1/56) did not differ from that of a historical series from 2007 to 2009 from the same colposcopy clinic in 223 women with cytologic results of HSIL and positive HR-HPV test results (0.0%, 0/223; p = .2) and was lower than the risk for endometrial cancer from the historical series from 2007 to 2009 in women with cytologic results of AGC and negative HR-HPV test results (14.4%, 4/27; p = .04). Women with cytologic results of HSIL and negative HR-HPV test results are more like those with cytologic results of HSIL and positive HR-HPV test results than those with cytologic results of AGC and negative HR-HPV test results and would unlikely to benefit from routine endometrial biopsy at the time of colposcopy.

  12. Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma.

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    Katelin N Townsend

    Full Text Available When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer.In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3 and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1 correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049-5.106; p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097-5.799; p = 0.0294].Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.

  13. Fluorescein-Guided Surgery for Resection of High-Grade Gliomas: A Multicentric Prospective Phase II Study (FLUOGLIO).

    Science.gov (United States)

    Acerbi, Francesco; Broggi, Morgan; Schebesch, Karl-Michael; Höhne, Julius; Cavallo, Claudio; De Laurentis, Camilla; Eoli, Marica; Anghileri, Elena; Servida, Maura; Boffano, Carlo; Pollo, Bianca; Schiariti, Marco; Visintini, Sergio; Montomoli, Cristina; Bosio, Lorenzo; La Corte, Emanuele; Broggi, Giovanni; Brawanski, Alexander; Ferroli, Paolo

    2018-01-01

    Purpose: Sodium fluorescein is a dye that, intravenously injected, selectively accumulates in high-grade glioma (HGG) tissue through a damaged blood-brain barrier. In this article, the final results of a multicentric prospective phase II trial (FLUOGLIO) on fluorescein-guided HGG resection through a dedicated filter on the surgical microscope were reported.Methods: Patients with suspected HGGs considered suitable for removal were eligible to participate in this trial. Fluorescein was intravenously injected at a dose of 5 to 10 mg/kg. The primary endpoint was the percentage of patients with histologically confirmed HGGs, without contrast-enhancing tumor at the immediate postoperative MRI. Secondary endpoints were PFS, residual tumor on postoperative MRI, overall survival, neurologic deficits, and fluorescein-related toxicity. The sensitivity and specificity of fluorescein in identifying tumor tissue were estimated by fluorescent and nonfluorescent biopsies at the tumor margin. The study was registered on the European Regulatory Authorities website (EudraCT 2011-002527-18).Results: Fifty-seven patients aged 45 to 75 years were screened for participation, and 46 were considered for primary and secondary endpoints. Mean preoperative tumor volume was 28.75 cm3 (range, 1.3-87.8 cm3). Thirty-eight patients (82.6%) underwent a complete tumor removal. Median follow-up was 11 months. PFS-6 and PFS-12 were 56.6% and 15.2%. Median survival was 12 months. No adverse reaction related to SF administration was recorded. The sensitivity and specificity of fluorescein in identifying tumor tissue were respectively 80.8% and 79.1%.Conclusions: Fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and enables a high percentage of contrast-enhancing tumor in patients with HGGs. Clin Cancer Res; 24(1); 52-61. ©2017 AACR. ©2017 American Association for Cancer Research.

  14. Microsatellite instability in pediatric high grade glioma is associated with genomic profile and differential target gene inactivation.

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    Marta Viana-Pereira

    Full Text Available High grade gliomas (HGG are one of the leading causes of cancer-related deaths in children, and there is increasing evidence that pediatric HGG may harbor distinct molecular characteristics compared to adult tumors. We have sought to clarify the role of microsatellite instability (MSI in pediatric versus adult HGG. MSI status was determined in 144 patients (71 pediatric and 73 adults using a well established panel of five quasimonomorphic mononucleotide repeat markers. Expression of MLH1, MSH2, MSH6 and PMS2 was determined by immunohistochemistry, MLH1 was assessed for mutations by direct sequencing and promoter methylation using MS-PCR. DNA copy number profiles were derived using array CGH, and mutations in eighteen MSI target genes studied by multiplex PCR and genotyping. MSI was found in 14/71 (19.7% pediatric cases, significantly more than observed in adults (5/73, 6.8%; p = 0.02, Chi-square test. MLH1 expression was downregulated in 10/13 cases, however no mutations or promoter methylation were found. MSH6 was absent in one pediatric MSI-High tumor, consistent with an inherited mismatch repair deficiency associated with germline MSH6 mutation. MSI was classed as Type A, and associated with a remarkably stable genomic profile. Of the eighteen classic MSI target genes, we identified mutations only in MSH6 and DNAPKcs and described a polymorphism in MRE11 without apparent functional consequences in DNA double strand break detection and repair. This study thus provides evidence for a potential novel molecular pathway in a proportion of gliomas associated with the presence of MSI.

