WorldWideScience

Sample records for high-grade transition area

  1. Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence.

    Science.gov (United States)

    Fierstra, Jorn; van Niftrik, Bas; Piccirelli, Marco; Burkhardt, Jan Karl; Pangalu, Athina; Kocian, Roman; Valavanis, Antonios; Weller, Michael; Regli, Luca; Bozinov, Oliver

    2016-07-01

    Current MRI sequences are limited in identifying brain areas at risk for high grade glioma recurrence. We employed intraoperative 3-Tesla functional MRI to assess cerebrovascular reactivity (CVR) after high-grade glioma resection and analyzed regional CVR responses in areas of tumor recurrence on clinical follow-up imaging. Five subjects with high-grade glioma that underwent an intraoperative Blood Oxygen-Level Dependent (BOLD) MRI CVR examination and had a clinical follow-up of at least 18months were selected from a prospective database. For this study, location of tumor recurrence was spatially matched to the intraoperative imaging to assess CVR response in that particular area. CVR is defined as the percent BOLD signal change during repeated cycles of apnea. Of the 5 subjects (mean age 44, 2 females), 4 were diagnosed with a WHO grade III and 1 subject with a WHO grade IV glioma. Three subjects exhibited a tumor recurrence on clinical follow-up MRI (mean: 15months). BOLD CVR measured in the spatially matched area of tumor recurrence was on average 94% increased (range-32% to 183%) as compared to contralateral hemisphere CVR response, 1.50±0.81 versus 1.03±0.46 respectively (p=0.31). For this first analysis in a small cohort, we found altered intraoperative CVR in brain areas exhibiting high grade glioma recurrence on clinical follow-up imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

  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...... 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...... 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...

  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. 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

  5. Low grade papillary transitional cell carcinoma pelvic recurrence masquerading as high grade invasive carcinoma, ten years after radical cystectomy

    Directory of Open Access Journals (Sweden)

    Mortazavi Amir

    2008-09-01

    Full Text Available Abstract Background Tumor recurrence following radical cystectomy for a low-grade superficial transitional cell carcinoma (TCC is exceedingly uncommon and has not been reported previously. Case presentation We describe a case of a young male presenting with anorexia, weight loss and a large, painful locally destructive pelvic recurrence, ten years after radical cystoprostatectomy. The pathology was consistent with a low-grade urothelial carcinoma. After an unsuccessful treatment with cisplatin-based chemotherapy, the patient underwent a curative intent hemipelvectomy with complete excision of tumor and is disease free at one year follow-up. Conclusion A literature review related to this unusual presentation is reported and a surgical solutions over chemotherapy and radiotherapy is proposed.

  6. Morphology and U-Pb ages of zircons from the high-grade metamorphic Precambrian in the Sirdal-Oersdal area, SW Norway

    International Nuclear Information System (INIS)

    Wielens, J.B.W.

    1979-01-01

    The U-Pb systematics of seven suites of zircons and two apatites were investigated in an attempt to obtain data about the pre-Sveconorwegian geochronology. Very little was known about this earlier history, as previous studies have shown that the high-grade metamorphism has obliterated most of the older Rb-Sr record. Three samples were investigated from the augengneisses, two from the pyroxene syenites, one garnetiferous migmatite and one magnetite-ilmenite-zircon veinlet cross-cutting the charnockitic migmatites. (Auth.)

  7. Renal Parenchyma to Hydronephrosis Area Ratio (PHAR) as a Predictor of Future Surgical Intervention for Infants With High-grade Prenatal Hydronephrosis.

    Science.gov (United States)

    Rickard, Mandy; Lorenzo, Armando J; Braga, Luis H

    2017-03-01

    To explore the potential value of an objective assessment, renal parenchyma to hydronephrosis area ratio (PHAR), as an early predictor of surgery. Initial sagittal renal ultrasound (US) images of patients prospectively entered into a prenatal hydronephrosis database from January 2008 to January 2016 with baseline Society for Fetal Urology (SFU) grades III and IV prenatal hydronephrosis, without vesicoureteral reflux, were evaluated using the National Institutes of Health-sponsored image processing software. PHAR, anteroposterior diameter, SFU grade, and urinary tract dilation risk categories were contrasted with nuclear scan data (differential renal function and drainage time [t 1/2 ]) and analyzed for predictive value in determining the decision to proceed with surgery by drawing receiver operating characteristic curves. Out of 196 infants (162 male; 138 left sided hydronephrosis), 58 (30%) underwent surgery to address obstruction. Surgical patients compared with those managed conservatively had longer t 1/2 (60 vs 18 min; P hydronephrosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. High grade magnesium from waste bittern

    International Nuclear Information System (INIS)

    El-Yamani, I.S.; Farah, M.Y.; Isaac, S.L.

    1979-01-01

    The production of high grade magnesia for nuclear purposes from sea water by use of both aqueous and gaseous ammonia has been described. The effect of precipitating conditions on the settling rate and magnesium recovery, was thoroughly examined. Ammonia gas approach was recommended and justified

  9. 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 ...

  10. Studies on high grade cerebral gliomas

    International Nuclear Information System (INIS)

    Bleehen, N.M.

    1990-01-01

    A brief review of attempts in the United Kingdom to improve the results of treatment of high grade (grade 3, 4) supra-tentorial astrocytomas is presented. The radiosensitizer misonidazole failed to improve the results of post-surgical radiotherapy, however, multivariate analysis of data from these patients has provided a prognostic index of use in defining good and poor prognosis patients. An overview study of adjuvant nitrosourea therapy trials has shown a small significant advantage for the chemotherapy. A study of chemosensitization by benznidazole of CCNU treatment of patients in relapse failed to demonstrate any effect. 13 references

  11. Contemporary management of high-grade gliomas.

    Science.gov (United States)

    Sim, Hao-Wen; Morgan, Erin R; Mason, Warren P

    2018-01-01

    High-grade gliomas, including glioblastoma, are the most common malignant brain tumors in adults. Despite intensive efforts to develop new therapies for these diseases, treatment options remain limited and prognosis is poor. Recently, there have been important advances in our understanding of the molecular basis of glioma, leading to refinements in our diagnostic and management approach. There is new evidence to guide the treatment of elderly patients. A multitude of new agents have been investigated, including targeted therapies, immunotherapeutics and tumor-treating fields. This review summarizes the key findings from this research, and presents a perspective on future opportunities to advance the field.

  12. Pharmacokinetic MRI of the prostate. Parameters for differentiating low-grade and high-grade prostate cancer

    International Nuclear Information System (INIS)

    Franiel, T.; Taupitz, M.; Asbach, P.; Beyersdorff, D.; Luedemann, L.; Rost, J.

    2009-01-01

    Purpose: to investigate whether pharmacokinetic MRI parameters ''perfusion, blood volume, mean transit time (MTT), interstitial volume, permeability, extraction coefficient, delay, and dispersion'' allow the differentiation of low-grade (Gleason score ≤ 6) and high-grade (Gleason score ≥ 7) prostate cancer. Materials and method: forty-two patients with prostate cancer verified by biopsy (PSA 2.7 to 31.4ng/ml) and scheduled for prostatectomy underwent MRI at 1.5 Tesla using the dynamic contrast-enhanced inversion-prepared dual-contrast gradient echo sequence (temporal resolution, 1.65 s) and a combined endorectal body phased array coil. Parametric maps were computed using a sequential 3-compartment model and the corresponding post-processing algorithms. A total of 41 areas of prostate cancer (15 low-grade, 26 high-grade cancers) in 32 patients were able to be correlated with the prostatectomy specimens and were included in the analysis. Results: low-grade prostate cancers had a higher mean blood volume (1.76% vs. 1.64%, p = 0.039), longer MTT (6.39 s vs. 3.25 s, p -1 vs. 3.86 min -1 , p = 0.011) than high-grade cancers. No statistically significant difference was found for perfusion (p = 0.069), interstitial volume (p = 0.849), extraction coefficient (p = 0.615), delay (p = 0.489), and dispersion (p = 0.306). (orig.)

  13. Pneumatic radiator of transition radiation for large working area arrangements

    International Nuclear Information System (INIS)

    Shikhlyarov, K.K.; Gavalyan, V.G.

    1993-01-01

    An unconventional approach to the constructions of large area regular radiator of X-rays transition radiation is proposed based on the use of a pack of hermetically sealed bags, in which elastic helium layers are formed. A prototype of such a radiator of about 1m 2 area was made for test of the proposed device. 9 refs

  14. Metal recovery from high-grade WEEE

    DEFF Research Database (Denmark)

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

    2012-01-01

    . 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 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....... 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...

  15. 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.

  16. Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating Its Early Changes

    Science.gov (United States)

    2014-10-01

    serous ovarian cancer carcinogenesis. Sophia HL George, Ramlogan Sowamber, Anca Milea, Noor Salman and Patricia Shaw. September 2014. Masha Rivkin Ovarian...in mesenchymal-to-epithelial transition during high-grade serous carcinogenesis. Masha Rivkin Ovarian Cancer Symposium September 2014, Seattle WA

  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. Clinical and molecular features of high-grade osteosarcoma

    NARCIS (Netherlands)

    Anninga, Jakob Klaas

    2013-01-01

    It can be concluded from this thesis that high-grade osteosarcoma is at clinical, pathological and molecular level a heterogeneous disease. To treat high-grade osteosarcoma, neo-adjuvant chemotherapy should be combined with radical surgery, irrespective the localization. There are only 4 effective

  1. Management of high-grade dysplasia in Barrett's esophagus.

    Science.gov (United States)

    Palley, S L; Sampliner, R E; Garewal, H S

    1989-08-01

    When Barrett's esophagus is complicated by adenocarcinoma, surgery is indicated in appropriate patients. Until now, high-grade dysplasia in Barrett's esophagus has been managed in a similar fashion. We explore this approach and review reported cases of high-grade dysplasia to suggest guidelines for collection of data to make future clinical decisions more rational.

  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. High-Grade Hydronephrosis Predicts Poor Outcomes After Radical Cystectomy in Patients with Bladder Cancer

    OpenAIRE

    Kim, Dong Suk; Cho, Kang Su; Lee, Young Hoon; Cho, Nam Hoon; Oh, Young Taek; Hong, Sung Joon

    2010-01-01

    We examined whether the presence and severity of preoperative hydronephrosis have prognostic significance in patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. The medical records of 457 patients who underwent radical cystectomy for bladder cancer between 1986 and 2005 were retrospectively reviewed. Following the Society for Fetal Urology grading system, patients were divided into low-, and high-grade hydronephrosis groups. Clinicopathologic factors asso...

  4. Biomarker discovery in high grade sarcomas by mass spectrometry imaging

    OpenAIRE

    Lou, S.

    2017-01-01

    This thesis demonstrates a detailed biomarker discovery Mass Spectrometry Imaging workflow for histologically heterogeneous high grade sarcomas. Panels of protein and metabolite signatures were discovered either distinguishing different histological subtypes or stratifying high risk patients with poor survival.

  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. High-Grade Hydronephrosis Predicts Poor Outcomes After Radical Cystectomy in Patients with Bladder Cancer

    Science.gov (United States)

    Kim, Dong Suk; Cho, Kang Su; Lee, Young Hoon; Cho, Nam Hoon; Oh, Young Taek

    2010-01-01

    We examined whether the presence and severity of preoperative hydronephrosis have prognostic significance in patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. The medical records of 457 patients who underwent radical cystectomy for bladder cancer between 1986 and 2005 were retrospectively reviewed. Following the Society for Fetal Urology grading system, patients were divided into low-, and high-grade hydronephrosis groups. Clinicopathologic factors associated with preoperative hydronephrosis and survival were evaluated. Of a total of 406 patients, unilateral hydronephrosis was found in 74 (18.2%), bilateral hydronephrosis in 11 (2.7%), and no hydronephoris in 321 (79.1%). Low-grade hydronephrosis was found in 57 (12.2%) patients and high-grade hydronephrosis in 28 (6%). Preoperative hydronephrosis was related to higher pT stage and lymph node invasion. In univariate analysis, the presence of hydronephrosis, hydronephrosis grade, age, pT and pN stage, tumor grade, surgical margin, number of retrieved nodes, carcinoma in situ, and lymphovascular invasion were significant prognostic factors for cancer-specific survival. In multivariate analysis, bilateral hydronephrosis and high-grade hydronephrosis remained significant predictors for decreased survival. The presence of preoperative hydronephrosis, and high-grade hydronephrosis are significant prognostic factors in patients with bladder cancer after radical cystectomy. PMID:20191034

  7. Differentiation of low- and high-grade clear cell renal cell carcinoma: Tumor size versus CT perfusion parameters.

    Science.gov (United States)

    Chen, Chao; Kang, Qinqin; Xu, Bing; Guo, Hairuo; Wei, Qiang; Wang, Tiegong; Ye, Hui; Wu, Xinhuai

    To compare the utility of tumor size and CT perfusion parameters for differentiation of low- and high-grade clear cell renal cell carcinoma (RCC). Tumor size, Equivalent blood volume (Equiv BV), permeability surface-area product (PS), blood flow (BF), and Fuhrman pathological grading of clear cell RCC were retrospectively analyzed. High-grade clear cell RCC had significantly higher tumor size and lower PS than low grade. Tumor size positively correlated with Fuhrman grade, but PS negatively did. Tumor size and PS were significantly independent indexes for differentiating high-grade from low-grade clear cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

    Science.gov (United States)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-02-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

  9. Underground Milling of High-Grade Uranium Ore

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, C., E-mail: chuck.edwards@amec.com [AMEC Americas Limited, Saskatoon, Saskatchewan (Canada)

    2014-05-15

    There are many safety and technical issues involved in the mining and progressing of high grade uranium ores such as those exploited in Northern Canada at present. With more of this type of mine due to commence production in the near future, operators have been looking at ways to better manage the situation. The paper describes underground milling of high-grade uranium ore as a means of optimising production costs and managing safety issues. In addition the paper presents some examples of possible process flowsheets and plant layouts that could be applicable to such operations. Finally an assessment of potential benefits from underground milling from a variety of viewpoints is provided. (author)

  10. Risk score predicts high-grade prostate cancer in DNA-methylation positive, histopathologically negative biopsies.

    Science.gov (United States)

    Van Neste, Leander; Partin, Alan W; Stewart, Grant D; Epstein, Jonathan I; Harrison, David J; Van Criekinge, Wim

    2016-09-01

    Prostate cancer (PCa) diagnosis is challenging because efforts for effective, timely treatment of men with significant cancer typically result in over-diagnosis and repeat biopsies. The presence or absence of epigenetic aberrations, more specifically DNA-methylation of GSTP1, RASSF1, and APC in histopathologically negative prostate core biopsies has resulted in an increased negative predictive value (NPV) of ∼90% and thus could lead to a reduction of unnecessary repeat biopsies. Here, it is investigated whether, in methylation-positive men, DNA-methylation intensities could help to identify those men harboring high-grade (Gleason score ≥7) PCa, resulting in an improved positive predictive value. Two cohorts, consisting of men with histopathologically negative index biopsies, followed by a positive or negative repeat biopsy, were combined. EpiScore, a methylation intensity algorithm was developed in methylation-positive men, using area under the curve of the receiver operating characteristic as metric for performance. Next, a risk score was developed combining EpiScore with traditional clinical risk factors to further improve the identification of high-grade (Gleason Score ≥7) cancer. Compared to other risk factors, detection of DNA-methylation in histopathologically negative biopsies was the most significant and important predictor of high-grade cancer, resulting in a NPV of 96%. In methylation-positive men, EpiScore was significantly higher for those with high-grade cancer detected upon repeat biopsy, compared to those with either no or low-grade cancer. The risk score resulted in further improvement of patient risk stratification and was a significantly better predictor compared to currently used metrics as PSA and the prostate cancer prevention trial (PCPT) risk calculator (RC). A decision curve analysis indicated strong clinical utility for the risk score as decision-making tool for repeat biopsy. Low DNA-methylation levels in PCa-negative biopsies led

  11. Levetiracetam improves verbal memory in high-grade glioma patients

    NARCIS (Netherlands)

    de Groot, Marjolein; Douw, Linda; Sizoo, Eefje M; Bosma, Ingeborg; Froklage, Femke E; Heimans, Jan J; Postma, Tjeerd J; Klein, Martin; Reijneveld, Jaap C

    BACKGROUND: Treatment of high-grade glioma (HGG) patients with anti-epileptic drugs (AEDs) has met with various side effects, such as cognitive deterioration. The cognitive effects of both older and newer AEDs in HGG patients are largely unknown. The aim of this study was to determine the effect of

  12. Bereaved Caregivers to Patients With High-Grade Glioma

    DEFF Research Database (Denmark)

    Piil, Karin; Jarden, Mary

    2018-01-01

    PURPOSE: The disease and treatment trajectory of patients with high-grade glioma is a burdensome period for the patients' closest relatives who become informal caregivers. Caregivers experiencing this demanding shift in role are at risk of developing symptoms such as depression. Few studies have...... care planning within neuro-oncology caregiving to establish evidence-based practice guidelines and recommendations....

  13. Socioeconomic Collapse of Rural Areas, Atlantic Forest Transition and Sustainability

    Science.gov (United States)

    Silva, R. F. B. D.; Batistella, M.; Moran, E. F.

    2017-12-01

    Centuries of human pressure over the Atlantic Forest has led the biome to encompass only 11.7 percent of forest remnants. On the other hand, natural regeneration has explained forest cover increase in specific regions since the 1960s as an outcome of land use policies, environmental legislation, agricultural modernization, economic development, and landscape biophysical conditions. We analyze Forest Transition (FT) pathways for the Paraíba Valley region, São Paulo State, Brazil looking for more sustainable relationships between land use and natural land cover. During the 18th and 19th centuries, the Valley's farms were responsible for providing the largest portion of the state's wealth. Nowadays, the Valley contributes with only 6% to the state's gross product and the share of rural activities is now insignificant. Between 1962 and 2011, forest cover area increased from 225 to 446 thousand hectares. Rural household survey was conducted in three municipalities (n=90, thirty in each municipality). To select the municipalities among the thirty-four present in the Paraíba Valley, we applied the modified Thompson Tau technique to detect outlier values for three selected variables: natural forest cover, eucalyptus plantation cover, and municipal revenue. The outliers were discharged and the municipality with the best performance (maximum value) for each variable was selected. Based on the rural household surveys and GIS analysis of satellite imagery classifications, topography and hydrology variables, we conclude that the diminished land use pressure in the Paraíba Valley is allowing the regeneration of forest cover. Over the observed period, the FT was strongly influenced by the unsuitable topography for agriculture (steep slopes) and the economic urban development since the 1960s. However, more recently (2000s), FT is more affected by the vicinity of eucalyptus plantations, the active role of local communities denouncing illegal environmental threats (e

  14. High Grade Leiomyosarcoma Mimicking a Recurrent Angiomyxoma in the Perineum.

    Science.gov (United States)

    Sood, Neha; Swaika, Abhisek; Hanooshi, Bashar; Waldorf, James; Peterson, Jennifer; Wu, Kevin; Attia, Steven; Dinh, Tri A

    2015-05-05

    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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.)

  19. High-grade surface osteosarcoma of the hand

    International Nuclear Information System (INIS)

    Abe, Kuniko; Hayashi, Tomayoshi; Kinoshita, Naoe; Kumagai, Kenji; Shindo, Hiroyuki; Uetani, Masataka; Ishida, Tsuyoshi

    2007-01-01

    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.)

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

    International Nuclear Information System (INIS)

    Douis, Hassan; Singh, Leanne; Saifuddin, Asif

    2014-01-01

    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.)

  1. 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.)

  2. 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.

  3. Midwest Joint Venture high-grade uranium mining

    International Nuclear Information System (INIS)

    Fredrickson, H.K.

    1992-01-01

    Midwest Joint Venture (MJV) owns a high-grade uranium deposit in northern Saskatchewan. The deposit is located too deep below surface to be mined economically by open pit methods, and as a consequence, present plans are that it will be mined by underground methods. High-grade uranium ore of the type at MJV, encased in weak, highly altered ground and with radon-rich water inflows, has not before been mined by underground methods. The test mining phase of the project, completed in 1989, had three objectives: To evaluate radiation protection requirements associated with the handling of large quantities of radon-rich water and mining high-grade uranium ore in an underground environment; to investigate the quantity and quality of water inflows into the mine; and, to investigate ground conditions in and around the ore zone as an aid in determining the production mining method to be used. With information gained from the test mining project, a mining method for the production mine has been devised. Level plans have been drawn up, ventilation system designed, pumping arrangements made and methods of ore handling considered. All this is to be done in a manner that will be safe for those doing the work underground. Some of the mining methods planned are felt to be unique in that they are designed to cope with mining problems not known to have been encountered before. New problems underground have required new methods to handle them. Remote drilling, blasting, mucking and backfilling form the basis of the planned mining method

  4. Mining the high grade McArthur River uranium deposit

    International Nuclear Information System (INIS)

    Jamieson, B.W.

    2002-01-01

    The McArthur River deposit, discovered in 1988, is recognized as the world's largest, highest grade uranium deposit, with current mineable reserves containing 255 million lb U 3 O 8 at an average grade of 17.33% U 3 O 8 . In addition the project has resources of 228 million pounds U 3 O 8 averaging 12.02% U 3 O 8 . Mining this high-grade ore body presents serious challenges in controlling radiation and in dealing with high water pressures. Experience from the underground exploration programme has provided the information needed to plan the safe mining of the massive Pelite ore zone, which represents the most significant source of ore discovered during the underground drilling programme, with 220 million pounds of U 3 O 8 at an average grade in excess of 17%. Non-entry mining will be used in the high-grade ore zones. Raise boring will be the primary method to safely extract the ore, with all underground development in waste rock to provide radiation shielding. Water will be controlled by grouting and perimeter freezing. The ore cuttings from the raise boring will be ground underground and pumped to surface as slurry, at an average daily production of 150 tonnes. The slurry will be transported to the Key Lake mill and diluted to 4% before processing. The annual production is projected to be 18 million lb U 3 O 8 . The paper focuses on the activities undertaken since discovery, including the initiation of the raise bore mining method utilized to safely mine this high grade ore body. Radiation protection, environmental protection and worker health and safety are discussed in terms of both design and practical implementation. (author)

  5. Determination of vanadium in high grade carbons by radioanalytical methods

    International Nuclear Information System (INIS)

    Jinno, K.; Sato, M.; Amemiya, S.; Katoh, T.

    1980-01-01

    The present work deals with the determination of vanadium in high grade carbons by three radioanalytical methods, viz. thermal neutron activation analysis with an accelerator, thermal neutron activation analysis with a reactor and proton induced X-ray emission analysis with an accelerator. It is shown that thermal neutron activation with an accelerator is more convenient for the rapid and non-destructive analysis of ppm-level vanadium in bulk carbons than thermal neutron activation analysis with a reactor. Proton-induced X-ray emission is less useful for the analysis of bulk samples. (author)

  6. 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

    BACKGROUND: Infection with human papillomavirus is considered a necessary factor in developing high-grade squamous intraepithelial lesions of the cervix. However, most human papillomavirus positive women do not develop high-grade squamous intraepithelial lesions and other factors may be important...... for this transition. The objective of the present study was to examine if smoking and alcohol intake are associated with the risk of developing high-grade squamous intraepithelial lesions in women positive for high-risk human papillomavirus types. METHODS: We used baseline information on exposures on 548 high......-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...

  7. Amphiboles and their host rocks in the high-grade metamorphic Precambrin of Rogaland/Vest-Agder, Sw. Norway

    NARCIS (Netherlands)

    Dekker, A.G.C.

    1978-01-01

    In the high-grade metamorphic Precambrian of the Sirdal-¢rsdal area, Rogaland/Vest-Agder,south-west Norway, the Ca-amphiboles show a change in pleochroic colours, not only with changes in metamorphic grade, but also to some extend in bulk composition. A regional study was performed on the

  8. Amphiboles and their host rocks in the high-grade metamorphic Precambrin of Rogaland/Vest-Agder, Sw. Norway

    NARCIS (Netherlands)

    Dekker, A.G.C.

    1978-01-01

    In the high-grade metamorphic Precambrian of the Sirdal-¢rsdal area, Rogaland/Vest-Agder,south-west Norway, the Ca-amphiboles show a change in pleochroic colours, not only with changes in metamorphic grade, but also to some extend in bulk composition. A regional study was performed on the amphiboles

  9. Symptom clusters in patients with high-grade glioma.

    Science.gov (United States)

    Fox, Sherry W; Lyon, Debra; Farace, Elana

    2007-01-01

    To describe the co-occurring symptoms (depression, fatigue, pain, sleep disturbance, and cognitive impairment), quality of life (QoL), and functional status in patients with high-grade glioma. Correlational, descriptive study of 73 participants with high-grade glioma in the U.S. Nine brief measures were obtained with a mailed survey. Participants were recruited from the online message board of The Healing Exchange BRAIN TRUST, a nonprofit organization dedicated to improving quality of life for people with brain tumors. Two symptom cluster models were examined. Four co-occurring symptoms were significantly correlated with each other and explained 29% of the variance in QoL: depression, fatigue, sleep disturbance, and cognitive impairment. Depression, fatigue, sleep disturbance, cognitive impairment, and pain were significantly correlated with each other and explained 62% of the variance in functional status. The interrelationships of the symptoms examined in this study and their relationships with QoL and functional status meet the criteria for defining a symptom cluster. The differences in the models of QoL and functional status indicates that symptom clusters may have unique characteristics in patients with gliomas.

  10. 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.

  11. High dose rate brachytherapy in treatment of high grade astrocytomas

    International Nuclear Information System (INIS)

    Garcia-Alejo, R.; Delgado, J.M.; Cerro, E. del; Torres, J.J.; Martinez, R.

    1996-01-01

    From May 1994 to June 1995, 18 patients with high grade astrocytomas were entered prospectively on a selective protocol combining surgery, external beam radiotherapy, stereotactic interstitial implantation with HDR Iridium 192 and chemotherapy. Only those patients with tumor size 100cc or less average dimension, high grade astrocytoma, Karnofsky 70 or greater, unilateral, circumscribed, unifocal, tumor stable or responding to external radiation and supratentorial were included in the study. Ages ranged from 16 to 69 years. There were 13 males and 5 females. Surgery consisted of biopsy only in 3 patients, subtotal resection in 11, and gross total resection in 4 patients. Focal external beam radiation portals included the contrast enhancing mass on CT scan plus a 3 cm margin. The protocol called for minimum tumor dose of 60 Gy to be given in 2 Gy daily fractions. An interstitial brachytherapy boost was to be performed two weeks after the conclusion of external beam radiation. The dose was 30 Gy in 4 fractions. The authors analyze on basis on their personal experience, the possibilities and the limits offered by this therapeutic procedure in neuro-oncology. Using stereotactic techniques, interstitial brachytherapy of brain tumors was technically possible with negligible acute morbidity and mortality, and appeared to be effective and may provide for an increase in tumor control in selected cases

  12. 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...

  13. 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...

  14. Carlsbad Area Office Waste Isolation Division Transition Plan

    International Nuclear Information System (INIS)

    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

  15. San Francisco Bay Area Rapid Transit District (BART) climate change adaptation assessment pilot.

    Science.gov (United States)

    2013-12-01

    The objective of this pilot study was to evaluate the impacts of climate change on the San Francisco Bay Area Rapid Transit District : (BART) infrastructure and to develop and implement adaptation strategies against those impacts. Climate change haza...

  16. Does Small Prostate Predict High Grade Prostate Cancer?

    International Nuclear Information System (INIS)

    Caliskan, S.; Kaba, S.; Koca, O.; Ozturk, M. I.

    2017-01-01

    Objective: The current study is aimed to assess the patients who underwent radical prostatectomy for prostate cancer and investigate the association between prostate size and adverse outcomes at final pathology. Study Design: Comparative, descriptive study. Place and Duration of Study: Haydarpasa Numune Training and Research Hospital, Turkey, from January 2008 to January 2016. Methodology: The patients treated with open radical prostatectomy for prostate cancer were reviewed. Patient characteristics including prostate specific antigen (PSA), free PSA levels, age, biopsy, and radical prostatectomy results were recorded. The patients whose data were complete or prostate weight was equal to or less than 80 gm, were included in the study. Patients with < 40 gm prostate weight was in group 1 and the patients in group 2 had a prostate weight from 40 to 80 gm. High grade prostate cancer was defined to have a Gleason score between 7 or higher at biopsy and final pathology. Pathology and biopsy results were compared within groups. MedCalc Statistical Software demo version was used for statistical analyses. Results: There were 162 patients in this study. Of these, 71 (43.82 percent) patients were in group 1 and 91 (56.17 percent) patients were in group 2. The age ranged from 49 to 76 years. Mean value of 62.70 +-6.82 and 65.82 +- 5.66 years in group 1 and 2, respectively. Fifty (70.42 percent) and 68 patients (74.74 percent) had a Gleason score of 6 in group 1 and 2, respectively. Organconfined disease was reported in 53 patients (74.64 percent) in group 1 and in 78 patients (85.71 percent) in group 2. Gleason score concordance between biopsy and prostatectomy was reported in 61 patients (67.03 percent) and downgrading was detected in 4 patients (4.4 percent) in group 2. The median tumor volume of the patients was 4.47 cm/sup 3/ in group 1 and 6 cm/sup 3/ in group 2 (p=0.502). High grade prostate cancer was reported in 52.11 percent and 45.05 percent of the patients in

  17. Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab.

    Science.gov (United States)

    Bahrami, N; Piccioni, D; Karunamuni, R; Chang, Y-H; White, N; Delfanti, R; Seibert, T M; Hattangadi-Gluth, J A; Dale, A; Farid, N; McDonald, C R

    2018-04-05

    Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis-edge contrast-improves the evaluation of response to bevacizumab in patients with high-grade gliomas. MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates. After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival ( P = .009) and overall survival ( P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank χ 2 = 8.3, P = .003) and overall survival (log-rank χ 2 = 5.5, P = .019). Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas. © 2018 by American Journal of Neuroradiology.

  18. High grade serous ovarian carcinomas originate in the fallopian tube.

    Science.gov (United States)

    Labidi-Galy, S Intidhar; Papp, Eniko; Hallberg, Dorothy; Niknafs, Noushin; Adleff, Vilmos; Noe, Michael; Bhattacharya, Rohit; Novak, Marian; Jones, Siân; Phallen, Jillian; Hruban, Carolyn A; Hirsch, Michelle S; Lin, Douglas I; Schwartz, Lauren; Maire, Cecile L; Tille, Jean-Christophe; Bowden, Michaela; Ayhan, Ayse; Wood, Laura D; Scharpf, Robert B; Kurman, Robert; Wang, Tian-Li; Shih, Ie-Ming; Karchin, Rachel; Drapkin, Ronny; Velculescu, Victor E

    2017-10-23

    High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited. Here, we perform whole-exome sequence and copy number analyses of laser capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients. The majority of tumor-specific alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN. Evolutionary analyses reveal that p53 signatures and STICs are precursors of ovarian carcinoma and identify a window of 7 years between development of a STIC and initiation of ovarian carcinoma, with metastases following rapidly thereafter. Our results provide insights into the etiology of ovarian cancer and have implications for prevention, early detection and therapeutic intervention of this disease.

  19. Terahertz reflectometry imaging for low and high grade gliomas

    Science.gov (United States)

    Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

    2016-01-01

    Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes. PMID:27782153

  20. Radio-fluoro guided surgery in high grade gliomas

    International Nuclear Information System (INIS)

    Lopez Piloto, Orestes; Salva Camano, Silvia; Gonzalez Gonzalez, Justo; Cruz Hernandez, Tania Margarita; Martinez Suarez, Eduardo; Lopez Arbolay, Omar; Ardisana Santana, Ernesto

    2015-01-01

    The MIBI (99mTc MIBI, methoxyisobutylisonitrile, MIBI, or sestamibi): is a wide readiness to the rich flow of photons, which improves the detection of pathological uptake with gamma probe, these physical properties make of this radiotracer the election to radioguided surgery. The sodium fluorescein is a water-soluble organic coloring substance used in the exam of the sanguine glasses of the eye. We carried out the report of five cases diagnosed with brain tumor of high grade of malignancy, with the objective to demonstrated that use of Radio-Fluro-guided Surgery (RFGS) we can achieve gross total resections without bigger deficit, completing the inclusion and exclusion criteria. The technique of RFGS demonstrated utility in the gross total resection, diminishing the residual tumor, without increasing surgery complexity and surgical times. In our study doesn't evidence of adverse effects for the administration of the radiopharmaceuticals and fluorescein

  1. Characterization of Anisotropic Behavior for High Grade Pipes

    Science.gov (United States)

    Yang, Kun; Huo, Chunyong; Ji, Lingkang; Li, Yang; Zhang, Jiming; Ma, Qiurong

    With the developing requirement of nature gas, the property needs of steel for pipe line are higher and higher, especially in strength and toughness. It is necessary to improve the steel grade in order to ensure economic demand and safety. However, with the rise of steel grade, the differences on properties in different orientations (anisotropic behaviors) become more and more obvious after the process of hot rolling, which may affect the prediction of fracture for the pipes seriously (Thinking of isotropic mechanical properties for material in traditional predict way). In order to get the reason for anisotropic mechanics, a series of tests are carried out for high grade steel pipes, including not only mechanical properties but also microstructures. Result indicates that there are obviously anisotropic behaviors for high grade steel pipes in two orientations (rolling orientation and transverse orientation). Strength is better in T orientation because Rm is higher and Rt 0.5 rises more in T orientation, and toughness is better in L orientation because of the higher Akv and SA in L orientation under a same temperature. Banded structures are formed in T orientation, and the spatial distribution of inclusion and precipitated phases are different in T, L and S orientation. The anisotropic arrangement for the matrix in space (banded structures), which is formed after the process of hot rolling, may affect the mechanical properties in different orientation. Moreover, the elasticity modulus of particles is different from the elasticity modulus of matrix, deformation between particles and matrix may cause stress concentration, and damage forms in this place. Because of the different distribution of particles in space, the level of damage is anisotropic in different orientations, and the anisotropic mechanical properties occur finally. Therefore, the anisotropic mechanical properties are determined by the anisotropic microstructures, both the anisotropic of matrix and the

  2. 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.

  3. 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…

  4. Quasi-VMAT in high-grade glioma radiation therapy.

    Science.gov (United States)

    Fadda, G; Massazza, G; Zucca, S; Durzu, S; Meleddu, G; Possanzini, M; Farace, P

    2013-05-01

    To compare a quasi-volumetric modulated arc therapy (qVMAT) with three-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) for the treatment of high-grade gliomas. The qVMAT technique is a fast method of radiation therapy in which multiple equispaced beams analogous to those in rotation therapy are radiated in succession. This study included 12 patients with a planning target volume (PTV) that overlapped at least one organ at risk (OAR). 3D-CRT was planned using 2-3 non-coplanar beams, whereby the field-in-field technique (FIF) was used to divide each field into 1-3 subfields to shield the OAR. The qVMAT strategy was planned with 15 equispaced beams and IMRT was planned using 9 beams with a total of 80 segments. Inverse planning for qVMAT and IMRT was performed by direct machine parameter optimization (DMPO) to deliver a homogenous dose distribution of 60 Gy within the PTV and simultaneously limit the dose received by the OARs to the recommended values. Finally, the effect of introducing a maximum dose objective (max. dose < 54 Gy) for a virtual OAR in the form of a 0.5 cm ring around the PTV was investigated. The qVMAT method gave rise to significantly improved PTV95% and conformity index (CI) values in comparison to 3D-CRT (PTV95% = 90.7 % vs. 82.0 %; CI = 0.79 vs. 0.74, respectively). A further improvement was achieved by IMRT (PTV95% = 94.4 %, CI = 0.78). In qVMAT and IMRT, the addition of a 0.5 cm ring around the PTV produced a significant increase in CI (0.87 and 0.88, respectively), but dosage homogeneity within the PTV was considerably reduced (PTV95% = 88.5 % and 92.3 %, respectively). The time required for qVMAT dose delivery was similar to that required using 3D-CRT. These findings suggest that qVMAT should be preferred to 3D-CRT for the treatment of high-grade gliomas. The qVMAT method could be applied in hospitals, for example, which have limited departmental

  5. Quasi-VMAT in high-grade glioma radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fadda, G.; Massazza, G.; Zucca, S.; Durzu, S.; Meleddu, G.; Possanzini, M.; Farace, P. [Regional Oncological Hospital, Cagliari (Italy). Dept. of Radio-Oncology

    2013-05-15

    Purpose: To compare a quasi-volumetric modulated arc therapy (qVMAT) with three-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) for the treatment of high-grade gliomas. The qVMAT technique is a fast method of radiation therapy in which multiple equispaced beams analogous to those in rotation therapy are radiated in succession. Patients and methods: This study included 12 patients with a planning target volume (PTV) that overlapped at least one organ at risk (OAR). 3D-CRT was planned using 2-3 non-coplanar beams, whereby the field-in-field technique (FIF) was used to divide each field into 1-3 subfields to shield the OAR. The qVMAT strategy was planned with 15 equispaced beams and IMRT was planned using 9 beams with a total of 80 segments. Inverse planning for qVMAT and IMRT was performed by direct machine parameter optimization (DMPO) to deliver a homogenous dose distribution of 60 Gy within the PTV and simultaneously limit the dose received by the OARs to the recommended values. Finally, the effect of introducing a maximum dose objective (max. dose < 54 Gy) for a virtual OAR in the form of a 0.5 cm ring around the PTV was investigated. Results: The qVMAT method gave rise to significantly improved PTV{sub 95%} and conformity index (CI) values in comparison to 3D-CRT (PTV{sub 95%} = 90.7 % vs. 82.0 %; CI = 0.79 vs. 0.74, respectively). A further improvement was achieved by IMRT (PTV{sub 95%} = 94.4 %, CI = 0.78). In qVMAT and IMRT, the addition of a 0.5 cm ring around the PTV produced a significant increase in CI (0.87 and 0.88, respectively), but dosage homogeneity within the PTV was considerably reduced (PTV{sub 95%} = 88.5 % and 92.3 %, respectively). The time required for qVMAT dose delivery was similar to that required using 3D-CRT. Conclusion: These findings suggest that qVMAT should be preferred to 3D-CRT for the treatment of high-grade gliomas. The qVMAT method could be applied in hospitals, for example

  6. Quasi-VMAT in high-grade glioma radiation therapy

    International Nuclear Information System (INIS)

    Fadda, G.; Massazza, G.; Zucca, S.; Durzu, S.; Meleddu, G.; Possanzini, M.; Farace, P.

    2013-01-01

    Purpose: To compare a quasi-volumetric modulated arc therapy (qVMAT) with three-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) for the treatment of high-grade gliomas. The qVMAT technique is a fast method of radiation therapy in which multiple equispaced beams analogous to those in rotation therapy are radiated in succession. Patients and methods: This study included 12 patients with a planning target volume (PTV) that overlapped at least one organ at risk (OAR). 3D-CRT was planned using 2-3 non-coplanar beams, whereby the field-in-field technique (FIF) was used to divide each field into 1-3 subfields to shield the OAR. The qVMAT strategy was planned with 15 equispaced beams and IMRT was planned using 9 beams with a total of 80 segments. Inverse planning for qVMAT and IMRT was performed by direct machine parameter optimization (DMPO) to deliver a homogenous dose distribution of 60 Gy within the PTV and simultaneously limit the dose received by the OARs to the recommended values. Finally, the effect of introducing a maximum dose objective (max. dose 95% and conformity index (CI) values in comparison to 3D-CRT (PTV 95% = 90.7 % vs. 82.0 %; CI = 0.79 vs. 0.74, respectively). A further improvement was achieved by IMRT (PTV 95% = 94.4 %, CI = 0.78). In qVMAT and IMRT, the addition of a 0.5 cm ring around the PTV produced a significant increase in CI (0.87 and 0.88, respectively), but dosage homogeneity within the PTV was considerably reduced (PTV 95% = 88.5 % and 92.3 %, respectively). The time required for qVMAT dose delivery was similar to that required using 3D-CRT. Conclusion: These findings suggest that qVMAT should be preferred to 3D-CRT for the treatment of high-grade gliomas. The qVMAT method could be applied in hospitals, for example, which have limited departmental resources and are not equipped with systems capable of VMAT delivery. (orig.)

  7. The end-of-life phase of high-grade glioma patients: dying with dignity?

    Science.gov (United States)

    Sizoo, Eefje M; Taphoorn, Martin J B; Uitdehaag, Bernard; Heimans, Jan J; Deliens, Luc; Reijneveld, Jaap C; Pasman, H Roeline W

    2013-01-01

    In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patient's personal dignity. We aimed to (a) assess the proportion of HGG patients dying with dignity as perceived by their relatives and (b) identify disease and care factors correlated with dying with dignity in HGG patients. We approached relatives of a cohort of 155 deceased HGG patients for the study. Participants completed a questionnaire concerning the EOL phase of the patient, covering several subthemes: (a) symptoms and signs, (b) health-related quality of life, (c) decision making, (d) place and quality of EOL care, and (e) dying with dignity. Relatives of 81 patients participated and 75% indicated that the patient died with dignity. These patients had fewer communication deficits, experienced fewer transitions between health care settings in the EOL phase, and more frequently died at their preferred place of death. Relatives were more satisfied with the physician providing EOL care and reported that the physician adequately explained treatment options. Multivariate analysis identified satisfaction with the physician, the ability to communicate, and the absence of transitions between settings as most predictive of a dignified death. Physicians caring for HGG patients in the EOL phase should timely focus on explaining possible treatment options, because patients experience communication deficits toward death. Physicians should strive to allow patients to die at their preferred place and avoid transitions during the last month of life.

  8. Benefits of adjuvant chemotherapy in high-grade gliomas.

    Science.gov (United States)

    DeAngelis, Lisa M

    2003-12-01

    The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. Adjuvant chemotherapy is not widely accepted because of the low sensitivity of gliomas to traditional antineoplastic agents, the poor penetration of most drugs across the blood-brain barrier, and the significant systemic toxicity associated with current agents. However, nitrosoureas and, subsequently, temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), a novel alkylating agent, cross the blood-brain barrier and have activity against gliomas. Nitrosoureas have been studied in phase III trials in the adjuvant setting. In individual trials, chemotherapy did not increase median survival but did increase the proportion of patients surviving >/=18 months by 15%. Only with large meta-analyses did the addition of chemotherapy achieve a statistically significant improvement in median survival. Currently there is no means of identifying which patients will benefit from adjuvant chemotherapy, but nitrosoureas and temozolomide are well tolerated in most patients, justifying the administration of adjuvant chemotherapy to all newly diagnosed patients with malignant glioma.

  9. 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.

  10. 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.

  11. Adjuvant radiotherapy in high-grade extremity sarcomas

    International Nuclear Information System (INIS)

    Franca, Carlos Antonio da Silva; Penna, Antonio Belmiro Rodrigues Campbell; Carvalho, Antonio Carlos Pires; Vieira, Sergio Lannes

    2010-01-01

    Objective: to evaluate the therapies utilized in the authors' institution for management of high-grade extremity sarcomas, analyzing the overall survival rates following multidisciplinary treatment. Materials and methods: retrospective study developed in the period from 1993 to 2007 with 36 patients diagnosed with stages IIb/III, submitted to postoperative external beam radiotherapy, with or without boost dose, utilizing high-dose brachytherapy. Results: thirty-six patients underwent surgery followed by adjuvant external beam radiation therapy. Four patients (11%) received boost dose with brachytherapy, and seven (19%) received chemotherapy. The average dose for radiotherapy was 50 Gy (CI 95%: 47-53 Gy), and the four patients with brachytherapy boost received doses ranging from 16.2 to 35 Gy. Chemotherapy was indicated for seven patients (19%) with positive margins. Fifteen patients (42%) presented local or distant recurrence, and all of them progressed to death. Twenty-one patients (58%) remain with no clinical/radiological evidence of local/distant recurrence. The mean follow-up time was 88 months (IC 95%: 74-102). The overall seven years survival rate was 80%. Conclusion: combined surgery and radiotherapy is an effective treatment with excellent outcomes in cases where brachytherapy is associated, with improved overall survival rates. (author)

  12. Smart Parking Management Field Test: A Bay Area Rapid Transit (BART) District Parking Demonstration

    OpenAIRE

    Shaheen, Susan

    2005-01-01

    In almost every major city in the U.S. and internationally, parking problems are ubiquitous. It is well known that the limited availability of parking contributes to roadway congestion, air pollution, and driver frustration and that the cost of expanding traditional parking capacity is frequently prohibitive. However, less research has addressed the effect of insufficient parking at transit stations on transit use. In the San Francisco Bay Area, parking has recently been at or near capacity a...

  13. Are the uterine serous carcinomas underdiagnosed? Histomorphologic and immunohistochemical correlates and clinical follow up in high-grade endometrial carcinomas initially diagnosed as high-grade endometrioid carcinoma.

    Science.gov (United States)

    Hu, Shaomin; Hinson, Jeff L; Matnani, Rahul; Cibull, Michael L; Karabakhtsian, Rouzan G

    2018-02-01

    Histologic subclassification of high-grade endometrial carcinomas can sometimes be a diagnostic challenge when based on histomorphology alone. Here we utilized immunohistochemical markers to determine the immunophenotype in histologically ambiguous high-grade endometrial carcinomas that were initially diagnosed as pure or mixed high-grade endometrioid carcinoma, aiming to determine the utility of selected immunohistochemical panel in accurate classification of these distinct tumor types, while correlating these findings with the clinical outcome. A total of 43 high-grade endometrial carcinoma cases initially classified as pure high-grade endometrioid carcinoma (n=32), mixed high-grade endometrioid carcinoma/serous carcinoma (n=9) and mixed high-grade endometrioid carcinoma/clear cell carcinoma (n=2) were retrospectively stained with a panel of immunostains, including antibodies for p53, p16, estrogen receptor, and mammaglobin. Clinical follow-up data were obtained, and stage-to-stage disease outcomes were compared for different tumor types. Based on aberrant staining for p53 and p16, 17/43 (40%) of the high-grade endometrial carcinoma cases initially diagnosed as high-grade endometrioid carcinoma were re-classified as serous carcinoma. All 17 cases showed negative staining for mammaglobin, while estrogen receptor was positive in only 6 (35%) cases. The remaining 26 cases of high-grade endometrioid carcinoma showed wild-type staining for p53 in 25 (96%) cases, patchy staining for p16 in 20 (77%) cases, and were positive for mammaglobin and estrogen receptor in 8 (31%) and 19 (73%) cases, respectively, thus the initial diagnosis of high-grade endometrioid carcinoma was confirmed in these cases. In addition, the patients with re-classified serous carcinoma had advanced clinical stages at diagnosis and poorer overall survival on clinical follow-up compared to that of the remaining 26 high-grade endometrioid carcinoma cases. These results indicate that selected

  14. Analysis of DTI-Derived Tensor Metrics in Differential Diagnosis between Low-grade and High-grade Gliomas.

    Science.gov (United States)

    Jiang, Liang; Xiao, Chao-Yong; Xu, Quan; Sun, Jun; Chen, Huiyou; Chen, Yu-Chen; Yin, Xindao

    2017-01-01

    Purpose: It is critical and difficult to accurately discriminate between high- and low-grade gliomas preoperatively. This study aimed to ascertain the role of several scalar measures in distinguishing high-grade from low-grade gliomas, especially the axial diffusivity (AD), radial diffusivity (RD), planar tensor (Cp), spherical tensor (Cs), and linear tensor (Cl) derived from diffusion tensor imaging (DTI). Materials and Methods: Fifty-three patients with pathologically confirmed brain gliomas (21 low-grade and 32 high-grade) were included. Contrast-enhanced T1-weighted images and DTI were performed in all patients. The AD, RD, Cp, Cs, and Cl values in the tumor zone, peritumoral edema zone, white matter (WM) adjacent to edema and contralateral normal-appearing white matter (NAWM) were calculated. The DTI parameters and tumor grades were statistically analyzed, and receiver operating characteristic (ROC) curve analysis was also performed. Results: The DTI metrics in the affected hemisphere showed significant differences from those in the NAWM, except for the AD values in the tumor zone and the RD values in WM adjacent to edema in the low-grade groups, as well as the Cp values in WM adjacent to edema in the high-grade groups. AD in the tumor zone as well as Cs and Cl in WM adjacent to edema revealed significant differences between the low- and high-grade gliomas. The areas under the curve (Az) of all three metrics were greater than 0.5 in distinguishing low-grade from high-grade gliomas by ROC curve analysis, and the best DTI metric was Cs in WM adjacent to edema (Az: 0.692). Conclusion: AD in the tumor zone as well as Cs and Cl in WM adjacent to edema will provide additional information to better classify gliomas and can be used as non-invasive reliable biomarkers in glioma grading.

  15. CIP2A protein expression in high-grade, high-stage bladder cancer

    International Nuclear Information System (INIS)

    Huang, Lisa P; Savoly, Diana; Sidi, Abraham A; Adelson, Martin E; Mordechai, Eli; Trama, Jason P

    2012-01-01

    Bladder cancer is one of the most common cancers in the United States. Numerous markers have been evaluated for suitability of bladder cancer detection and surveillance. However, few of them are acceptable as a routine tool. Therefore, there exists a continuing need for an assay that detects the presence of bladder cancer in humans. It would be advantageous to develop an assay with a protein that is associated with the development of bladder cancer. We have identified the cancerous inhibitor of PP2A (CIP2A) protein as a novel bladder cancer biomarker. In this study, Western blot analysis was used to assess the expression level of CIP2A protein in bladder cancer cell lines and bladder cancer patient tissues (n = 43). Our studies indicated CIP2A protein was abundantly expressed in bladder cancer cell lines but not in nontumor epithelial cell lines. Furthermore, CIP2A was specifically expressed in transitional cell carcinoma (TCC) of the bladder tumor tissues but not in adjacent nontumor bladder tissue. Our data showed that CIP2A protein detection in high-grade TCC tissues had a sensitivity of 65%, which is 3.4-fold higher than that seen in low-grade TCC tissues (19%). The level of CIP2A protein expression increased with the stage of disease (12%, 27%, 67%, and 100% for pTa, pT1, pT2, and pT3 tumor, respectively). In conclusion, our studies suggest that CIP2A protein is specifically expressed in human bladder tumors. CIP2A is preferentially expressed in high-grade and high-stage TCC tumors, which are high-risk and invasive tumors. Our studies reported here support the role of CIP2A in bladder cancer progression and its usefulness for the surveillance of recurrence or progression of human bladder cancer

  16. Genomic characterization of recurrent high-grade astroblastoma.

    Science.gov (United States)

    Bale, Tejus A; Abedalthagafi, Malak; Bi, Wenya Linda; Kang, Yun Jee; Merrill, Parker; Dunn, Ian F; Dubuc, Adrian; Charbonneau, Sarah K; Brown, Loreal; Ligon, Azra H; Ramkissoon, Shakti H; Ligon, Keith L

    2016-01-01

    Astroblastomas are rare primary brain tumors, diagnosed based on histologic features. Not currently assigned a WHO grade, they typically display indolent behavior, with occasional variants taking a more aggressive course. We characterized the immunohistochemical characteristics, copy number (high-resolution array comparative genomic hybridization, OncoCopy) and mutational profile (targeted next-generation exome sequencing, OncoPanel) of a cohort of seven biopsies from four patients to identify recurrent genomic events that may help distinguish astroblastomas from other more common high-grade gliomas. We found that tumor histology was variable across patients and between primary and recurrent tumor samples. No common molecular features were identified among the four tumors. Mutations commonly observed in astrocytic tumors (IDH1/2, TP53, ATRX, and PTEN) or ependymoma were not identified. However one case with rapid clinical progression displayed mutations more commonly associated with GBM (NF1(N1054H/K63)*, PIK3CA(R38H) and ERG(A403T)). Conversely, another case, originally classified as glioblastoma with nine-year survival before recurrence, lacked a GBM mutational profile. Other mutations frequently seen in lower grade gliomas (BCOR, BCORL1, ERBB3, MYB, ATM) were also present in several tumors. Copy number changes were variable across tumors. Our findings indicate that astroblastomas have variable growth patterns and morphologic features, posing significant challenges to accurate classification in the absence of diagnostically specific copy number alterations and molecular features. Their histopathologic overlap with glioblastoma will likely confound the observation of long-term GBM "survivors". Further genomic profiling is needed to determine whether these tumors represent a distinct entity and to guide management strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. 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.

  18. Combining Diffusion Tensor Metrics and DSC Perfusion Imaging: Can It Improve the Diagnostic Accuracy in Differentiating Tumefactive Demyelination from High-Grade Glioma?

    Science.gov (United States)

    Hiremath, S B; Muraleedharan, A; Kumar, S; Nagesh, C; Kesavadas, C; Abraham, M; Kapilamoorthy, T R; Thomas, B

    2017-04-01

    Tumefactive demyelinating lesions with atypical features can mimic high-grade gliomas on conventional imaging sequences. The aim of this study was to assess the role of conventional imaging, DTI metrics ( p:q tensor decomposition), and DSC perfusion in differentiating tumefactive demyelinating lesions and high-grade gliomas. Fourteen patients with tumefactive demyelinating lesions and 21 patients with high-grade gliomas underwent brain MR imaging with conventional, DTI, and DSC perfusion imaging. Imaging sequences were assessed for differentiation of the lesions. DTI metrics in the enhancing areas and perilesional hyperintensity were obtained by ROI analysis, and the relative CBV values in enhancing areas were calculated on DSC perfusion imaging. Conventional imaging sequences had a sensitivity of 80.9% and specificity of 57.1% in differentiating high-grade gliomas ( P = .049) from tumefactive demyelinating lesions. DTI metrics ( p : q tensor decomposition) and DSC perfusion demonstrated a statistically significant difference in the mean values of ADC, the isotropic component of the diffusion tensor, the anisotropic component of the diffusion tensor, the total magnitude of the diffusion tensor, and rCBV among enhancing portions in tumefactive demyelinating lesions and high-grade gliomas ( P ≤ .02), with the highest specificity for ADC, the anisotropic component of the diffusion tensor, and relative CBV (92.9%). Mean fractional anisotropy values showed no significant statistical difference between tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI and DSC parameters improved the diagnostic accuracy (area under the curve = 0.901). Addition of a heterogeneous enhancement pattern to DTI and DSC parameters improved it further (area under the curve = 0.966). The sensitivity increased from 71.4% to 85.7% after the addition of the enhancement pattern. DTI and DSC perfusion add profoundly to conventional imaging in differentiating tumefactive

  19. 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...... analyses with different approaches depending on the desired level of detail. A simple but straightforward approach to implement is the Circular Buffer Approach where catchment areas are circular. A more detailed approach is the Service Area Approach where catchment areas are determined by a street network...... 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...

  20. [Partial regression of Barret esophagus with high grade dysplasia and adenocarcinoma after photocoagulation and endocurietherapy under antisecretory treatment].

    Science.gov (United States)

    Fremond, L; Bouché, O; Diébold, M D; Demange, L; Zeitoun, P; Thiefin, G

    1995-01-01

    Barrett's oesophagus is a premalignant condition. The possibility of eradicating at least partially the metaplastic epithelium has been reported recently. In this case report, a patient with Barrett's oesophagus complicated by high grade dysplasia and focal adenocarcinoma was treated by Nd:Yag laser then high dose rate intraluminal irradiation while on omeprazole 40 mg/day. A partial eradication of Barrett's oesophagus and a transient tumoural regression were obtained. Histologically, residual specialized-type glandular tissue was observed beneath regenerative squamous epithelium. Four months after intraluminal irradiation, a local tumoural recurrence was detected while the area of restored squamous epithelium was unchanged on omeprazole 40 mg/day. This indicates that physical destruction of Barrett's oesophagus associated with potent antisecretory treatment can induce a regression of the metaplastic epithelium, even in presence of high grade dysplasia. The persistence of specialized-type glands beneath the squamous epithelium raises important issues about its potential malignant degeneration.

  1. Histogram analysis of diffusion kurtosis imaging derived maps may distinguish between low and high grade gliomas before surgery.

    Science.gov (United States)

    Qi, Xi-Xun; Shi, Da-Fa; Ren, Si-Xie; Zhang, Su-Ya; Li, Long; Li, Qing-Chang; Guan, Li-Ming

    2018-04-01

    To investigate the value of histogram analysis of diffusion kurtosis imaging (DKI) maps in the evaluation of glioma grading. A total of 39 glioma patients who underwent preoperative magnetic resonance imaging (MRI) were classified into low-grade (13 cases) and high-grade (26 cases) glioma groups. Parametric DKI maps were derived, and histogram metrics between low- and high-grade gliomas were analysed. The optimum diagnostic thresholds of the parameters, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were achieved using a receiver operating characteristic (ROC). Significant differences were observed not only in 12 metrics of histogram DKI parameters (PHistogram analysis of DKI may be more effective in glioma grading.

  2. 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.

  3. Medical and endoscopic management of high-grade dysplasia in Barrett's esophagus

    NARCIS (Netherlands)

    Wang, K. K.; Tian, J. M.; Gorospe, E.; Penfield, J.; Prasad, G.; Goddard, T.; WongKeeSong, M.; Buttar, N. S.; Lutzke, L.; Krishnadath, S.

    2012-01-01

    The management of high-grade dysplasia in Barrett's esophagus has clearly changed over recent years. The risk of cancer development is still substantial, with about one in three patients developing cancer, but a number of patients do not develop cancer. The nature of high-grade dysplasia has also

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

    NARCIS (Netherlands)

    Koeneman, M. M.; Kruse, Arnold-Jan; Kooreman, L. F. S.; zur Hausen, Axel; Hopman, Anton H N; Sep, S. J. S.; Van Gorp, T.; Slangen, B. F. M.; van Beekhuizen, H. J.; de Sande, Michiel A. J. van; Gerestein, Cornelis G.; Nijman, H. W.; Kruitwagen, R. F. M. P.

    2017-01-01

    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

  5. HPV-genotypes in high-grade intraepithelial cervical lesions in Danish women

    DEFF Research Database (Denmark)

    Kirschner, Benny; Schledermann, Doris; Holl, Katsiaryna

    2013-01-01

    A study was undertaken to assess the distribution of high-risk HPV-genotypes in high-grade cervical intraepithelial neoplastic lesions in Danish women.......A study was undertaken to assess the distribution of high-risk HPV-genotypes in high-grade cervical intraepithelial neoplastic lesions in Danish women....

  6. Neoadjuvant chemotherapy for high-grade soft-tissue sarcomas of the limbs

    International Nuclear Information System (INIS)

    Ramos, Pedro; Gonzalez, Manuel; Perry, Fernando; Cardona, Andres Felipe

    2005-01-01

    Background: the use of neoadjuvant chemotherapy for high-grade soft-tissue sarcomas of the limbs continues to be an area of controversy; however, the number of clinical studies favoring the use of an anthracycline and iphosphamide-based regimen is increasing steadily. This approach may provide some advantages for facilitating the surgical resection of the tumor and for local disease control. The historical 5-year survival rate of approximately 50% in this high-risk group treated with local therapy alone represents a poor standard of care; thus, there is a need to incorporate systemic therapy early in the management of these patients. Objective: to describe the role of neoadjuvant chemotherapy in the treatment of soft-tissue sarcomas. Materials and methods: the records of 42 patients who attended the national cancer institute of Colombia in search for management of primary soft-tissue sarcomas were retrospectively reviewed. Ten patients with high-grade tumors larger than 8 cm, treated from June 2000 to February 2002 with neoadjuvant chemotherapy based on an anthracycline and iphosphamide regimen, plus vincristin and cisplatinum in selected cases, followed by surgery and adjuvant therapy with chemotherapy combined with local radiotherapy, were included. Evaluations of objective tumor response, survival, and toxicity were carried out. Results: after neoadjuvant therapy, s ix patients underwent conservative and limb-salvage surgery, three required radical interventions, and one refused surgical treatment. Seven experienced an objective response: it was complete in four and partial in three; the disease kept stable in two patients, and the tumor progressed in one case. After an average 46-month follow-up, four patients were permanently free of disease. Hematological and gastrointestinal toxicity was remarkable, and no patient had a long-term morbidity related to the treatment. Conclusions: this limited retrospective review suggests an advantage for the use of

  7. High grade gilomas and solitary metastases: differentiation using perfusion MR imaging and spectroscopic MR imaging

    International Nuclear Information System (INIS)

    Law, M.; Cha, S.; Knopp, E.A.; Johnson, G.; Litt, A.W.

    2002-01-01

    Full text: To determine whether perfusion MRI (pMRI) and spectroscopic MR imaging (sMRI) can be used to differentiate high grade primary gliomas and solitary metastases on the basis of differences in vascularity and metabolite levels in the peritumoral. Fifty-one patients with a solitary brain tumor (33 gliomas, 18 metastases) underwent conventional MRI, contrast enhanced pMRI and sMRI before surgical resection or stereotactic biopsy. The peri-tumoral region is defined as the area within the white matter, immediately adjacent to the enhancing portion of the tumor (hyperintense on T2- weighted imaging but no enhancement on post-contrast T1-weighted imaging). Relative cerebral blood volume (rCBV) measurements were made in these regions from the pMRI data. Spectra from the enhancing tumor, the peritumoral region and normal brain, were obtained from the 2D multi-voxel CSI acquisition (TE = 135ms). The measured rCBV within the abnormal peritumoral region in highgrade gliomas and metastasis were 1.31 ± 0.97 (mean ± standard deviation) and 0.39 ± 0.19, respectively. The difference was statistically significant (p<0.0001). Spectroscopic imaging demonstrated elevated choline (Cho/Cr 2.28 ± 1.24) in the peritumoral region of gliomas but not in metastasis (Cho/Cr = 0.76 ± 0.23). The difference was again statistically significant (p 0.001), with Student's t-test. Although conventional imaging characteristics of solitary metastases and primary high grade gliomas may sometimes be similar, pMRI and sMRI are able to distinguish between the two, based on the rCBV and metabolite ratios within the peri-tumoral region. Copyright (2002) Blackwell Science Pty Ltd

  8. Analysis of travel patterns between road and transit-oriented development areas

    International Nuclear Information System (INIS)

    Lee, S.; Park, D.; Lee, C.

    2010-01-01

    Rapid economic growth has caused severe traffic congestion and air pollution in the Seoul metropolitan area (SMA). As a consequence, traffic demand management (TDM) policies have been implemented to mitigate traffic congestion in the region. This study analyzed travel patterns that occurred as a result of transport policy changes in Seoul between 1996 and 2002. General travel pattern changes in the SMA were compared with the travel patterns of regions with car-oriented road construction policies and public transit-invested regions. Results of the study showed that investment in road construction had no significant impact on reducing traffic congestion. The modal shift to public transit modes caused a reduction in the number of cars on roads. The study demonstrated that transit-oriented policies can be used to overcome severe traffic congestion. 7 refs., 7 tabs., 6 figs.

  9. HER-2 immunohistochemical expression as prognostic marker in high-grade T1 bladder cancer (T1G3

    Directory of Open Access Journals (Sweden)

    Luca Bongiovanni

    2013-06-01

    Full Text Available Objectives: To evaluate if the Human epidermal growth factor receptor 2 (HER-2 expression levels may be used as potential prognostic marker in high grade T1 blad- der cancer (T1G3 Methods: Specimens from transurethral resection of bladder tumour (TURBT of 103 patients with high-grade T1 bladder cancer were collected. This pathologic database was reviewed. Four-year follow-up data were matched with pathologic data. Eighty-three patients entered the study. HER-2 staining was performed. Patients were grouped for HER-2 status. Statistical analysis included Kaplan Meier survival analysis and Log-rank test. Results: Pathological review of TURBT specimens confirmed high-grade T1 transitional cell bladder cancer in all patients. Median follow-up was 12 months (mean 23,5; range 3-48. Twenty-one patients (25.4% present strong HER-2 expression (3+, 28 (33.7% moderate expression (2+, 26 (33.7% weak staining (1+ and 8 (9.6% negative expression (0. Thirty- one patients of 83 (37.4% had not evidence of disease, 41 (49.4% recurred, 11 (13.2% had a progression of disease. Forty-one patients had high grade T1 recurrence. Patients with HER-2 status 0 did not showed progression of disease. Patients with HER-2 status 3+, undergoing cys- tectomy because progression of disease, had a pathological stage > pT2 and a nodal involve- ment. Median Disease-Free Survival (DFS for all patients was 12 months (DFS probability (pDFS = 49.3%; 95% CI, -11.1/+10.1. Median DFS in HER-2 groups was 8 (pDFS 37.5%; 95% CI,-28.8/+29.9, 24 (pDFS 46.1%; 95% CI,-19.5/+17.5, 20 (pDFS 46.4%; 95% CI,-18.8/+16.9 and 10 months (pDFS 47.6%; 95% CI,-21.9/+19.1 respectively in HER-2 status 0,1+,2+,3+. Log-Rank test is not statistically significant (p = 0,39. Conclusions: This study showed that HER-2 expression does not represent a prognostic mark- er of recurrence/progression of disease in high-grade T1 bladder cancer.

  10. 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...

  11. Surface area, crystal morphology and characterization of transition alumina powders from a new gibbsite precursor

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Vieira Coelho

    2007-06-01

    Full Text Available A new procedure was used to prepare a microcrystalline powder constituted by thin euhedral hexagonal gibbsite plates, 0.2 to 0.6 µm in diameter and 32 nm thick. The powder, fired between 200 and 1000 °C, produced chi and kappa transition aluminas. Alpha-alumina is formed from 1000 °C and recrystallized up to 1500 °C. At 1000 °C, kappa- and alpha-alumina coexisted, but kappa-alumina could only be characterized by SAED. The details of the internal organization of the transition alumina pseudomorphs were clearly observable in TEM due to the great thinness of the I-gibbsite plates. The specific surface area varied from pristine I-gibbsite (24.9 m².g-1 to chi- and kappa transition aluminas (25.4 m².g-1 at 1000 °C to alpha-alumina (4.0 m².g-1 at 1500 °C. The maximum value of specific surface area is 347 m².g-1 in chi-alumina powder at 300 °C, a difference from Bayer gibbsite, in which the chi-alumina highest surface area is 370 m².g-1 at 400 °C.

  12. The Minister Council decree about conditions for to bring into the Polish customs area, to take away from the Polish customs area, and to transit through this area nuclear materials, radioactive sources and device including such sources

    International Nuclear Information System (INIS)

    Miller, L.

    2002-01-01

    The decree refers to conditions for to bring into the Polish customs area, to take away from the Polish customs area, and to transit through this area nuclear materials, radioactive sources and devices containing such sources

  13. Undifferentiated pleomorphic sarcoma: indolent, tail-like recurrence of a high-grade tumor

    Energy Technology Data Exchange (ETDEWEB)

    Alpert, Justin S. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Boland, Patrick [Memorial Sloan Kettering Cancer Center, Division of Orthopaedic Surgery, Department of Surgery, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States); Hameed, Meera [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Panicek, David M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States)

    2018-01-15

    Recurrence of a soft tissue sarcoma typically manifests as a round or oval mass at imaging, and recurrent high-grade soft tissue sarcomas generally enlarge relatively rapidly. We present a case of high-grade undifferentiated pleomorphic sarcoma in the calf of a 48-year-old male that recurred as a thin, curvilinear ''tail'' of enhancing tissue at magnetic resonance imaging (MRI), with extremely indolent growth over a 7-year period. The unusual imaging finding of a slowly enlarging ''tail'' should not be dismissed as postoperative changes, even for a high-grade soft tissue sarcoma. (orig.)

  14. MR-monitored LITT as a palliative concept in patients with high grade gliomas: preliminary clinical experience.

    Science.gov (United States)

    Reimer, P; Bremer, C; Horch, C; Morgenroth, C; Allkemper, T; Schuierer, G

    1998-01-01

    The purpose of this study was to evaluate the clinical utility of laser-induced thermotherapy (LITT) as a palliative treatment for patients with high-grade gliomas. Four consenting patients with recurrent high grade III/IV gliomas near the primary language or motor areas were palliatively treated with LITT (2-5 W, 3-13 minutes; Neodym YAG Laser, Dornier, Friedrichshafen, Germany). Temperature monitoring was performed by T1-weighted turbo-fast low-angle shot (FLASH) imaging at 1.5 T (Siemens Magnetom SP 4000, Siemens, Erlangen, Germany). MRI studies before LITT included contrast-enhanced conventional scans and functional activation studies to localize the primary motor cortex or language areas using an echo-planar imaging (EPI) spin-echo (SE) sequence. Follow-up studies consisted of contrast-enhanced conventional scans as well as diffusion studies (contrast-enhanced Fourier-acquired steady-state technique and EPI-SE) and perfusion studies (EPI-SE with .2 mmol of gadolinium (Gd)/kg body weight) to differentiate post-therapeutic effects from residual or recurrent tumor growth. Local tumor control was achieved in areas with laser energy deposition with clinically stable conditions > or = 6 months. Conventional contrast-enhanced scans demonstrated strong enhancement surrounding ablated tumor components, which showed a reduction in CBV/CBF. Perfusion studies were useful to discriminate granulomatous tissue enhancement from residual or recurrent tumor growth. Careful application of LITT may evolve as an alternative palliative concept for patients with end-stage high-grade cerebral gliomas reducing clinical symptoms from circumscribed areas of pathology.

  15. 5-aminolevulinic acid and neuronavigation in high-grade glioma surgery: results of a combined approach.

    Science.gov (United States)

    Panciani, Pier Paolo; Fontanella, Marco; Garbossa, Diego; Agnoletti, Alessandro; Ducati, Alessandro; Lanotte, Michele

    2012-02-01

    In high-grade glioma surgery, several techniques are used to achieve the maximum cytoreductive treatment preserving neurological functions. However, the effectiveness of all the methods used alone is reduced by specific limitations of each. We assessed the reliability of a multimodal strategy based on 5-aminolevulinic acid (5-ALA) and neuronavigation. We prospectively studied 18 patients with suspected, non eloquent-area malignant gliomas amenable for complete resection. Conventional illumination was used until the excision appeared complete. The cavity was then systematically inspected in violet-blue light to identify any residual tumour. Multiple biopsies of both fluorescent and non-fluorescent tissue were performed in all cases. Each specimen was labelled according to the sampling location (inside or outside the boundary set by the neuronavigator). The samples were analysed by a neuropathologist blinded to the intraoperative classification. We reviewed the results of both methods, either singly or in combination. Individual analysis showed higher 5-ALA reliability compared to neuronavigation. However, several false-negative fluorescent specimens were detected. With the combined use of fluorescence and neuroimaging, only 1 sample (negative for both 5-ALA and navigation) was tumoral tissue. In our experience, the combined approach showed the best sensitivity and it is recommended in cases of lesions involving non-eloquent areas. Copyright © 2011 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  16. 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.

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

    KAUST Repository

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

    2018-01-01

    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.

  18. 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.

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

    KAUST Repository

    Matsuoka, Hirofumi

    2018-01-18

    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.

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

    OpenAIRE

    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.

    2015-01-01

    © 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...

  1. High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

    Science.gov (United States)

    Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

    2015-01-01

    Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

  2. 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.

  3. A study of riders' noise exposure on Bay Area Rapid Transit trains.

    Science.gov (United States)

    Dinno, Alexis; Powell, Cynthia; King, Margaret Mary

    2011-02-01

    Excessive noise exposure may present a hazard to hearing, cardiovascular, and psychosomatic health. Mass transit systems, such as the Bay Area Rapid Transit (BART) system, are potential sources of excessive noise. The purpose of this study was to characterize transit noise and riders' exposure to noise on the BART system using three dosimetry metrics. We made 268 dosimetry measurements on a convenience sample of 51 line segments. Dosimetry measures were modeled using linear and nonlinear multiple regression as functions of average velocity, tunnel enclosure, flooring, and wet weather conditions and presented visually on a map of the BART system. This study provides evidence of levels of hazardous levels of noise exposure in all three dosimetry metrics. L(eq) and L(max) measures indicate exposures well above ranges associated with increased cardiovascular and psychosomatic health risks in the published literature. L(peak) indicate acute exposures hazardous to adult hearing on about 1% of line segment rides and acute exposures hazardous to child hearing on about 2% of such rides. The noise to which passengers are exposed may be due to train-specific conditions (velocity and flooring), but also to rail conditions (velocity and tunnels). These findings may point at possible remediation (revised speed limits on longer segments and those segments enclosed by tunnels). The findings also suggest that specific rail segments could be improved for noise.

  4. Pediatric High Grade Glioma: a Review and Update on Tumor Clinical Characteristics and Biology

    International Nuclear Information System (INIS)

    Fangusaro, Jason

    2012-01-01

    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 to be 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.

  5. Identifying high-grade uranium deposits in the Proterozoic basins of India- a challenge to exploration

    International Nuclear Information System (INIS)

    Mahadevan, T.M.

    1995-01-01

    The favorability factors that bestow on the Proterozoic formation of India, a potential to host high grade uranium deposits are discussed in the light of the known features of the new class of unconformity- related and strata bound uranium deposits. The need to reorient several past approaches is emphasised and it is suggested that future programmes must avail of the constraining benefits of a spectrum of geophysical, geochemical, and sedimentological studies in the choice of target areas for detailed exploration and development. A synthesis of geological and geochemical data with such geophysical features as magnetic and gravity anomalies, velocity structure, seismic reflectivity, electrical conductivity, and radioactivity can effectively lead to relatively more favourable exploration targets. Such efforts may lead to the generation of more than one model of the deep basinal features, which then provide wider options for drilling and proving of ore bodies. The alternative to the above approach is saturation drilling, which is a costly and time-consuming process and, therefore, very often self-defeating. (author). 28 refs., 2 figs., 2 tabs

  6. Pediatric High Grade Glioma: a Review and Update on Tumor Clinical Characteristics and Biology

    Energy Technology Data Exchange (ETDEWEB)

    Fangusaro, Jason, E-mail: jfangusaro@luriechildrens.org [Pediatric Neuro-Oncology, The Ann & Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL (United States)

    2012-08-24

    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 to be 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.

  7. Seismic signatures of the Pan-African orogeny: implications for southern Indian high-grade terranes

    Science.gov (United States)

    Rai, Abhishek; Gaur, V. K.; Rai, S. S.; Priestley, K.

    2009-02-01

    We present the results of a study designed to investigate and compare the seismic characteristics of the once contiguous terranes of eastern Gondwanaland, now incorporated in five separated continental masses, which, during the Neoproterozoic (~600Ma) Pan-African orogeny, suffered a high degree of thermal stress and deformation. Receiver functions and surface wave data from stations located in East Antarctica, Sri Lanka, the southern-Indian high-grade terranes, Madagascar and the Tanzania-Mozambique belt, were used to determine the shear-wave velocity structure, Moho depth and VP/VS values of the respective crustal segments. This study provides an additional dimension to the otherwise well-documented characteristic petrology of their surface exposures and other geological signatures such as their extensive granulitization and gem formation during the Pan-African event. Analysis of the receiver functions and surface wave data for these seismic stations located on their present day widely distributed continental fragments have been made. It is observed that with the exception of KOD (at Kodaikanal hill), situated on the southern Indian granulites having the thickest crust (~43.5 km), most of the Pan-African granulitic terranes have a crustal thicknesses of ~37 +/- 0.8km, with a transition to higher velocity at mid-crustal depths, and that their bulk composition is felsic. Average crustal VP/VS values (1.704 +/- 0.03) and thicknesses (37.8 +/- 0.8km), for four stations (SYO, PALK, TRV and ABPO), now located in East Antarctica, Sri Lanka, India and Madagascar, respectively, show remarkable similarity, indicating that the Pan-African orogeny was extensive enough to reorder the crustal structure of a wide region with a broadly similar stamp.

  8. 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...

  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. ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grade astrocytomas

    International Nuclear Information System (INIS)

    Tomaselli, Sara; Galeano, Federica; Massimi, Luca; Di Rocco, Concezio; Lauriola, Libero; Mastronuzzi, Angela; Locatelli, Franco; Gallo, Angela

    2013-01-01

    High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas. Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed high-grade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients. Total RNAs extracted from all tumor samples and controls were tested for RNA editing levels (by direct sequencing on cDNA pools) and for ADAR2 mRNA expression (by qRT-PCR). A significant loss of ADAR2-editing activity was observed in the newly diagnosed and recurrent astrocytomas in comparison to normal brain. Surprisingly, we found a substantial rescue of ADAR2 editing activity in the relapsed tumor of the only patient showing prolonged survival. High-grade astrocytomas display a generalized loss of ADAR2-mediated RNA editing at both diagnosis and relapse. However, a peculiar Case, in complete remission of disease, displayed a total rescue of RNA editing at relapse, intriguingly suggesting ADAR2 activity/expression as a possible marker for long-term survival of patients with high-grade astrocytomas

  11. TRANSIT

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. TRANSIT. SYSTEM: DETERMINE 2D-POSITION GLOBALLY BUT INTERMITTENT (POST-FACTO). IMPROVED ACCURACY. PRINCIPLE: POLAR SATELLITES WITH INNOVATIONS OF: GRAVITY-GRADIENT ATTITUDE CONTROL; DRAG COMPENSATION. WORKS ...

  12. Effect of In-Vehicle Audio Warning System on Driver’s Speed Control Performance in Transition Zones from Rural Areas to Urban Areas

    Directory of Open Access Journals (Sweden)

    Xuedong Yan

    2016-06-01

    Full Text Available Speeding is a major contributing factor to traffic crashes and frequently happens in areas where there is a mutation in speed limits, such as the transition zones that connect urban areas from rural areas. The purpose of this study is to investigate the effects of an in-vehicle audio warning system and lit speed limit sign on preventing drivers’ speeding behavior in transition zones. A high-fidelity driving simulator was used to establish a roadway network with the transition zone. A total of 41 participants were recruited for this experiment, and the driving speed performance data were collected from the simulator. The experimental results display that the implementation of the audio warning system could significantly reduce drivers’ operating speed before they entered the urban area, while the lit speed limit sign had a minimal effect on improving the drivers’ speed control performance. Without consideration of different types of speed limit signs, it is found that male drivers generally had a higher operating speed both upstream and in the transition zones and have a larger maximum deceleration for speed reduction than female drivers. Moreover, the drivers who had medium-level driving experience had the higher operating speed and were more likely to have speeding behaviors in the transition zones than those who had low-level and high-level driving experience in the transition zones.

  13. Silicic, high- to extremely high-grade ignimbrites and associated deposits from the Paraná Magmatic Province, southern Brazil

    Science.gov (United States)

    Luchetti, Ana Carolina F.; Nardy, Antonio J. R.; Madeira, José

    2018-04-01

    The Cretaceous trachydacites and dacites of Chapecó type (ATC) and dacites and rhyolites of Palmas type (ATP) make up 2.5% of the 800.000 km3 of volcanic pile in the Paraná Magmatic Province (PMP), emplaced at the onset of Gondwana breakup. Together they cover extensive areas in southern Brazil, overlapping volcanic sequences of tholeiitic basalts and andesites; occasional mafic units are also found within the silicic sequence. In the central region of the PMP silicic volcanism comprises porphyritic ATC-type, trachydacite high-grade ignimbrites (strongly welded) overlying aphyric ATP-type, rhyolite high- to extremely high-grade ignimbrites (strongly welded to lava-like). In the southwestern region strongly welded to lava-like high-grade ignimbrites overlie ATP lava domes, while in the southeast lava domes are found intercalated within the ignimbrite sequence. Characteristics of these ignimbrites are: widespread sheet-like deposits (tens to hundreds of km across); absence of basal breccias and basal fallout layers; ubiquitous horizontal to sub-horizontal sheet jointing; massive, structureless to horizontally banded-laminated rock bodies locally presenting flow folding; thoroughly homogeneous vitrophyres or with flow banding-lamination; phenocryst abundance presenting upward and lateral decrease; welded glass blobs in an 'eutaxitic'-like texture; negligible phenocryst breakage; vitroclastic texture locally preserved; scarcity of lithic fragments. These features, combined with high eruption temperatures (≥ 1000 °C), low water content (≤ 2%) and low viscosities (104-7 Pa s) suggest that the eruptions were characterized by low fountaining, little heat loss during collapse, and high mass fluxes producing extensive deposits.