  15. Altered expression of MGMT in high-grade gliomas results from the combined effect of epigenetic and genetic aberrations.

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    João Ramalho-Carvalho

    Full Text Available MGMT downregulation in high-grade gliomas (HGG has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA. By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation and genetic (monosomy, locus deletion changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy.

  16. Peritoneal Involvement Is More Common Than Nodal Involvement in Patients With High-Grade Appendix Tumors Who Are Undergoing Prophylactic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

    Science.gov (United States)

    Mehta, Akash; Mittal, Rohin; Chandrakumaran, Kandiah; Carr, Norman; Dayal, Sanjeev; Mohamed, Faheez; Moran, Brendan; Cecil, Tom

    2017-11-01

    Right hemicolectomy is routinely recommended in patients with histologic findings of high-grade appendix tumors after appendicectomy. Undetected peritoneal disease may be encountered at surgery. In high-grade appendix tumors with disease detected radiologically, complete cytoreduction may not be possible and outcomes poor. For these reasons, we adopted a policy of prophylactic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The purpose of this study was to quantify the rates of peritoneal and nodal metastatic disease in patients with high-grade appendix tumors without obvious metastatic disease and to report the long-term outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients. Data regarding peritoneal and nodal metastatic disease were extracted from surgical and histologic records. The study was conducted at a high-volume tertiary referral center for peritoneal malignancy. Patients referred with histologically high-grade appendix tumors at appendicectomy, without detectable metastatic spread, between January 1994 and September 2016 were included MAIN OUTCOME MEASURES:: A total of 62 patients with high-grade pathology at appendicectomy, without clinical or radiological peritoneal disease, underwent complete cytoreduction with hyperthermic intraperitoneal chemotherapy. Thirty-five (57%) of 62 patients had peritoneal disease (median peritoneal cancer index 5 (range, 1-28)). Eleven (31%) of 35 had microscopic peritoneal disease. Overall, 23 (37%) of 62 had peritoneal disease beyond the confines of a standard right hemicolectomy. Nine (15%) of 62 had nodal involvement. Mean overall and disease-free survival were 110.9 (95% CI, 94.8-127.0 mo) and 102.1 months (95% CI, 84.3-119.9 mo), with 5-year overall and disease-free survival of 83.2% and 76.0%. The retrospective nature limits the interpretation of these results. Complete cytoreduction was achieved in all of the patients, with excellent long

  17. Association of Admission Glycaemia With High Grade Atrioventricular Block in ST-Segment Elevation Myocardial Infarction Undergoing Reperfusion Therapy: An Observational Study.

    Science.gov (United States)

    Huang, Bi; Wang, Xinjie; Yang, Yanmin; Zhu, Jun; Liang, Yan; Tan, Huiqiong; Yu, Litian; Gao, Xin; Zhang, Han; Wang, Juan

    2015-07-01

    Several studies have demonstrated the association between elevated admission glycaemia (AG) and the occurrence of some arrhythmias such as atrial fibrillation, ventricular tachycardia, and ventricular fibrillation after myocardial infarction. However, the impact of elevated AG on the high grade atrioventricular block (AVB) occurrence after ST-segment elevation myocardial infarction (STEMI) remains unclear. Included were 3359 consecutive patients with STEMI who received reperfusion therapy. The primary endpoint was the development of high grade AVB during hospital course. Patients were divided into non-diabetes mellitus (DM), newly diagnosed DM, and previously known DM according to the hemoglobin A1c level. The optimal AG value was determined by receiver operating characteristic curves analysis with AG predicting the high grade AVB occurrence. The best cut-off value of AG for predicting the high grade AVB occurrence was 10.05 mmol/L by ROC curve analysis. The prevalence of AG ≥ 10.05 mmol/L in non-DM, newly diagnosed DM, and previously known DM was 15.7%, 34.1%, and 68.5%, respectively. The incidence of high grade AVB was significantly higher in patients with AG ≥ 10.05  mmol/L than grade AVB occurrence in non-DM (HR = 1.826, 95% CI 1.073-3.107, P = 0.027) and in newly diagnosed DM (HR = 5.252, 95% CI 1.890-14.597, P = 0.001). Moreover, both AG ≥ 10.05  mmol/L and high grade AVB were independent risk factors of 30-day all cause-mortality (HR = 1.362, 95% CI 1.006-1.844, P = 0.046 and HR = 2.122, 95% CI 1.154-3.903, P = 0.015, respectively). Our study suggested that elevated AG level (≥10.05  mmol/L) might be an indicator of increased risk of high grade AVB occurrence in patients with STEMI.

  18. Transition of high-grade cervical intraepithelial neoplasia to micro-invasive carcinoma is characterized by integration of HPV 16/18 and numerical chromosome abnormalities.

    NARCIS (Netherlands)

    Hopman, A.H.N.; Smedts, F.; Dignef, W.; Ummelen, M.; Sonke, G.; Mravunac, M.; Vooijs, G.P.; Speel, E.J.; Ramaekers, F.C.S.

    2004-01-01

    Cervical intraepithelial neoplasia (CIN I, II, and III) and cases of CIN III associated with micro-invasive cervical carcinoma (CIN III & mCA) were analysed for evidence of episomal or integrated human papillomavirus (HPV) 16/18 DNA by fluorescence in situ hybridization (FISH). In parallel,

  19. Metabolic syndrome factors and risk of postoperative depression in high-grade glioma patients in a 1.5-year prospective study.

    Science.gov (United States)

    Jiao, Jian-Tong; Jiang, Chen; Huang, Jin; Dai, Min-Chao; Wang, Cheng; Cheng, Chao; Shao, Jun-Fei

    2014-10-01

    To date, the relationship between metabolic syndrome factors and the risk of glioma-related depression is still unclear, and no study investigates this relationship. Our aim was to investigate the relationship between metabolic syndrome factors and the risk of postoperative depression in high-grade patients. A total of 386 high-grade glioma patients participated in blood sample collection for metabolic syndrome factors analysis and the hospital anxiety and depression scale testing. The association between metabolic syndrome factors and the risk of postoperative depression was assessed using Cox regression proportional hazards models, and Student's t tests were used to evaluate the differences in demographic variables and clinical characteristics in subgroups. The incidence of postoperative depression in our 1.5-year follow-up was 30.5%. We found the risk of postoperative depression was elevated with increased blood glucose level [hazard ratios (HR) 2.277, 95% confidence interval (CI) 1.201-4.320, top vs. bottom quartile]. The hazard ratio was increased for z-scores of blood glucose (HR 1.672 per unit standard deviation, 95% CI 1.311-2.133] and of the combined metabolic syndrome score (HR 1.080, 95% CI 1.000-1.167). In addition, risk of postoperative depression risk was increased in high-grade glioma patients with high blood glucose levels (≥6.0 mmol/l) (HR 2.084, 95% CI 1.235-3.515). However, we did not find significant associations between postoperative depression and other metabolic syndrome factors, including body mass index, systolic blood pressure, diastolic blood pressure, cholesterol, and triglycerides. Depression is prevalent among patients with high-grade glioma after operation. Blood glucose level is positively associated with the risk of postoperative depression, and might be involved in the etiology of postoperative depression, and may predict its development in high-grade glioma patients.

  20. Quality of life of patients with high-grade spondylolisthesis: minimum 2-year follow-up after surgical and nonsurgical treatments.

    Science.gov (United States)

    Bourassa-Moreau, Étienne; Mac-Thiong, Jean-Marc; Joncas, Julie; Parent, Stefan; Labelle, Hubert