  14. High-Grade Transformation of Adenoid Cystic Carcinoma Delineated with a Fibrous Rim: A Case Report

    Directory of Open Access Journals (Sweden)

    Hamide Sayar

    2013-09-01

    Full Text Available Background: High-grade transformation or dedifferentiation in carcinoma is progression of a low-grade malignant neoplasm to a high-grade carcinoma or poorly differentiated adenocarcinoma. This is rarely observed in adenoid cystic carcinoma of the salivary glands. Case Report: A 39 year-old woman presented with a painless mass at the left submandibulary region that had been growing slowly for 5 years. Submandibulary mass resection revealed a mass with peripheral adenoid cystic carcinoma and a central high-grade tumor delineated with a fibrous rim, raising the possibility of a hybrid or composite carcinoma, requiring differential diagnosis depending upon morphology and immunohistochemistry findings. The final histopathological diagnosis was high-grade transformation of adenoid cystic carcinoma. After surgical therapy, the patient was irradiated to the neck and submandibulary region. No sign of tumor recurrence has been evident for 36 months. Conclusion: This present case seems to be another rare case with high-grade transformation of adenoid cystic carcinoma and the fibrous rim may be a histopathological feature of such cases, which should be kept in mind.

  15. [Experience of diagnosis and treatment of exogenous high-grade fever].

    Science.gov (United States)

    Xiong, Xing-jiang; Wang, Jie

    2011-06-01

    There is a regular pattern in the diagnosis and treatment of exogenous high-grade fever, of which the key point is formula syndrome identification. Syndrome differentiation of the six channels is appropriate for not only exogenous cold but also various other conditions. The diagnosis and treatment of high-grade fever can also follow the law of syndrome differentiation of the six channels. The theory of epidemic febrile diseases stems from and elaborates on an understanding of exogenous febrile conditions, so many effective formulas used to treat epidemic febrile diseases also have great value in the treatment of high-grade fever. Deteriorated syndrome, which is central to this condition, is very commonly seen in cases of high-grade fever, the key therapeutic principle of which is established according to syndromes. Allowing analysis that does not rigidly adhere to either established modern diagnosis or traditional Chinese syndromes, prominent achievements could be made in treating high-grade fever by summarizing the regular presenting patterns in terms of the constitution and symptoms.

  16. 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.)

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

    International Nuclear Information System (INIS)

    Yoo, Hye Jin; Hong, Sung Hwan; Choi, Ja-Young; Choi, Jung-Ah; Kang, Heung Sik; Moon, Kyung Chul; Kim, Han-Soo

    2009-01-01

    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.)

  18. Cardiovascular epidemiological transition in a rural habitat of Nigeria: the case of mangu local government area.

    Science.gov (United States)

    Okeahialam, B N; Ogbonna, C; Otokwula, A E; Joseph, D E; Chuhwak, E K; Isiguzoro, I O

    2012-01-01

    Epidemiological transition is at various stages in different places. The true situation in sub-Saharan Africa (SSA) is largely unknown. Having studied this rural habitat 17 years ago, we returned there to study several cardiovascular disease (CVD) risk factors to see if any change had occurred. The communities studied in 1991 as part of the national CVD survey were returned to in 2008 and re-studied descriptively in a cross-sectional manner. All adults 15 years and above, apart from demographic and personal data had blood pressure (BP) and some blood indices determined. Over the period, some changes occurred. The mean (SD) age increased from 34.1(16.9) to 45.5(18.2) years suggesting an ageing population. More people in 2008 than 1991 lived most of their last 5 years in the urban areas suggesting some influence of urbanisation. Significantly fewer people smoked and drank after 17 years. However mean (SD) of Body Mass Index rose [20.7(2.8) to 23.7(4.5) kg/m²], as well as SBP and DBP. Prevalence of hypertension rose from 7.4% to 20.9%. Both total and HDL cholesterol rose, although atherogenic index dropped. Mean (SD) blood sugar interestingly dropped from 5.0(2.9) to 4.6(1.0) mmol/l. Epidemiological transition is evident in this rural SSA habitat, and proactive steps to stem the tide and curb the consequences of CVD should be instituted.

  19. Suppression of the Transit -Time Instability in Large-Area Electron Beam Diodes

    Science.gov (United States)

    Myers, Matthew C.; Friedman, Moshe; Swanekamp, Stephen B.; Chan, Lop-Yung; Ludeking, Larry; Sethian, John D.

    2002-12-01

    Experiment, theory, and simulation have shown that large-area electron-beam diodes are susceptible to the transit-time instability. The instability modulates the electron beam spatially and temporally, producing a wide spread in electron energy and momentum distributions. The result is gross inefficiency in beam generation and propagation. Simulations indicate that a periodic, slotted cathode structure that is loaded with resistive elements may be used to eliminate the instability. Such a cathode has been fielded on one of the two opposing 60 cm × 200 cm diodes on the NIKE KrF laser at the Naval Research Laboratory. These diodes typically deliver 600 kV, 500 kA, 250 ns electron beams to the laser cell in an external magnetic field of 0.2 T. We conclude that the slotted cathode suppressed the transit-time instability such that the RF power was reduced by a factor of 9 and that electron transmission efficiency into the laser gas was improved by more than 50%.

  20. Suppression of the transit-time instability in large-area electron beam diodes

    International Nuclear Information System (INIS)

    Myers, Matthew C.; Friedman, Moshe; Sethian, John D.; Swanekamp, Stephen B.; Chan, L.-Y.; Ludeking, Larry

    2002-01-01

    Experiment, theory, and simulation have shown that large-area electron-beam diodes are susceptible to the transit-time instability. The instability modulates the electron beam spatially and temporally, producing a wide spread in electron energy and momentum distributions. The result is gross inefficiency in beam generation and propagation. Simulations indicate that a periodic, slotted cathode structure that is loaded with resistive elements may be used to eliminate the instability. Such a cathode has been fielded on one of the two opposing 60 cm x 200 cm diodes on the NIKE KrF laser at the Naval Research Laboratory. These diodes typically deliver 600 kV, 500 kA, 250 ns electron beams to the laser cell in an external magnetic field of 0.2 T. We conclude that the slotted cathode suppressed the transit-time instability such that the RF power was reduced by a factor of 9 and that electron transmission efficiency into the laser gas was improved by more than 50%

  1. 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.

  2. Association of invasive breast carcinoma and multicentric high grade astrocytoma: a case report with a review.

    Science.gov (United States)

    Pour, P Hossein; Forouzandeh, M; Beni, A Naderi; Beni, Z Naderi; Hoseinpour, P

    2011-03-01

    Breast cancer is the most common cancer in women. Multicentric gliomas are uncommon lesions of the central nervous system (CNS) with an unprecise rate of occurrence that diffusely infiltrate large portions of the brain. High grade astrocytoma is the most agressive form of gliomas and often has a distinct neuroimaging pattern with a poor prognosis. We report a case of a 29-year-old woman patient with primary breast carcinoma and high grade astrocytoma subsequently developed. The woman was treated by mastectomy and 20 months post-diagnosis of the cancer she exhibited a transient facial paralysis. Magnetic resonance imaging (MRI) revealed two cranial masses suspicious of metastasis. A complete tumor removal from the brain was performed. On histological examination, this tumor was a high grade astrocytoma.

  3. Transition plan: Project C-018H, 200-E Area Effluent Treatment Facility

    International Nuclear Information System (INIS)

    Connor, M.D.

    1994-01-01

    The purpose of this transition plan is to ensure an orderly transfer of project information to operations to satisfy Westinghouse Hanford Company (WHC) operational requirements and objectives, and ensure safe and efficient operation of Project C-018H, the 200-E Area Effluent Treatment Facility (ETF). This plan identifies the deliverables for Project C-018H upon completion of construction and turnover to WHC for operations, and includes acceptance criteria to objectively assess the adequacy of the contract deliverables in relation to present requirements. The scope of this plan includes a general discussion of the need for complete and accurate design basis documentation and design documents as project deliverables. This plan also proposes that a configuration management plan be prepared to protect and control the transferred design documents and reconstitute the design basis and design requirements, in the event that the deliverables and project documentation received from the contractor are less than adequate at turnover

  4. 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

  5. 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

    Background: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.Methods:Database review was performed...

  6. High-grade myxofibrosarcoma-presented as a large mass of right upper arm

    Directory of Open Access Journals (Sweden)

    Sunil Vitthalrao Jagtap

    2015-01-01

    Full Text Available Myxofibrosarcoma is one of the rare soft tissue sarcomas. We present a case of a 65-year-old male having large soft tissue mass over right upper arm associated with surface ulceration. On histopathological study tumor was diagnosed as myxofibrosarcoma - high grade according to modified FNCLCC grading system. Like many other tumors of connective tissue, soft tissue sarcoma exhibits high recurrence. In our case, tumor showed features of high grade with local recurrence, large size; however, no evidence of metastasis was noted. For this unpredictable clinical behavior, we are presenting this case.

  7. Rural settlements transition (RST) in a suburban area of metropolis: Internal structure perspectives.

    Science.gov (United States)

    Ma, Wenqiu; Jiang, Guanghui; Wang, Deqi; Li, Wenqing; Guo, Hongquan; Zheng, Qiuyue

    2018-02-15

    Rural settlements transition (RST) is one of the most significant indices for understanding the phenomena of rural reconstruction and urban-rural transformation in China. However, a systematic overview of RST is missing, and there is a lack of evidence regarding its characteristics from the internal structure perspectives. In this paper, we systematically explore the RST regarding spatio-temporal change characteristics of internal structure, patterns and impacts on rural environment and development by using practical survey internal land-use data from 2005 to 2015. The results show that the temporal change characteristics of the internal structure of rural settlements demonstrate a tendency for housing land to decrease and other land-use types to increase. The spatial change characteristics reveal that the structure inclines to more complexity and diversity from an exurban area to an urban-rural fringe area. Based on this finding, we identify that rapid development of rural industrialization, more agglomerate and effective industrial land-use, and improved public infrastructure construction are the general RST patterns. Spatially, there exists a physical decay pattern in the exurban area, thereby resulting in the hollowing-out of rural industries and of the population. In addition, the extensive and disorderly pattern in the suburban area causes low efficiency output and serious environmental pollution. The RST pattern in the urban hinterland promoted the "men-environment" compatible development. The study concludes that regional differentiation in patterns and impacts are significant in the process of RST. Future adaptive strategies for rural settlements adjustment should be conducted according to regional characteristics, including socio-economic status, physical geography condition and economic location to improve the rural environmental sustainability. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The value of diffusion tensor imaging in differentiating high-grade gliomas from brain metastases: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Rui Jiang

    Full Text Available Differentiation of high-grade gliomas and solitary brain metastases is an important clinical issue because the treatment strategies differ greatly. Our study aimed to investigate the potential value of diffusion tensor imaging (DTI in differentiating high-grade gliomas from brain metastases using a meta-analytic approach.We searched Pubmed, Embase and the Cochrane Library for relevant articles published in English. Studies that both investigated high-grade gliomas and brain metastases using DTI were included. Random effect model was used to compare fractional anisotropy (FA and mean diffusivity (MD values in the two tumor entities.Nine studies were included into the meta-analysis. In the peritumoral region, compared with brain metastases, high-grade gliomas had a significant increase of FA (SMD  = 0.47; 95% CI, 0.22-0.71; P<0.01 and a significant decrease of MD (SMD  = -1.49; 95% CI, -1.91 to -1.06; P<0.01. However, in the intratumoral area, no significant change in FA (SMD  = 0.16; 95% CI, -0.49 to 0.82; P = 0.73 or MD (SMD  = 0.34; 95% CI, -0.91 to 1.60; P = 0.59 was detected between gliomas and metastases.High-grade gliomas may be distinguished from brain metastases by comparing the peritumoral FA and MD values. DTI appears to be a promising tool in diagnosing solitary intracranial lesions.

  9. Investigating the determining factors for transit travel demand by bus mode in US metropolitan statistical areas.

    Science.gov (United States)

    2015-05-01

    Proper understanding of the nature of the transit travel demand is at the heart of transportation policy making and the success of : transit systems. Unfortunately, most of the existing studies have focused on a single or few transit systems or metro...

  10. Health-related quality of life of long-term high-grade glioma survivors

    NARCIS (Netherlands)

    Bosma, Ingeborg; Reijneveld, Jaap C.; Douw, Linda; Vos, Maaike J.; Postma, Tjeerd J.; Aaronson, Neil K.; Muller, Martin; Vandertop, W. Peter; Slotman, Ben J.; Taphoorn, Martin J. B.; Heimans, Jan J.; Klein, Martin

    2009-01-01

    The objective of this study was to compare the health-related quality of life (HRQOL) of long-term to short-term high-grade glioma (HGG) survivors, determine the prognostic value of HRQOL for overall survival, and determine the effect of tumor recurrence on HRQOL for long-term survivors. Following

  11. 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.

  12. Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type

    NARCIS (Netherlands)

    Costa, A.F.; Altemani, A.; Vékony, H.; Bloemena, E.; Fresno, F.; Suárez, C.; Llorente, J.L.; Hermsen, M.

    2010-01-01

    Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACCHGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGTis generally considered to be an aggressive variant of ACC, even more

  13. Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type

    NARCIS (Netherlands)

    Costa, A.F.; Altemani, A.; Vékony, H.; Bloemena, E.; Fresno, F.; Suárez, C.; Llorente, J.L.; Hermsen, M.

    2011-01-01

    Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more

  14. 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...

  15. Symptoms and problems in the end-of-life phase of high-grade glioma patients

    NARCIS (Netherlands)

    Sizoo, Eefje M.; Braam, Lies; Postma, Tjeerd J.; Pasman, H. Roeline W.; Heimans, Jan J.; Klein, Martin; Reijneveld, Jaap C.; Taphoorn, Martin J. B.

    2010-01-01

    Despite multimodal treatment, it is not possible to cure high-grade glioma (HGG) patients. Therefore, the aim of treatment is not only to prolong life, but also to prevent deterioration of health-related quality of life as much as possible. When the patient's condition declines and no further tumor

  16. High-grade malignant transformation of a radiation-naïve nasopharyngeal angiofibroma.

    Science.gov (United States)

    Allensworth, Jordan J; Troob, Scott H; Lanciault, Christian; Andersen, Peter E

    2016-04-01

    Nasopharyngeal angiofibromas are typically considered benign vascular neoplasms, with descriptions of high-grade sarcomatous change found only in lesions with prior radiotherapy. We describe the first reported case of high-grade malignant change in a nasopharyngeal angiofibroma naive to radiation. A 45-year-old man presented with left-sided nasal congestion and fullness and was found to have a left-sided nasopharyngeal mass with intracranial extension on CT scan. A biopsy of the mass revealed nasopharyngeal angiofibroma. The patient opted for MRI surveillance, which revealed interval growth 3 years later. Decompression surgery revealed only angiofibroma, but resection 9 months later demonstrated high-grade sarcoma and concomitant angiofibroma. The patient had residual disease which progressed through chemoradiation, and is now pursuing clinical trial enrollment. Malignant transformation of nasopharyngeal angiofibroma is extremely rare. As highlighted by this report, high-grade undifferentiated lesions may arise in tumors without previous radiation. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2425-E2427, 2016. © 2016 Wiley Periodicals, Inc.

  17. Multiparametric Magnetic Resonance Imaging for Discriminating Low-Grade From High-Grade Prostate Cancer

    NARCIS (Netherlands)

    Vos, E.K.; Kobus, T.; Litjens, G.J.S.; Hambrock, T.; Hulsbergen-van de Kaa, C.A.; Barentsz, J.O.; Maas, M.C.; Scheenen, T.W.J.

    2015-01-01

    The aim of this study was to determine and validate the optimal combination of parameters derived from 3-T diffusion-weighted imaging, dynamic contrast-enhanced imaging, and magnetic resonance (MR) spectroscopic imaging for discriminating low-grade from high-grade prostate cancer (PCa).The study was

  18. Survival and prognostic factors at time of diagnosis in high-grade appendicular osteosarcoma

    DEFF Research Database (Denmark)

    Colding-Rasmussen, Thomas; Thorn, Andrea Pohly; Horstmann, Peter

    2018-01-01

    BACKGROUND: Survival of patients with high-grade osteosarcoma (HOS), the most common primary bone cancer, has not improved significantly the last 30 years and the disease remains a major challenge. The purpose of this study is to evaluate survival in relation to prognostic factors at time of diag...

  19. The end-of-life phase of high-grade glioma patients: a systematic review

    NARCIS (Netherlands)

    Sizoo, Eefje M.; Pasman, H. Roeline W.; Dirven, Linda; Marosi, Christine; Grisold, Wolfgang; Stockhammer, Günther; Egeter, Jonas; Grant, Robin; Chang, Susan; Heimans, Jan J.; Deliens, Luc; Reijneveld, Jaap C.; Taphoorn, Martin J. B.

    2014-01-01

    High-grade gliomas (HGG) are rare and incurable; yet, these neoplasms result in a disproportionate share of cancer morbidity and mortality. Treatment of HGG patients is directed not merely towards prolonging life but also towards quality of life, which becomes the major goal in the end of life

  20. The end-of-life phase of high-grade glioma patients: a systematic review

    NARCIS (Netherlands)

    Sizoo, E.M.; Pasman, H.R.W.; Dirven, L.; Marosi, C.; Grisold, W.; Stockhammer, G.; Egeter, J.; Grant, R.; Chang, S.; Heimans, J.J.; Deliens, L.; Reijneveld, J.C.; Taphoorn, M.J.B.

    2014-01-01

    Background: High-grade gliomas (HGG) are rare and incurable; yet, these neoplasms result in a disproportionate share of cancer morbidity and mortality. Treatment of HGG patients is directed not merely towards prolonging life but also towards quality of life, which becomes the major goal in the end

  1. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer.

    Science.gov (United States)

    Moran-Jones, Kim; Gloss, Brian S; Murali, Rajmohan; Chang, David K; Colvin, Emily K; Jones, Marc D; Yuen, Samuel; Howell, Viive M; Brown, Laura M; Wong, Carol W; Spong, Suzanne M; Scarlett, Christopher J; Hacker, Neville F; Ghosh, Sue; Mok, Samuel C; Birrer, Michael J; Samimi, Goli

    2015-12-29

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer.

  2. The End-of-Life Phase of High-Grade Glioma Patients: Dying With Dignity?

    NARCIS (Netherlands)

    Sizoo, E.M.; Taphoorn, M.J.B.; Uitdehaag, B.M.J.; Heimans, J.J.; Deliens, L.; Reijneveld, J.C.; Pasman, H.R.W.

    2013-01-01

    Background. In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patient's personal dignity. We aimed to (a) assess the proportion of HGG patients dying with

  3. Symptoms and medication management in the end of life phase of high-grade glioma patients

    NARCIS (Netherlands)

    Koekkoek, J.A.F.; Dirven, L.; Sizoo, E.M.; Pasman, H.R.W.; Heimans, J.J.; Postma, T.J.; Deliens, L.; Grant, R.; McNamara, S.; Stockhammer, G.; Medicus, E.; Taphoorn, M.J.B.; Reijneveld, J.C.

    2014-01-01

    During the end of life (EOL) phase of high-grade glioma (HGG) patients, care is primarily aimed at reducing symptom burden while maintaining quality of life as long as possible. In this study, we evaluated the prevalence of symptoms and medication management in HGG patients during the EOL phase. We

  4. The end-of-life phase of high-grade glioma patients: dying with dignity?

    NARCIS (Netherlands)

    Sizoo, Eefje M.; Taphoorn, Martin J. B.; Uitdehaag, Bernard; Heimans, Jan J.; Deliens, Luc; Reijneveld, Jaap C.; Pasman, H. Roeline W.

    2013-01-01

    In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patient's personal dignity. We aimed to (a) assess the proportion of HGG patients dying with dignity as

  5. Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma.

    Science.gov (United States)

    Chuang, Ai-Ying; DeMarzo, Angelo M; Veltri, Robert W; Sharma, Rajni B; Bieberich, Charles J; Epstein, Jonathan I

    2007-08-01

    The histologic distinction between high-grade prostate cancer and infiltrating high-grade urothelial cancer may be difficult, and has significant implications because each disease may be treated very differently (ie, hormone therapy for prostate cancer and chemotherapy for urothelial cancer). Immunohistochemistry of novel and established prostatic and urothelial markers using tissue microarrays (TMAs) were studied. Prostatic markers studied included: prostate-specific antigen (PSA), prostein (P501s), prostate-specific membrane antigen (PSMA), NKX3.1 (an androgen-related tumor suppressor gene), and proPSA (pPSA) (precursor form of PSA). "Urothelial markers" included high molecular weight cytokeratin (HMWCK), p63, thrombomodulin, and S100P (placental S100). TMAs contained 38 poorly differentiated prostate cancers [Gleason score 8 (n=2), Gleason score 9 (n=18), Gleason score 10 (n=18)] and 35 high-grade invasive urothelial carcinomas from radical prostatectomy and cystectomy specimens, respectively. Each case had 2 to 8 tissue spots (0.6-mm diameter). If all spots for a case showed negative staining, the case was called negative. The sensitivities for labeling prostate cancers were PSA (97.4%), P501S (100%), PSMA (92.1%), NKX3.1 (94.7%), and pPSA (94.7%). Because of PSA's high sensitivity on the TMA, we chose 41 additional poorly differentiated primary (N=36) and metastatic (N=5) prostate carcinomas which showed variable PSA staining at the time of diagnosis and performed immunohistochemistry on routine tissue sections. Compared to PSA, which on average showed 18.8% of cells with moderate to strong positivity, cases stained for P501S, PSMA, and NKX3.1 had on average 42.5%, 53.7%, 52.9% immunoreactivity, respectively. All prostatic markers showed excellent specificity. HMWCK, p63, thrombomodulin, and S100P showed lower sensitivities in labeling high-grade invasive urothelial cancer in the TMAs with 91.4%, 82.9%, 68.6%, and 71.4% staining, respectively. These urothelial

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

    Science.gov (United States)

    Albitar, Maher; Ma, Wanlong; Lund, Lars; Shahbaba, Babak; Uchio, Edward; Feddersen, Søren; Moylan, Donald; Wojno, Kirk; Shore, Neal

    2018-03-01

    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. 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 standard formulas, while comparisons between groups were performed using the Wilcoxon Rank Sum, Kruskal-Wallis, Chi-Square, and Fisher's exact test. GS as assigned by standard 10-12 core biopsies was 3 + 3 in 90 (29.4%), 3 + 4 in 122 (39.8%), 4 + 3 in 50 (16.3%), and > 4 + 3 in 44 (14.4%) patients. The urine/plasma assay confirmed a previous validation and was highly accurate in predicting the presence of high-grade PCa (Gleason ≥3 + 4) with sensitivity between 88% and 95% as verified by prostatectomy findings. GS was upgraded after prostatectomy in 27% of patients and downgraded in 12% of patients. This plasma/urine biomarker test accurately predicts high grade cancer as determined by prostatectomy with a sensitivity at 92-97%, while the sensitivity of core biopsies was 78%. © 2018 Wiley Periodicals, Inc.

  7. Yield of Cytology Surveillance After High-Grade Vulvar Intraepithelial Neoplasia or Cancer.

    Science.gov (United States)

    Kuroki, Lindsay M; Frolova, Antonina I; Wu, Ningying; Liu, Jingxia; Powell, Matthew; Thaker, Premal H; Massad, L Stewart

    2017-07-01

    The aim of the study was to estimate the risk of high-grade cervical and vaginal intraepithelial neoplasia (CIN/VAIN 2+) and cancer among women treated surgically for high-grade vulvar intraepithelial neoplasia (HGVIN) and vulvar cancer. We performed a retrospective cohort study of women who underwent surgery for HGVIN/vulvar cancer between 2006 and 2010. Univariate and multivariate analyses using stepwise selection were used to identify correlates of abnormal cytology after treatment for VIN and vulvar cancer. Among 191 women under surveillance for a median of 3.7 years who underwent treatment for HGVIN/vulvar cancer, primary vulvar lesions included VIN 2 (10, 5%), VIN 3 (102, 53%), and carcinoma (79, 41%). During follow-up, 71 (37%) had abnormal cytology, including 47 (25%) low grade, 23 (12%) high grade, and 1 (0.5%) carcinoma. Subsequent risk for VAIN 2+ was 11% (6/57) after previous hysterectomy and 8% for CIN 2+ (10/124) with intact cervix. Overall risk for CIN 3+ was 5%. Correlates of high-grade cytology after treatment for HGVIN/vulvar cancer included nonwhite race (odds ratio [OR] = 3.3, 95% CI = 1.50-7.36), immunodeficiency (OR = 4.2, 95% CI = 1.76-9.94), and previous abnormal cytology (OR = 2.7, 95% CI = 1.29-5.78). Stepwise multivariate analysis revealed immunosuppression as the only significant correlate of high-grade cytology after vulvar treatment (adjusted OR = 3.7, 95% CI = 1.26-10.83). Women with HGVIN/cancer should have cervical/vaginal cytology before vulvar surgery. Those with a negative cervical or vaginal cytology result should undergo cytology testing at 1- to 3-year intervals, based on the threshold for CIN 3+ set forth by the American Society for Colposcopy and Cervical Pathology.

  8. 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.

  9. Small-Scale, Local Area, and Transitional Millimeter Wave Propagation for 5G Communications

    Science.gov (United States)

    Rappaport, Theodore S.; MacCartney, George R.; Sun, Shu; Yan, Hangsong; Deng, Sijia

    2017-12-01

    This paper studies radio propagation mechanisms that impact handoffs, air interface design, beam steering, and MIMO for 5G mobile communication systems. Knife edge diffraction (KED) and a creeping wave linear model are shown to predict diffraction loss around typical building objects from 10 to 26 GHz, and human blockage measurements at 73 GHz are shown to fit a double knife-edge diffraction (DKED) model which incorporates antenna gains. Small-scale spatial fading of millimeter wave received signal voltage amplitude is generally Ricean-distributed for both omnidirectional and directional receive antenna patterns under both line-of-sight (LOS) and non-line-of-sight (NLOS) conditions in most cases, although the log-normal distribution fits measured data better for the omnidirectional receive antenna pattern in the NLOS environment. Small-scale spatial autocorrelations of received voltage amplitudes are shown to fit sinusoidal exponential and exponential functions for LOS and NLOS environments, respectively, with small decorrelation distances of 0.27 cm to 13.6 cm (smaller than the size of a handset) that are favorable for spatial multiplexing. Local area measurements using cluster and route scenarios show how the received signal changes as the mobile moves and transitions from LOS to NLOS locations, with reasonably stationary signal levels within clusters. Wideband mmWave power levels are shown to fade from 0.4 dB/ms to 40 dB/s, depending on travel speed and surroundings.

  10. State safety oversight program : audit of the tri-state oversight committee and the Washington metropolitan area transit authority, final audit report, March 4, 2010.

    Science.gov (United States)

    2010-03-04

    The Federal Transit Administration (FTA) conducted an on-site audit of the safety program implemented by the Washington Metropolitan Area Transit Authority (WMATA) and overseen by the Tri-State Oversight Committee (TOC) between December 14 and 17, 20...

  11. 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

  12. Histochemical and ultrastructural study of an elastofibroma dorsi coexisting with a high grade spindle cell sarcoma

    Directory of Open Access Journals (Sweden)

    M Alberghini

    2009-06-01

    Full Text Available Elastofibroma dorsi is a pseudotumoral fibroproliferative lesion characterized by polymorphic fiber-like deposits of elastinophilic material. Several theories have been reported explaining the pathogenesis of elastofibroma. Recent cytogenetic studies have demonstrated chromosomal instability in elastofibromas, not normally observed in non-neoplastic tissues. These chromosomal defects are commonly observed in aggressive fibromatosis too. Such clinical observations suggest a multistage pathogenetic mechanism for the onset of elastofibroma. This study, using histochemical, immunohistochemical staining techniques, and ultrastructural examination, describes the detection of an otherwise typical elastofibroma contextual to a high grade sarcoma. Hence, the coexistence of elastofibroma and high-grade sarcoma may suggest a causal link between the two pathological entities. The results obtained suggest that the coexistence of the two pathological entities is conceivably coincidental.

  13. 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.

  14. Complementary therapy use and quality of life in persons with high-grade gliomas.

    Science.gov (United States)

    Fox, Sherry; Laws, Edward R; Anderson, Frederick; Farace, Elana

    2006-08-01

    Studies have indicated that 30%-80% of cancer patients use complementary and alternative practices and products (CAPPs), but little is known about CAPPs use by persons with brain tumors. This secondary analysis of Glioma Outcomes Project data compared CAPPs users with nonusers, compared those who stopped using CAPPs with those who continued use, described frequency and patterns of CAPPs use, and compared the relationship of CAPPs use to self-reported quality of life (QOL) over time, in 186 persons with high-grade gliomas. CAPPs users at all three measurement points rated QOL higher, although not significantly higher, than nonusers. Study findings support further exploration of CAPPs use and its effects on key outcomes in persons with high-grade gliomas.

  15. Bevacizumab in High Grade Gliomas: A Case Report and Review of the Literature

    International Nuclear Information System (INIS)

    Balana, Carme; Cardona, Andres Felipe

    2007-01-01

    Patients with anaplastic astrocytoma or glioblastoma generally have adverse prognosis. Currently, standard treatment for high grade glial cell tumors consists of the concomitant use of radiotherapy and Themozolamide, followed by six months with the alkilant. However, subjects diagnosed with novo or recurrent tumors have overall survival rates from 3 to 15 months. Multiple chemotherapeutic and biological agents have been used to control progression, with no improvement in survival rates. New medication is being developed aimed at molecular targets such as the endothelial growth factor which can be regulated by, among others, Bevacizumab (BEV). Recent results from phase 11 trials combining BEV and Irinotecan (CPT-11) in patients with high grade gliomas revealed improved response rates, as well as disease free and overall survival rates. The case of a female with recurrent glioblastoma who achieved complete response after initiating BEV/CPT- 11 is presented

  16. Evaluation of anatomic and morphologic nomogram to predict malignant and high-grade disease in a cohort of patients with small renal masses.

    Science.gov (United States)

    Bagrodia, Aditya; Harrow, Brian; Liu, Zhuo-Wei; Olweny, Ephrem O; Faddegon, Stephen; Yin, Gang; Tan, Yung Khan; Han, Woong Kyu; Lotan, Yair; Margulis, Vitaly; Cadeddu, Jeffrey A

    2014-01-01

    To evaluate a nomogram using the RENAL Nephrometry Score (RENAL-NS) that was developed to characterize masses as benign vs. malignant and high vs. low grade in our patients with small renal masses treated with partial nephrectomy (PN). The nomogram was previously developed and validated in patients with widely variable tumor sizes. Retrospective review of PN performed between 1/2003 and 7/2011. Imaging was reviewed by a urologic surgeon for RENAL-NS. Final pathology was used to classify tumors as benign or malignant and low (I/II) or high (III/IV) Fuhrman grade. Patient age, gender, and RENAL score were entered into the nomogram described by Kutikov et al. to determine probabilities of cancer and high-grade disease. Area under the curve was determined to assess agreement between observed and expected outcomes for prediction of benign vs. malignant disease and for prediction of high- vs. low-grade or benign disease. A total of 250 patients with 252 masses underwent PN during the study period; 179/250 (71.6%) had preoperative imaging available. RENAL-NS was assigned to 181 masses. Twenty-two percent of tumors were benign. Eighteen percent of tumors were high grade. Area under the curve was 0.648 for predicting benign vs. malignant disease and 0.955 for predicting low-grade or benign vs. high-grade disease. The RENAL-NS score nomogram by Kutikov does not discriminate well between benign and malignant disease for small renal masses. The nomogram may potentially be useful in identifying high-grade tumors. Further validation is required where the nomogram probability and final pathologic specimen are available. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. PREVALENCE OF HUMAN PAPILLOMAVIRUS GENOTYPES IN LOW AND HIGH GRADE SQUAMOUS INTRAEPITHELIAL LESIONS AT CERVICAL TISSUE

    OpenAIRE

    Prasetyo, Rizki Eko; Mastutik, Gondo; Mustokoweni, Sjahjenny

    2017-01-01

    HPV infection is known to cause cervical cancer. This study aimed to identify the variant of HPV genotypes of cervical precancerous lesions from low grade squamous intraepithelial lesion  (LSIL) and high grade squamous intraepithelial lesion (HSIL). This was an explorative study using formalin fix paraffin embedded (FFPE) from cervical precancerous lesions at Dr. Soetomo Hospital, Surabaya. DNA was extracted from FFPE and hybridized for HPV genotyping using Ampliquality HPV Type Express kit (...

  18. Rad51 expression levels predict synthetic lethality and metastatic potential in high grade breast cancers

    International Nuclear Information System (INIS)

    Wiegmans, A.P.; Al-Ejeh, F.; Khanna, K.K.

    2012-01-01

    Among women with breast cancer, 30-40% will develop metastatic disease and only achieve an overall survival of less than 5 years. Despite new-targeted therapy, breast tumors that harbour similar histology or molecular phenotype differ in their response to treatment. To uncover potential new therapeutic targets and improve outcome, we performed data mining of cancer micro array databases. We found that high expression of the homologous recombination protein, RAD51, was significantly associated with high-grade breast cancer, aggressive subtypes and increased risk of metastasis. We confirmed using immunohistochemistry that RAD5 1 was highly expressed in metastatic tumours and high-grade triple negative, HER2+ and luminal-B tumours. This provided a rationale for targeting RAD5 1 in high-grade, therapy-resistant breast cancers. Here, we report for the first time preclinical evaluation of RAD5 1 as a therapeutic target. We found that, in-vitro high RAD5 expressing cell lines were resistant to PARP inhibitor while knockdown reversed this resistance. In-vivo, knockdown of RAD5 1 inhibited metastatic progression using a syngeneic breast cancer model and the seeding of human xenografts to distant sites, including brain and lung. Concurrent PARP inhibition reduced primary tumor growth and delayed metastasis supporting synthetic lethality in-vivo. Together these insights provide pre-clinical data demonstrating RAD5 1 as a new biomarker and potential therapeutic target against aggressive metastatic breast cancer. (author)

  19. High grade glioma: Imaging combined with pathological grade defines management and predicts prognosis

    International Nuclear Information System (INIS)

    Burnet, Neil G.; Lynch, Andrew G.; Jefferies, Sarah J.; Price, Stephen J.; Jones, Phil H.; Antoun, Nagui M.; Xuereb, John H.; Pohl, Ute

    2007-01-01

    Introduction: There is ambiguity in pathological grading of high grade gliomas within the WHO 2000 classification, especially those with predominant oligodendroglial differentiation. Patients and methods: All adult high grade gliomas treated radically, 1996-2005, were assessed. Cases in which pathology was grade III but radiology suggested glioblastoma (GBM) were classified as 'grade III/IV'; their pathology was reviewed. Results: Data from 245 patients (52 grade III, 18 grade III/IV, 175 GBM) were analysed using a Cox Proportional Hazards model. On pathology review, features suggestive of more aggressive behaviour were found in all 18 grade III/IV tumours. Oligodendroglial components with both necrosis and microvascular proliferation were present in 7. MIB-1 counts for the last 8 were all above 14%, mean 27%. Median survivals were: grade III 34 months, grade III/IV 10 months, GBM 11 months. Survival was not significantly different between grade III/IV and GBM. Patients with grade III/IV tumours had significantly worse outcome than grade III, with a hazard of death 3.7 times higher. Conclusions: The results highlight the current inconsistency in pathological grading of high grade tumours, especially those with oligodendroglial elements. Patients with histological grade III tumours but radiological appearances suggestive of GBM should be managed as glioblastoma

  20. [Diagnostic imaging of high-grade astrocytoma: heterogeneity of clinical manifestation, image characteristics, and histopathological findings].

    Science.gov (United States)

    Okajima, Kaoru; Ohta, Yoshio

    2012-10-01

    Recent developments in diagnostic radiology, which have enabled accurate differential diagnoses of brain tumors, have been well described in the last three decades. MR and PET imaging can also provide information to predict histological grades and prognoses that might influence treatment strategies. However, high-grade astrocytomas consist of many different subtypes that are associated with different imaging and histological characteristics. Hemorrhage and necrosis results in a variety of imaging features, and infiltrative tumor growth entrapping normal neurons may cause different clinical manifestations. We reviewed patients with high-grade astrocytomas that showed various imaging characteristics, with special emphasis on initial symptoms and histological features. Clinicopathological characteristics of astrocytomas were also compared with other malignant tumors. Neurological deficits were not notable in patients with grade 3-4 astrocytomas when they showed infiltrative tumor growth, while brain metastases with compact cellular proliferation caused more neurological symptoms. Infiltrative tumors did not show any enhancing masses on MR imaging, but these tumors may show intratumor heterogeneity. Seizures were reported to be more frequent in low-grade glioma and in secondary glioblastoma. Tumor heterogeneity was also reported in molecular genetic profile, and investigators identified some subsets of astrocytomas. They investigated IHD1/2 mutation, EGFR amplification, TP53 mutation, Ki-67 index, etc. In summary, high-grade astrocytomas are not homogenous groups of tumors, and this is associated with the heterogeneity of clinical manifestation, image characteristics, and histopathological findings. Molecular studies may explain the tumor heterogeneity in the near future.

  1. Concomitant injuries are an important determinant of outcome of high-grade blunt hepatic trauma.

    Science.gov (United States)

    Schnüriger, B; Inderbitzin, D; Schafer, M; Kickuth, R; Exadaktylos, A; Candinas, D

    2009-01-01

    Little is known about the clinical importance of concomitant injuries in polytraumatized patients with high-grade blunt liver injury. A retrospective single-centre study was performed to investigate the safety of non-operative management of liver injury and the impact of concomitant intra- and extra-abdominal injuries on clinical outcome. Some 183 patients with blunt liver injury were admitted to Berne University Hospital, Switzerland, between January 2000 and December 2006. Grade 3-5 injuries were considered to be high grade. Immediate laparotomy was required by 35 patients (19.1 per cent), owing to extrahepatic intra-abdominal injury (splenic and vascular injuries, perforations) in 21 cases. The mortality rate was 16.9 per cent; 22 of the 31 deaths were due to concomitant lesions. Of 81 patients with high-grade liver injury, 63 (78 per cent) were managed without surgery; liver-related and extra-abdominal complication rates in these patients were 11 and 17 per cent respectively. Grades 4 and 5 liver injury were associated with hepatic-related and extra-abdominal complications. Concomitant injuries are a major determinant of outcome in patients with blunt hepatic injury and should be given high priority by trauma surgeons. An algorithm for the management of blunt liver injury is proposed. Copyright (c) 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  2. 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.

  3. Basic Principles of Creation of Topometrical Cards of Beam Therapy in the Cases of High-grade Malignant Supratentorial Gliomas

    International Nuclear Information System (INIS)

    Liepa, Z.; Platkajis, A.; Apskalne, D.