    2013-07-01

    Surgical intervention is generally indicated in a pediatric high-grade spondylolisthesis to prevent the progression of deformity or neurologic deterioration and improve the quality of life. However, the outcome of the treatment on the health-related quality of life (HRQOL) of patients with high-grade spondylolisthesis remains largely unknown. To describe the changes in the HRQOL of patients with pediatric high-grade spondylolisthesis after surgical and nonsurgical managements. Observational case series with a minimal of 2-year follow-up. Twenty-eight pediatric patients with high-grade spondylolisthesis from a single institution filled the inclusion criteria. Twenty-three patients were managed surgically and five were managed nonsurgically. Self-report measures: Scoliosis Research Society questionnaires (SRS-22). Neurologic examination, radiographic evaluation of slip grade. The SRS-22 questionnaire was collected at the baseline (initial presentation for the nonsurgical group and preoperative visit for the surgical group) and at the last follow-up. Differences between baseline and last follow-up were evaluated in both groups. Correlation between the baseline score of SRS-22 score and improvement in the SRS-22 score was determined in surgical patients. In surgical patients, total SRS-22 scores were 3.31 ± 0.50 at the baseline and 4.26 ± 0.50 at the last follow-up. In nonsurgical patients, total SRS-22 scores were 4.12 ± 0.16 at the baseline and 4.14 ± 0.38 at the last follow-up. Therefore, variation in the SRS-22 total score was +0.94 ± 0.77 (pHRQOL improves after a surgical intervention for high-grade spondylolisthesis. Patients with lower baseline HRQOL scores are those who benefit the most from surgery. Close observation is a safe and feasible option in selected patients with a good baseline HRQOL and no neurologic impairment. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Mammary analog secretory carcinoma of salivary gland with high-grade histology arising in hard palate, report of a case and review of literature

    Science.gov (United States)

    Luo, Wenyi; Lindley, Sarah W; Lindley, Peter H; Krempl, Gregory A; Seethala, Raja R; Fung, Kar-Ming

    2014-01-01

    Mammary gland analog secretary carcinoma (MASC) of salivary gland is typically a tumor of low histologic grade and behaves as a low-grade malignancy with relatively benign course. This tumor shares histologic features, immunohistochemical profile, and a highly specific genetic translocation, ETV6-NTRK3, with secretory carcinoma of breast. Histologically, it is often mistaken as acinic cell carcinoma, adenocarcinoma not otherwise specified, and other primary salivary gland tumors. Here we report a case of MASC with high-grade transformation and cervical lymph node metastases confirmed with ETV6-NTRK3 translocation arising in the hard palate of a 41 year-old adult. Interestingly, the metastatic carcinoma has lower grade than the original tumor which strongly support malignant transformation of the original tumor. Most commonly, MASC arises from the parotid gland and less often in minor salivary glands. Metastasis is relatively uncommon and high-grade histology has only been reported in four cases with three of them arising from the parotid gland and the location of the fourth one has not been reported. This is the first case with high grade histology that arise from minor salivary gland and it emphasizes the importance of molecular screening of salivary gland tumor with high-grade histology for ETV6-NTRK3 translocation. In our literature of 115 cases that includes the current case, MASC occurred predominantly in adult with only a few cases under 18 years of age and a male to female ratio of 1.2:1. Parotid gland is more commonly affected but there is also significant occurrence in minor salivary glands. Except for the cases with high grade histology, the overall prognosis is good. PMID:25674280

  2. Semi-Quantitative Calculations of Primary Tumor Metabolic Activity Using F-18 FDG PET/CT as a Predictor of Survival in 92 Patients With High-Grade Bone or Soft Tissue Sarcoma

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Fuglo, Hanna Maria; Rasmussen, Sine Hvid

    2015-01-01

    To assess the prognostic value of primary tumor metabolic activity in patients with high-grade bone sarcomas (BS) or soft tissue sarcomas (STS) using F-18 FDG PET/CT. A single-site, retrospective study including 92 patients with high-grade BS or STS. Pretreatment F-18 FDG PET/CT scan was performe...... metabolic activity with pretherapeutic SUVmax using F-18 FDG PET/CT demonstrates independent properties beyond histologic grading for prediction of survival in patients with high-grade STS, but not with high-grade BS.......To assess the prognostic value of primary tumor metabolic activity in patients with high-grade bone sarcomas (BS) or soft tissue sarcomas (STS) using F-18 FDG PET/CT. A single-site, retrospective study including 92 patients with high-grade BS or STS. Pretreatment F-18 FDG PET/CT scan was performed...

  3. Transitions in Mathematics Education

    National Research Council Canada - National Science Library

    Verschaffel, Ghislaine GueudetMarianna BoschAndrea A. diSessaOh Nam KwonLieven

    2016-01-01

    .... The book focuses on research in the area of mathematics education, and starts out with a literature review, describing the epistemological, cognitive, institutional and sociocultural perspectives on transition...

  4. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia: A case-control study among Chinese adults.

    Science.gov (United States)

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-08-01

    Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized.A case-control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted.After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24-2.81) and women (adjusted OR = 2.72, 95% CI = 1.44-5.16). The 2 highest BMI categories (27.5-29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5-29.9: adjusted OR = 1.78, 95% CI = 1.02-3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27-5.08) and women (BMI = 27.5-29.9: adjusted OR = 2.88, 95% CI = 1.27-6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36-5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25-3.14) and women (adjusted OR = 2.88, 95% CI = 1.43-5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25-2.69) in women.Increased BMI was associated with an increased risk of gastric high-grade dysplasia in

  5. Risk factors for anal high-grade squamous intraepithelial lesions in HIV-positive MSM: is targeted screening possible?

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    Siegenbeek van Heukelom, Matthijs L; Marra, Elske; de Vries, Henry J C; Schim van der Loeff, Maarten F; Prins, Jan M

    2017-10-23

    HIV-positive MSM are at increased risk for developing anal squamous cell carcinoma. Detection of precursor lesions of anal cancer [anal high-grade squamous intraepithelial lesions (HSIL)] is cumbersome and expensive. Our objective was to identify potential risk factors for anal HSIL in HIV-positive MSM to develop more stringent screening criteria. We studied a cohort of MSM screened by high-resolution anoscopy at three HIV clinics in Amsterdam, the Netherlands. For every first high-resolution anoscopy performed in a patient, we analyzed five demographic and seven HIV-related potential risk factors for four different outcome measures: histologically proven anal HSIL vs. no squamous intraepithelial lesions (SIL), HSIL-anal intraepithelial neoplasia 2 vs. no SIL, HSIL-anal intraepithelial neoplasia 3 vs. no SIL, and HSIL vs. no HSIL. We used univariable and multilevel, multivariable logistic regression. From 2008 through 2015, 497 out of 1678 (30%) screened HIV-positive MSM had anal HSIL. The mean age was 49 years (SD 9.6), 96% used combination antiretroviral therapy, and median duration of combination antiretroviral therapy use was 7.8 years (interquartile range 4.0-12.4). Increasing age [adjusted odds ratio (aOR) 0.82, 95% confidence interval (CI) 0.70-0.94, P = 0.006] and years living with suppressed viral load [1-5 years suppressed aOR 0.52 (95% CI 0.34-0.80), 5.01-10 years aOR 0.47 (95% CI 0.29-0.74), >10 years aOR 0.54 [0.34-0.87], all compared to less than 1 year suppressed, P = 0.009] were found to be protective for HSIL vs. no SIL. Young HIV-positive MSM without viral suppression are statistically at highest risk for anal HSIL, but given the high prevalence among all virally suppressed men, we advise that all HIV-positive MSM should be screened for HSIL.

  6. Inhibitors of GLUT/SLC2A Enhance the Action of BCNU and Temozolomide against High-Grade Gliomas

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    Alberto Azzalin

    2017-04-01

    Full Text Available Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV and ritonavir (RTV, and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2 superfamily, phlorizin (PHZ, in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma. PHZ was inactive on the same cells. Similar results were obtained when cells were grown in adherence or as 3D multicellular tumor spheroids. RTV treatment but not IDV treatment induced AMP-activated protein kinase (AMPKα phosphorylation that paralleled the decrease in glycolytic activity and cell growth. IDV, but not RTV, induced an increase in GLUT1/SLC2A1 whose activity could compensate for the inhibition of GLUT4/SLC2A4 by IDV. RTV and IDV pass poorly the blood brain barrier and are unlikely to reach sufficient liquoral concentrations in vivo to inhibit glioblastoma growth as single agents. Isobologram analysis of the association of RTV or IDV and 1,3-bis(2-chloroethyl-1-nitrosourea (BCNU or 4-methyl-5-oxo-2,3,4,6,8-pentazabicyclo[4.3.0]nona-2,7,9-triene-9-carboxamide (TMZ indicated synergy only with RTV on inhibition of glioblastoma cells. Finally, we tested in vivo the combination of RTV and BCNU on established GL261 tumors. This drug combination increased the overall survival and allowed a five-fold reduction in the dose of BCNU.

  7. [The role of HPV genotyping testing in follow-up of high grade squamous intraepithelial lesion after treatment].