    2007-01-01

    Background. High-grade malignant supratentorial gliomas: anaplastic astrocytomas (AA), anaplastic oligodendrogliomas (AO), anaplastic oligoatrocitomas (AOA), anaplastic ependimomas (AE), glioblastomas (GB) and other less occasional forms of gliomas are approximately 1,82% of all cases of malignant tumors. Life expectancy for such patients still is very low, for several forms of tumors -12-18 months. High-grade malignant gliomas need for combined approach, and one part of such approach is beam therapy. For reaching qualitative results of beam therapy, method of topometrical planning of beam therapy is crucial, because it allow planning therapy due to anatomic features of every patient. The aim of work was comparison of basic principles of creation of 2-dimensional (2D) and 3-dimensional (3D) topometrical cards of beam therapy. Material and methods. In the process of research, analyse of creation of 2D and 3D cards for patients in period 2000-2005 were made. For creation of 2D cards pelviometer, conturometer of head (Picture 1), pictures of tests of brains in the biggest cross - section of tumor (Picture 2) were used. For creation 3D cards computertomography LightSpeed Rt, which is suitable for topometry (Picture 3), planning system of 3D reconstruction ECLIPSE (Picture 4), 3D reconstruction by data from pre - surgery and/or after - surgery tests of brain (Picture 5), and matching in format of DICOM (Picture 6) were used. In this research 214 patients with supratentorial malign gliomas were covered (Table 1,2). Results. In 98 cases 2D topometrical cards were made, which allows creating only two contrary areas of entry of beams or two areas of entry under angle (Picture 7, 8). In 55 cases in 2D topographic cards two contrary areas of entry were made and in 43 cases plan of beam therapy with areas of entry under angle were made. 3D cards anatomic features of patient as well as location of critical organs were taken into account (picture 10). In case of 3D the number of

  4. Shortened telomeres in serous tubal intraepithelial carcinoma: an early event in ovarian high-grade serous carcinogenesis.

    Science.gov (United States)

    Kuhn, Elisabetta; Meeker, Alan; Wang, Tian-Li; Sehdev, Ann Smith; Kurman, Robert J; Shih, Ie-Ming

    2010-06-01

    Short telomeres are one of the main genetic manifestations in human cancer, as they have been shown to play an important role in inducing chromosomal instability and in contributing to tumor progression. The purpose of this study was to determine if changes in telomere length occur in serous tubal intraepithelial carcinoma (STIC), the putative precursor of "ovarian" high-grade serous carcinoma (HGSC). Twenty-two STICs from 15 patients with concurrent but discrete HGSCs were analyzed for telomere length on formalin-fixed, paraffin-embedded sections by conducting p53 immunofluorescence to assist in identifying STICs and telomere-specific FISH. Telomere length (short, long, or no change) in STICs was compared with HGSCs using normal fallopian tube epithelium and stromal cells as controls. We found that STICs had the shortest telomeres, as 18 (82%) of 22 STICs had short telomeres, whereas only 2 (9%) showed no change and 2 (9%) had long telomeres compared with the normal-looking tubal epithelium. In contrast, among 12 paired HGSCs and STICs, 6 HGSCs showed an increase in telomere length, one showed a decrease in length and 5 did not show any change when compared with their matched STICs, although, such as STICs, the majority of HGSCs had shorter telomeres than the associated normal tubal epithelial cells. These differences in telomere length between normal tubal epithelial cells and STICs, and between STICs and HGSCs were statisticaly significant (PSTICs provides further support to the proposal that STICs are precursors of HGSC and opens new areas of research in elucidating the early events of ovarian high-grade serous carcinogenesis.

  5. Fluorescent imaging of high-grade bladder cancer using a specific antagonist for chemokine receptor CXCR4.

    Science.gov (United States)

    Nishizawa, Koji; Nishiyama, Hiroyuki; Oishi, Shinya; Tanahara, Noriko; Kotani, Hirokazu; Mikami, Yoshiki; Toda, Yoshinobu; Evans, Barry J; Peiper, Stephen C; Saito, Ryoichi; Watanabe, Jun; Fujii, Nobutaka; Ogawa, Osamu

    2010-09-01

    We previously reported that the expression of CXC chemokine receptor-4 (CXCR4) was upregulated in invasive bladder cancers and that the small peptide T140 was a highly sensitive antagonist for CXCR4. In this study, we identified that CXCR4 expression was induced in high-grade superficial bladder tumors, including carcinoma in situ and invasive bladder tumors. To visualize the bladder cancer cells using urinary sediments from the patients and chemically induced mouse bladder cancer model, a novel fluorescent CXCR4 antagonist TY14003 was developed, that is a T140 derivative. TY14003 could label bladder cancer cell lines expressing CXCR4, whereas negative-control fluorescent peptides did not label them. When labeling urinary sediments from patients with invasive bladder cancer, positive-stained cells were identified in all patients with bladder cancer and positive urine cytology but not in controls. Although white blood cells in urine were also labeled with TY14003, they could be easily discriminated from urothelial cells by their shape and size. Finally, intravesical instillation of TY14003 into mouse bladder, using N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer model, demonstrated that fluorescent signals were detected in the focal areas of bladder of all mice examined at 12 weeks of BBN drinking by confocal microscopy and fluorescent endoscopy. On the contrary, all the normal bladders were found to be negative for TY14003 staining. In conclusion, these results indicate that TY14003 is a promising diagnostic tool to visualize small or flat high-grade superficial bladder cancer.

  6. 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

  7. Non-operative management versus operative management in high-grade blunt hepatic injury.

    Science.gov (United States)

    Cirocchi, Roberto; Trastulli, Stefano; Pressi, Eleonora; Farinella, Eriberto; Avenia, Stefano; Morales Uribe, Carlos Hernando; Botero, Ana Maria; Barrera, Luis M

    2015-08-24

    Surgery used to be the treatment of choice in cases of blunt hepatic injury, but this approach gradually changed over the last two decades as increasing non-operative management (NOM) of splenic injury led to its use for hepatic injury. The improvement in critical care monitoring and computed tomographic scanning, as well as the more frequent use of interventional radiology techniques, has helped to bring about this change to non-operative management. Liver trauma ranges from a small capsular tear, without parenchymal laceration, to massive parenchymal injury with major hepatic vein/retrohepatic vena cava lesions. In 1994, the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma (AAST) revised the Hepatic Injury Scale to have a range from grade I to VI. Minor injuries (grade I or II) are the most frequent liver injuries (80% to 90% of all cases); severe injuries are grade III-V lesions; grade VI lesions are frequently incompatible with survival. In the medical literature, the majority of patients who have undergone NOM have low-grade liver injuries. The safety of NOM in high-grade liver lesions, AAST grade IV and V, remains a subject of debate as a high incidence of liver and collateral extra-abdominal complications are still described. To assess the effects of non-operative management compared to operative management in high-grade (grade III-V) blunt hepatic injury. The search for studies was run on 14 April 2014. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (Ovid), PubMed, ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), clinical trials registries, conference proceedings, and we screened reference lists. All randomised trials that compare non-operative management versus operative management in high-grade blunt hepatic injury. Two authors independently

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

    Science.gov (United States)

    Bala, Miklosh; Gazalla, Samir Abu; Faroja, Mohammad; Bloom, Allan I; Zamir, Gideon; Rivkind, Avraham I; Almogy, Gidon

    2012-03-23

    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. 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. 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. A high complication rate following high-grade liver injuries should

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

    KAUST Repository

    Li, Henan; Li, Peng; Huang, Jing Kai; Li, Ming-yang; Yang, Chih-Wen; Shi, Yumeng; Zhang, Xixiang; Li, Lain-Jong

    2016-01-01

    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

  10. 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

  11. Recurrence Patterns and Survival for Patients With Intermediate- and High-Grade Myxofibrosarcoma

    International Nuclear Information System (INIS)

    Haglund, Karl E.; Raut, Chandrajit P.; Nascimento, Alessandra F.; Wang, Qian; George, Suzanne; Baldini, Elizabeth H.

    2012-01-01

    Purpose: Myxofibrosarcoma (MFS) is a rare sarcoma with a predilection for multiple local recurrences (LR), for which optimal treatment has not been defined. We reviewed our experience to determine the impact of surgery and radiation therapy (RT) on pattern of recurrence, limb salvage, and overall survival (OS). Methods and Materials: Between 1995 and 2005, 36 patients with localized intermediate- or high-grade MFS were treated at our institution. Data on clinicopathologic features, treatments, and patient outcomes were reviewed and analyzed. Results: Median age was 72.5 years (range, 42–96 years). Median tumor size was 7.5 cm, and 34 tumors (94%) were high grade. All patients underwent surgery at our institution, including re-resections in 20 patients (56%) after initial surgery elsewhere. Margins were microscopically positive in 9 patients (25%). RT was given to 28 patients (78%) pre - and/or postoperatively. After a median follow-up of 3.5 years (range, 0.4–12.4 years), 11 patients (31%) developed LR. There were no significant predictors for LR on univariate analysis, including margin status or use of RT. Limb salvage was ultimately achieved in only 5 of 11 LRs (45%) because of multiple subsequent LRs. Distant recurrence (DR) occurred in 6 patients (17%). Median and 4-year OS were 96 months and 65%, respectively. Seven patients (19%) died of tumor-related causes, 6 of whom had DRs. On univariate analysis, tumor size was associated with OS. Conclusions: Despite aggressive surgery and RT, intermediate- and high-grade MFS are associated with a high rate of LR that adversely affects limb preservation. More aggressive local treatment strategies are necessary.

  12. 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, pinjury scale scores. Sports related trauma was more likely to be isolated without other significant injury (69% vs. 39% (psports and non-sports renal injuries (p=0.30). Sports injuries had lower transfusion (7% vs. 47%, psports vs. 18% non-sports, p=0.95). High-grade sports-related blunt renal trauma 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.

  13. Co-Testing of Cervical Screening Tests in Detection of High Grade Cervical Intraepithelial Neoplasia

    Directory of Open Access Journals (Sweden)

    Smita Asthana

    2017-10-01

    Full Text Available Introduction: Co-testing performance for detection of high grade Cervical Intraepithelial Neoplasia (CIN has not been adequately addressed from Low Resource Countries (LRCs. Where isolated tests do not have adequate performance, further explorations are recommended. Aim: To evaluate the co-testing of conventional cervical screening tests such as Papanicolaou (Pap and Visual Inspection Cervix with Acetic Acid (VIA, with care HPV on Cervical Samples (CHPV or on Vaginal Samples (VHPV in the detection of high grade CIN. Materials and Methods: The cross-sectional study was conducted on ever married women of age 30 to 59 years in a rural community of Dadri. Women were screened by CHPV, VHPV, and Pap and VIA methods. Confirmation of screen positives was done by histology. Sensitivity, Specificity and likelihood ratios of different combinations of test determined to evaluate the performance. Results: Total eligible women, 66.2% (5032/7604 responded for screening. Analysis was performed on 4658, after excluding those who did not complete all screenings. Co-testing of CHPV (OR=246 or VHPV (OR=278 with Pap had highest association. Positive likelihood ratios of CHPV and VHPV with Pap in CIN II+ detection rates were 13.0 and 11.8 and in CIN III+ the detection rates were 18.0 and 16.0 respectively. Higher sensitivities and specificities were observed in co-testing for CIN III+ detection as against CIN II+ lesions. Conclusion: Choice of co-testing in a pair of tests for detection of high grade CIN is likely to depend on whether screening is targeted for developed or low resource country. VIA in isolation might not yield optimal results for LRCs.

  14. Genetic Variants in TAP Are Associated with High-Grade Cervical Neoplasia

    Science.gov (United States)

    Einstein, Mark H.; Leanza, Suzanne; Chiu, Lydia G.; Schlecht, Nicolas F.; Goldberg, Gary L.; Steinberg, Bettie M.; Burk, Robert D.

    2018-01-01

    Purpose The transporter associated with antigen processing (TAP) is essential in assembling MHC-I proteins. Human papillomavirus (HPV) evades immune recognition by decreasing class I MHC cell surface expression through down-regulation of TAP1 levels. Consistent with heterogeneity in MHC expression is the individual variability in clearing detectable HPV infections. Genetic polymorphisms in TAP genes may affect protein structure, function, and the ability to clear HPV infection. Experimental Design Case-control study of women with cervical intraepithelial neoplasia (CIN) II or III (n = 114) and women without high-grade CIN (n = 366). Five nonsynonymous single nucleotide polymorphisms (SNP) in TAP1 and TAP2 were genotyped using DNA collected in cervicovaginal lavage samples using microsphere array technology (Luminex ×MAP). HPV typing was done using a PCR-based system with MY09/MY11 primers. TAP1 and TAP2 SNPs were validated by direct sequencing. Results Differences in allele distribution between women with high-grade cervical neoplasia and women without was seen for TAP1 I333V (P = 0.02) and TAP1 D637G (p = 0.01).The odds ratios (OR) for CIN III were significantly lower among carriers of the TAP1 I333V polymorphism (OR, 0.28; 95% confidence interval, 0.1-0.8), and TAP1 D637G polymorphism (OR, 0.27; 95% confidence interval, 0.1-0.7). These associations remained significant even after restricting the evaluation to women who were positive for high-risk HPV types. Conclusions In addition to the down-regulation of MHC-1 by oncogenic HPV, HPV pathogenesis might be facilitated by polymorphisms in the TAP proteins. Identifying TAP polymorphisms may potentially be used to identify women less susceptible to progression to high-grade CIN and cervical cancer. PMID:19188174

  15. 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.

  16. Complications of nonoperative management of high-grade blunt hepatic injuries.

    Science.gov (United States)

    Kozar, Rosemary A; Moore, John B; Niles, Sarah E; Holcomb, John B; Moore, Ernest E; Cothren, C Clay; Hartwell, Elizabeth; Moore, Frederick A

    2005-11-01

    Nonoperative management of blunt hepatic injuries is highly successful. Complications associated with high-grade injuries, however, have not been well characterized. The purpose of the present study was therefore to define hepatic-related complications and associated treatment modalities in patients undergoing nonoperative management of high-grade blunt hepatic injuries. Three hundred thirty-seven patients from two regional Level I trauma centers with grade 3 to 5 blunt hepatic injuries during a 40-month period were reviewed. Complications and treatment of hepatic-related complications in patients not requiring laparotomy in the first 24 hours were identified. Of 337 patients with a grade 3 to 5 injury, 230 (68%) were managed nonoperatively. There were 37 hepatic-related complications in 25 patients (11%); 63% (5 of 8) of patients with grade 5 injuries developed complications, 21% (19 of 92) of patients with grade 4 injuries, but only 1% (1 of 130) of patients with grade 3 injuries. Complications included bleeding in 13 patients managed by angioembolization (n = 12) and laparotomy (n = 1), liver abscesses in 2 patients managed with computed tomography-guided drainage (n = 2) and subsequent laparotomy (n = 1). In one patient with bleeding, hepatic necrosis followed surgical ligation of the right hepatic artery and required delayed hepatic lobectomy. Sixteen biliary complications were managed with endoscopic retrograde cholangiopancreatography and stenting (n = 7), drainage (n = 5), and laparoscopy (n = 4). Three patients had suspected abdominal sepsis and underwent a negative laparotomy, whereas an additional three patients underwent laparotomy for abdominal compartment syndrome. Nonoperative management of high-grade liver injuries can be safely accomplished. Mortality is low; however, complications in grade 4 and 5 injuries should be anticipated and may require a combination of operative and nonoperative management strategies.

  17. Radiation dose estimates from a mining plan for a high-grade uranium deposit

    International Nuclear Information System (INIS)

    Scott, L.M.

    1981-01-01

    The significance of gamma exposure to uranium miners has been recognized only in the last few years. Most ore deposits which have been underground mined, were 1% or less U 3 O 8 . Full-time mining of this grade ore can result in exposure exceeding 1 Rem per year. Several companies in Saskatchewan are planning to mine recently discovered ore bodies which contain ore pods in excess of 10% U 3 O 8 . The purpose of this paper is to present dose data which can be used to estimate gamma exposure from high-grade ore deposits, and to present mining techniques which will minimize miner exposure

  18. EG-01EPIGENETIC INACTIVATION OF ARGININE BIOSYNTHESIS PATHWAY IN PAEDIATRIC HIGH GRADE GLIOMA

    Science.gov (United States)

    Channathodiyil, Prasanna; Kardooni, Hoda; Khozoie, Combiz; Nelofer, Syed; Darling, John; Morris, Mark; Warr, Tracy

    2014-01-01

    Aberrant cellular metabolism contributes significantly to the growth and proliferation of several tumour types. Identification of genes that control critical metabolic pathways is a major factor in the development of novel therapies that target metabolic defects in tumour cells. Our aim is to identify such genes in paediatric high grade glioma that are altered due to promoter hyper-methylation of cytosine residues in CpG dinucleotides. Genome wide DNA methylation profiling using Illumina infinium methylation 450K bead chip array was performed on 18 well-characterised short term cultures derived from paediatric high grade astrocytoma including 3 from diffuse intrinsic pontine glioma. Data analyses were based on beta scores of probes for each gene as measures of intensities of methylation. Genes were selected with beta scores of tumour > =0.70 and that of normal human astrocytes < =0.30. We identified that two vital genes involved in the regulation of arginine biosynthetic pathway, argininosuccinate synthetase 1(ASS1) and argininosuccinate lyase (ASL) were methylated in 9/18 (50%) cases. Hyper methylation was confirmed by methylation-specific PCR and up-regulation of gene expression following treatment with 2 µM 5-aza-2'-deoxyctidine. Down-regulation of ASS1 in hyper methylated samples was confirmed by Western blot analysis. Our findings report epigenetic deregulation of ASS1 and ASL in a subset of paediatric high grade glioma. The enzymes encoded by these genes are essential elements of urea cycle that function together in the de novo synthesis of arginine from citrulline. Tumour cells with deficient ASS1/ASL depend on external sources of arginine for survival and have been reported to be sensitive to autophagic cell death induced by arginine starvation. Therefore, further investigation may render the possibility of arginine-deprivation therapy in such sub type of paediatric high grade glioma. This therapeutic approach is of interest as tumour cells with abnormal

  19. Reirradiation and lomustine in patients with relapsed high-grade gliomas

    International Nuclear Information System (INIS)

    Arcicasa, Mauro; Roncadin, Mario; Bidoli, Ettore; Dedkov, Anatolyi; Gigante, Marco; Trovo, Mauro G.

    1999-01-01

    Purpose: The aim of this study was to evaluate the toxicity, response, and survival of patients with relapsed high-grade gliomas after radiation therapy (RT) combined with lomustine (CCNU). Methods and Materials: Thirty-one patients with relapsed gliomas at least 6 months after completion of RT were reirradiated. Twenty-four patients had a pathological diagnosis of high-grade gliomas, whereas 7 had a radiological diagnosis of relapsed malignant gliomas. The study focused on patients with high-grade relapsed gliomas. A total dose of 34.5 Gy was delivered in 23 fractions over 4.5 weeks. Oral administration of CCNU (130 mg/m 2 ) was begun at the same time as RT, and was repeated every 6 weeks until disease progression, or up to 12 courses. Results: Twelve of 24 patients had surgery before RT plus CCNU treatment. Median interval between RT courses was 14 months (range 6-73). All patients received a complete course of RT, and 22 of 24 patients received at least one course of CCNU. Objective responses were seen in 14 evaluable patients: 3 with partial response, 5 with stable disease, and 6 with progressive disease. Duration of partial response was 20, 9, and 8 months. Median time to progression and overall survival from the onset of retreatment were 8.4 months (range 1-22) and 13.7 months (range 1-63+), respectively. One case of G4 thrombocytopenia was observed. Five patients had G1 or G2 leucopenia and 3 patients had G3 leucopenia. Moderate nausea and vomiting were reported in 4 patients. One patient, after one course of CCNU, refused further chemotherapy. No significant difference in survival from relapse was found between patients who underwent surgery before RT plus CCNU and those who received only RT plus CCNU (p = 0.74). Conclusion: Overall, the acute toxicity was moderate, and patient compliance was good. Reirradiation of high-grade glioma was associated with modest subjective and objective response rates. It is remarkable that median overall survival from relapse

  20. 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 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 supports the hypothesis that lycopene may inhibit progression of

  1. Permanent I-125 interstitial implant in the management of high grade CNS malignancies in children

    International Nuclear Information System (INIS)

    Vaishampayan, N.; Zamorano, L.; Aronin, P.; Gaspar, L.; Canady, A.; Lattin, P.; Ezzell, G.; Yakar, D.; Chungbin, S.; Fontanesi, J.

    1996-01-01

    Purpose/Objective: To evaluate the efficacy and complications associated with the use of permanent I-125 interstitial implants in children with high grade CNS malignancies. Materials and Methods: Between May of 1990 and September of 1994, fourteen children received permanent I-125 interstitial implant brachytherapy as initial therapy (n=8) or at time of recurrence (n=6). Histologies included Glioblastoma Multiforme (n=2), Anaplastic Astrocytoma (n=9) and others (n=3). Pre-implant surgical procedures included: Gross Total Resection (n=2), Subtotal Resection (n=8) or Biopsy alone (n=4). Six patients received pre-implant external beam irradiation (dose range 3,500-6500 cGy) and three patients received post-implant external beam irradiation (dose range 5,040-5,060 cGy). Implant dose range was 8,294-10,368 cGy over the lifetime of the implant (median 10,368 cGy). Results: At last follow-up (median 17.5 months; range 4-56 months), eight children were alive. Six out of the eight had no evidence of disease progression while the remaining had radiologic evidence of progression. Implant complications (n=2) included skin necrosis and bone flap infection. Conclusions: Based on this initial review, we continue to investigate the use of permanent I-125 interstitial brachytherapy in the treatment of high grade CNS malignancies in children and will discuss and compare these results with those of other 'Boost' series

  2. Novel therapies for high-grade gliomas: A vision for future

    Directory of Open Access Journals (Sweden)

    Vivek Tandon

    2012-01-01

    Full Text Available The treatment for high-grade glioma remains an enigma. The standard treatment using surgery, radiation therapy and chemotherapy for such highly malignant lesions has only yielded modest results, in terms of survival and improving the quality of life of patients. Less than 10% of such patients survive beyond two years. All conventional therapies have failed to increase the survival beyond this extent. There has been a growing interest in the molecular approaches for the treatment of high-grade gliomas which include gene therapy, oncolytic virotherapy, and immunotherapy. These new therapies are in preclinical and investigational stages. They may not substitute the conventional therapies; they may not be the ultimate elixir for this deadly disease. However, in the coming years, they are likely to have synergistic and complimentary roles alongside conventional therapies. Through this paper, we have attempted to highlight the rationale behind gene therapy which can be used for cytotoxic approaches, immunomodulation strategy, and targeted toxin delivery in the tumor cell. We have reviewed current available literature and through this paper focus on reporting such therapeutic options, their potential usage, benefits and limitations.

  3. Utility of intraoperative diagnostic C-arm angiography for management of high grade subarachnoid hemorrhage

    Directory of Open Access Journals (Sweden)

    Zhikui Wei

    2015-06-01

    Full Text Available The accurate and efficient localization of underlying vascular lesions is crucial for prompt and definitive treatment of subarachnoid hemorrhage (SAH. To demonstrate the utility and feasibility of intraoperative C-arm angiography in cerebrovascular emergencies, we report five cases of high grade SAH and/or intracerebral hemorrhage (ICH where intraoperative diagnostic C-arm angiography was safely and effectively utilized. Initial evaluations of all patients included a non-contrast head CT scan, which was followed by urgent decompressive hemicraniectomy as a life-saving measure in the presence of markedly elevated intracranial pressure. Further diagnostic evaluations were performed intraoperatively using a multi-purpose C-arm angiography system. The C-arm angiography findings greatly aided the intraoperative planning and led to definitive treatments in four cases of SAH by elucidating the underlying neurovascular lesions. With this treatment strategy, two of the patients made moderately good recoveries from their SAH and/or ICH with a Glasgow outcome score (GOS of 4. Three of the patients expired despite maximal therapy mostly due to unfavorable presenting grade. These results suggest that C-arm angiography is a reasonable diagnostic and surgical planning tool for selected patients with high grade diffuse SAH who require immediate decompression.

  4. 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

    2018-05-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Effect of smoking on high-grade cervical cancer in women on the basis of human papillomavirus infection studies

    Directory of Open Access Journals (Sweden)

    Jian-Hong Fang

    2018-01-01

    Conclusion: We concluded here that smoking leads to an enhanced risk of high-grade cervical lesions in persistent high-risk HPV-infected women. This makes a good understanding of smoking's role in cervical cancer.

  8. 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

  9. Performance of visual inspection with acetic acid and human papillomavirus testing for detection of high-grade cervical lesions in HIV positive and HIV negative Tanzanian women

    DEFF Research Database (Denmark)

    Dartell, Myassa Arkam; Rasch, Vibeke; Iftner, Thomas

    2014-01-01

    The aim of this cross sectional study was to assess type distribution of human papillomavirus (HPV) among HIV positive and HIV negative women who underwent cervical cancer screening, and to examine the ability of visual inspection with acetic acid (VIA), the standard detection method in Tanzania......, and HPV-testing to detect cytologically diagnosed high grade lesions or cancer (HSIL+). Women from different areas in Tanzania were invited by public announcement to cervical cancer screening organized by Ocean Road Cancer Institute (Dar-es-Salaam). A total of 3,767 women were enrolled. Women underwent...

  10. Long-term data set of small mammals from owl pellets in the Atlantic-Mediterranean transition area.

    Science.gov (United States)

    Escribano, Nora; Galicia, David; Ariño, Arturo H; Escala, Carmen

    2016-09-27

    We describe the pellet sampling data set from the Vertebrate Collection of the Museum of Zoology of the University of Navarra. This data set compiles all information about small mammals obtained from the analysis of owl pellets. The collection consists on skulls, mandibles, and some skeletons of 36 species of more than 72,000 georeferenced specimens. These specimens come from the Iberian Peninsula although most samples were collected in Navarra, a highly diverse transitional area of 10,000 kilometre square sitting across three biogeographical regions. The collection spans more than forty years and is still growing as a result of the establishment of a barn owl pellet monitoring network in 2015. The program will provide critical information about the evolution of the small mammals' community in this transition zone as it changes over time.

  11. Prevalence of Human Papillomavirus Genotypes Among Women With High-Grade Cervical Lesions in Beijing, China

    Science.gov (United States)

    Xiao, Meizhu; Xu, Qiuxiang; Li, Hongyan; Gao, Huiqiao; Bie, Yachun; Zhang, Zhenyu

    2016-01-01

    Abstract The aim of the study is to investigate the prevalence of high-risk human papillomavirus (hr-HPV) genotypes among Han women with high-grade cervical lesions in Beijing, China. Cervical cell specimens from patients with histopathologically confirmed cervical lesions at 7 hospitals in Beijing were examined with a validated HPV kit for 13 hr-HPV genotypes during the study period. The patients were divided into a low-grade cervical lesions group (cervical intraepithelial neoplasia grade 1, CIN1) and a high-grade cervical lesions group (CIN2+, including cervical intraepithelial neoplasia grade 2, CIN2; cervical intraepithelial neoplasia grade 3, CIN3; squamous cervical cancer, SCC; and adenocarcinoma of the cervix, ACC) based on the histopathology results. A total of 2817 eligible patients were enrolled, including 610 cases identified as CIN1 and 2207 as CIN2+. The hr-HPV positive rates in the CIN1 and CIN2+ groups were 78.2% (477/610) and 93.3% (2060/2207), respectively. The most frequently detected genotypes were HPV16, 58, 52 and18 in the CIN1 group and HPV16, 58, 33, and 52 in the CIN2+ group, in descending order of prevalence. In addition, the prevalence of HPV18 among the patients with ACC was 28.6% (14/49), significantly >7.2% (54/752) prevalence among the SCC patients (P HPV infections gradually deceased to 44.2% in the CIN2 patients, 36.7% in the CIN3 patients, and 35.3% in the cervical cancer (CC) patients, which included SCC and ACC patients. In cases of multiple hr-HPV infections in the CIN2+ group, double infections accounted for ∼76.6%, and HPV16+58, HPV16+52, and HPV16+18 were the most common combinations, in descending order. The most frequent combination for triple infections was HPV16+58+31, with a rate of 4.2%. The highest positive rate occurred in the ≤24 year-old group for all types of cervical lesions. The prevalence of HPV genotypes in the targeted population with high-grade cervical lesions differs from that of other countries. This

  12. High-grade and low-grade gliomas: differentiation by using perfusion MR imaging

    International Nuclear Information System (INIS)

    Hakyemez, B.; Erdogan, C.; Ercan, I.; Ergin, N.; Uysal, S.; Atahan, S.

    2005-01-01

    AIM: Relative cerebral blood volume (rCBV) is a commonly used perfusion magnetic resonance imaging (MRI) technique for the evaluation of tumour grade. Relative cerebral blood flow (rCBF) has been less studied. The goal of our study was to determine the usefulness of these parameters in evaluating the histopathological grade of the cerebral gliomas. METHODS: This study involved 33 patients (22 high-grade and 11 low-grade glioma cases). MRI was performed for all tumours by using a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence followed by conventional MRI. The rCBV and rCBF were calculated by deconvolution of an arterial input function. The rCBV and rCBF ratios of the lesions were obtained by dividing the values obtained from the normal white matter of the contralateral hemisphere. For statistical analysis Mann-Whitney testing was carried out. A p value of less than 0.05 indicated a statistically significant difference. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBV and rCBF ratios and grade of gliomas. Their cut-off value permitting discrimination was calculated. The correlation between rCBV and CBF ratios and glioma grade was assessed using Pearson correlation analysis. RESULTS: In high-grade gliomas, rCBV and rCBF ratios were measured as 6.50±4.29 and 3.32±1.87 (mean±SD), respectively. In low-grade gliomas, rCBV and rCBF ratios were 1.69±0.51 and 1.16±0.38, respectively. The rCBV and rCBF ratios for high-grade gliomas were statistically different from those of low-grade gliomas (p 0.05). The cut-off value was taken as 1.98 in the rCBV ratio and 1.25 in the rCBF ratio. There was a strong correlation between the rCBV and CBF ratios (Pearson correlation = 0.830, p<0.05). CONCLUSION: Perfusion MRI is useful in the preoperative assessment of the histopathologicalal grade of gliomas; the rCBF ratio in addition to the rCBV ratio can be incorporated

  13. Return-to-activity after anatomical reconstruction of acute high-grade acromioclavicular separation.

    Science.gov (United States)

    Saier, T; Plath, J E; Beitzel, K; Minzlaff, P; Feucht, J M; Reuter, S; Martetschläger, F; Imhoff, Andreas B; Aboalata, M; Braun, S

    2016-04-02

    To evaluate return-to-activity (RtA) after anatomical reconstruction of acute high-grade acromioclavicular joint (ACJ) separation. A total of 42 patients with anatomical reconstruction of acute high-grade ACJ-separation (Rockwood Type V) were surveyed to determine RtA at a mean 31 months follow-up (f-u). Sports disciplines, intensity, level of competition, participation in overhead and/or contact sports, as well as activity scales (DASH-Sport-Module, Tegner Activity Scale) were evaluated. Functional outcome evaluation included Constant score and QuickDASH. All patients (42/42) participated in sporting activities at f-u. Neither participation in overhead/contact sports, nor level of activity declined significantly (n.s.). 62 % (n = 26) of patients reported subjective sports specific ACJ integrity to be at least the same as prior to the trauma. Sporting intensity (hours/week: 7.3 h to 5.4 h, p = .004) and level of competition (p = .02) were reduced. If activity changed, in 50 % other reasons but clinical symptoms/impairment were named for modified behavior. QuickDASH (mean 6, range 0-54, SD 11) and DASH-Sport-Module (mean 6, range 0-56, SD 13) revealed only minor disabilities at f-u. Over time Constant score improved significant to an excellent score (mean 94, range 86-100, SD 4; p < .001). Functional outcome was not correlated with RtA (n.s.). All patients participated in sporting activities after anatomical reconstruction of high-grade (Rockwood Type V) ACJ-separation. With a high functional outcome there was no significant change in activity level (Tegner) and participation in overhead and/or contact sports observed. There was no correlation between functional outcome and RtA. Limiting, there were alterations in time spent for sporting activities and level of competition observed. But in 50 % those were not related to ACJ symptoms/impairment. Unrelated to successful re-established integrity and function of the ACJ it should be considered that

  14. Recurrent respiratory papillomatosis: HPV genotypes and risk of high-grade laryngeal neoplasia.

    Directory of Open Access Journals (Sweden)

    Turid Omland

    Full Text Available Patients with recurrent respiratory papillomatosis (RRP in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma. High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR = 2.35, 95% CI 1.1, 4.99, as well as respiratory tract carcinomas (RR = 48, 95% CI 10.72, 214.91. In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract.

  15. 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

  16. 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.

  17. Segmentation of solid subregion of high grade gliomas in MRI images based on active contour model (ACM)

    Science.gov (United States)

    Seow, P.; Win, M. T.; Wong, J. H. D.; Abdullah, N. A.; Ramli, N.

    2016-03-01

    Gliomas are tumours arising from the interstitial tissue of the brain which are heterogeneous, infiltrative and possess ill-defined borders. Tumour subregions (e.g. solid enhancing part, edema and necrosis) are often used for tumour characterisation. Tumour demarcation into substructures facilitates glioma staging and provides essential information. Manual segmentation had several drawbacks that include laborious, time consuming, subjected to intra and inter-rater variability and hindered by diversity in the appearance of tumour tissues. In this work, active contour model (ACM) was used to segment the solid enhancing subregion of the tumour. 2D brain image acquisition data using 3T MRI fast spoiled gradient echo sequence in post gadolinium of four histologically proven high-grade glioma patients were obtained. Preprocessing of the images which includes subtraction and skull stripping were performed and then followed by ACM segmentation. The results of the automatic segmentation method were compared against the manual delineation of the tumour by a trainee radiologist. Both results were further validated by an experienced neuroradiologist and a brief quantitative evaluations (pixel area and difference ratio) were performed. Preliminary results of the clinical data showed the potential of ACM model in the application of fast and large scale tumour segmentation in medical imaging.

  18. Segmentation of solid subregion of high grade gliomas in MRI images based on active contour model (ACM)

    International Nuclear Information System (INIS)

    Seow, P; Win, M T; Wong, J H D; Ramli, N; Abdullah, N A

    2016-01-01

    Gliomas are tumours arising from the interstitial tissue of the brain which are heterogeneous, infiltrative and possess ill-defined borders. Tumour subregions (e.g. solid enhancing part, edema and necrosis) are often used for tumour characterisation. Tumour demarcation into substructures facilitates glioma staging and provides essential information. Manual segmentation had several drawbacks that include laborious, time consuming, subjected to intra and inter-rater variability and hindered by diversity in the appearance of tumour tissues. In this work, active contour model (ACM) was used to segment the solid enhancing subregion of the tumour. 2D brain image acquisition data using 3T MRI fast spoiled gradient echo sequence in post gadolinium of four histologically proven high-grade glioma patients were obtained. Preprocessing of the images which includes subtraction and skull stripping were performed and then followed by ACM segmentation. The results of the automatic segmentation method were compared against the manual delineation of the tumour by a trainee radiologist. Both results were further validated by an experienced neuroradiologist and a brief quantitative evaluations (pixel area and difference ratio) were performed. Preliminary results of the clinical data showed the potential of ACM model in the application of fast and large scale tumour segmentation in medical imaging. (paper)

  19. Evidence for a dualistic model of high-grade serous carcinoma: BRCA mutation status, histology, and tubal intraepithelial carcinoma.

    Science.gov (United States)

    Howitt, Brooke E; Hanamornroongruang, Suchanan; Lin, Douglas I; Conner, James E; Schulte, Stephanie; Horowitz, Neil; Crum, Christopher P; Meserve, Emily E

    2015-03-01

    Most early adnexal carcinomas detected in asymptomatic women with germline BRCA mutations (BRCA) present as serous tubal intraepithelial carcinomas (STIC). However, STICs are found in only ∼40% of symptomatic high-grade serous carcinomas (HGSCs) and less frequently in pseudoendometrioid variants of HGSC. Consecutive cases of untreated HGSC from BRCA and BRCA women with detailed fallopian tube examination (SEE-FIM protocol) were compared. STIC status (+/-) was determined, and tumors were classified morphologically as SET ("SET", >50% solid, pseudoendometrioid, or transitional) or classic predominate ("Classic"). SET tumors trended toward a higher frequency in BRCA versus BRCA women (50% vs. 28%, P=0.11), had a significantly younger mean age than those with classic HGSC in BRCA women (mean 56.2 vs. 64.8 y, P=0.04), and displayed a better clinical outcome in both groups combined (P=0.024). STIC was significantly more frequent in tumors from the BRCA cohort (66% vs. 31%, P=0.017) and specifically the BRCA tumors with classic morphology (83%) versus those with SET morphology (22%, P=0.003). Overall, several covariables-histology, BRCA status, age, coexisting STIC, and response to therapy-define 2 categories of HGSC with differences in precursor (STIC) frequency, morphology, and outcome. We introduce a dualistic HGSC model that could shed light on the differences in frequency of STIC between symptomatic and asymptomatic women with HGSC. This model emphasizes the need for further study of HGSC precursors to determine their relevance to the prevention of this lethal malignancy.

  20. Composition and Redox Potential of High-Grade Fluids: An Example from the Nilgiri Block, Southern India

    Science.gov (United States)

    Samuel, V. O.; Harlov, D. E.; Kwon, S.

    2017-12-01

    Composition and redox potential of fluids present during high-grade metamorphism exert an enormous influence on mineral textures and their regional trends within metamorphic complexes. We examine silicate, oxide, and sulfide trends in the Nilgiri Block, southern India. This terrain formed through subduction-related arc magmatic processes in the Neoarchean (ca. 2500 Ma). The Nilgiri highlands are characterized by granulite-facies metagabbro in the north, a two-pyroxene granulite transition zone, and tonalitic-granodioritic charnockites in the central and southern part. Garnet-orthopyroxene and orthopyroxene-clinopyroxene thermometry and garnet-orthopyroxene-plagioclase-quartz barometric results indicate a regional trend both in temperature ( 650 to 800 °C) and in pressure (700 to 1100 MPa) from SW to NE across the Nilgiri highlands. Regional trends are also seen in the oxide-sulfide mineralogy. The main oxide assemblage in the charnockites is rutile-ilmenite, whereas in the two-pyroxene granulites and metagabbros, hemo-ilmenite-magnetite dominates. The key sulfide mineral in the charnockites is pyrrhotite, with minor chalcopyrite. In the two-pyroxene granulites and metagabbros, the principle sulfide assemblage is pyrite +/- minor pyrrhotite. This reveals a regional oxidation trend. The metagabbros and two-pyroxene granulites are highly oxidized compared to the charnockites. Their higher oxidation state is proposed to be the result of highly oxidizing agents (probably as SO2) in low H2O activity fluids (most likely concentrated NaCl brines) during granulite-facies metamorphism of the metagabbros and two-pyroxene granulites. These agents were considerably more reducing (possibly as H2S) during granulite-facies metamorphism of the charnockites. This study emphasizes the potential role of oxidizing and reducing, low H2O activity fluids during granulite-facies metamorphism.

  1. Determinants of Transitional Zone Area and Porosity of the Proximal Femur Quantified In Vivo in Postmenopausal Women.

    Science.gov (United States)

    Shigdel, Rajesh; Osima, Marit; Lukic, Marko; Ahmed, Luai A; Joakimsen, Ragnar M; Eriksen, Erik F; Bjørnerem, Åshild

    2016-04-01

    Bone architecture as well as size and shape is important for bone strength and risk of fracture. Most bone loss is cortical and occurs by trabecularization of the inner part of the cortex. We therefore wanted to identify determinants of the bone architecture, especially the area and porosity of the transitional zone, an inner cortical region with a large surface/matrix volume available for intracortical remodeling. In 211 postmenopausal women aged 54 to 94 years with nonvertebral fractures and 232 controls from the Tromsø Study, Norway, we quantified femoral subtrochanteric architecture in CT images using StrAx1.0 software, and serum levels of bone turnover markers (BTM, procollagen type I N-terminal propeptide and C-terminal cross-linking telopeptide of type I collagen). Multivariable linear and logistic regression analyses were used to quantify associations of age, weight, height, and bone size with bone architecture and BTM, and odds ratio (OR) for fracture. Increasing age, height, and larger total cross-sectional area (TCSA) were associated with larger transitional zone CSA and transitional zone CSA/TCSA (standardized coefficients [STB] = 0.11 to 0.80, p ≤ 0.05). Increasing weight was associated with larger TCSA, but smaller transitional zone CSA/TCSA and thicker cortices (STB = 0.15 to 0.22, p zone (STB = 0.12 to 0.46, p zone CSA/TCSA, and higher porosity of each of the cortical compartments (p zone CSA and higher porosity than controls (p zone, OR for fracture was 1.71 (95% CI, 1.37 to 2.14) and 1.51 (95% CI, 1.23 to 1.85), respectively. Cortical bone architecture is determined mainly by bone size as built during growth and is modified by lifestyle factors throughout life through bone turnover. Fracture cases exhibited larger transitional zone area and porosity, highlighting the importance of cortical bone architecture for fracture propensity. © 2015 American Society for Bone and Mineral Research.

  2. Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia.

    Science.gov (United States)

    Montironi, Rodolfo; Thompson, Deborah; Scarpelli, Marina; Mazzucchelli, Roberta; Peketi, Prasanthi; Hamilton, Peter W; Bostwick, David G; Bartels, Peter H

    2004-08-01

    This digital texture analysis-based study evaluates the chromatin organization state in flat and cribriform high-grade prostatic intraepithelial neoplasia (PIN), in the adjacent normal looking secretory epithelium and in the co-occurring adenocarcinoma. Digital texture analysis (karyometry) was carried out on hematoxylin and eosin-stained sections from 24 radical prostatectomy specimens with high-grade PIN (12 with flat and 12 with cribriform architectural pattern, respectively) and cancer. Quantification was also conducted on the normal looking secretory epithelium. Discriminant analysis and the nonsupervised learning algorithm P-index were used to identify suitable subsets of features useful for the discrimination and classification of pathological groups and to explore multivariate data structure in the pathological subgroups. The average nuclear abnormality increases monotonically from the histologically normal appearing secretory epithelium to high-grade PIN and to adenocarcinoma. The nuclei from the so-called perimeter compartment of the flat high-grade PIN lesions show a higher nuclear abnormality compared to the nuclei of the cribriform high-grade PINs. Discriminant analysis shows that flat and cribriform high-grade PINs fall into two populations. Processing by the nonsupervised learning algorithm P-index revealed the existence of three well-defined, distinct subpopulations of nuclei of different chromatin phenotype. In the flat high-grade PIN lesions the proportions of nuclei in the three subpopulations are 16.5% (low abnormality), 25.0% (mid abnormality) and 58.5% (high abnormality), respectively. In the cribriform high-grade PIN lesions, 100% of the nuclei are in the mid-abnormality subpopulation. These differences are also discernible in the co-occurring adenocarcinoma and the histologically normal appearing secretory epithelium. To conclude, karyometry and statistical analysis detect the existence of distinct cell subpopulations of different chromatin

  3. 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).

  4. Adenoid cystic carcinoma of the breast, high grade with basal phenotype, literature review

    Directory of Open Access Journals (Sweden)

    Enaam Junainah

    Full Text Available Adenoid cystic carcinoma (ACC is a rare type of breast carcinoma resembling adenoid cystic carcinoma of other sites. this type of tumors usually characterized by the exhibiting dual cell population of luminal and basaloid with specific growth pattern Most of these sub types are triple-negative with basal-like breast features (tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers, they are usually low-grade but can be high grade, clinical behavior is indolent despite the nuclear grade, lymph node involvement or distant metastases which is rarely occur. Treatment is either simple mastectomy or lumpectomy. Chemotherapy, radiation and hormonal treatment have limited used in those cases. Keywords: Adenoid cystic carcinoma, Breast, Triple-negative and basal-like phenotype

  5. 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

    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......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...

  6. 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

    standard formulas, while comparisons between groups were performed using the Wilcoxon Rank Sum, Kruskal-Wallis, Chi-Square, and Fisher's exact test. RESULTS: GS as assigned by standard 10-12 core biopsies was 3 + 3 in 90 (29.4%), 3 + 4 in 122 (39.8%), 4 + 3 in 50 (16.3%), and > 4 + 3 in 44 (14.4%) patients....... CONCLUSIONS: This plasma/urine biomarker test accurately predicts high grade cancer as determined by prostatectomy with a sensitivity at 92-97%, while the sensitivity of core biopsies was 78%....... 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...

  7. Precursor lesions of high-grade serous ovarian carcinoma: morphological and molecular characteristics.

    Science.gov (United States)

    Gross, Amy L; Kurman, Robert J; Vang, Russell; Shih, Ie-Ming; Visvanathan, Kala

    2010-01-01

    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).

  8. 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.

  9. High Grade Glioma Mimicking Voltage Gated Potassium Channel Complex Associated Antibody Limbic Encephalitis

    Directory of Open Access Journals (Sweden)

    Dilan Athauda

    2014-01-01

    Full Text Available Though raised titres of voltage gated potassium channel (VGKC complex antibodies have been occasionally associated with extracranial tumours, mainly presenting as Morvan's Syndrome or neuromyotonia, they have not yet been reported to be associated with an intracranial malignancy. This is especially important as misdiagnosis of these conditions and delay of the appropriate treatment can have important prognostic implications. We describe a patient with a high grade glioma presenting with clinical, radiological, and serological features consistent with the diagnosis of VGKC antibody associated limbic encephalitis (LE. This is the first association between a primary brain tumour and high titre of VGKC complex antibodies. Clinicoradiological progression despite effective immunosuppressive treatment should prompt clinicians to look for alternative diagnoses. Further studies to elucidate a possible association between VGKC complex and other surface antigen antibodies with primary brain tumours should be carried out.

  10. [High-grade small bowel angiosarcoma associated with angiosarcomatosis: a case report].

    Science.gov (United States)

    Chahbouni, Sanae; Barnoud, Raphaëlle; Watkin, Emmanuel; Devouassoux-Shisheboran, Mojgan

    2011-08-01

    Angiosarcoma is a rare soft-tissue neoplasm occurring most often in the skin and the subcutaneous tissues and very rarely in the gastrointestinal tract. We report a case of a 25-year-old woman who presented with a small intestinal angiosarcoma associated with angiosarcomatosis. The diagnosis was established on surgical intestinal resection, that showed a high-grade angiosarcoma with epithelioid component and foci of agressive form of hemangioendothelioma. Immunohistochemical study revealed tumour cell positivity with endothelial markers CD31 and factor VIII whereas CD34 and epithelial markers were negative. The tumour displayed KIT (CD117) immunoreactivity without KIT or PDGFRA mutation on molecular analysis. Clinical and pathological features as well as differential diagnosis of this rare entity in gastrointestinal tract are discussed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  11. Isotopic evidence for two neoproterozoic high-grade metamorphic events in the Brazilia belt

    International Nuclear Information System (INIS)

    Pimentel, Marcio Martins; Fuck, Reinhardt Adolfo; Piuzanna, Danielle; Moraes, Renato de; Gioia, Simone Maria C.L

    2001-01-01

    The Brasilia Belt is part of a Brasiliano/Pan African orogen developed between the Amazon and Sao Francisco cratons. The stabilization of the belt occurred after the last metamorphic event at ca. 620 Ma. There has been increasing geochronological evidence, however, for an older Neoproterozoic metamorphic event at ca. 780 Ma, observed mainly in high grade rocks of three large mafic-ultramafic complexes in the northern part of the belt. In this study we present: (i) new U-Pb and Sm-Nd geochronological data, (ii) a review of the existing metamorphic ages in the Brasilia Belt, and (iii) a discussion on the tectonic model to explain the two Neoproterozoic metamorphic ages (au)

  12. An Overview of Fotemustine in High-Grade Gliomas: From Single Agent to Association with Bevacizumab

    Directory of Open Access Journals (Sweden)

    Giuseppe Lombardi

    2014-01-01

    Full Text Available Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas.

  13. An overview of fotemustine in high-grade gliomas: from single agent to association with bevacizumab.

    Science.gov (United States)

    Lombardi, Giuseppe; Farina, Patrizia; Della Puppa, Alessandro; Cecchin, Diego; Pambuku, Ardi; Bellu, Luisa; Zagonel, Vittorina

    2014-01-01

    Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas.

  14. 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.

  15. Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas

    DEFF Research Database (Denmark)

    Galleberg, R B; Knigge, U; Tiensuu Janson, E

    2017-01-01

    Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce......., particularly for the group with a Ki-67 in the relatively lower G3 range. Our findings indicate a possible role for surgical treatment of liver metastases in the management of this patient population.......Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce....... The aim of this study was to evaluate the results of curatively intended resection/radiofrequency ablation (RFA) of liver metastases in patients with metastatic GEP-NEC. Methods: 32 patients with a diagnosis of high-grade gastroenteropancreatic neuroendocrine neoplasm (Ki-67 > 20%) and with intended...

  16. High grade glioma mimicking voltage gated potassium channel complex associated antibody limbic encephalitis.

    Science.gov (United States)

    Athauda, Dilan; Delamont, R S; Pablo-Fernandez, E De

    2014-01-01

    Though raised titres of voltage gated potassium channel (VGKC) complex antibodies have been occasionally associated with extracranial tumours, mainly presenting as Morvan's Syndrome or neuromyotonia, they have not yet been reported to be associated with an intracranial malignancy. This is especially important as misdiagnosis of these conditions and delay of the appropriate treatment can have important prognostic implications. We describe a patient with a high grade glioma presenting with clinical, radiological, and serological features consistent with the diagnosis of VGKC antibody associated limbic encephalitis (LE). This is the first association between a primary brain tumour and high titre of VGKC complex antibodies. Clinicoradiological progression despite effective immunosuppressive treatment should prompt clinicians to look for alternative diagnoses. Further studies to elucidate a possible association between VGKC complex and other surface antigen antibodies with primary brain tumours should be carried out.

  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. 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.

  19. ADC texture—An imaging biomarker for high-grade glioma?

    Energy Technology Data Exchange (ETDEWEB)

    Brynolfsson, Patrik; Hauksson, Jón; Karlsson, Mikael; Garpebring, Anders; Nyholm, Tufve, E-mail: tufve.nyholm@radfys.umu.se [Department of Radiation Sciences, Radiation Physics, Umeå University, Umeå SE-901 87 (Sweden); Nilsson, David; Trygg, Johan [Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, Umeå SE-901 87 (Sweden); Henriksson, Roger [Department of Radiation Sciences, Oncology, Umeå University, Umeå SE-901 87, Sweden and Regionalt Cancercentrum Stockholm, Karolinska Universitetssjukhuset, Solna, Stockholm SE-102 39 (Sweden); Birgander, Richard [Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå SE-901 87 (Sweden); Asklund, Thomas [Department of Radiation Sciences, Oncology, Umeå University, Umeå SE-901 87 (Sweden)

    2014-10-15

    Purpose: Survival for high-grade gliomas is poor, at least partly explained by intratumoral heterogeneity contributing to treatment resistance. Radiological evaluation of treatment response is in most cases limited to assessment of tumor size months after the initiation of therapy. Diffusion-weighted magnetic resonance imaging (MRI) and its estimate of the apparent diffusion coefficient (ADC) has been widely investigated, as it reflects tumor cellularity and proliferation. The aim of this study was to investigate texture analysis of ADC images in conjunction with multivariate image analysis as a means for identification of pretreatment imaging biomarkers. Methods: Twenty-three consecutive high-grade glioma patients were treated with radiotherapy (2 Gy/60 Gy) with concomitant and adjuvant temozolomide. ADC maps and T1-weighted anatomical images with and without contrast enhancement were collected prior to treatment, and (residual) tumor contrast enhancement was delineated. A gray-level co-occurrence matrix analysis was performed on the ADC maps in a cuboid encapsulating the tumor in coronal, sagittal, and transversal planes, giving a total of 60 textural descriptors for each tumor. In addition, similar examinations and analyses were performed at day 1, week 2, and week 6 into treatment. Principal component analysis (PCA) was applied to reduce dimensionality of the data, and the five largest components (scores) were used in subsequent analyses. MRI assessment three months after completion of radiochemotherapy was used for classifying tumor progression or regression. Results: The score scatter plots revealed that the first, third, and fifth components of the pretreatment examinations exhibited a pattern that strongly correlated to survival. Two groups could be identified: one with a median survival after diagnosis of 1099 days and one with 345 days, p = 0.0001. Conclusions: By combining PCA and texture analysis, ADC texture characteristics were identified, which seems

  20. Effects of high grade bentonite on performance, organ weights and serum biochemistry during aflatoxicosis in broilers

    Directory of Open Access Journals (Sweden)

    H. C. Indresh

    2013-12-01

    Full Text Available Aim: To evaluate the effect of different levels of High Bentonite on growth performance, organ weight and serum biochemistry in broiler fed on diets containing aflatoxin. Materials and Methods: A total of 360 day-old commercial broiler chicks were divided at random into 8 dietary treatment groups of 42 chicks each having 3 replicates. Dietary levels of aflatoxin (0.5 ppm and High-grade bentonite (0.5, 0.75 and 1.00% were tested in a completely randomized design manner, forming a total of 8 dietary treatments each with three replicates. Body weight and feed intake were recorded weekly. At 5 wk, six birds from each treatment were sacrificed and liver, kidney, gizzard, pancreas, spleen, bursa of Fabricius and thymus were extracted and weighed. The serum samples were analyzed for total proteins, uric acid, serum albumin, serum globulin and the activities of gamma glutamyl transferase (GGT, alanine amino transferase (ALT and for antibody titers against Newcastle disease (ND and infectious bursal disease (IBD using ELISA technique. Results: A significant (P<0.05 decrease in body weight, feed consumption, relative weights of bursa, thymus, serum protein, anti body titers against NDV and IBDV, and increase in FCR, mortality, relative weight of liver, kidney, and the activity of Gamma Glutamyl Transferase (GGT was observed. However, the relative weights of gizzard, pancreas, spleen, serum albumin, uric acid and the activity of Alanine Amino Transferase (ALT were not influenced by inclusion of AF or HGB. Conclusion: The addition of HGB restored the harmful effects of AF on body weight, feed consumption, FCR, mortality, relative weight of liver, kidney, serum protein, IBDV and NDV. Supplementation of high grade bentonite at 1.0 per cent level was found to be beneficial in ameliorating the adverse effects of aflatoxin (AF in broiler chickens. [Vet World 2013; 6(6.000: 313-317

  1. Pion radiation for high grade astrocytoma: results of a randomized study

    International Nuclear Information System (INIS)

    Pickles, Tom; Goodman, George B.; Rheaume, Dorianne E.; Duncan, Graeme G.; Fryer, Chris J.; Bhimji, Shamim; Ludgate, Charles; Syndikus, Isabel; Graham, Peter; Dimitrov, Mario; Bowen, Julie

    1997-01-01

    Purpose: This study attempted to compare within a randomized study the outcome of pion radiation therapy vs. conventional photon irradiation for the treatment of high-grade astrocytomas. Methods and Materials: Eighty-four patients were randomized to pion therapy (33-34.5 Gyπ), or conventional photon irradiation (60 Gy). Entry criteria included astrocytoma (modified Kernohan high Grade 3 or Grade 4), age 18-70, Karnofsky performance status (KPS) ≥50, ability to start irradiation within 30 days of surgery, unifocal tumor, and treatment volume < 850 cc. The high-dose volume in both arms was computed tomography enhancement plus a 2-cm margin. The study was designed with the power to detect a twofold difference between arms. Results: Eighty-one eligible patients were equally balanced for all known prognostic variables. Pion patients started radiation 7 days earlier on average than photon patients, but other treatment-related variables did not differ. There were no significant differences for either early or late radiation toxicity between treatment arms. Actuarial survival analysis shows no differences in terms of time to local recurrence or overall survival where median survival was 10 months in both arms (p = 0.22). The physician-assessed KPS and patient-assessed quality of life (QOL) measurements were generally maintained within 10 percentage points until shortly before tumor recurrence. There was no apparent difference in the serial KPS or QOL scores between treatment arms. Conclusion: In contrast to high linear energy transfer (LET) therapy for central nervous system tumors, such as neutron or neon therapy, the safety of pion therapy, which is of intermediate LET, has been reaffirmed. However, this study has demonstrated no therapeutic gain for pion therapy of glioblastoma

  2. High-grade hemorrhoids requiring surgical treatment are common after laparoscopic ventral mesh rectopexy.

    Science.gov (United States)

    van Iersel, J J; Formijne Jonkers, H A; Verheijen, P M; Draaisma, W A; Consten, E C J; Broeders, I A M J

    2016-04-01

    To describe patients developing grade III and IV hemorrhoids requiring surgery after laparoscopic ventral mesh rectopexy (LVMR) and to explore the relationship between developing such hemorrhoids and recurrence of rectal prolapse after LVMR. All consecutive patients receiving LVMR at the Meander Medical Centre, Amersfoort, the Netherlands, between 2004 and 2013 were analyzed. Kaplan-Meier estimates were calculated for recurrences. A total of 420 patients underwent LVMR. Sixty-five of these patients (actuarial 5-year incidence 24.3, 95 % confidence interval (CI) 18.6-30.0) developed symptomatic grade III/IV hemorrhoids requiring stapled or excisional hemorrhoidectomy. Re-do surgery for recurrent grade III/IV hemorrhoids was required for 15 of the 65 patients (actuarial 5-year recurrence rate 40.6, 95 % CI 23.2-58.0) after the primary hemorrhoidectomy. Three of the 65 patients developed an external rectal prolapse (ERP) recurrence and eight an internal rectal prolapse (IRP) recurrence. This generated a 5-year recurrence rate of 25.3 % (95 % CI 0-53.9) for ERP recurrence and 24.4 % (95 % CI 9.1-39.7) for IRP recurrence. The rest of the LVMR cohort not receiving additional surgery for hemorrhoids (n = 355) showed significantly lower actuarial 5-year ERP (0.8 %, p = 0.011) and IRP (11 %, p = 0.020) recurrence rates. High-grade hemorrhoids requiring surgery may be common after LVMR. The development of high-grade hemorrhoids after LVMR might be considered a predictor of rectal prolapse recurrence.

  3. 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®

  4. Concomitant glenohumeral pathologies in high-grade acromioclavicular separation (type III - V).

    Science.gov (United States)

    Markel, Jochen; Schwarting, Tim; Malcherczyk, Dominik; Peterlein, Christian-Dominik; Ruchholtz, Steffen; El-Zayat, Bilal Farouk

    2017-11-10

    Acromioclavicular joint (ACJ) dislocations are common injuries of the shoulder associated with physical activity. The diagnosis of concomitant injuries proves complicated due to the prominent clinical symptoms of acute ACJ dislocation. Because of increasing use of minimally invasive surgery techniques concomitant pathologies are diagnosed more often than with previous procedures. The aim of this study was to identify the incidence of concomitant intraarticular injuries in patients with high-grade acromioclavicular separation (Rockwood type III - V) as well as to reveal potential risk constellations. The concomitant pathologies were compiled during routine arthroscopically assisted treatment in altogether 163 patients (147 male; 16 female; mean age 36.8 years) with high-grade acromioclavicular separation (Rockwood type III: n = 60; Rockwood type IV: n = 6; Rockwood type V: n = 97). Acromioclavicular separation occurred less often in women than men (1:9). In patients under 35, the most common cause for ACJ dislocation was sporting activity (37.4%). Rockwood type V was observed significantly more often than the other types with 57.5% (Rockwood type III = 36.8%, Rockwood type IV 3.7%). Concomitant pathologies were diagnosed in 39.3% of the patients with that number rising to as much as 57.3% in patients above 35 years. Most common associated injuries were rotator cuff injuries (32.3%), chondral defects (30.6%) and SLAP-lesions (22.6%). Of all patients, 8.6% needed additional reconstructive surgery. Glenohumeral injuries are a much more common epiphenomenon during acromioclavicular separation than previously ascertained. High risk group for accompanying injuries are patients above 35 years with preexisting degenerative disease. The increasing use of minimally invasive techniques allows for an easier diagnosis and simultaneous treatment of the additional pathologies.

  5. Management and prognosis of patients with high-grade soft tissue sarcomas

    International Nuclear Information System (INIS)

    Alvegaard, T.A.

    1989-01-01

    Doxorubicin is one of the most active single agents in metastatic soft tissue sarcoma. This was the rationale for the evaluation og doxorubicin in an adjuvant situation for patients with high-grade soft tissue sarcoma in a randomized, Scandinavian, multicenter joint care program, which was carried out from January 1981 to February 1986, and included 240 patients. These patients comprised the base series for the investigations of the importance of the surgical margin and radiotherapy for local tumor control; the accuracy of malignancy grading and tumor typing; prognostic factors, including DNA content; and epidemiologic risk factors. The results showed that the use of doxorubicin as adjuvant chemotherapy did not have clinical benefit in patients with high-grade soft tissue sarcoma. The overall local tumor control was high (94 %) for radically operated on extremity-located tumors due to strict classification of surgical margins. The only risk factor for local recurrence was marginal surgery without radiotherapy with a four times higher risk than after compartmental or wide surgery. Twelve percent of the operations reported as radical were classified as marginal, demonstrating the importance of reevaluation of surgical margins, and in these patients the local recurrence rate was 37 %. The 5-year metastasis-free survival for the whole patients series was 55 %, with the extremes 79 % for the patients with no or only one risk factor and 0 % for those with four or five risk factors. The five prognostic factors found could be used for selection of high-risk patients for adjuvant chemotherapy in the future. The epidemiologic study gave limited support for an association between occupational phenoxy-acid exposure and soft tissue sarcoma development. (98 refs.)

  6. 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.

  7. Valuation of fissured steam generator tubes at the level of the roll transition area, repaired by nickel plating

    International Nuclear Information System (INIS)

    Laire, C.; Stubbe, J.; Slama, G.; Michaut, M.; Anxionnaz-Steltzlen, F.; Leblois

    1990-01-01

    At DOEL 2, SG-tubes cracked at the roll transition area were repaired by nickel plating in 1985 and in 1986 by Laborelec and Framatome using different process parameters. The characteristics of these different deposits and their service behaviour were investigated on tubes pulled out after 1 or 2 cycles. It is confirmed that this repair technique can be used for through wall cracked tubes, when: - the cracks are not too broad; - the deposit is of good quality, free of irregularities due to deposition. After this expertise the improvement of the plating procedure was focused on ductile nickel without initial deposit defects [fr

  8. 76 FR 60587 - Environmental Impact Statement; North Corridor Transit Project, Seattle (WA) Metropolitan Area...

    Science.gov (United States)

    2011-09-29

    ... Lake Washington to the east, which limits transportation options. This dense urban area comprises one... and activity centers located in the North Corridor and the other urban centers in the Central Puget... elevated or at-grade profiles or station locations and layouts. Potential SR 99 Light Rail Alternatives A...

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

    KAUST Repository

    Pu, Jiang; Funahashi, Kazuma; Chen, Chang-Hsiao; Li, Ming-yang; Li, Lain-Jong; Takenobu, Taishi

    2016-01-01

    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

  10. Report of a case combining solitary Peutz-Jeghers polyp, colitis cystica profunda, and high-grade dysplasia of the epithelium of the colon.

    Science.gov (United States)

    Papalampros, Alexandros; Vailas, Michail G; Sotiropoulou, Maria; Baili, Efstratia; Davakis, Spiridon; Moris, Demetrios; Felekouras, Evangelos; Deladetsima, Ioanna

    2017-10-18

    Colitis cystica profunda is a rare nonneoplastic disease defined by the presence of intramural cysts that contain mucus, usually situated in the rectosigmoid area, which can mimic various malignant lesions and polyps. Its etiology still remains not fully elucidated, and several mechanisms such as congenital, post-traumatic, and infectious have been implicated in the development of this rare entity. Herein, we describe a unique case of colitis cystica profunda in the setting of Peutz-Jeghers-type polyp of the sigmoid colon, associated with high-grade dysplasia of the overlying epithelium in a 48-year-old female patient, who presented to the emergency room with signs of intestinal obstruction. To the best of our insight, this is the first manifestation ever reported in the literature regarding the coexistence of solitary Peutz-Jeghers-type polyp, colitis cystica profunda, and high-grade dysplasia of the epithelium of the colon. The purpose of this case report is to highlight colitis cystica profunda and its clinical significance. An uncommon nonneoplastic entity, many times masquerading as malignant lesion of the rectosigmoid area of the colon. Clinicians and pathologists should be aware of this benign condition that is found incidentally postoperatively in patients undergoing colectomies, leading to unnecessary increase of morbidity and mortality in these patients, who otherwise could have been cured with conservative treatment only.

  11. 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)

  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

    International Nuclear Information System (INIS)

    Leapman, Michael S.; Wang, Zhen J.; Behr, Spencer C.; Kurhanewicz, John; Zagoria, Ronald J.; Carroll, Peter R.; Westphalen, Antonio C.

    2017-01-01

    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 ("1H-MRSI). Materials and Methods: Thirty-nine men underwent 3-tesla endorectal multiparametric MRI including "1H-MRSI and prostatectomy. Two radiologists assigned PI-RADS v2 and "1H-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 "1H-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 "1H-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 "1H-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 "1H-MRSI (p > 0.05). Conclusion: "1H-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. A large area transition radiation detector to measure the energy of muons in the Gran Sasso underground laboratory

    International Nuclear Information System (INIS)

    Barbarito, E.; Bellotti, R.; Cafagna, F.; Castellano, M.; De Cataldo, G.; De Marzo, C.; Favuzzi, C.; Fusco, P.; Giglietto, N.; Guarnaccia, P.; Mazziotta, M.N.; Mongelli, M.; Montaruli, T.; Perchiazzi, M.; Raino, A.; Sacchetti, A.; Spinelli, P.

    1995-01-01

    We have designed and built a transition radiation detector of 36 m 2 area in order to measure the residual energy of muons penetrating in the Gran Sasso cosmic ray underground laboratory up to the TeV region. It consists of three adjacent modules, each of 2x6 m 2 area. Polystyrene square tubes, filled with a argon-carbon dioxide gas mixture, and polyethylene foam layers are used as proportional detectors and radiators respectively. We cover such a large surface with only 960 channels that provide adequate energy resolution and particle tracking for the astroparticle physics items to investigate. The detector has been calibrated using a reduced size prototype in a test beam. Results from one module exposed to cosmic rays at sea level are shown. (orig.)

  14. 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.)

  15. Smart Parking Management Pilot Project: A Bay Area Rapid Transit (BART) District Parking Demonstration

    OpenAIRE

    Shaheen, Susan; Rodier, Caroline; Eaken, Amanda M.

    2005-01-01

    This report presents early findings from an application of advanced parking technologies to maximize existing parking capacity at the Rockridge BART station, which was launched in December 2004 in the East San Francisco Bay Area. The smart parking system includes traffic sensors that count the number of vehicles entering and exiting the parking lots at the station. A reservation system allows travelers to reserve spaces by Internet, personal digital assistant (PDA), phone, and cell phone. The...

  16. The nutrition/excretion system of urban areas: socioecological regimes and transitions.

    OpenAIRE

    Esculier , Fabien

    2018-01-01

    Nutrition and excretion are fundamental physiological needs for all human beings. Analysis of their materiality, from the cellular scale up to the great planetary-scale biogeochemical cycles, shows that nutrition and excretion form a system. The focus of our study is the sustainability of the nutrition/excretion systems of urban areas, which we have sought to assess by analysing substance flows.The most relevant of these substances seems to be nitrogen, so by assessing urban nitrogen flows we...

  17. [Entomologic study on the transmission of onchocerciasis in a forest-savanna transition area of Cameroon].

    Science.gov (United States)

    Barbazan, P; Escaffre, H; Mbentengam, R; Boussinesq, M

    1998-01-01

    An entomological study was conducted in the basin area of middle Sanaga (Cameroon) in order to document the pattern of onchocerciasis transmission in a region where a high prevalence of infection had been recorded in villages located 30 km from the main rivers. The main vector of O. volvulus was found to be S. squamosum s.s. No breeding site was found in the small tributaries of the Sanaga and Mbam Rivers, and the dispersal of S. damnosum s.l. in the area thus appeared to be particularly high. The highest blackfly population densities were recorded during the long rainy season, and a second peak of density occurred along the Mbam River during the short rainy season. A seasonal variation in dispersal patterns was found at three of the four transects studied. The transmission of Onchocerca volvulus in the area occurred principally between January and May (i.e. at the end of the long dry season and the beginning of the short rainy season). Vector control operations might well reinforce the effect of ivermectin distributions in this onchocerciasis focus.

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

    International Nuclear Information System (INIS)

    Stall, Bronwyn; Zach, Leor; Ning, Holly; Ondos, John; Arora, Barbara; Shankavaram, Uma; Miller, Robert W; Citrin, Deborah; Camphausen, Kevin

    2010-01-01

    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. 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). The FLAIR CTVs and PTVs were significantly larger than the T2 CTVs and PTVs (p < 0.0001 and p = 0.0001 respectively). Based on the discordance index, the abnormality identified using the different sequences also differed in location. Fractional component analysis showed that the intersection of the tumor volumes as defined on both T2 and FLAIR defined the majority of the union volume contributing 63.6% to the CTV union and 82.1% to the PTV union. T2 alone uniquely identified 12.9% and 5.2% of the CTV and PTV unions respectively while FLAIR alone uniquely identified 25.7% and 12% of the CTV and PTV unions respectively. There was no difference in predicted toxicity to normal structures using T2 or FLAIR. At the

  19. 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, pexternal 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 clinical settings.

  20. Combined arthroscopically assisted coraco- and acromioclavicular stabilization of acute high-grade acromioclavicular joint separations.

    Science.gov (United States)

    Hann, Carmen; Kraus, Natascha; Minkus, Marvin; Maziak, Nina; Scheibel, Markus

    2018-01-01

    Due to high rate of persisting dynamic posterior translation (DPT) following isolated coracoclavicular double-button technique for reconstruction of the acromioclavicular (AC) joint reported in the literature, an additional acromioclavicular cerclage was added to the procedure. The aim of this study was to evaluate the clinical and radiological results of patients with high-grade AC-joint instability treated with a double TightRope technique with an additional percutaneous acromioclavicular cerclage. Fifty-nine patients (6 f/53 m; median age 38.3 (range 21.5-63.4 years) who sustained an acute high-grade AC-joint dislocation (Rockwood type V) were treated using the above-mentioned technique. At the final follow-up, the constant score (CS), the subjective shoulder value (SSV), the Taft score (TF) and the acromioclavicular joint instability score (ACJI) as well as bilateral anteroposterior stress views with 10 kg of axial load and bilateral modified Alexander views were obtained. At a median follow-up of 26.4 (range 20.3-61.0) months, 34 patients scored a median of 90 (33-100) points in the CS, 90 (25-100) % in the SSV, 11 (4-12) points in the TF and 87 (43-100) points in the ACJI. The coracoclavicular (CC) distance was 12.1 (6.5-19.8) mm and the CC difference 2.0 (0.0-11.0) mm. Two patients (5.8%) showed a complete DPT of the AC joint, and fourteen patients (41.1%) displayed a partial DPT. The overall revision rate was 11.7%. Two patients presented implant irritation, one patient a recurrent instability, and one patient suffered from a local infection. The arthroscopically assisted and image-intensifier-controlled double TightRope technique with an additional percutaneous acromioclavicular cerclage leads to good and excellent clinical results after a follow-up of 2 years. The incidence of persisting dynamic horizontal translation is lower compared to isolated coracoclavicular stabilization. Thus, we recommend using the double TightRope implant with an additional

  1. Technical program plan for the transitioning, decommissioning, and final disposition focus area

    International Nuclear Information System (INIS)

    1994-01-01

    The end of the Cold War and the decision to reduce the size of the nuclear weapons production complex have created a need for DOE to deactivate, decontaminate, and decommission (D ampersand D) a large number of aging, surplus facilities. The nature and magnitude of the facility D ampersand D problems require EM to facilitate the development and application of technologies that will address these problems quickly and cost-effectively. The needed technologies can best be provided by integrating the strengths of DOE's national laboratories with those of industry, universities, and other government agencies. To help focus and direct these activities toward achieving DOE's goals, the EM Office of Technology Development (OTD) devised the strategic concept of an Integrated Demonstration (ID), which involves selecting, demonstrating, testing, and evaluating an integrated set of technologies tailored to provide a complete solution to specific EM problems, such as those posed by D ampersand D. The ID approach allows optimal use of DOE's resources by avoiding duplication of effort and ensuring rapid demonstration of applicable technologies. Many technologies, including both the commercially mature and the innovative, are combined and evaluated for a cradle-to-grave solution to specific EM problems in areas such as D ampersand D. The process will involve transforming an existing problem condition to a desired end state, recycling waste materials generated, wherever feasible, and minimizing requirements for waste disposal. The D ampersand D ID Strategic Plan has been prepared by a Technical Support Group (TSG) assembled from various sites within the DOE Complex and intended to identify cross-cutting problem areas amenable to applications of the D ampersand D ID concept and to develop specific ID proposals for these problem areas

  2. Linked Climatic, Environmental, and Societal Changes in the Lower Yellow River Area during the Neolithic-Bronze Age Transition

    Science.gov (United States)

    Yu, S. Y.

    2017-12-01

    Understanding human-environment interactions during times of large and rapid climatic changes in the second half of the Holocene may deepen our insight into human adaptation and resilience against potential climate anomalies in the future. However, the drivers and societal responses tend to be different from area to area, and the degree and nature of this link are still a matter of debate. Flooding sediments preserved within the cultural stratigraphical context at archaeological sites in the lower Yellow River area may offer an ideal framework for evaluating the association between evolution of Neolithic cultures and climate fluctuations. Here, we present evidence from a mound site for the prevalence of extreme overbank floods during the Neolithic-Bronze Age transition most likely triggered by excessive summer precipitation in the Yellow River valley when prolonged weak El Niño condition prevailed. Repeated flooding during around 4000-3500 cal yr BP substantially modified the floodplain landscape, thereby driving people to disperse to areas dominated by the Erlitou culture and eventually giving rise to a state-level society in central China historiographically identified as the Xia Dynasty. Changes in the drainage network due to repeated flooding also exerted a profound impact on the rice farming-based communities centered in the region of the floods. Our results provide a precise past analogue of the linked climatic, environmental, and societal changes at a time when human societies were evolving into a hierarchy similar to those of today.

  3. Study of the mobility, surface area, and sintering behavior of agglomerates in the transition regime by tandem differential mobility analysis

    International Nuclear Information System (INIS)

    Cho, Kuk; Hogan, Christopher J.; Biswas, Pratim

    2007-01-01

    The surface area of nanosized agglomerates is of great importance as the reactivity and health effects of such particles are highly dependent on surface area. Changes in surface area through sintering during nanoparticle synthesis processes are also of interest for precision control of synthesised particles. Unfortunately, information on particle surface area and surface area dynamics is not readily obtainable through traditional particle mobility sizing techniques. In this study, we have experimentally determined the mobility diameter of transition regime agglomerates with 3, 4, and 5 primary particles. Agglomerates were produced by spray drying well-characterised polystyrene latex particles with diameters of 55, 67, 76, and 99 nm. Tandem differential mobility analysis was used to determine agglomerate mobility diameter by selecting monodisperse agglomerates with the same number of primary particles in the first DMA, and subsequently completely sintering the agglomerates in a furnace aerosol reactor. The size distribution of the completely sintered particles was measured by an SMPS system, which allowed for the determination of the number of primary particles in the agglomerates. A simple power law regression was used to express mobility diameter as a function of primary particle size and the number of primary particles, and had an excellent correlation (R 2 = 0.9971) with the experimental data. A scaling exponent was determined from the experimental data to relate measured mobility diameter to surface area for agglomerates. Using this relationship, the sintering characteristics of agglomerates were also examined for varying furnace temperatures and residence times. The sintering data agreed well with the geometric sintering model (GSM) model proposed by Cho and Biswas (2006a) as well as with the model proposed Koch and Friedlander (1990) for sintering by viscous flow

  4. Proton magnetic resonance spectroscopy in the distinction of high-grade cerebral gliomas from single metastatic brain tumors

    International Nuclear Information System (INIS)

    Server, Andres; Schellhorn, Till; Haakonsen, Monika; Nakstad, Per H.; Josefsen, Roger; Kulle, Bettina; Maehlen, Jan; Kumar, Theresa; Gadmar, Oeystein; Langberg, Carl W.

    2010-01-01

    Background: Brain metastases and primary high-grade gliomas, including glioblastomas multiforme (GBM) and anaplastic astrocytomas (AA), may be indistinguishable by conventional magnetic resonance (MR) imaging. Identification of these tumors may have therapeutic consequences. Purpose: To assess the value of MR spectroscopy (MRS) using short and intermediate echo time (TE) in differentiating solitary brain metastases and high-grade gliomas on the basis of differences in metabolite ratios in the intratumoral and peritumoral region. Material and Methods: We performed MR imaging and MRS in 73 patients with histologically verified intraaxial brain tumors: 53 patients with high-grade gliomas (34 GBM and 19 AA) and 20 patients with metastatic brain tumors. The metabolite ratios of Cho/Cr, Cho/NAA, and NAA/Cr at intermediate TE and the presence of lipids at short TE were assessed from spectral maps in the tumoral core, peritumoral edema, and contralateral normal-appearing white matter. The differences in the metabolite ratios between high-grade gliomas/GBM/AA and metastases were analyzed statistically. Cutoff values of Cho/Cr, Cho/NAA, and NAA/Cr ratios in the peritumoral edema, as well as Cho/Cr and NAA/Cr ratios in the tumoral core for distinguishing high-grade gliomas/GBM/AA from metastases were determined by receiver operating characteristic (ROC) curve analysis. Results: Significant differences were noted in the peritumoral Cho/Cr, Cho/NAA, and NAA/ Cr ratios between high-grade gliomas/GBM/AA and metastases. ROC analysis demonstrated a cutoff value of 1.24 for peritumoral Cho/Cr ratio to provide sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of 100%, 88.9%, 80.0%, and 100%, respectively, for discrimination between high-grade gliomas and metastases. By using a cutoff value of 1.11 for peritumoral Cho/NAA ratio, the sensitivity was 100%, the specificity was 91.1%, the PPV was 83.3%, and the NPV was 100%. Conclusion: The results of this

  5. Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone

    OpenAIRE

    Palmerini, E.; Jones, R. L.; Marchesi, E.; Paioli, A.; Cesari, M.; Longhi, A.; Meazza, C.; Coccoli, L.; Fagioli, F.; Asaftei, S.; Grignani, G.; Tamburini, A.; Pollack, S. M.; Picci, P.; Ferrari, S.

    2016-01-01

    Background Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Methods Patients receiving G 900?mg/m2 d 1, 8; D 75?mg/m2 d 8, every 21?days were eligible. Primary end-point: progression-free survival (PFS) at 4?months; secondary end-point: overall survival (OS) and response rate. Results Fifty-one patients w...

  6. Transition of Attention in Terminal Area NextGen Operations Using Synthetic Vision Systems

    Science.gov (United States)

    Ellis, Kyle K. E.; Kramer, Lynda J.; Shelton, Kevin J.; Arthur, Shelton, J. J., III; Prinzel, Lance J., III; Norman, Robert M.

    2011-01-01

    This experiment investigates the capability of Synthetic Vision Systems (SVS) to provide significant situation awareness in terminal area operations, specifically in low visibility conditions. The use of a Head-Up Display (HUD) and Head-Down Displays (HDD) with SVS is contrasted to baseline standard head down displays in terms of induced workload and pilot behavior in 1400 RVR visibility levels. Variances across performance and pilot behavior were reviewed for acceptability when using HUD or HDD with SVS under reduced minimums to acquire the necessary visual components to continue to land. The data suggest superior performance for HUD implementations. Improved attentional behavior is also suggested for HDD implementations of SVS for low-visibility approach and landing operations.