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    Li, Ning; Zuo, Jing; Huang, Ying; An, Jusheng; Yao, Hongwen; Li, Xiaoguang; Zhang, Rong; Li, Bin; Zhang, Xun; Guo, Huiqin; Wu, Lingying

    2015-04-01

    To assess the clinical value of HPV genotyping in follow-up after treatment for cervical high grade squamous intraepithelial lesion (HSIL). Two hundred and thirty eight patients with HSIL receiving conization in Cancer Hospital, Chinese Academy of Medical Sciences from Dec, 2006 to Jan, 2009 were accrued in our study. All the patients were prospectively observed after conization every 6 months for 3 times or till histologically confirmed recurrence. The items in every visit included pelvic examination, cervical cytology and HPV genotyping. Twenty-one HPV genotypes were detected by PCR-hybridization method. The last follow-up was July 31, 2010, and the median follow-up time was 28.3 months (range 6.5-43.0 months). Kaplan-Meire method as used for analyzed the median recurrent time, and the relationships between HPV status and recurrent disease were calculated by and log-rank test and Cox-regression model. Among the 238 patients, 110 cases (46.2%, 110/238) had positive result of HPV DNA testing at any visit. The most common HPV types detected in follow-up were HPV16 (45.6%), HPV58 (26.5%), and HPV52 (16.9%). There was no correlation between recurrent disease and any individual high risk HPV infections (P>0.05). Seventeen recurrent cases (7.1%) were identified in 238 patients within a median recurrent time of 14.9 months (range 6.0-32.1 months). In univariate analyses, HPV positive at any visit, persistent infection, multiple infection, type specific persistent infection and positive HPV at 18 months after conization were indicators for residual/recurrent disease (PHPV infection (HR=8.6, 95% CI: 1.8-41.7, P=0.008) and type specific persistent HPV infection (HR=5.1, 95% CI: 1.0-24.8, P=0.042) had an elevated risk of recurrent disease. HSIL with multiple HPV infection and type specific persistent HPV infection in follow-up are at high risk of recurrent disease. Patients with HPV turning into negative within 18 months after treatment have a low risk of recurrence.

  8. CIGB-128, as compassionate intracranial treatment in patients with non-operable or progressive high grade gliomas

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    Garcia-Vega Y

    2015-12-01

    Full Text Available Background: High grade glioma (HGG is the most aggressive and lethal primary brain tumor. The treatment of patients with HGG still remains palliative with improvement in the quality of life and encompasses surgery, radiotherapy, and chemotherapy. The use of interferons (IFNs in the treatment of HGG has been showed useful for these patients. Patients and methods: We report the use, outside of clinical trials, of recombinant IFNs-α and γ(CIGB-128 in 10 patients with glioma grade III-IV (1 anaplastic astrocytoma and 9 GBM. The aim of the study was to offer a treatment option to patients with malignant gliomas, primary (non-surgical or progressive (Karnofsky performance status (KPS >20, without other possible therapeutic options, and non-eligible for clinical trials. Patients received intralesional CIGB-128, 3 times per week, during one month, in doses from 3.5 MIU scalable up to 14.0 MIU. Safety was evaluated by the occurrence of adverse events. Others measurements were tumor responses measured by RECIST, KPS, muscular power (ASIA neurological assessment scale and overall survival. Depending of treatment tolerability, clinical improvement and medical criteria, patients were maintained under treatment for 3 more months. Results: 70% of treated patients had KS<50. Seven patients had objective response (3 CR, 4 PR, one lesion progressed and 2 were not evaluable. The treatment prolonged the survival of patients to a mean of 34±14 months since diagnosis. The quality of life improved as measured by the increase in the KPS (66% of patients scaled the category and improvement in muscular power in 50% of patients. CIGB-128 had an acceptable safety profile with fever as the most frequent adverse event, observed in 54.7%, followed by extrapyramidal symptoms and hypopotassemia in 14.2% of treated patients. All detected adverse events were reversible. There was no evidence of cumulative hematologic toxicity. Conclusions: CIGB-128 demonstrated signs of

  9. Risk factors for anal high-grade squamous intraepithelial lesions in HIV-positive MSM: is targeted screening possible?

    Science.gov (United States)

    Siegenbeek van Heukelom, Matthijs L.; Marra, Elske; de Vries, Henry J.C.; van der Loeff, Maarten F.