  7. Permian Triassic palynofloral transition in Chintalapudi area, Godavari Graben, Andhra Pradesh, India

    Science.gov (United States)

    Jha, Neerja; Chary, M. Basava; Aggarwal, Neha

    2012-10-01

    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 (Palynoassemblage-I, II and III) having dominance of striate disaccates along with presence of some stratigraphically significant taxa, belongs to Late Permian (Raniganj) palynoflora, while the other group (Palynoassemblages IV and V) shows sharp decline in percentage of characteristic taxa of first group, i.e., striate disaccates, and consequent rise or dominance of taeniate and cingulate cavate spores, belongs to Early Triassic (Panchet) palynoflora. Palynoassemblage-I, II and III (Group I) are characterized by dominance of striate disaccates chiefly, Striatopodocarpites spp. and Faunipollenites spp. along with presence of rare but stratigraphically significant taxa, viz., Gondisporites raniganjensis, Falcisporites nuthaliensis, Klausipollenites schaubergeri, Chordasporites sp., Striomonosaccites, ovatus, Crescentipollenites multistriatus, Verticipollenites debiles, Strotersporites crassiletus, Guttulapollenites hannonicus, G. gondwanensis, Hamiapollenites insolitus, Corisaccites alutus, Lunatisporites ovatus, Weylandites spp. and Vitreisporites pallidus. Palynoassemblage-I is distinguished by significant presence of Densipollenites spp. while Palynoassemblage-II shows significant presence of Crescentipollenites spp. and Palynoassemblage-III differs from the above two assemblages in having significant presence of Guttulapollenites hannonicus. Palynoassemblage-IV (Group II) is characterized by high percentage of taeniate disaccates chiefly Lunatisporites spp., while Palynoassemblage-V (Group II) is characterized by cingulate-cavate trilete spores chiefly, Lundbladispora spp. and Densoisporites spp. Striate disaccates show a sharp decline in these two assemblages. In

  8. 18F-fluoromisonidazole (FMISO) and 18F-fluorodeoxyglucose (FDG) PET in patients undergoing radiotherapy or chemotherapy following surgery for high-grade glioma

    International Nuclear Information System (INIS)

    Lee, S. T.

    2009-01-01

    Full text:Background: Tumour hypoxia is associated with disease progression and resistance to therapy. High grade cerebral gliomas have a poor outcome despite advancements in chemotherapy and radiotherapy. 18F-fluoromisonidazole (18F-FMISO) concentrates in hypoxic cells and is associated with tumour grade in gliomas. The aim of this study was to compare the patterns of uptake of 18F-FDG PET and 18F-FMISO PET post-surgery with MRI and areas of recurrence post-radiotherapy. Methods: Patients with high grade cerebral glioma were recruited into this prospective study. All patients had post-surgical, pre-radiotherapy 18F-FDG, 18F-FMISO and MRI scans, which were all repeated 4-6 weeks post-completion to radiotherapy. The patients were followed-up clinically three monthly and re-imaged if indicated. Results: Ten patients were enrolled in this study, mean age 62 years (range 55-69 years), who all had pre-radiotherapy scans performed. Seven patients had scans done pre- and post-radiotherapy, with 3 patients with only pre-therapy scans. Nine patients had significant FMISO uptake and 8 patients demonstrated abnormal FDG uptake. The areas of FMISO uptake on pre-radiotherapy scans correlated with the most abnormal areas of contrast-enhancement on pre-treatment MRI and areas of locally recurrent disease on post-treatment MRI in eight patients. Nine patients had locally recurrent disease on follow-up MRI. FMISO was more predictive of tumour recurrence compared to FDG. Conclusion: Post-surgical 18F-FMISO PET in patients with cerebral glioma is more predictive of areas of recurrent disease compared to 18F-FDG PET.

  9. Clinical Implications of the Epidermal Growth Factor Receptor overexpression in the High-grade Astrocytomas

    International Nuclear Information System (INIS)

    Hong, Seong Eon; Kang, Jin Oh; Lee, Hye Kyoung; Yang, Moon Ho; Leem, Won; Cho, Kyung Sam

    1996-01-01

    To determine the incidence and prognostic effects of EGFR overexpression in the high-grade astrocytomas. With 23 paraffin blocks of the high-garde astrocytomas, expression of EGFR were evaluated by immunohistochemical staining employing polyclonal antibody raised to short cytoplasmic domain of the molecule. Two out of 7 anaplastic astrocytomas and 9 out of 16 glioblastoma multiform patients showed overexpression of EGFR(p=0.44). Three out of 11 patients of age below 55 and 8 out of 12 patients of age over 54 showed EGFR overexpression(p=0.141). Median survival of the EGFR negative anaplastic astrocytoma patient was 37 months. Median survival of the glioblastoma multiform patients were 11 months in EGFR negative group and 7 months in EGFR positive group. But survival difference was not significant(p=0.17). There was a marked trend of increasing overexpression of EGFR in older patients. But survival of the glioblastoma multiform decreased by the overexpression of the EGFR without significant

  10. Feasibility of combined modality therapy for localized high-grade soft tissue sarcomas in adults

    International Nuclear Information System (INIS)

    Blum, R.H.; Greenberger, J.S.; Wilson, R.E.; Corson, J.M.

    1979-01-01

    Seventeen consecutive patients with localized, high grade soft tissue sarcomas had resection of their primary tumor, radiation therapy and chemotherapy. The soft tissue sarcoma was primary in 14 patients and regionally recurrent in 3 patients. Chemotherapy consisted of cyclophosphamide 500 mg/M 2 day 1, Adriamycin (ADR) 60 mg/M 2 day 2, and DTIC 400 mg/M 2 days 1 and 2, given every 21 days to a maximum ADR dose of 450 mg/M 2 . Cyclophosphamide and DTIC were then given to a total duration of 1 year. Radiation therapy consisted of 4000 to 5000 rad by megavoltage photons in 5 weeks, and in selected cases, an additional 1500 to 2000 rad by electron beam boost in the tumor bed delivered over 2 additional weeks. Following surgery, 12 patients were treated sequentially with an interval of chemotherapy, radiation therapy and then the completion of chemotherapy. The added morbidity of this sequential approach is minimal: one patient of 12 had delayed primary healing of her wound, 1 of 10 patients required a break in radiation therapy because of skin erythema. Four patients were treated with intensive pre-chemotherapy radiation therapy because of inadequate surgical margins. The median time on study was 18 months from onset of treatment (range, 8 to 41 months). Although there have been no local, regional or distant recurrences, the follow-up time is inadequate to assess the therapeutic benefit of this combined modality treatment

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer.

    Science.gov (United States)

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G; Meier, Samuel M; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-09-20

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors.

  13. PHASE ANALYSES OF URANIUM BEARING MINERALS FROM THE HIGH GRADE ORE, NOPAL I, PENA BLANCA, MEXICO

    International Nuclear Information System (INIS)

    Ren, M.; Goodell, P.; Kelts, A.; Anthony, E.Y.; Fayek, M.; Fan, C.; Beshears, C.

    2005-01-01

    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

  14. Cytologic diagnosis of primary peritoneal high grade serous carcinoma in a man.

    Science.gov (United States)

    Umphress, Brandon; Philip, John; Zhang, Yaxia; Lin, Xiaoqi

    2018-04-16

    Primary peritoneal serous carcinoma (PPSC) is a rare neoplasm histologically indistinguishable from ovarian serous carcinoma primarily occurring in the female population. To date, extremely rare cases of PPSC have been reported in men; however, diagnosis by cytology has yet to be described. Here we present the clinical, radiographic, cytomorphologic, histologic and immunohistochemical (IHC) findings of a high-grade (HG) PPSC in a 70-year-old man with a history of prostatic adenocarcinoma. Core needle biopsy (CNB) touch preparation smears showed pleomorphic, round, columnar and polygonal epithelioid cells present singly or arranged in loosely cohesive three-dimensional clusters. The tumor cells are characterized by enlarged nuclei containing prominent nucleoli, and variable scant to moderate, slightly dense cytoplasm. Scattered cells contained cytoplasmic vacuoles. Examination of CNB revealed an infiltrating tumor in sheets with focal papillary configuration. Tumor cells were morphologically consistent with HG carcinoma. IHC studies demonstrated diffuse positivity for CK7, PAX-8, ER, WT1, p53, p16 and BerEP4 with focal/weak staining for calretinin and CK5/6, which supporting the diagnosis of HG PPSC. The patient was treated with 6 cycles of carboplatin and paclitaxel with near resolution of the mass at 10 month follow-up. To the best of our knowledge, this is the first reported case in the literature of PPSC in a man diagnosed by cytology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. 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.

  16. Multiphoton imaging of low grade, high grade intraepithelial neoplasia and intramucosal invasive cancer of esophagus

    Science.gov (United States)

    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2017-04-01

    Esophageal squamous cell carcinoma (ESCC) is devastating because of its aggressive lymphatic spread and clinical course. It is believed to occur through low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal invasive cancer (IMC) before transforming to submucosal cancer. In particular, these early lesions (LGIN, HGIN and IMC), which involve no lymph node nor distant metastasis, can be cured by endoscopic treatment. Therefore, early identification of these lesions is important so as to offer a curative endoscopic resection, thus slowing down the development of ESCC. In this work, spectral information and morphological features of the normal esophageal mucosa are first studied. Then, the morphological changes of LGIN, HGIN and IMC are described. Lastly, quantitative parameters are also extracted by calculating the nuclear-to-cytoplasmic ratio of epithelial cells and the pixel density of collagen in the lamina propria. These results show that multiphoton microscopy (MPM) has the ability to identify normal esophageal mucosa, LGIN, HGIN and IMC. With the development of multiphoton endoscope systems for in vivo imaging, combined with a laser ablation system, MPM has the potential to provide immediate pathologic diagnosis and curative treatment of ESCC before the transformation to submucosal cancer in the future.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. Linac radiosurgery for high-grade gliomas: the University of Florida experience

    Energy Technology Data Exchange (ETDEWEB)

    Buatti, John M; Friedman, William A; Bova, Frank J; Mendenhall, William M

    1995-04-30

    Purpose: Stereotactic radiosurgery has been reported as a promising boost technique for the treatment of selected patients with high-grade glioma. The first 11 patients given this treatment at the University of Florida are reported. Methods and Materials: Six patients with glioblastoma multiforme and five with anaplastic astrocytoma were carefully selected for treatment with linac radiosurgery. All patients had a Karnofsky performance status {>=} 90%. Median age of patients was 42.1 years. External-beam radiotherapy delivered a median dose of 60 Gy. Stereotactic radiosurgery was delivered to the enhancing tumor volume without margin. Median treatment volume was 14 cm{sup 3} (equivalent sphere diameter, 3 cm). The maximum volume of any tumor treated was 22.5 cm{sup 3} (equivalent sphere diameter, 3.5 cm). Median stereotactic radiosurgery boost dose was 12.5 Gy, and median prescription sphere was the 80% isodose shell. Results: Despite rigorous selection and aggressive stereotactic boost irradiation, this patient cohort had a median actuarial survival of 17 months. All patients have had progression of intracranial disease within 1 year of radiosurgery, and only 3 of 11 remain alive with a median follow-up of 13 months. Conclusion: These results differ significantly from others reported. Comparative analysis suggests tumor volume may be an important prognostic factor in patients treated with stereotactic radiosurgery. Future studies need to define appropriate patient cohorts for the boost technique.

  20. Correlation of diffusion and perfusion MRI with Ki-67 in high-grade meningiomas.

    Science.gov (United States)

    Ginat, Daniel T; Mangla, Rajiv; Yeaney, Gabrielle; Wang, Henry Z

    2010-12-01

    Atypical and anaplastic meningiomas have a greater likelihood of recurrence than benign meningiomas. The risk for recurrence is often estimated using the Ki-67 labeling index. The purpose of this study was to determine the correlation between Ki-67 and regional cerebral blood volume (rCBV) and between Ki-67 and apparent diffusion coefficient (ADC) in atypical and anaplastic meningiomas. A retrospective review of the advanced imaging and immunohistochemical characteristics of atypical and anaplastic meningiomas was performed. The relative minimum ADC, relative maximum rCBV, and specimen Ki-67 index were measured. Pearson's correlation was used to compare these parameters. There were 23 cases with available ADC maps and 20 cases with available rCBV maps. The average Ki-67 among the cases with ADC maps and rCBV maps was 17.6% (range, 5-38%) and 16.7% (range, 3-38%), respectively. The mean minimum ADC ratio was 0.91 (SD, 0.26) and the mean maximum rCBV ratio was 22.5 (SD, 7.9). There was a significant positive correlation between maximum rCBV and Ki-67 (Pearson's correlation, 0.69; p = 0.00038). However, there was no significant correlation between minimum ADC and Ki-67 (Pearson's correlation, -0.051; p = 0.70). Maximum rCBV correlated significantly with Ki-67 in high-grade meningiomas.

  1. Neurocognitive training in patients with high-grade glioma: a pilot study.

    Science.gov (United States)

    Hassler, Marco Ronald; Elandt, Katarzyna; Preusser, Matthias; Lehrner, Johann; Binder, Petra; Dieckmann, Karin; Rottenfusser, Andrea; Marosi, Christine

    2010-03-01

    Although their neurocognitive performance is one of the major concerns of patients with high-grade gliomas (HGG) and although neurocognitive deficits have been described to be associated with negative outcome, neurocognitive rehabilitation is usually not integrated into the routine care of patients with malignant gliomas. In this pilot trial, a weekly group training session for attention, verbal, and memory skills was offered to patients with HGG with pre and post-training evaluation. Eleven patients, six with glioblastoma multiforme and five with WHO grade III gliomas, median age 50 years, with a Karnofsky performance score of 80-100 participated in ten group training sessions of 90 min. For evaluation at baseline and after the training by a neuropsychologist not involved in care or training of the patients, Trail Making Tests A and B (TMTA and TMTB), Hopkins Verbal Learning Test (HVLT), and the Controlled Oral Word Association Test (COWA) were used. Comparison of mean group differences between baseline and at post-training evaluation after 12 weeks revealed improvement across all neurocognitive variables. The patients showed a great diversity in their performances, with worsening, improvement, and stabilization. However, a significant group difference was detected only for the HVLT (score 19.6 +/- 8.9 at baseline, 23.6 +/- 8.8 after 12 weeks, P = 0.04). This pilot study shows that neurocognitive training in patients with HGG is feasible as group training with weekly sessions and might be able to induce improvements in attention and memory skills.

  2. ERBB2 mutations associated with solid variant of high-grade invasive lobular breast carcinomas.

    Science.gov (United States)

    Deniziaut, Gabrielle; Tille, Jean Christophe; Bidard, François-Clément; Vacher, Sophie; Schnitzler, Anne; Chemlali, Walid; Trémoulet, Laurence; Fuhrmann, Laetitia; Cottu, Paul; Rouzier, Roman; Bièche, Ivan; Vincent-Salomon, Anne

    2016-11-08

    ERBB2 and ERBB3 somatic gain-of-function mutations, which may be targeted by anti-ERBB2 therapies, were reported by high-throughput sequencing studies in 1% and 2% of invasive breast cancers respectively. Our study aims to determine ERBB2 and ERBB3 mutations frequencies in grade 3 and/or ERBB2-positive invasive lobular breast carcinomas (ILC). All the 529 ILC surgically-excised registered at Institut Curie in the years 2005 to 2008 were reviewed. Thirty-nine grade 3 ERBB2-negative ILC and 16 ERBB2-positive ILC were retrieved and subjected to Sanger sequencing of the ERBB2 and ERBB3 activation mutation hotspots (ERBB2: exons 8, 17, 19, 20, 21; ERBB3: exons 3, 6, 7, 8). Among the 39 grade 3 ERBB2-negative ILC, six tumors were found to have at least one detectable ERBB2 activating mutation (incidence rate: 15%, 95%CI [4%-27%]). No ERBB2 mutation was found among the 16 ERBB2-positive ILC. No ERBB3 mutation was found in any of the 55 ILC. ERBB2 mutations were statistically associated with solid ILC features (p=0.01). Survival analyses showed no significant prognostic impact of ERBB2 mutations. Our study demonstrates that high grade ERBB2-negative ILC display a high frequency of ERBB2 mutations, and should be subjected to systematic genetic screening.

  3. HiGate (High Grade Anti-Tamper Equipment Prototype and Application to e-Discovery

    Directory of Open Access Journals (Sweden)

    Yui Sakurai

    2010-06-01

    Full Text Available These days, most data is digitized and processed in various ways by computers. In the past, computer owners were free to process data as desired and to observe the inputted data as well as the interim results. However, the unrestricted processing of data and accessing of interim results even by computer users is associated with an increasing number of adverse events. These adverse events often occur when sensitive data such as personal or confidential business information must be handled by two or more parties, such as in the case of e-Discovery, used in legal proceedings, or epidemiologic studies. To solve this problem, providers encrypt data, and the owner of the computer performs decoding in the memory for encrypted data. The computer owner can be limited to performing only certain processing of data and to observing only the final results. As an implementation that uses existing technology to realize this solution, the processing of data contained in a smart card was considered, but such an implementation would not be practical due to issues related to computer capacity and processing speed. Accordingly, the authors present the concept of PC-based High Grade Anti-Tamper Equipment (HiGATE, which allows data to be handled without revealing the data content to administrators or users. To verify this concept, an e-Discovery application on a prototype was executed and the results are reported here.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  6. 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.

  7. Historical Transition of Eco-Structure in a Tidal Flat Caused by Expansion of Sewerage Treatment Area

    Directory of Open Access Journals (Sweden)

    Hideki Tatsumoto

    2004-01-01

    Full Text Available An artificial tidal flat was prepared for the mitigation tool on coastal environment. However, it is considered that most of the flat was not restored to the sufficient amenities for aquatic living things, migratory birds, etc. because none of the ecological mechanisms were understood or planned for. It is therefore investigated in this paper that historical transition factors in ecosystem structure are selected and traced with the diffusion of a public sewerage system, and with environmental factors such as water quality, sediment condition, and aquatic producers in the Yatsu Tidal Flat. As a result, it can be defined that the tidal flat, just like a lagoon, was formed artificially with reclamation and development of its circumference at the first step of transition; the water quality and sediment condition gradually became brackish water and muddy sediment conditions, interactively. The ecosystem pyramid forming orderly layers according to trophic level appeared as a high-bio-production potential in its tidal flat. In the second step, i.e., in recent years, the characteristics of water quality and sediment conditions evolved into a foreshore tidal flat, namely, conditions in the flat observed were that the progression of water included a high concentration of chloride ion as seawater and sediment conditions became sandy. Because of that, the inflowing fresh water and organic mater from the land area decreased with the improvement of the public sewerage system. The ecosystem pyramid was distorted into a chaos pyramid, with inversion of Ulva spp.

  8. Historical transition of eco-structure in a tidal flat caused by expansion of sewerage treatment area.

    Science.gov (United States)

    Tatsumoto, Hideki; Ishii, Yuichi; Machida, Motoi; Taki, Kazuo

    2004-05-11

    An artificial tidal flat was prepared for the mitigation tool on coastal environment. However, it is considered that most of the flat was not restored to the sufficient amenities for aquatic living things, migratory birds, etc. because none of the ecological mechanisms were understood or planned for. It is therefore investigated in this paper that historical transition factors in ecosystem structure are selected and traced with the diffusion of a public sewerage system, and with environmental factors such as water quality, sediment condition, and aquatic producers in the Yatsu Tidal Flat. As a result, it can be defined that the tidal flat, just like a lagoon, was formed artificially with reclamation and development of its circumference at the first step of transition; the water quality and sediment condition gradually became brackish water and muddy sediment conditions, interactively. The ecosystem pyramid forming orderly layers according to trophic level appeared as a high-bio-production potential in its tidal flat. In the second step, i.e., in recent years, the characteristics of water quality and sediment conditions evolved into a foreshore tidal flat, namely, conditions in the flat observed were that the progression of water included a high concentration of chloride ion as seawater and sediment conditions became sandy. Because of that, the inflowing fresh water and organic mater from the land area decreased with the improvement of the public sewerage system. The ecosystem pyramid was distorted into a chaos pyramid, with inversion of Ulva spp.

  9. 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.

  10. Contribution of an alveolar cell of origin to the high-grade malignant phenotype of pregnancy-associated breast cancer.

    Science.gov (United States)

    Haricharan, S; Hein, S M; Dong, J; Toneff, M J; Aina, O H; Rao, P H; Cardiff, R D; Li, Y

    2014-12-11

    Pregnancy-associated breast cancers (PABCs) are tumors diagnosed during pregnancy or up to 5 years following parturition, and are usually high-grade, connective tissue-rich, and estrogen receptor (ER)/progesterone receptor-negative. Little is known about the cellular origin of PABCs or the mechanisms by which PABCs are initiated. Using the RCAS retrovirus to deliver the ErbB2 oncogene into the mammary epithelium of our previously reported MMTV-tva transgenic mice, we detected high-grade, poorly differentiated, stroma-rich and ER-negative tumors during pregnancy and lactation. These high-grade and stroma-rich tumors were less frequent in involuted mice or in age-matched nulliparous mice. More importantly, by generating a WAP-tva transgenic line for expression of ErbB2 selectively in WAP(+) mammary alveolar cells, we found that tumors had similar morphological phenotypes (high grade, poorly differentiated, stroma-rich and ER-negative), irrespective of the time since pregnancy and even in the absence of pregnancy. These data suggest that PABCs arise preferentially from an alveolar cell population that expands during pregnancy and lactation. This somatic mouse model may also be useful for preclinical testing of new prophylactic and therapeutic strategies against PABC.

  11. Assessment of a Chemotherapy Response Score (CRS) System for Tubo-Ovarian High-Grade Serous Carcinoma (HGSC)

    DEFF Research Database (Denmark)

    Ditzel, Helena M; Strickland, Kyle C; Meserve, Emily E

    2018-01-01

    A chemotherapy response score (CRS) system was recently described to assess the histopathologic response and prognosis of patients with tubo-ovarian high-grade serous carcinoma (HGSC) receiving neoadjuvant chemotherapy. The current study was performed as an independent assessment of this CRS syst...

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

    DEFF Research Database (Denmark)

    Nyström, H; 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...

  13. 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...

  14. Small RNA sequencing reveals a comprehensive miRNA signature of BRCA1-associated high-grade serous ovarian cancer

    NARCIS (Netherlands)

    Brouwer, Jan; Kluiver, Joost; de Almeida, Rodrigo C.; Modderman, Rutger; Terpstra, Martijn; Kok, Klaas; Withoff, Sebo; Hollema, Harry; Reitsma, Welmoed; de Bock, Geertruida H.; Mourits, Marian J. E.; van den Berg, Anke

    2016-01-01

    AimsBRCA1 mutation carriers are at increased risk of developing high-grade serous ovarian cancer (HGSOC), a malignancy that originates from fallopian tube epithelium. We aimed to identify differentially expressed known and novel miRNAs in BRCA1-associated HGSOC. Methods Small RNA sequencing was

  15. Boron neutron capture therapy (BNCT) for high-grade gliomas of the brain: a cautionary note

    International Nuclear Information System (INIS)

    Laramore, George E.; Spence, Alexander M.

    1996-01-01

    Purpose/Objective: Boron neutron capture therapy (BNCT) is a method of treating high-grade gliomas of the brain that involves incorporating 10 B into the tumor using appropriate pharmacological agents and then irradiating the tumor with thermal or epithermal neutron beams. To date, over 120 patients have been treated in this manner by Japanese investigators using a thermal neutron beam from a nuclear reactor. Favorable reports on outcome have motivated considerable current research in BNCT. The purpose of this study is to provide an independent analysis of the Japanese data by identifying the subset of patients from the United States who received this treatment in Japan and comparing their outcomes relative to a matched cohort who received conventional therapy in various Radiation Therapy Oncology Group (RTOG) studies. Methods and Materials: The principal referral sources of patients to Japan for BNCT were identified and the names of patients sent for treatment obtained. The treating physicians in Japan were also contacted to see if additional patients from the United States had been treated. Either the patients or their next of kin were contacted, and permission was obtained to retrieve medical records including tumor pathology for central review. Prognostic variables according to an analysis of the RTOG brain tumor database by Curran et al. were determined from these records and used to construct a matched cohort of patients treated conventionally. Results: A total of 14 patients were identified who had traveled to Japan for BNCT treatment between July, 1987 and June, 1994. In the case of one patient (deceased), it was not possible to contact the next of kin. Material was obtained on the other 13 patients and review of the pathology indicated that 1 patient had a central nervous system lymphoma rather than a high-grade glioma. Survival data was analyzed for the other 12 patients on an actuarial basis, and this showed no difference compared to survival data for a

  16. Prevalence of remaining horizontal instability in high-grade acromioclavicular joint injuries surgically managed.

    Science.gov (United States)

    Cisneros, Luis Natera; Reiriz, Juan Sarasquete

    2017-04-01

    To determine the prevalence of remaining horizontal instability in high-grade acromioclavicular joint (ACJ) injuries surgically managed by means of four different surgical strategies and to assess its relation to the clinical outcomes and the quality of life. In this multicentric non-randomized retrospective study, 53 patients with high-grade ACJ injuries surgically managed (by means of open or arthroscopic surgery) were clinically and radiographically assessed at 24 months or more after shoulder surgery. The presence of post-surgical remaining horizontal instability was evaluated by means of Alexander or axillary X-ray views. The study population was divided into two groups: patients with evidence of post-surgical remaining horizontal instability and patients without evidence of post-surgical remaining horizontal instability at the last follow-up visit. The relationship between remaining horizontal instability and the quality-of-life questionnaires was analyzed. 18.87% (10/53) of the Alexander or axillary X-rays views showed post-surgical remaining horizontal instability at the last follow-up visit (INSTAB-group). Results of the questionnaires were: (1) physical SF36 score (INSTAB-group 57.02 ± 3.17  and NO-INSTAB-group 57.66 ± 3.30, p = 0.583); (2) mental SF36 score (INSTAB-group 53.95 ± 3.98  and NO-INSTAB-group 55.71 ± 3.30, p = 0.150); (3) NRS for pain (INSTAB-group 1.30 ± 1.49 and NO-INSTAB-group 0.83  ± 1.08, p = 0.260); (4) DASH questionnaire (INSTAB-group 5.27 ± 5.42 and NO-INSTAB-group 3.06 ± 2.30, p = 0.049); (5) Constant score (INSTAB-group 93.4 ± 3.5 and NO-INSTAB-group 94.83  ± 4.3, p = 0.333); and Global satisfaction (INSTAB-group 8.7  ± 0.95 and NO-INSTAB-group 8.64 ± 1.03, p = 0.874). Independently of the type of procedure, post-surgical remaining horizontal instability was present in almost one-fifth of the patients, and this group of patients showed a significantly worse DASH score. The

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

    Science.gov (United States)

    Farzin, Mostafa; Molls, Michael; Astner, Sabrina; Rondak, Ina-Christine; Oechsner, Markus

    2015-12-01

    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 (Dmax and Dmean) 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.

  18. First results of the radiological surveillance of RIT trial for high grade astrocytomas in Cuba

    Energy Technology Data Exchange (ETDEWEB)

    Amador Balbona, Z.H.; Pardo Ayra, F.E.; Torres Berdeguez, M.B. [Isotope Centre, Havana (Cuba). Radiation Protection Dept.

    2004-07-01

    The first phase of the clinical trial using the humanized monoclonal antibody h-R3 labeled with {sup 188} Re, for radioimmunotherapy (RIT) of brain tumors began in the Republic of Cuba in 2002. This monoclonal antibody was obtained in the country and it is required to evaluate its toxicity, biodistribution and internal radiation dosimetry. Five groups of three patients of each one with an administered activity from 0.37 GBq to 1.1 GBq, are considered. The aim of this work is to assess workers doses and public doses for this research and to compare projected doses with the first results related to the radiological surveillance. The contribution to the total effective dose and equivalent dose in extremities are calculated with the code Microshield version 4.0 by each activity level, operation and total quantity of patients. We take into account radioactive decay of {sup 188} Re and consider that only a person made all of the operations during this study. It is demonstrated that individual doses are acceptable and lower than world average effective annual dose of natural radiation background (2.4 mSv), because for the operations of more risk are used individual protection means. Nevertheless, it is identified that nurses are the most exposed. The projected maximum equivalent dose to hands is about 4 mSv and it belongs to the neurosurgeon. Radiological surveillance is performed to verify our calculations. Five workers and public (four individuals) are monitoring for each patient with direct reading dosimeters DOSICARD and TLD for extremities. For the first seven patients results are obtained. The conservative assumptions in the dose assessment and the compliance with established safety procedures determine that the registered doses are lower than those were projected. RIT with 188 Re for high-grade astrocytomas is a safety practice from radiation protection point of view. There is not a reference of a similar study in Latin America. (author)

  19. 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

    Background 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. Methods 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). Results 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%. Conclusion 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. PMID:25053853

  20. Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma

    International Nuclear Information System (INIS)

    Narayana, Ashwatha; Kunnakkat, Saroj D.; Medabalmi, Praveen; Golfinos, John; Parker, Erik; Knopp, Edmond; Zagzag, David; Eagan, Patricia; Gruber, Deborah; Gruber, Michael L.

    2012-01-01

    Purpose: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. Methods and Materials: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. Results: At a median follow-up of 7 months (range, 1–37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R 2 = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). Conclusion: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials.

  1. First results of the radiological surveillance of RIT trial for high grade astrocytomas in Cuba

    International Nuclear Information System (INIS)

    Amador Balbona, Z.H.; Pardo Ayra, F.E.; Torres Berdeguez, M.B.

    2004-01-01

    The first phase of the clinical trial using the humanized monoclonal antibody h-R3 labeled with 188 Re, for radioimmunotherapy (RIT) of brain tumors began in the Republic of Cuba in 2002. This monoclonal antibody was obtained in the country and it is required to evaluate its toxicity, biodistribution and internal radiation dosimetry. Five groups of three patients of each one with an administered activity from 0.37 GBq to 1.1 GBq, are considered. The aim of this work is to assess workers doses and public doses for this research and to compare projected doses with the first results related to the radiological surveillance. The contribution to the total effective dose and equivalent dose in extremities are calculated with the code Microshield version 4.0 by each activity level, operation and total quantity of patients. We take into account radioactive decay of 188 Re and consider that only a person made all of the operations during this study. It is demonstrated that individual doses are acceptable and lower than world average effective annual dose of natural radiation background (2.4 mSv), because for the operations of more risk are used individual protection means. Nevertheless, it is identified that nurses are the most exposed. The projected maximum equivalent dose to hands is about 4 mSv and it belongs to the neurosurgeon. Radiological surveillance is performed to verify our calculations. Five workers and public (four individuals) are monitoring for each patient with direct reading dosimeters DOSICARD and TLD for extremities. For the first seven patients results are obtained. The conservative assumptions in the dose assessment and the compliance with established safety procedures determine that the registered doses are lower than those were projected. RIT with 188 Re for high-grade astrocytomas is a safety practice from radiation protection point of view. There is not a reference of a similar study in Latin America. (author)

  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. Serous tubal intraepithelial carcinomas associated with high-grade serous ovarian carcinomas: a systematic review.

    Science.gov (United States)

    Chen, F; Gaitskell, K; Garcia, M J; Albukhari, A; Tsaltas, J; Ahmed, A A

    2017-05-01

    Serous tubal intraepithelial carcinomas (STICs) have been documented in high-grade serous ovarian carcinomas (HGSOCs). However, the rate of association between STICs and HGSOCs and, therefore, the fraction of HGSOCs that are likely to have originated from the fallopian tube (FT), has remained unclear. To appraise the literature describing the association between STICs and established HGSOCs. Ovid MEDLINE and EMBASE were searched. Studies were included if they evaluated the frequency of STICs in HGSOCs, and were published in an English peer-reviewed journal. Appropriate studies were evaluated for their compliance with the 'Strengthening and Reporting of Observational Studies in Epidemiology (STROBE)' criteria. Ten articles met the study selection criteria. The reported coexistence between STICs and HGSOCs ranged from 11% to 61% (mean: 31%, 95% CI: 17-46%). STICs were rarely found in other gynaecological cancers. Small sample size, lack of objective criteria to identify STICs and the retrospective nature of the studies contributed to the variability in reporting the rate of the association. STICs were identified commonly in the FTs of women with HGSOC. Finding the true rate of association between STICs and HGSOCs will require further investigations. While there is evidence that a fraction of HGSOCs arise from the FTs, an accurate estimate of that fraction remains to be determined. The lack of an accurate estimate of the association makes it difficult to evaluate the potential magnitude of reduction of HGSOCs following prophylactic salpingectomy. A systematic review of the incidence of STICs in HGSOCs identifies significant methodological inconsistencies. © 2017 Royal College of Obstetricians and Gynaecologists.

  4. Natural history of de novo High Grade Glioma: first description of growth parabola.

    Science.gov (United States)

    Altieri, Roberto; Hirono, Seiichiro; Duffau, Hugues; Ducati, Alessandro; Fontanella, Marco; LA Rocca, Giuseppe; Melcarne, Antonio; Panciani, Pier P; Spena, Giannantonio; Garbossa, Diego

    2017-07-26

    Etiopathogenesis and physiopathology of gliomas are largely unknown. Recently, many authors have proved a strict correlation between the velocity of diametric expansion (VDE) on the Magnetic Resonance Imaging (MRI) and the biological behavior of these tumors, especially in Low Grade Gliomas (LGGs). Unfortunately, natural history of High Grade Gliomas (HGGs) has not been well clarified because of its fast progression, late diagnoses and early surgical intervention. We describe, for the first time to our knowledge, the case of asymptomatic patient with an incidentally discovered de novo HGG with a total of 17 months of follow-up. A male patient was referred to our consultation for routinely follow-up after meningioma resection 5 years before. He underwent MRI every year without any neuroradiological alterations. A new MRI image presented a non-enhancing lesion in the right temporal lobe with 3.55 cm of Mean Tumor Diameter (MTD) and 35.6 mm/year of VDE. After two months interval, the lesion had 3.97 cm of MTD and 27.8 mm/year of VDE. Although we have strongly suggested surgical resection, patient have delayed the operation for personal issues. After other 3 months, the tumor showed enhancement with 4.5 of MTD and 17.4 mm/year of VDE. We speculate that the descending parabola is due to initial mass effect and hypoxia of the tumor core. We also underline the crucial role of the VDE determining, in order to predict the nature of the lesion and address the most effective treatment for each patient.

  5. 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.

  6. Dynamics of the Intratumoral Immune Response during Progression of High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Mandy Stanske

    2018-03-01

    Full Text Available PURPOSE: Tumor-infiltrating lymphocytes (TILs have an established impact on the prognosis of high-grade serous ovarian carcinoma (HGSOC, however, their role in recurrent ovarian cancer is largely unknown. We therefore systematically investigated TIL densities and MHC class I and II (MHC1, 2 expression in the progression of HGSOC. EXPERIMENTAL DESIGN: CD3+, CD4+, CD8+ TILs and MHC1, 2 expression were evaluated by immunohistochemistry on tissue microarrays in 113 paired primary and recurrent HGSOC. TILs were quantified by image analysis. All patients had been included to the EU-funded OCTIPS FP7 project. RESULTS: CD3+, CD4+, CD8+ TILs and MHC1 and MHC2 expression showed significant correlations between primary and recurrent tumor levels (Spearman rho 0.427, 0.533, 0.361, 0.456, 0.526 respectively; P<.0001 each. Paired testing revealed higher CD4+ densities and MHC1 expression in recurrent tumors (Wilcoxon P=.034 and P=.018. There was also a shift towards higher CD3+ TILs levels in recurrent carcinomas when analyzing platinum-sensitive tumors only (Wilcoxon P=.026 and in pairs with recurrent tumor tissue from first relapse only (Wilcoxon P=.031. High MHC2 expression was the only parameter to be significantly linked to prolonged progression-free survival after first relapse (PFS2, log-rank P=.012. CONCLUSIONS: This is the first study that analyzed the development of TILs density and MHC expression in paired primary and recurrent HGSOC. The level of the antitumoral immune response in recurrent tumors was clearly dependent on the one in the primary tumor. Our data contribute to the understanding of temporal heterogeneity of HGSOC immune microenvironment and have implications for selection of samples for biomarker testing in the setting of immune-targeting therapeutics.

  7. Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma

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    Narayana, Ashwatha, E-mail: ashwatha.narayana@nyumc.org [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Department of Neurosurgery, New York University Langone Medical Center, New York, NY (United States); Kunnakkat, Saroj D. [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Medabalmi, Praveen [Department of Biostatistics, New York University Langone Medical Center, New York, NY (United States); Golfinos, John; Parker, Erik [Department of Neurosurgery, New York University Langone Medical Center, New York, NY (United States); Knopp, Edmond [Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Zagzag, David [Department of Pathology, New York University Langone Medical Center, New York, NY (United States); Eagan, Patricia [Department of Neuro-Oncology, New York University Langone Medical Center, New York, NY (United States); Atlantic Health System, Overlook Hospital, Summit, NJ (United States); Gruber, Deborah [Department of Neuro-Oncology, New York University Langone Medical Center, New York, NY (United States); Gruber, Michael L. [Department of Neurosurgery, New York University Langone Medical Center, New York, NY (United States); Department of Neuro-Oncology, New York University Langone Medical Center, New York, NY (United States); Atlantic Health System, Overlook Hospital, Summit, NJ (United States)

    2012-01-01

    Purpose: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. Methods and Materials: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. Results: At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R{sup 2} = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). Conclusion: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials.

  8. Liquid nitrogen spray cryotherapy in Barrett's esophagus with high-grade dysplasia: long-term results.

    Science.gov (United States)

    Gosain, Sonia; Mercer, Kim; Twaddell, William S; Uradomo, Lance; Greenwald, Bruce D

    2013-08-01

    Liquid nitrogen endoscopic spray cryotherapy can safely and effectively eradicate high-grade dysplasia in Barrett's esophagus (BE-HGD). Long-term data on treatment success and safety are lacking. To assess the long-term safety and efficacy of spray cryotherapy in patients with BE-HGD. Single-center, retrospective study. Tertiary-care referral center. A total of 32 patients with BE-HGD of any length. Patients were treated with liquid nitrogen spray cryotherapy every 8 weeks until complete eradication of HGD (CE-HGD) and intestinal metaplasia (CE-IM) was found by endoscopic biopsy. Surveillance endoscopy with biopsies was performed for at least 2 years. CE-HGD, CE-IM, durability of response, disease progression, and adverse events. CE-HGD was 100% (32/32), and CE-IM was 84% (27/32) at 2-year follow-up. At last follow-up (range 24-57 months), CE-HGD was 31/32 (97%), and CE-IM was 26/32 (81%). Recurrent HGD was found in 6 (18%), with CE-HGD in 5 after repeat treatment. One patient progressed to adenocarcinoma, downgraded to HGD after repeat cryotherapy. BE segment length ≥3 cm was associated with a higher recurrence of IM (P = .004; odds ratio 22.6) but not HGD. No serious adverse events occurred. Stricture was seen in 3 patients (9%), all successfully dilated. Retrospective study design, small sample size. In patients with BE-HGD, liquid nitrogen spray cryotherapy has an acceptable safety profile and success rate for eliminating HGD and IM and is associated with a low rate of recurrence or progression to cancer with long-term follow-up. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  9. Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin

    International Nuclear Information System (INIS)

    Paganelli, G.; Grana, C.; Chinol, M.; Cremonesi, M.; De Cicco, C.; Zoboli, S.; De Braud, F.; Robertson, C.; Zurrida, S.; Veronesi, U.; Casadio, C.; Siccardi, A.G.

    1999-01-01

    While the incidence of brain tumours seems to be increasing, median survival in patients with glioblastoma remains less than 1 year, despite improved diagnostic imaging and neurosurgical techniques, and innovations in treatment. We have developed an avidin-biotin pre-targeting approach for delivering therapeutic radionuclides to gliomas, using anti-tenascin monoclonal antibodies, which seems potentially effective for treating these tumours. We treated 48 eligible patients with histologically confirmed grade III or IV glioma and documented residual disease or recurrence after conventional treatment. Three-step radionuclide therapy was performed by intravenous administration of 35 mg/m 2 of biotinylated anti-tenascin monoclonal antibody (1st step), followed 36 h later by 30 mg of avidin and 50 mg of streptavidin (2nd step), and 18-24 h later by 1-2 mg of yttrium-90-labelled biotin (3rd step). 90 Y doses of 2.22-2.96 GBq/m 2 were administered; maximum tolerated dose (MTD) was determined at 2.96 GBq/m 2 . Tumour mass reduction (>25%-100%), documented by computed tomography or magnetic resonance imaging, occurred in 12/48 patients (25%), with 8/48 having a duration of response of at least 12 months. At present, 12 patients are still in remission, comprising four with a complete response, two with a parital response, two with a minor response and four with stable disease. Median survival from 90 Y treatment is 11 months for grade IV glioblastoma and 19 months for grade III anaplastic gliomas. Avidin-biotin based three-step radionuclide therapy is well tolerated at the dose of 2.2 GBq/m 2 , allowing the injection of 90 Y-biotin without bone marrow transplantation. This new approach interferes with the progression of high-grade glioma and may produce tumour regression in patients no longer responsive to other therapies. (orig.)

  10. 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.

  11. 3D-conformal radiotherapy treatment of high grade gliomas of malignancy

    International Nuclear Information System (INIS)

    Chon Rivas, Ivonne; Chi Ramirez, Daysi; Alert Silva, Jose; Roca Muchuli, Carlos; Leon Gonzalez, Roberto; Perez Penna, Lourdes

    2009-01-01

    Patients diagnosed with high grade gliomas of malignancy (A), have a high mortality rate, about 10% achieve survivals than one year due to poor local control resulting from the inability of high doses of radiation to tumor volume by dose-limiting provided by healthy peritumoral tissues and structures. 3D conformal radiotherapy (RT-3DC) achieves effective tumoricidal high doses with high precision on the tumor with minimal involvement of critical structures near the tumor target volume. From 2005 until 2008 at INOR, a total of 23 patients with histologically confirmed supratentorial gliomas location, histological subtypes of anaplastic astrocytoma (AA) in 8 patients (35%) and Glioblastoma Multiforme (GBM) in 15 patients (65%), aged between 18 and 65, Karnofski scale of 70 or more and total previous surgical resection in 10 patients (43%) or partial in 13 (57%) were included prospectively in this study. The total tumor dose of 66-70 Gy was prescribed with a daily fractionation of 1.8 Gy. All patients underwent CT images (CT) and MRI (MRI) cranial volumes were defined treatment planning according to the concepts of ICRU 50 and 62 with precise immobilization of the head by thermo deformed mask, CT 3mm cuts planning system and 3D treatment planning. Median survival was better in patients younger than 55 years, with high rates of Karnofski, histology of AA and higher percentage of surgical resection. Median survival (Kaplan-Meier method) obtained was 16 months. Survival at 1 and 2 years was 51% and 28% respectively. The RT-3DC can administer higher doses on the tumor with peritumoral healthy protection structures in selected patients with a diagnosis of AA or GBM, increasing local control and potentially overall survival without exacerbating toxicity, thus demonstrating the dose- response of malignant brain tumors. (Author)

  12. Clinical outcomes of gamma knife radiosurgery in the salvage treatment of patients with recurrent high-grade glioma.

    Science.gov (United States)

    Elaimy, Ameer L; Mackay, Alexander R; Lamoreaux, Wayne T; Demakas, John J; Fairbanks, Robert K; Cooke, Barton S; Lamm, Andrew F; Lee, Christopher M

    2013-12-01

    Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external beam radiation therapy and chemotherapy when compared to patients treated with external beam radiation therapy and chemotherapy alone. In recent years, gamma knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of gamma knife radiosurgery for patients who suffer from this malignancy. Retrospective, prospective, and randomized clinical studies published between the years 2000 and 2012 analyzing gamma knife radiosurgery for patients with high-grade glioma were reviewed. After assessing patient age, Karnofsky performance status, tumor histology, and extent of resection, gamma knife radiosurgery is a viable, minimally invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that gamma knife radiosurgery provides patients with a high local tumor control rate and a median survival after tumor recurrence ranging from 13 to 26 months. Gamma knife radiosurgery followed by chemotherapy for recurrent high-grade glioma may provide select patients with increased levels of survival. However, further investigation into this matter is needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities of fractionated gamma knife radiosurgery due to its potential to limit treatment-associated morbidity. Gamma knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating

  13. Enhancing transit service in rural areas and native american tribal communities : potential mechanisms to improve funding and service.

    Science.gov (United States)

    2014-08-01

    Primary funding for rural transit comes from federal and state Departments of Transportation (DOTs). However, through numerous : surveys, rural transit providers have cited financial constraints as a major limitation to providing adequate desired tra...

  14. 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

  15. HPV type-related chromosomal profiles in high-grade cervical intraepithelial neoplasia

    Directory of Open Access Journals (Sweden)

    Bierkens Mariska

    2012-01-01

    Full Text Available Abstract Background The development of cervical cancer and its high-grade precursor lesions (Cervical Intraepithelial Neoplasia grade 2/3 [CIN2/3] result from a persistent infection with high-risk human papillomavirus (hrHPV types and the accumulation of (epigenetic host cell aberrations. Epidemiological studies have demonstrated variable CIN2/3 and cancer risks between different hrHPV types. Recent genomic profiling studies revealed substantial heterogeneity in the chromosomal aberrations detected in morphologically indistinguishable CIN2/3 suggestive of varying cancer risk. The current study aimed to investigate whether CIN2/3 with different hrHPV types vary with respect to their chromosomal profiles, both in terms of the number of aberrations and chromosomal loci affected. Methods Chromosomal profiles were determined of 43 p16INK4a-immunopositive CIN2/3 of women with long-term hrHPV infection (≥ 5 years. Sixteen lesions harboured HPV16, 3 HPV18, 14 HPV31, 1 HPV33, 4 HPV45, 1 HPV51, 2 HPV52 and 2 HPV58. Results Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two major clusters, characterised by either few or multiple chromosomal aberrations, respectively. A majority of 87.5% of lesions with HPV16 were in the cluster with relatively few aberrations, whereas no such unbalanced distribution was seen for lesions harbouring other hrHPV types. Analysis of the two most prevalent types (HPV16 and HPV31 in this data set revealed a three-fold increase in the number of losses in lesions with HPV31 compared to HPV16-positive lesions. In particular, losses at chromosomes 2q, 4p, 4q, 6p, 6q, 8q & 17p and gain at 1p & 1q were significantly more frequent in HPV31-positive lesions (FDR Conclusions Chromosomal aberrations in CIN2/3 are at least in part related to the hrHPV type present. The relatively low number of chromosomal aberrations observed in HPV16-positive CIN2/3 suggests that the development of these lesions is

  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. Acute high-grade acromioclavicular dislocations treated with triple button device (MINAR): Preliminary results.

    Science.gov (United States)

    Cano-Martínez, José Antonio; Nicolás-Serrano, Gregorio; Bento-Gerard, Julio; Picazo-Marín, Francisco; Andrés-Grau, Josefina

    2016-11-01

    Describe the clinical and radiological results of triple button device in the treatment of high-grade AC dislocations (Rockwood, type V) and assess whether improves vertical and horizontal stability compared to the techniques previously described. This retrospective study included 39 patients with type V acromioclavicular dislocations treated with Twin Tail TightRope™ system (triple button device). Of the 39 patients, 33 (26 men and 7 women) were able to participate in clinical and radiographic follow up. At the time of surgery, the mean age was 25years±7(range, 17-49). All patients underwent bilateral-weighted Zanca (CC distance) and Alexander view (AC distance) as well as the Constant Score (CS) and Acromioclavicular Joint Instability Scoring System (ACJI). Radiological and clinical outcome was assessed during routine follow-up examinations preoperatively, postoperatively, 1, 3, 6 months and every year after the surgery. The presence of calcification, degenerative changes, mobilization of implants and bone resorption were also assessed. After a mean follow up of 25±4months (range 14-38), the results of the Constant (CS) were 94.1±5,5 (range 76-100) and test ACJI 87.3±9,8 (range 65-100), showing no significant differences with the uninjured shoulder (CS 95.8±2.5, range 83-100; ACJI 94.1±3.7, range 80-100). At final review, we observed that preoperative coracoclavicular distance (Zanca View) improved from 21,75±1.97mm to 8,73mm±0.75 and the acromioclavicular distance (Alexander View) from 12,65mm±1.99 to 0,35±0.3mm. Compared with healthy shoulder, these differences were not significant. There was no loss of reduction with this system in the vertical plane. 4 patients (12.12%) revealed signs of posterior instability with worse clinical test results. The presence of degenerative joint changes (6,06%), calcifications (27,2%) or mobilization of the implant (18,18%) was not associated with worse clinical outcomes. Twin Tail device using minimally invasive

  18. 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

  19. The Swedish infant high-grade reflux trial: UTI and renal damage.

    Science.gov (United States)

    Nordenström, Josefin; Sjöström, Sofia; Sillén, Ulla; Sixt, Rune; Brandström, Per

    2017-04-01

    High-grade vesicoureteral reflux (VUR) in children is associated with recurrent urinary tract infection (UTI) and renal damage. Breakthrough UTI despite continuous antibiotic prophylaxis (CAP) during the first years of life is a matter of concern and evokes early intervention. We investigated whether early endoscopic treatment (ET) of VUR grade 4-5 can reduce the risk of UTI recurrence and renal scarring. This prospective, randomized, controlled, multicentre, 1-year follow-up trial comprised 77 infants, UTIs were reported. There were 27 recurrent febrile UTIs in 6 (16%) children in the ET group and in 10 (26%) in the CAP group (p = 0.43), in eight (36%) girls and eight (15%) boys (p = 0.039). Successful VUR outcome (VUR 0-2) was seen in 22 (59%) in the ET and eight (21%) in the CAP group (p = 0.0014). Multiple recurrences were only seen in patients with persistent dilating reflux at follow-up (p = 0.019). Deterioration on scintigraphy was seen in eight children (9 kidneys) with no difference between treatment groups (p = 0.48) or sex (p = 0.17). Renal deterioration was associated with high bladder capacity (BC) and large residual volume (PVR) at 1 year (p = 0.0092 and p = 0.041). Six of the eight children with renal deterioration had a recurrent UTI (p = 0.0032). Seven of nine renal units with deterioration were seen in children with persistent VUR 3-5 at follow-up. Univariable logistic regression identified female sex and high PVR as positive predictors for recurrent UTI (p = 0.039 and 0.034) and high PVR tended to predict renal deterioration (p = 0.053). No differences between the treatment groups regarding recurrent UTI and renal deterioration could be found. Increased PVR and female sex were positive predictors for UTI recurrences. VUR grade at follow-up was correlated to UTI recurrence and renal deterioration. This study did not show any difference between ET and CAP in reducing the risk of UTI recurrence or renal deterioration. The rate

  20. Clinical outcome of trans-sacral interbody fusion after partial reduction for high-grade l5-s1 spondylolisthesis.

    Science.gov (United States)

    Smith, J A; Deviren, V; Berven, S; Kleinstueck, F; Bradford, D S

    2001-10-15

    A clinical retrospective study was conducted. To evaluate the clinical and radiographic outcome of reduction followed by trans-sacral interbody fusion for high-grade spondylolisthesis. In situ posterior interbody fusion with fibula allograft has improved the fusion rates for patients with high-grade spondylolisthesis. The use of this technique in conjunction with partial reduction has not been reported. Nine consecutive patients underwent treatment of high-grade (Grade 3 or 4) spondylolisthesis with partial reduction followed by posterior interbody fusion using cortical allograft. The average age at the time of surgery was 27 years (range, 8-51 years), and the average follow-up period was 43 months (range, 24-72 months). Before surgery, eight patients had low back pain, seven patients had radiating leg pain, and five patients had hamstring tightness. The average grade of spondylolisthesis by Meyerding grading was 3.9 (range, 3-5). Charts and radiographs were evaluated, and outcomes were collected by use of the modified SRS outcomes instrument. Radiographic indexes demonstrated significant improvement with partial reduction and fusion. The slip angle, as measured from the inferior endplate of L5, improved from 41.2 degrees (range, 24-82 degrees ) before surgery to 21 degrees (range, 5-40 degrees ) after surgery. All the patients were extremely or somewhat satisfied with surgery. The two patients who underwent this operation without initial instrumentation experienced fractures of their interbody grafts. Both of these patients underwent repair of the pseudarthrosis with placement of trans-sacral pedicle screw instrumentation and subsequent fusion. Partial reduction followed by posterior interbody fusion is an effective technique for the management of high-grade spondylolisthesis in pediatric and adult patient populations, as assessed by radiographic and clinical criteria. Pedicle screw instrumentation with the sacral screws capturing L5 is recommended when this

  1. Patterns of failure after multimodal treatments for high-grade glioma: effectiveness of MIB-1 labeling index

    International Nuclear Information System (INIS)

    Uehara, Kazuyuki; Fujii, Osamu; Soejima, Toshinori; Sugimura, Kazuro; Kohmura, Eiji; Sasaki, Ryohei; Sasayama, Takashi; Miyawaki, Daisuke; Nishimura, Hideki; Yoshida, Kenji; Okamoto, Yoshiaki; Mukumoto, Naritoshi; Akasaka, Hiroaki; Nishihara, Masamitsu

    2012-01-01

    The purpose of the present study was to analyze the recurrence pattern of high-grade glioma treated with a multimodal treatment approach and to evaluate whether the MIB-1 labeling index (LI) could be a useful marker for predicting the pattern of failure in glioblastoma (GB). We evaluated histologically confirmed 131 patients with either anaplastic astrocytoma (AA) or GB. A median dose was 60 Gy. Concomitant and adjuvant chemotherapy were administered to 111 patients. MIB-1 LI was assessed by immunohistochemistry. Recurrence patterns were categorized according to the areas of recurrence as follows: central failure (recurrence in the 95% of 60 Gy); in-field (recurrence in the high-dose volume of 50 Gy; marginal (recurrence outside the high-dose volume) and distant (recurrence outside the RT field). The median follow-up durations were 13 months for all patients and 19 months for those remaining alive. Among AA patients, the 2-year progression-free and overall survival rates were 23.1% and 39.2%, respectively, while in GB patients, the rates were 13.3% and 27.6%, respectively. The median survival time was 20 months for AA patients and 15 months for GB patients. Among AA patients, recurrences were central in 68.7% of patients; in-field, 18.8%; and distant, 12.5%, while among GB patients, 69.0% of recurrences were central, 15.5% were in-field, 12.1% were marginal, and 3.4% were distant. The MIB-1 LI medians were 18.2% in AA and 29.8% in GB. Interestingly, in patients with GB, the MIB-1 LI had a strong effect on the pattern of failure (P = 0.014), while the extent of surgical removal (P = 0.47) and regimens of chemotherapy (P = 0.57) did not. MIB-1 LI predominantly affected the pattern of failure in GB patients treated with a multimodal approach, and it might be a useful tool for the management of the disease

  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

    and Embase were searched for literature published from 1995 to May 2013. Data from eight studies were reviewed for substantive methods and results. Methodological quality was described and assessed using the scoring system for appraising mixed methods research and concomitantly appraising qualitative......, 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....... CONCLUSIONS: As evidence is beginning to emerge, there is a need for well-designed longitudinal and randomised controlled trials of non-pharmacological interventions in high-grade glioma patients and their caregivers in order to develop clinical guidelines for supportive and rehabilitative approaches...

  3. Longitudinal DSC-MRI for Distinguishing Tumor Recurrence From Pseudoprogression in Patients With a High-grade Glioma.

    Science.gov (United States)

    Boxerman, Jerrold L; Ellingson, Benjamin M; Jeyapalan, Suriya; Elinzano, Heinrich; Harris, Robert J; Rogg, Jeffrey M; Pope, Whitney B; Safran, Howard

    2017-06-01

    For patients with high-grade glioma on clinical trials it is important to accurately assess time of disease progression. However, differentiation between pseudoprogression (PsP) and progressive disease (PD) is unreliable with standard magnetic resonance imaging (MRI) techniques. Dynamic susceptibility contrast perfusion MRI (DSC-MRI) can measure relative cerebral blood volume (rCBV) and may help distinguish PsP from PD. A subset of patients with high-grade glioma on a phase II clinical trial with temozolomide, paclitaxel poliglumex, and concurrent radiation were assessed. Nine patients (3 grade III, 6 grade IV), with a total of 19 enhancing lesions demonstrating progressive enhancement (≥25% increase from nadir) on postchemoradiation conventional contrast-enhanced MRI, had serial DSC-MRI. Mean leakage-corrected rCBV within enhancing lesions was computed for all postchemoradiation time points. Of the 19 progressively enhancing lesions, 10 were classified as PsP and 9 as PD by biopsy/surgery or serial enhancement patterns during interval follow-up MRI. Mean rCBV at initial progressive enhancement did not differ significantly between PsP and PD (2.35 vs. 2.17; P=0.67). However, change in rCBV at first subsequent follow-up (-0.84 vs. 0.84; P=0.001) and the overall linear trend in rCBV after initial progressive enhancement (negative vs. positive slope; P=0.04) differed significantly between PsP and PD. Longitudinal trends in rCBV may be more useful than absolute rCBV in distinguishing PsP from PD in chemoradiation-treated high-grade gliomas with DSC-MRI. Further studies of DSC-MRI in high-grade glioma as a potential technique for distinguishing PsP from PD are indicated.

  4. MGMT promoter methylation determined by HRM in comparison to MSP and pyrosequencing for predicting high-grade glioma response.

    Science.gov (United States)

    Switzeny, Olivier J; Christmann, Markus; Renovanz, Mirjam; Giese, Alf; Sommer, Clemens; Kaina, Bernd

    2016-01-01

    The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) causes resistance of cancer cells to alkylating agents and, therefore, is a well-established predictive marker for high-grade gliomas that are routinely treated with alkylating drugs. Since MGMT is highly epigenetically regulated, the MGMT promoter methylation status is taken as an indicator of MGMT silencing, predicting the outcome of glioma therapy. MGMT promoter methylation is usually determined by methylation specific PCR (MSP), which is a labor intensive and error-prone method often used semi-quantitatively. Searching for alternatives, we used closed-tube high resolution melt (HRM) analysis, which is a quantitative method, and compared it with MSP and pyrosequencing regarding its predictive value. We analyzed glioblastoma cell lines with known MGMT activity and formalin-fixed samples from IDH1 wild-type high-grade glioma patients (WHO grade III/IV) treated with radiation and temozolomide by HRM, MSP, and pyrosequencing. The data were compared as to progression-free survival (PFS) and overall survival (OS) of patients exhibiting the methylated and unmethylated MGMT status. A promoter methylation cut-off level relevant for PFS and OS was determined. In a multivariate Cox regression model, methylation of MGMT promoter of high-grade gliomas analyzed by HRM, but not MSP, was found to be an independent predictive marker for OS. Univariate Kaplan-Meier analyses revealed for PFS and OS a significant and better discrimination between methylated and unmethylated tumors when quantitative HRM was used instead of MSP. Compared to MSP and pyrosequencing, the HRM method is simple, cost effective, highly accurate and fast. HRM is at least equivalent to pyrosequencing in quantifying the methylation level. It is superior in predicting PFS and OS of high-grade glioma patients compared to MSP and, therefore, can be recommended being used routinely for determination of the MGMT status of gliomas.

  5. PAX1 methylation analysis by MS-HRM is useful in triage of high-grade squamous intraepithelial lesions.

    Science.gov (United States)

    Wang, Zhen-Ming

    2014-01-01

    This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylation- sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study, 130 cases with a diagnosis of ASC-H from the cervical cytological screening by Thinprep cytologic test (TCT) technique were selected for triage. Their cervical scrapings were collected and evaluated by using PAX1 methylation analysis (MS-HRM) and high-risk HPV DNA test (HC2), followed by colposcopy and cervical biopsy. Chi-square test were used to test the differences of PAX1 methylation or HPV infection between groups. In the detection of CIN2+, the sensitivity, specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV (HR-HPV) tests were respectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%, 94.0% vs 84.4%, and 91.5% vs 57.7%. The PAX1 MS-HRM assay proved superior to HR-HPV testing in the detection of high grade lesions (CIN2+) in ASC-H. This approach could screen out the majority of high grade lesion cases of ASC-H, and thus could reduce the referral rate to colposcopy.

  6. Angio-Architectural Features of High-Grade Intracranial Dural Arteriovenous Fistulas: Correlation With Aggressive Clinical Presentation and Hemorrhagic Risk.

    Science.gov (United States)

    Della Pepa, Giuseppe Maria; Parente, Paolo; D'Argento, Francesco; Pedicelli, Alessandro; Sturiale, Carmelo Lucio; Sabatino, Giovanni; Albanese, Alessio; Puca, Alfredo; Fernandez, Eduardo; Olivi, Alessando; Marchese, Enrico

    2017-08-01

    High-grade dural arteriovenous fistulas (dAVFs) can present shunts with very different angio-architectural characteristics. Specific hemodynamic factors may affect clinical history and determine very different clinical courses. To evaluate the relationship between some venous angio-architectural features in high-grade dAVFs and clinical presentation. Specific indicators of moderate or severe venous hypertension were analyzed, such as altered configurations of the dural sinuses (by a single or a dual thrombosis), or overload of cortical vessels (restrictions of outflow, pseudophlebitic cortical vessels, and venous aneurysms). The institutional series was retrospectively reviewed (49 cases), and the pattern of venous drainage was analyzed in relationship with clinical presentation (benign/aggressive/hemorrhage). Thirty-five of 49 cases displayed cortical reflux (high-grade dAVFs). This subgroup displayed a benign presentation in 31.42% of cases, an aggressive in 31.42%, and hemorrhage in 37.14%. Our data confirm that within high-grade dAVFs, 2 distinct subpopulations exist according to severity of clinical presentation. Some indicators we examined showed correlation with aggressive nonhemorrhagic manifestations (outflow restriction and pseudophlebitic cortical vessels), while other showed a correlation with hemorrhage (dual thrombosis and venous aneurysms). Current classifications appear insufficient to identify a wide range of conditions that ultimately determine the organization of the cortical venous drainage. Intermediate degrees of venous congestion correlate better with the clinical risk than the simple definition of cortical reflux. The angiographic aspects of venous drainage presented in this study may prove useful to assess dAVF hemodynamic characteristics and identify conditions at higher clinical risk. Copyright © 2017 by the Congress of Neurological Surgeons

  7. Improvement in High-Grade Osteosarcoma Survival: Results from 202 Patients Treated at a Single Institution in Taiwan.

    Science.gov (United States)

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-04-01

    The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995-2003 vs 2004-2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%-16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients.

  8. Improved Survival With Radiation Therapy in High-Grade Soft Tissue Sarcomas of the Extremities: A SEER Analysis

    International Nuclear Information System (INIS)

    Koshy, Matthew; Rich, Shayna E.; Mohiuddin, Majid M.

    2010-01-01

    Purpose: The benefit of radiation therapy in extremity soft tissue sarcomas remains controversial. The purpose of this study was to determine the effect of radiation therapy on overall survival among patients with primary soft tissue sarcomas of the extremity who underwent limb-sparing surgery. Methods and Materials: A retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included data from January 1, 1988, to December 31, 2005. A total of 6,960 patients constituted the study population. Overall survival curves were constructed using the Kaplan-Meir method and for patients with low- and high-grade tumors. Hazard ratios were calculated based on multivariable Cox proportional hazards models. Results: Of the cohort, 47% received radiation therapy. There was no significant difference in overall survival among patients with low-grade tumors by radiation therapy. In high-grade tumors, the 3-year overall survival was 73% in patients who received radiation therapy vs. 63% for those who did not receive radiation therapy (p < 0.001). On multivariate analysis, patients with high-grade tumors who received radiation therapy had an improved overall survival (hazard ratio 0.67, 95% confidence interval 0.57-0.79). In patients receiving radiation therapy, 13.5% received it in a neoadjuvant setting. The incidence of patients receiving neoadjuvant radiation did not change significantly between 1988 and 2005. Conclusions: To our knowledge, this is the largest population-based study reported in patients undergoing limb-sparing surgery for soft tissue sarcomas of the extremities. It reports that radiation was associated with improved survival in patients with high-grade tumors.

  9. 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.

  10. [High-grade pressure sores in frail older high-risk persons. A retrospective postmortem case-control-study].

    Science.gov (United States)

    Von Renteln-Kruse, W; Krause, T; Anders, J; Kühl, M; Heinemann, A; Püschel, K

    2004-04-01

    Some old persons at risk do develop, but others, at comparable risk, do not develop high-grade pressure sores. To evaluate potentially different risk factors, we performed a post mortem case-control study in old persons who developed high-grade pressure sores within six months until 14 days before death. Consecutive cases with pressure sores grade >/=3 and potential controls at comparably high risk for pressure sores were examined before cremation. After written informed consent had been obtained by the next relatives, all available nursing and medical records of the deceased were thoroughly evaluated. Cases and controls were matched according to age, gender, immobility, and cachexia.A total of 100 cases with 71 pressure sores grade 3 and 29 pressure sores grade 4 were compared to 100 controls with 27 pressure sores grade pressure sores in frail older high-risk persons. Sedative drug effects and impaired patient compliance with preventive and therapeutic measures may also be associated with the development of high-grade pressure sores in old persons at high risk.

  11. World wide web-based cytological analysis of atypical squamous cells cannot exclude high-grade intraepithelial lesions.

    Science.gov (United States)

    Washiya, Kiyotada; Takamizu, Ryuichi; Kumagai, Yukie; Himeji, Yukari; Kobayashi, Takako; Iwai, Muneo; Watanabe, Jun

    2012-01-01

    It has been reported that the low level of consistency of diagnosis of atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions (ASC-H) in uterine cervical cancer screening using the Bethesda System, indicating the necessity of a large-scale survey. We presented cases cytologically judged as ASC-H on our website and invited our members to give their opinions regarding the diagnosis by voting online. The Web voting results were analyzed and ASC-H was cytologically investigated. Virtual slides of atypical cells in cytology preparations of 53 cases were prepared and presented on a website. ASC-H cases were divided into 42 cases sampled by brush scraping and 11 cases sampled by cotton swab scraping. Fifty-three cases cytologically judged as ASC-H were classified into benign and CIN2/3, and their patterns of arrangement of atypical cells and 8 cytological parameters were morphologically investigated. The frequency of ASC-H diagnosis in the Web votes was low: 29.2% for brush-scraped and 26.2% for cotton swab-scraped cases. Three-dimensionality, coarse chromatin and irregular nuclei were significantly different between high-grade squamous intraepithelial lesions and benign cases. Web-based surveys showed the difference of cytological findings between high-grade squamous intraepithelial lesions and benign cases. To increase interobserver consistency, it may be useful to share information online, which avoids geographical and temporal limitations. Copyright © 2012 S. Karger AG, Basel.

  12. One lesion, one virus: individual components of high-grade anal intraepithelial neoplasia in HIV-positive men contain a single HPV type

    NARCIS (Netherlands)

    Richel, Olivier; Quint, Koen D.; Lindeman, Jan; van Noesel, Carel J. M.; de Koning, Maurits N. C.; van den Munckhof, Henk A. M.; de Vries, Henry J. C.; Prins, Jan M.; Quint, Wim G. V.

    2014-01-01

    High-grade anal intraepithelial neoplasia (AIN) is present in many human immunodeficiency virus (HIV)-positive men who have sex with men. The major etiologic factor is infection with an oncogenic human papillomavirus (HPV) genotype. We investigated whether individual components of high-grade AIN are

  13. The health care burden of high grade chronic obstructive pulmonary disease in Korea: analysis of the Korean Health Insurance Review and Assessment Service data.

    Science.gov (United States)

    Kim, JinHee; Rhee, Chin Kook; Yoo, Kwang Ha; Kim, Young Sam; Lee, Sei Won; Park, Yong Bum; Lee, Jin Hwa; Oh, YeonMok; Lee, Sang Do; Kim, Yuri; Kim, KyungJoo; Yoon, HyoungKyu

    2013-01-01

    Patients with high grade chronic pulmonary obstructive disease (COPD) account for much of the COPD-related mortality and incur excessive financial burdens and medical care utilization. We aimed to determine the characteristics and medical care use of such patients using nationwide data from the Korean Health Insurance Review and Assessment Service in 2009. Patients with COPD were identified by searching with the International Classification of Diseases-10th Revision for those using medication. Patients with high grade COPD were selected based on their patterns of tertiary institute visits and medication use. The numbers of patients with high grade COPD increased rapidly in Korea during the study period, and they showed a high prevalence of comorbid disease. The total medical costs were over three times higher in patients with high grade COPD compared with those without it ($3,744 versus $1,183; P system in Korea. Prevention of progression to high grade COPD is important, both clinically and economically.

  14. The value of diffusion weighted imaging in differentiating intracranial tuberculomas from high-grade astrocytomas and metastases

    International Nuclear Information System (INIS)

    Peng Juan; Luo Tianyou; Lv Fajin; Fang Weidong; Wu Jingquan; Ouyang Yu; Li Yongmei

    2007-01-01

    Objective: To explore the value of diffusion weighted imaging (DWI) in differentiating intracranial tuberculomas from high-grade astrocytomas and metastases. Methods: The conventional MR imaging and DWI were performed in 50 eases (14 cases with intracranial tuberculomas, 15 cases with high- grade astrocytomas, and 21 cases with metastases) before treatment or operation. The mean apparent diffusion coefficient (ADC) values and relative apparent diffusion coefficient (rADC) values were calculated from the mass as well as from the peripheral edema regions of intracranial lesions. Results: The mean ADC values and rADC values were (1.2±0.2) x 10 -3 mm 2 ·s -1 and 1.6±0.3 in the mass of intracranial tuberculomas respectively; (0.8±0.1) x 10 -3 mm 2 ·s -1 and 1.1±0.1 in the parenehyma of high-grade astrocytomas; (0.8±0.1) x 10 -3 mm 2 ·s -1 and 1.0±0.2 in the parenchyma of metastases. There was significant difference of the mean ADC values (F=33.57, P -3 mm 2 ·s -1 and 2.5±0.2 in the peripheral edema regions of intracranial tuberculomas respectively; (1.4±0.2) x 10 -3 mm 2 ·s -1 and 1.8±0.3 in the peripheral edema regions of high-grade astrocytomas; and (1.9±0.2) x 10 -3 mm 2 ·s -1 and 2.3±0.5 in the peripheral edema regions of metastases. There was also significant difference in the mean ADC values (F23.17, P<0.01) or rADC values (F=5.94, P<0.01) among the peripheral edema regions of the three groups. Conclusion: The ADC values and rADC values are quite effective in differentiating intracranial tuberculoma from high-grade astrocytoma and metastasis. (authors)

  15. PROPOSING AN INTEGRATIVE-PROGRESSIVE MODEL IN HANDLING TROUBLED INDONESIAN OVERSEAS WORKERS IN THE TRANSIT AREA (A SOCIO-LEGAL RESEARCH IN TANJUNG PINANG CITY, KEPULAUAN RIAU PROVINCE

    Directory of Open Access Journals (Sweden)

    Rina Shahriyani Shahrullah

    2015-12-01

    Full Text Available Tanjung Pinang City of the Riau Islands Province (Provinsi Kepulauan Riau is a transit area for the troubled Indonesian overseas workers from Singapore and Malaysia. The Indonesian National Board for the Placement and Protection of Indonesian Workers (Badan Nasional Penempatan dan Perlindungan Tenaga Kerja Indonesia/BNP2TKI reported that 15,105 troubled Indonesian overseas workers were deported from January to November 2014 via Tanjung Pinang City.  Previous research revealed that citizens of Tanjung Pinang City criticized the treatments given by the local government to the deported workers by reason that they were not the citizens of the Riau Islands Province, yet the local government has to provide shelters and funds prior to returning them to their home towns. The treatments for the deported workers in the transit area have also raised pros and cons among the stakeholders who are in charge of handling the deported workers. This circumstance may not occur if a special regional regulation of the Riau Islands Province has been issued to govern the troubled Indonesian overseas workers in the transit area.  Due to this vacuum of law, this research aims to establish a mechanism in handling the deported workers in the transit area by designing an integrative-progressive model which can be adopted by the stakeholders. The model is to link the legal and non- legal issues and as well as to provide the collaborative mechanisms for the stakeholders based on the approaches of the integrative and progressive legal theory.

  16. "I Am Reading to Her and She Loves It": Benefits of Engaging Fathers from Disadvantaged Areas in Their Children's Early Learning Transitions

    Science.gov (United States)

    Potter, Carol; Walker, Gary; Keen, Bev

    2013-01-01

    Findings presented here relate to the evaluation of a one-year father-inclusion project, which took place in an area of multiple deprivation in the North of England. The project's goal was to engage fathers and male carers in their children's transition from an early years setting to a reception class and to maintain that involvement in the…

  17. General Mechanism of Morphology Transition and Spreading Area-dependent Phase Diagram of Block Copolymer Self-assembly at the Air/Water Interface

    Science.gov (United States)

    Kim, Dong Hyup; Kim, So Youn

    Block copolymers (BCPs) can be self-assembled forming periodic nanostructures, which have been employed in many applications. While general agreements exist for the phase diagrams of BCP self-assembly in bulk or thin films, a fundamental understanding of BCP structures at the air/water interface still remain elusive. The current study explains morphology transition of BCPs with relative fraction of each block at the air/water interface: block fraction is the only parameter to control the morphology. In this study, we show morphology transitions from spherical to cylindrical and planar structures with neat polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) via reducing the spreading area of BCP solution at the air/water interface. For example, PS-b-P2VP in a fixed block fraction known to form only spheres can experience sphere to cylinder or lamellar transitions depending on the spreading area at the air/water interface. Suggesting a new parameter to control the interfacial assembly of BCPs, a complete phase diagram is drawn with two paramters: relative block fraction and spreading area. We also explain the morphology transition with the combinational description of dewetting mechanism and spring effect of hydrophilic block.

  18. 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

  19. Risk of persistent high-grade squamous intraepithelial lesion after electrosurgical excisional treatment with positive margins: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Caroline Alves de Oliveira

    Full Text Available CONTEXT AND OBJECTIVE: Even if precursor lesions of cervical cancer are properly treated, there is a risk of persistence or recurrence. The aim here was to quantify the risks of persistence of high-grade intraepithelial squamous lesions, one and two years after cervical electrosurgical excisional treatment with positive margins. DESIGN AND SETTING: Systematic review of the literature and meta-analysis at Instituto Fernandes Figueira. METHODS: This meta-analysis was on studies published between January 1989 and July 2009 that were identified in Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, ISI Web of Science and Sigle. Articles were selected if they were cohort studies on electrosurgical excisional treatment of high-grade squamous intraepithelial lesions with a minimum follow-up of one year, a histopathological outcome of persistence of these lesions and a small risk of bias. RESULTS: The search identified 7,066 articles and another 21 in the reference lists of these papers. After applying the selection and exclusion criteria, only four articles were found to have extractable data. The risk of persistence of high-grade intraepithelial lesions after one year was 11.36 times greater (95% confidence interval, CI: 5.529-23.379, P < 0.0001 in patients with positive margins and after two years, was four times greater (95% CI: 0.996-16.164, although without statistical significance. CONCLUSION: This meta-analysis confirms the importance of positive margins as an indicator of incomplete treatment after the first year of follow-up and highlights the need for appropriately chosen electrosurgical techniques based on disease location and extent, with close surveillance of these patients.

  20. 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

  1. BMP and TGFbeta pathways in human central chondrosarcoma: enhanced endoglin and Smad 1 signaling in high grade tumors

    International Nuclear Information System (INIS)

    Boeuf, Stephane; Bovée, Judith VMG; Lehner, Burkhard; Akker, Brendy van den; Ruler, Maayke van; Cleton-Jansen, Anne-Marie; Richter, Wiltrud

    2012-01-01

    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. 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. 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. 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

  2. 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

  3. Lack of prognostic significance of C-erbB-2 expression in low- and high- grade astrocytomas.

    Science.gov (United States)

    Muallaoglu, Saik; Besen, Ali Ayberk; Ata, Alper; Mertsoylu, Huseyin; Arican, Ali; Kayaselcuk, Fazilet; Ozyilkan, Ozgur

    2014-01-01

    Astrocytic tumors, the most common primary glial tumors of the central nervous system, are classified from low to high grade according to the degree of anaplasia and presence of necrosis. Despite advances in therapeutic management of high grade astrocytic tumors, prognosis remains poor. In the present study, the frequency and prognostic significance of c-erb-B2 in astrocytic tumors was investigated. Records of 72 patients with low- and high-grade astrocytic tumors were evaluated. The expression of C-erbB-2 was determined immunohistochemically and intensity was recorded as 0 to 3+. Tumors with weak staining (1+) or no staining (0) were considered Her-2 negative, while tumors with moderate (2+) and strong (3+) staining were considered Her-2 positive. Of the 72 patients, 41 (56.9%) had glioblastoma (GBM), 10 (13.9%) had diffuse astrocytoma, 15 (20.8%) had anaplastic astrocytoma, 6 (8.3%) had pilocytic astrocytoma. C-erbB-2 overexpression was detected in the tumor specimens of 17 patients (23.6%). Six (8.3%) tumors, all GBMs, exhibited strong staining, 2 (2.7%) specimens, both GBMs, exhibited moderate staining, and 9 specimens, 5 of them GBMs (12.5%), exhibited weak staining. No staining was observed in diffuse astrocytoma and pilocytic astrocytoma specimens. Median overall survival of patients with C-erbB-2 negative and C-erbB-2 positive tumors were 30 months (95%CI: 22.5-37.4 months) and 16.9 months (95%CI: 4.3-29.5 months), respectively (p=0.244). Although there was no difference in survival, C-erbB-2 overexpression was observed only in the GBM subtype.

  4. Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.

    Science.gov (United States)

    Deevi, Ravi Kiran; Javadi, Arman; McClements, Jane; Vohhodina, Jekaterina; Savage, Kienan; Loughrey, Maurice Bernard; Evergren, Emma; Campbell, Frederick Charles

    2018-04-01

    Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring. PKCz regulates interdependent processes that control centrosome positioning. Among these, interaction between the cytoskeletal linker protein ezrin and its binding partner NHERF1 promotes the formation of a localized cue for anchoring interphase centrosomes to the cell cortex. Perturbation of these phenomena induced different outcomes in cells with single or extra centrosomes. Defective anchoring of a single centrosome promoted bipolar spindle misorientation, multi-lumen formation, and aberrant epithelial stratification. Collectively, these disturbances induce cribriform multicellular morphology that is typical of some categories of low-grade CRC. By contrast, defective anchoring of extra centrosomes promoted multipolar spindle formation, chromosomal instability (CIN), disruption of glandular morphology, and cell outgrowth across the extracellular matrix interface characteristic of aggressive, high-grade CRC. Because PKCz enhances apical NHERF1 intensity in 3D epithelial cultures, we used an immunohistochemical (IHC) assay of apical NHERF1 intensity as an indirect readout of PKCz activity in translational studies. We show that apical NHERF1 IHC intensity is inversely associated with multipolar spindle frequency and high-grade morphology in formalin-fixed human CRC samples. To conclude, defective PKCz control of interphase centrosome anchoring may underlie distinct categories of

  5. Phase I Clinical Trial Assessing Temozolomide and Tamoxifen With Concomitant Radiotherapy for Treatment of High-Grade Glioma

    International Nuclear Information System (INIS)

    Patel, Shilpen; DiBiase, Steven; Meisenberg, Barry; Flannery, Todd; Patel, Ashish; Dhople, Anil; Cheston, Sally; Amin, Pradip

    2012-01-01

    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 2 divided twice daily. If no dose-limiting toxicities (DLTs) occurred in 3 patients, the dose was escalated in 25-mg/m 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 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 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 2 . Conclusions: The MTD of tamoxifen was 100 mg/m 2 when given concurrently with temozolomide 75 mg/m 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.

  6. The high-grade interpolator: a means for enhancing the resolution of helical computed tomography images of the lung

    International Nuclear Information System (INIS)

    Garcia-Santos, J. M.; Torres del rio, S.; Blanco, A.; Rodriguez, R.; Parlorio, E.; Garcia, A.; Girela, E.; Hernandez, M. D.; Canteras, M.

    2002-01-01

    The purpose of this study was to demonstrate that the use of a high-grade interpolator in the reconstruction of images of the chest increases the resolution, independently of the high-resolution filter. Eight independent observers in two groups (experts and non experts) assessed (two readings separated by a time interval) the same section of the chest reconstructed four times (st-st, st-xs, b-st, b-xs), combining standard (st) and high-resolution (b) filters and standard (st) and high-grade (xs) interpolators. The images were classified from greater to lesser in terms of the resolution perceived. The results were used to compare the degree of resolution introduced by the interpolator and the filter and to determine whether or not there existed variability between observers and between the observations of each, and whether experience played a role in the findings. Six of the eight observers assigned the b-xs images the highest degree of resolution in the majority of cases, followed by the b-st image, the st-xs image and, finally, the st-st image). The other tow observers (one expert and one nonexpert) different only with respect to the order of the st-xs and b-st images, which they assigned the second and third places, respectively. The expert group showed no intra observer variability, while two of the nonexpert observers did. The high-grade interpolator enhances the resolution of images of the chest regardless of who evaluates them, while it does not substantially increase image noise. Thus, its use is recommended in helical computed tomography imaging of the lung. (Author) 10 refs

  7. Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone.

    Science.gov (United States)

    Palmerini, E; Jones, R L; Marchesi, E; Paioli, A; Cesari, M; Longhi, A; Meazza, C; Coccoli, L; Fagioli, F; Asaftei, S; Grignani, G; Tamburini, A; Pollack, S M; Picci, P; Ferrari, S

    2016-04-20

    Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Patients receiving G 900 mg/m(2) d 1, 8; D 75 mg/m(2) d 8, every 21 days were eligible. Primary end-point: progression-free survival (PFS) at 4 months; secondary end-point: overall survival (OS) and response rate. Fifty-one patients were included, with a median age of 17 years (8-71), 26 (51%) were pediatric patients. GD line of treatment: 2nd in 14 patients, ≥3rd in 37. 25 (49%) patients had metastases limited to lungs, 26 (51%) multiple sites. 40 (78%) osteosarcoma, 11 (22%) HGS. Eight (16%) patients achieved surgical complete response (sCR2) after GD. Four-month PFS rate was 46%, and significantly better for patients with ECOG 0 (ECOG 0: 54% vs ECOG 1: 43% vs ECOG 2: 0%; p = 0.003), for patients undergoing metastasectomy after GD (sCR2 75% vs no-sCR2 40 %, p = 0.02) and for osteosarcoma (osteosarcoma 56% vs HGS 18%; p = 0.05), with no differences according to age, line of treatment, and pattern of metastases. Forty-six cases had RECIST measurable disease: 6 (13%) patients had a partial response (PR), 20 (43%) had stable disease (SD) and 20 (43%) had progressive disease (PD). The 1-year OS was 30%: 67% for PR, 54% for SD and 20% for PD (p = 0.005). GD is an active treatment for relapsed high-grade osteosarcoma, especially for ECOG 0 patients, and should be included in the therapeutic armamentarium of metastatic osteosarcoma.

  8. Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone

    International Nuclear Information System (INIS)

    Palmerini, E.; Jones, R. L.; Marchesi, E.; Paioli, A.; Cesari, M.; Longhi, A.; Meazza, C.; Coccoli, L.; Fagioli, F.; Asaftei, S.; Grignani, G.; Tamburini, A.; Pollack, S. M.; Picci, P.; Ferrari, S.

    2016-01-01

    Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Patients receiving G 900 mg/m 2 d 1, 8; D 75 mg/m 2 d 8, every 21 days were eligible. Primary end-point: progression-free survival (PFS) at 4 months; secondary end-point: overall survival (OS) and response rate. Fifty-one patients were included, with a median age of 17 years (8–71), 26 (51 %) were pediatric patients. GD line of treatment: 2nd in 14 patients, ≥3rd in 37. 25 (49 %) patients had metastases limited to lungs, 26 (51 %) multiple sites. Histology: 40 (78 %) osteosarcoma, 11 (22 %) HGS. Eight (16 %) patients achieved surgical complete response (sCR2) after GD. Four-month PFS rate was 46 %, and significantly better for patients with ECOG 0 (ECOG 0: 54 % vs ECOG 1: 43 % vs ECOG 2: 0 %; p = 0.003), for patients undergoing metastasectomy after GD (sCR2 75 % vs no-sCR2 40 %, p = 0.02) and for osteosarcoma (osteosarcoma 56 % vs HGS 18 %; p = 0.05), with no differences according to age, line of treatment, and pattern of metastases. Forty-six cases had RECIST measurable disease: 6 (13 %) patients had a partial response (PR), 20 (43 %) had stable disease (SD) and 20 (43 %) had progressive disease (PD). The 1-year OS was 30 %: 67 % for PR, 54 % for SD and 20 % for PD (p = 0.005). GD is an active treatment for relapsed high-grade osteosarcoma, especially for ECOG 0 patients, and should be included in the therapeutic armamentarium of metastatic osteosarcoma

  9. Needs and preferences among patients with high-grade glioma and their caregivers - A longitudinal mixed methods study

    DEFF Research Database (Denmark)

    Piil, K; Jakobsen, J; Christensen, K B

    2018-01-01

    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...

  10. High-grade cervical lesions among women attending a reference clinic in Brazil: associated factors and comparison among screening methods.

    Directory of Open Access Journals (Sweden)

    Neide T Boldrini

    Full Text Available Although screening for cervical cancer is recommended for women in most countries, the incidence of cervical cancer is greater in developing countries. Our goal was to determine the prevalence and factors associated with high-grade lesions/cervical cancer among women attending a reference clinic in Brazil and evaluate the correlation of histology with cytology, colposcopy and the high-risk HPV (HR-HPV tests.A cross-sectional study of women attending a colposcopy clinic was carried out. The patients were interviewed to collect demographic, epidemiological and clinical data. Specimens were collected for cervical cytology, Chlamydia trachomatis and HPV testing using the Hybrid Capture (HC and PCR tests. Colposcopy was performed for all patients and biopsy for histology when cell abnormalities or cervical intraepithelial neoplasia (CIN were present.A total of 291 women participated in the study. The median age was 38 years (DIQ: 30-48 years. The prevalence of histologically confirmed high-grade lesions/cervical cancer was 18.2% (95%, CI: 13.8%-22.6%, with 48 (16.5% cases of CIN-2/CIN-3 and 5 (1.7% cases of invasive carcinoma. In the final logistic regression model, for ages between 30 and 49 years old [OR = 4.4 (95%: 1.01-19.04, history of smoking [OR = 2.4 (95%, CI: 1.14-5.18], practice of anal intercourse [OR = 2.4 (95%, CI: 1.10-5.03] and having positive HC test for HR-HPV [OR = 11.23 (95%, CI: 4 0.79-26, 36] remained independently associated with high-grade lesions/cervical cancer. A total of 64.7% of the cases CIN-3\\Ca in situ were related to HPV-16. Non-oncogenic HPV were only found in CIN-1 biopsy results. Compared to histology, the sensitivity of cytology was 31.8%, the specificity 95.5%; the sensitivity of colposcopy for high-grade lesions/cervical cancer was 51.0%, specificity was 91.4% and the concordance with HPV testing was high.The results confirm an association of HR-HPV with precursor lesions for cervical cancer

  11. 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.

  12. Low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion: a category with an increased outcome of high-grade lesions: use as a quality assurance measure.

    Science.gov (United States)

    Nishino, Ha T; Wilbur, David C; Tambouret, Rosemary H

    2012-08-01

    "Low-grade squamous intraepithelial lesion (LSIL), cannot exclude high-grade squamous intraepithelial lesion" (LSIL-H) is an increasingly used, equivocal interpretive category in gynecologic cytology. In an effort to evaluate its potential usefulness as a measure of quality assurance, we studied patterns of use of the LSIL-H diagnosis compared with "LSIL" and "high-grade squamous intraepithelial lesion" (HSIL) with corresponding histologic outcomes for 10 cytopathologists in our practice. In our laboratory, while the overall rate of associated cervical intraepithelial neoplasia 2 or greater on histologic follow-up for LSIL-H was intermediate between that of LSIL and HSIL, the outcomes for individual cytopathologists varied widely. Monitoring this particular utilization-outcome data with periodic confidential feedback to individual cytopathologists offers an opportunity for practice improvement within a laboratory and serves as an additional measure of quality assurance. These data may be useful for establishing and/or realigning the diagnostic criteria for this equivocal cytologic interpretation endorsed by a pathology practice.

  13. In vivo single-voxel proton MR spectroscopy in the differentiation of high-grade gliomas and solitary metastases

    International Nuclear Information System (INIS)

    Fan, G.; Sun, B.; Wu, Z.; Guo, Q.; Guo, Y.

    2004-01-01

    AIM: To determine whether single-voxel proton magnetic resonance spectroscopy (1HMRS) could be used to differentiate gliomas from metastases on the basis of differences in metabolite levels in the different involved regions. MATERIALS AND METHODS: Twenty-two patients (age range from 32 to 62 years, with a median age of 46.7 years) with a solitary brain tumour (14 gliomas, eight metastases) underwent conventional, gadolinium-DTPA enhanced T1-weighted images, and 1HMRS before surgical resection. Spectra from the enhancing tumour, the peritumoural region, and normal brain were obtained from 1HMRS. A point resolved spectroscopy sequence was required for 1HMRS. The metabolites in the spectra include: N-acetylaspartate (NAA), choline (CHO), creatine compounds (CR), myo-inositol (MI), lactate (LAC), glutamate and glutamine (Glu-n). Relative concentrations of metabolites were related to the peak area, and expressed with reference to CR. Student's t-test was used to determine whether there was a statistically significant difference in relative metabolic ratios between high-grade gliomas and metastases. Meanwhile, 16 of all 22 patients were re-examined using magnetic resonance imaging (MRI) within 6 months of surgical resection. Recurrence was present in three patients (two gliomas, one metastasis). RESULTS: Of the 14 patients with gliomas, the peaks of NAA were reduced in three cases; the peaks of LAC, which were elevated, appeared as typical double-peaks in the peritumoural region in nine cases; the peaks of Glu-n, which were also elevated, had a zigzag appearance in seven cases. The peaks of MI were increased in the tumoural region in eight cases, and CHO levels were elevated in all 14 cases. Of the eight patients with metastases, Glu-n peaks in the tumoural region in three cases and CHO peaks in the tumoural region in four cases were elevated, respectively, while the peaks of CR were reduced in three cases, and the peaks of NAA were markedly reduced in four cases within

  14. 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

  15. 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.

  16. Textural evidence for high-grade ignimbrites formed by low-explosivity eruptions, Paraná Magmatic Province, southern Brazil

    Science.gov (United States)

    Luchetti, Ana Carolina F.; Gravley, Darren M.; Gualda, Guilherme A. R.; Nardy, Antonio J. R.

    2018-04-01

    The Paraná-Etendeka Province is a Lower Cretaceous huge bimodal tholeiitic volcanic province (1 million·km3) that predated the Gondwana breakup. Its silicic portion makes up a total volume of at least 20,000 km3 and in southern Brazil it comprises the Chapecó porphyritic high-Ti trachydacites-dacites and the Palmas microporphyritic-aphyric low-Ti dacites-rhyolites. The widespread silicic sheets are debated in the literature because they bear similarities between lavas and high grade ignimbrites. Here we provide new observations and interpretations for flow units with large, dark, and vesicle-poor lens-shaped blobs surrounded by a light-colored matrix. The textural features (macro- to micro-scale) of these blobs are different from typical pumice and/or fiamme and support a low explosivity pyroclastic origin, possibly low-column fountain eruptions with discharge rates high enough to produce laterally extensive high-grade ignimbrites. Such an interpretation, combined with a conspicuous absence of lithic fragments in the deposits, is aligned with a lack of identified calderas in the Paraná-Etendeka Province. Maximum timescales of crystallization associated with the juvenile blobs and estimated from CSD slopes are on the order of millennia for phenocryst populations and on the order of decades for microphenocryst populations.

  17. Argininosuccinate synthetase (ASS) deficiency in high-grade pulmonary neuroendocrine carcinoma: an opportunity for personalized targeted therapy.

    Science.gov (United States)

    Walts, Ann E; Bomalaski, John S; Ines, Delma; Orsulic, Sandra

    2015-08-01

    Cells deficient in argininosuccinate synthetase (ASS) must absorb the arginine they need for growth from circulating blood. Treatment with pegylated arginine deiminase (ADI-PEG 20) selectively eliminates arginine from the circulation and has shown some efficacy against ASS-deficient tumors including small cell lung cancer (SCLC). We sought to assess ASS expression in a cohort of high-grade pulmonary neuroendocrine carcinomas (PNEC) which include SCLC and large cell neuroendocrine carcinoma (LCNEC). Sixty-nine PNEC (49 SCLC and 20 LCNEC) were retrieved from our pathology archives. Formalin-fixed paraffin-embedded sections of the 54 primary tumors, 15 metastases and appropriate positive and negative controls were immunostained using an ASS-specific monoclonal antibody. Positive staining in ASS negative. 58 % of the PNEC including 61.2 % of the SCLC and 50 % of the LCNEC were ASS negative. These ASS-negative tumors included 63 % of the primary and 40 % of the metastatic lesions tested. More than 50 % of the high-grade PNEC tested lack immunohistochemically detectable ASS, suggesting that they are auxotrophic for arginine and potential candidates for arginine deprivation therapy. PNEC comprise about 25 % of primary lung cancers and have a 5-year overall survival of only 5-10 %, underscoring the need for new and more effective therapies. Immunostaining for ASS has potential to improve the selection of patients with PNEC for arginine deprivation therapy with ADI-PEG 20.

  18. 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.

  19. Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma.

    Science.gov (United States)

    Ducie, Jennifer; Dao, Fanny; Considine, Michael; Olvera, Narciso; Shaw, Patricia A; Kurman, Robert J; Shih, Ie-Ming; Soslow, Robert A; Cope, Leslie; Levine, Douglas A

    2017-10-17

    Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA sequence and the miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.High-grade serous carcinomas (HGSCs) are associated with precursor lesions (STICs) in the fallopian epithelium in only half of the cases. Here the authors report the molecular analysis of HGSCs with and without associated STICs and show similar profiles supporting a common origin for all HGSCs.

  20. Prognostic factors and treatment results of high-grade osteosarcoma in norway: a scope beyond the "classical" patient.

    Science.gov (United States)

    Berner, Kjetil; Hall, Kirsten Sundby; Monge, Odd R; Weedon-Fekjær, Harald; Zaikova, Olga; Bruland, Øyvind S

    2015-01-01

    Purpose. A retrospective study of prognostic factors and treatment outcome of osteosarcoma (OS) during modern chemotherapy era with focus on patients with primary metastatic disease, nonextremity localisation, or age >40 years (nonclassical OS). Methods. A nationwide cohort, comprising 424 high-grade Norwegian bone OS patients, was based on registry sources supplemented with clinical records from hospitals involved in sarcoma management between 1975 and 2009. Results. Only 48% were younger patients with tumour in the extremities and without metastasis at diagnosis (classical OS). A considerable discrepancy in survival between classical and nonclassical OS was observed: 61% versus 26% 10-year sarcoma specific survival. Twice as many of the former received both adequate surgery and chemotherapy compared to the latter. This could only partly explain the differences in survival due to inherent chemoresistance in primary metastatic disease and a higher rate of local relapse among patients with axial tumours. Metastasis at diagnosis, increased lactate dehydrogenase, age > 40 years, and tumour size above median value were all adverse prognostic factors for overall survival. Conclusion. We confirm a dramatic difference in outcome between classical and nonclassical high-grade OS patients, but treatment variables could only partly explain the dismal outcome of the latter.

  1. Nitrosourea efficacy in high-grade glioma: a survival gain analysis summarizing 504 cohorts with 24193 patients.

    Science.gov (United States)

    Wolff, Johannes E A; Berrak, Su; Koontz Webb, Susannah E; Zhang, Ming

    2008-05-01

    Even though past studies have suggested efficacy of nitrosourea drugs in patients with high-grade glioma and temozolomide has recently been shown significantly to be beneficial, no conclusive comparisons between these agents have been published. We performed a survival gain analysis of 364 studies describing 24,193 patients with high-grade glioma treated in 504 cohorts, and compared the effects of drugs. The most frequent diagnoses were glioblastoma multiforme (GBM) (72%) and anaplastic astrocytoma (22%). The mean overall survival (mOS) was 14.1 months. The outcome was influenced by several of the known prognostic factors including the histological grade, if the tumors were newly diagnosed or recurrent, the completeness of resection, patients' age, and gender. This information allowed the calculation of a predicted mOS for each cohort based on their prognostic factors independent of treatment. Survival gain to characterize the influence of treatment was subsequently defined and validated as the difference between the observed and the predicted mOS. In 62 CCNU-treated cohorts and 15 ACNU-treated cohorts the survival gain was 5.3 months and 8.9 months (P < 0.0005), respectively. No detectable survival gain for patients treated with various BCNU-containing regimens was found. Conclusion CCNU- and ACNU-containing regimens were superior to BCNU containing regiments.

  2. Dynamic Contrast-Enhanced Perfusion MRI of High Grade Brain Gliomas Obtained with Arterial or Venous Waveform Input Function.

    Science.gov (United States)

    Filice, Silvano; Crisi, Girolamo

    2016-01-01

    The aim of this study was to evaluate the differences in dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) perfusion estimates of high-grade brain gliomas (HGG) due to the use of an input function (IF) obtained respectively from arterial (AIF) and venous (VIF) approaches by two different commercially available software applications. This prospective study includes 20 patients with pathologically confirmed diagnosis of high-grade gliomas. The data source was processed by using two DCE dedicated commercial packages, both based on the extended Toft model, but the first customized to obtain input function from arterial measurement and the second from sagittal sinus sampling. The quantitative parametric perfusion maps estimated from the two software packages were compared by means of a region of interest (ROI) analysis. The resulting input functions from venous and arterial data were also compared. No significant difference has been found between the perfusion parameters obtained with the two different software packages (P-value < .05). The comparison of the VIFs and AIFs obtained by the two packages showed no statistical differences. Direct comparison of DCE-MRI measurements with IF generated by means of arterial or venous waveform led to no statistical difference in quantitative metrics for evaluating HGG. However, additional research involving DCE-MRI acquisition protocols and post-processing would be beneficial to further substantiate the effectiveness of venous approach as the IF method compared with arterial-based IF measurement. Copyright © 2015 by the American Society of Neuroimaging.

  3. Dynamic CT perfusion imaging of intra-axial brain tumours: differentiation of high-grade gliomas from primary CNS lymphomas

    International Nuclear Information System (INIS)

    Schramm, Peter; Xyda, Argyro; Knauth, Michael; Klotz, Ernst; Tronnier, Volker; Hartmann, Marius

    2010-01-01

    Perfusion computed tomography (PCT) allows to quantitatively assess haemodynamic characteristics of brain tissue. We investigated if different brain tumor types can be distinguished from each other using Patlak analysis of PCT data. PCT data from 43 patients with brain tumours were analysed with a commercial implementation of the Patlak method. Four patients had low-grade glioma (WHO II), 31 patients had glioblastoma (WHO IV) and eight patients had intracerebral lymphoma. Tumour regions of interest (ROIs) were drawn in a morphological image and automatically transferred to maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and permeability (K Trans ). Mean values were calculated, group differences were tested using Wilcoxon and Mann Whitney U-tests. In comparison with normal parenchyma, low-grade gliomas showed no significant difference of perfusion parameters (p > 0.05), whereas high-grade gliomas demonstrated significantly higher values (p Trans , p Trans values compared with unaffected cerebral parenchyma (p = 0.0078) but no elevation of CBV. High-grade gliomas show significant higher CBV values than lymphomas (p = 0.0078). PCT allows to reliably classify gliomas and lymphomas based on quantitative measurements of CBV and K Trans . (orig.)

  4. 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.

  5. Estimate of throughput of bridge transitions and pipe passages built on minor rivers of piedmont areas of Krasnodar Territory-Russia

    Directory of Open Access Journals (Sweden)

    Bryukhan Fedor

    2018-01-01

    Full Text Available Stability and accident-free operation of engineering road structures including bridge transitions and pipe passages built on mountain rivers mostly depends on a stream regime and lack of obstructions for water flow. Such structures pose a prominent potential hazard being built in piedmont areas of Caucasus Mountains characterized by flash floods and blockage of structures by floating debris, mudflow deposits and wastes of construction. This notwithstanding, the threats caused by these phenomena are poorly studied. The purpose of this study is in estimation of throughput of bridge transitions and pipe passages built on minor rivers of piedmont areas and analysis of hazards caused by floods and obstructions to water flow. The results of calculation of capacities of existing road structures are provided herein. A qualitative assessment of potential emergencies in case of severe flood is also given. A major hazard of possible blockage of waterways that can cause emergency even in regular flood conditions is noted.

  6. 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

  7. The snake assemblage (Squamata: Serpentes) of a Cerrado-Caatinga transition area in Castelo do Piauí, state of Piauí, Brazil

    OpenAIRE

    Rodrigues, Francílio da Silva; Prudente, Ana Lúcia da Costa

    2011-01-01

    This study records and analyzes the diversity and structure of a snake assemblage in a transition area between Cerrado and Caatinga, in the municipality of Castelo do Piauí, state of Piauí, comparing the distribution and similarity of the species composition with other open localities already studied in Brazil. We used three complementary sampling methods: time constrained search (TCS), pitfall traps with drift fences (PFT), and incidental encounters (IE). During the TCS and PFT, 912 hours/ob...

  8. 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...

  9. 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

  10. Integrin alpha 5 beta 1 Plays a Critical Role in Resistance to Temozolomide by Interfering with the p53 Pathway in High-Grade Glioma

    Czech Academy of Sciences Publication Activity Database

    Janoušková, Hana; Maglott, A.; Leger, D.Y.; Bossert, C.; Noulet, F.; Guerin, E.; Guenot, D.; Pinel, S.; Chastagner, P.; Plenat, F.; Entz-Werle, N.; Lehmann-Che, J.; Godet, J.; Martin, S.; Teisinger, Jan; Dontenwill, M.

    2012-01-01

    Roč. 72, č. 14 (2012), s. 3463-3470 ISSN 0008-5472 Institutional support: RVO:67985823 Keywords : cancer * integrins * high-grade glioma Subject RIV: CE - Biochemistry Impact factor: 8.650, year: 2012

  11. A Case of High-Grade Neuroendocrine Carcinoma That Improved with Bevacizumab plus Modified FOLFOX6 as the Fourth-Line Chemotherapy

    Directory of Open Access Journals (Sweden)

    Satoshi Takeuchi

    2011-05-01

    Full Text Available High-grade neuroendocrine carcinoma differs from usual neuroendocrine carcinoma, and its prognosis is dismal. In this case report, a case of high-grade neuroendocrine carcinoma that improved with bevacizumab plus modified FOLFOX6 as the fourth-line chemotherapy is presented. A 29-year-old male with a huge liver tumor was diagnosed with high-grade neuroendocrine carcinoma originating from the liver. Multiple liver and bone metastases were found one month after surgery. He was treated with three chemotherapy regimens used for the management of small-cell lung cancer with extensive disease. However, none of them could be maintained because of tumor progression. He was then treated with bevacizumab plus modified FOLFOX6 as the fourth-line regimen. Dramatic tumor shrinkage was obtained, and a partial response was achieved. This case suggests that high-grade neuroendocrine carcinoma can be treated with bevacizumab in combination with cytotoxic chemotherapy.

  12. 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

  13. Subsolidus migmatization in high-grade meta-tuffs (Kurkijärvi, southwest Finland)

    Science.gov (United States)

    Blom, K. A.

    1988-07-01

    The phenomenon of migmatization was studied in Precambrian metavolcanic gneisses of calc-alkaline chemistry, outcropping along a prograde amphibolite/granulite facies transition in the West Uusimaa Complex of SW Finland. This paper discusses one of the studied gneiss levels (a garnet-bearing Qtz/Plag/Ksp/Bio-gneiss) which was observed to transsect the metamorphic isograd pattern at almost right angle. The gneiss was studied for structures, whole-rock chemistry (major, trace and REE), mineral content, microtextures, plagioclase anorthite content and fluid inclusions. Data concerning the latter four subjects are presented. Migmatization proved to: (1) have occurred parallel to compositional banding of the rocks; (2) have produced identical leucosome/melanosome/mesosome mineral parageneses; (3) have initiated feldspar/garnet-poikiloblasthesis (and occasionally biotite porphyroblasthesis) in leucosome, and biotite-/garnet-poikiloblasthesis in melanosome; (4) have caused entrapment of unstrained quartz blebs carrying isolated (primary) two-phase pure H 2O fluid inclusions of unique filling degree range in the above-mentioned feldspar- and garnet-poikiloblasts; (5) have occurred post-D 1/pre-D 2, synchronous to amphibolitefacies metamorphism, in the subsolidus regime; (6) have been affected by D 2 in the way of localized mylonitization of the melanosome, and quartz migration (exudation) from adjacent mesosome into leucosome; and (7) have had some control by the biotite content of the original compositionally banded rock. Initial leucosome formation appears to have been controlled by the pre-leucosome biotite content: the recalculated modal biotite content of the leucosome/melanosome combination conspicuously is in the range of 5-20 vol.% of biotite. Final extent of the leucosome shows on its turn a marked correlation with mesosome modal biotite content. Because leucosomes occur carrying a recalculated modal biotite content equalling adjacent mesosome biotite content, a

  14. Cytological Diagnosis of an Uncommon High Grade Malignant Thyroid Tumour: A Case Report.

    Science.gov (United States)

    Nagpal, Ruchi; Kaushal, Manju; Kumar, Sawan

    2017-07-01

    Anaplastic Thyroid Carcinoma (ATC) is a relatively uncommon highly malignant tumour originating from the follicular cells of thyroid gland having poor prognosis. It accounts for 2% to 5% of all thyroid carcinomas and patients typically present with a rapidly growing anterior neck mass with aggressive symptoms. A 53-year-old male presented with diffuse neck swelling measuring 8x6 cm and right cervical lymph node measuring 2x2 cm since one month which was associated with dyspepsia and dyspnoea. Ultrasound and Contrast Enhanced Computed Tomography (CECT) neck revealed enlarged right lobe of thyroid and multiple enlarged cervical lymph nodes with soft tissue density nodules in bilateral lungs. Fine Needle Aspiration (FNA) from the swelling revealed giant cell, spindle cell and squamoid pattern. Focal areas showed follicular epithelial cells arranged in repeated microfollicular pattern suggesting an underlying follicular neoplasm. FNAC smears from the lymph node also revealed similar findings. Based on the cytomorphological and radiological findings, final diagnosis of ATC probably arising from underlying follicular carcinoma with cervical lymph node and lung metastasis was given. FNAC leads to prompt and definitive diagnosis, so that therapy can be initiated as soon as possible for better outcome. Multimodality therapy (surgery, external beam radiation, and chemotherapy) is the mainstay of treatment.

  15. Neutrophilia as a biomarker for overall survival in newly diagnosed high-grade glioma patients undergoing chemoradiation

    Directory of Open Access Journals (Sweden)

    Antoine Schernberg

    2018-03-01

    Full Text Available Objective: To study the prognostic value of neutrophil disorders in a retrospective cohort of high-grade glioma patients receiving definitive concurrent temozolomide and radiation. Materials and methods: Clinical records of consecutive patients treated in our Institution between January 2005 and December 2010 with concurrent temozolomide (75 mg/m2 daily and radiation were collected. The prognostic value of pretreatment neutrophilia on survival, defined as a neutrophil count exceeding 7 G/L, was examined. Results: We identified 164 patients, all treated with concurrent temozolomide-based chemoradiotherapy. Initial surgery was achieved in most (75%, with resection > 90% in 55 patients (34%. Total 151 patients (92% had glioblastoma, and 13 patients (8% had WHO grade III glioma. Eighty-two patients (50% displayed pretreatment neutrophilia. Neutrophilia was not associated with concurrent or adjuvant temodal discontinuation (p > 0.3. The 2-year actuarial overall survival was 45%. Steroid consumption, i.e. 60 mg or more of daily prednisolone, increased pretreatment neutrophil count (p = 0.005. In univariate analysis, neutrophilia was associated with worse overall survival (p = 0.019, as well as age ≥ 65 years (p = 0.009, surgical resection < 90% (p = 0.003 and prednisolone consumption ≥ 60 mg/day (p = 0.016. In multivariate analysis, neutrophilia (p = 0.013, age ≥ 65 (p = 0.001, and surgical tumor resection < 90% (p = 0.010 independently decreased overall survival, while, steroid consumption was not (p = 0.088. Conclusion: In high-grade gliomas treated with concurrent temozolomide and radiation, pretreatment neutrophilia may be a significant prognosis factor for overall survival. In addition with previously available markers, this independent cost-effective biomarker could help identifying patients with worsened prognosis. Keywords: High grade gliomas, Glioblastoma

  16. Perceived cervical cancer risk among women treated for high-grade cervical intraepithelial neoplasia: The importance of specific knowledge.

    Directory of Open Access Journals (Sweden)

    Sonia Andersson

    Full Text Available Women with high-grade cervical intraepithelial neoplasia (CIN are at increased risk for developing cervical cancer. We examine how women with high-grade CIN perceive their own risk, and about pertinent knowledge concerning human high-risk papillomavirus (HPV, CIN and cervical cancer.All patients who underwent first-time treatment of high-grade CIN (grade 2+ were followed-up at 6-months at the Karolinska University Hospital, Stockholm, Sweden and were invited to participate in the present study. This included completion of a questionnaire examining sociodemographic characteristics, self-perceived risk of cervical cancer without regular gynecologic follow-up, and 14 queries about HPV, CIN and cervical cancer knowledge, inter alia.The participation rate was 96.6%, with 479 women enrolled in this study. Over 75% were age 40 or younger, over half had completed university education. Most were married or co-living with their partner and were gainfully employed. On a scale scored from 10 (highest self-perceived risk of cervical cancer without regular gynecologic follow-up to 1 (lowest self-perceived risk, 64% rated their risk ≥ 7; almost 30% viewed their risk ≤ 6 and 7.5% did not rate their risk. A Specific Knowledge Scale with six of the queries explained 58.3% of the total variance. Nearly 30% of the women answered four or fewer of the six queries correctly. The Specific Knowledge Scale predicted self-perceived cervical cancer risk (Odds ratio = 11.3, 95% Confidence Interval 5.6 - 22.6 after adjusting for age, income and education. Most of the women with low self-perceived cervical cancer risk did not rate their HPV-related knowledge as good. However, 32 predominantly university-educated women, with low self-perceived cervical cancer risk, considered their HPV-related knowledge good.It is vital to effectively convey accurate information about these patients' cervical cancer risk, needed preventive and follow-up measures, together with the relevant

  17. 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.

  18. Cytological study of DNA content and nuclear morphometric analysis for aid in the diagnosis of high-grade dysplasia within oral leukoplakia.

    Science.gov (United States)

    Yang, Xi; Xiao, Xuan; Wu, Wenyan; Shen, Xuemin; Zhou, Zengtong; Liu, Wei; Shi, Linjun

    2017-09-01

    To quantitatively examine the DNA content and nuclear morphometric status of oral leukoplakia (OL) and investigate its association with the degree of dysplasia in a cytologic study. Oral cytobrush biopsy was carried out to obtain exfoliative epithelial cells from lesions before scalpel biopsy at the same location in a blinded series of 70 patients with OL. Analysis of nuclear morphometry and DNA content status using image cytometry was performed with oral smears stained with the Feulgen-thionin method. Nuclear morphometric analysis revealed significant differences in DNA content amount, DNA index, nuclear area, nuclear radius, nuclear intensity, sphericity, entropy, and fractal dimension (all P content analysis identified 34 patients with OL (48.6%) with DNA content abnormality. Nonhomogeneous lesion (P = .018) and high-grade dysplasia (P = .008) were significantly associated with abnormal DNA content. Importantly, the positive correlation between the degree of oral dysplasia and DNA content status was significant (P = .004, correlation coefficient = 0.342). Cytology analysis of DNA content and nuclear morphometric status using image cytometry may support their use as a screening and monitoring tool for OL progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Middle Temporal Gyrus Versus Inferior Temporal Gyrus Transcortical Approaches to High-Grade Astrocytomas in the Mediobasal Temporal Lobe: A Comparison of Outcomes, Functional Restoration, and Surgical Considerations.

    Science.gov (United States)

    Quinones-Hinojosa, Alfredo; Raza, Shaan M; Ahmed, Ishrat; Rincon-Torroella, Jordina; Chaichana, Kaisorn; Olivi, Alessandro

    2017-01-01

    High-grade astrocytomas of the mesial temporal lobe may pose surgical challenges. Several approaches (trans-sylvian, subtemporal, and transcortical) have been designed to circumnavigate the critical neurovascular structures and white fiber tracts that surround this area. Considering the paucity of literature on the transcortical approach for these lesions, we describe our institutional experience with transcortical approaches to Grade III/IV astrocytomas in the mesial temporal lobe. Between 1999 and 2009, 23 patients underwent surgery at the Johns Hopkins Medical Institutions for Grade III/IV astrocytomas involving the mesial temporal lobe (without involvement of the temporal neocortex). Clinical notes, operative records, and imaging were reviewed. Thirteen patients had tumors in the dominant hemisphere. All patients underwent surgery via a transcortical approach (14 via the inferior temporal gyrus and 9 via the middle temporal gyrus). Gross total resection was obtained in 92 % of the cohort. Neurological outcomes were: clinically significant stroke (2 patients), new visual deficits (2 patients), new speech deficit (1 patient); seizure control (53 %). In comparison to reported results in the literature for the transylvian and subtemporal approaches, the transcortical approach may provide the access necessary for a gross total resection with minimal neurological consequences. In our series of patients, there was no statistically significant difference in outcomes between the middle temporal gyrus versus the inferior temporal gyrus trajectories.

  20. Apparent Diffusion Coefficient Values of the Benign Central Zone of the Prostate: Comparison With Low- and High-Grade Prostate Cancer.

    Science.gov (United States)

    Gupta, Rajan T; Kauffman, Christopher R; Garcia-Reyes, Kirema; Palmeri, Mark L; Madden, John F; Polascik, Thomas J; Rosenkrantz, Andrew B

    2015-08-01

    The apparent diffusion coefficient (ADC) values for benign central zone (CZ) of the prostate were compared with ADC values of benign peripheral zone (PZ), benign transition zone (TZ), and prostate cancer, using histopathologic findings from radical prostatectomy as the reference standard. The study included 27 patients with prostate cancer (mean [± SD] age, 60.0 ± 7.6 years) who had 3-T endorectal coil MRI of the prostate performed before undergoing prostatectomy with whole-mount histopathologic assessment. Mean ADC values were recorded from the ROI within the index tumor and within benign CZ, PZ, and TZ, with the use of histopathologic findings as the reference standard. ADC values of the groups were compared using paired t tests and ROC curve analysis. The ADC of benign CZ in the right (1138 ± 123 × 10(-6) mm(2)/s) and left (1166 ± 141 × 10(-6) mm(2)/s) lobes was not significantly different (p = 0.217). However, the ADC of benign CZ (1154 ± 129 × 10(-6) mm(2)/s) was significantly lower (p 51.9%), and the AUC of ADC for differentiation from tumors with a Gleason score greater than 6 was 76.7% (sensitivity, 75.0%; specificity, 65.0%). The ADC of benign CZ is lower than the ADC of other zones of the prostate and overlaps with the ADC of prostate cancer tissue, including high-grade tumors. Awareness of this potential diagnostic pitfall is important to avoid misinterpreting the normal CZ as suspicious for tumor.

  1. Changes in the Extracellular Matrix Are Associated With the Development of Serous Tubal Intraepithelial Carcinoma Into High-Grade Serous Carcinoma.

    Science.gov (United States)

    van der Steen, Sophieke C H A; Bulten, Johan; Van de Vijver, Koen K; van Kuppevelt, Toin H; Massuger, Leon F A G

    2017-07-01

    The identification of a marker for early progression of preinvasive lesions into invasive pelvic high-grade serous carcinoma (HGSC) may provide novel handles for innovative screening and prevention strategies. The interplay between cancer cells and the extracellular matrix (ECM) is one of the main principles in cancer development and growth, but has been largely neglected in preinvasive lesions. This is the first study addressing the involvement of the ECM in the "step-by-step" transition of normal fallopian tube epithelium into preinvasive lesions, and eventually the progression of preinvasive lesions into invasive HGSC. The expression of highly sulfated chondroitin sulfate (CS-E), a characteristic glycosaminoglycan of the cancer-associated ECM, was assessed by immunohistochemistry in a large cohort of precursor lesions of the full spectrum of HGSC development, including 97 serous tubal intraepithelial carcinomas (STICs), 27 serous tubal intraepithelial lesions, and 24 p53 signatures. In addition, the immunological reactivity in the microenvironment was evaluated. Increased stromal expression of highly sulfated CS-E was observed in 3.7%, 57.7%, and 90.6% of serous tubal intraepithelial lesions, STICs, and invasive HGSCs, respectively (P STIC, P STIC and paired HGSC was demonstrated. Intense stromal CS-E expression in STIC was significantly associated with an immune infiltrate (P < 0.001). Our study showed that increased stromal CS-E expression is related to the degree of the tubal epithelium abnormality. Specific alterations in the ECM (ie, CS-E expression) occur early in pelvic HGSC development and may represent a novel biomarker of early cancer progression, useful for the identification of novel clinical strategies.

  2. Advanced magnetic resonance imaging methods for planning and monitoring radiation therapy in patients with high-grade glioma.

    Science.gov (United States)

    Lupo, Janine M; Nelson, Sarah J

    2014-10-01

    This review explores how the integration of advanced imaging methods with high-quality anatomical images significantly improves the characterization, target definition, assessment of response to therapy, and overall management of patients with high-grade glioma. Metrics derived from diffusion-, perfusion-, and susceptibility-weighted magnetic resonance imaging in conjunction with magnetic resonance spectroscopic imaging, allows us to characterize regions of edema, hypoxia, increased cellularity, and necrosis within heterogeneous tumor and surrounding brain tissue. Quantification of such measures may provide a more reliable initial representation of tumor delineation and response to therapy than changes in the contrast-enhancing or T2 lesion alone and have a significant effect on targeting resection, planning radiation, and assessing treatment effectiveness. In the long term, implementation of these imaging methodologies can also aid in the identification of recurrent tumor and its differentiation from treatment-related confounds and facilitate the detection of radiationinduced vascular injury in otherwise normal-appearing brain tissue.

  3. High-grade soft tissue sarcoma arising in a desmoid tumor: case report and review of the literature.

    Science.gov (United States)

    Bertucci, François; Faure, Marjorie; Ghigna, Maria-Rosa; Chetaille, Bruno; Guiramand, Jérôme; Moureau-Zabotto, Laurence; Sarran, Anthony; Perrot, Delphine

    2015-01-01

    Desmoid tumors are rare benign monoclonal fibroblastic tumors. Their aggressiveness is local with no potential for metastasis or dedifferentiation. Here we report on a 61-year-old patient who presented a locally advanced breast desmoid tumor diagnosed 20 years after post-operative radiotherapy for breast carcinoma. After 2 years of medical treatment, a high-grade undifferentiated pleomorphic soft tissue sarcoma arose within the desmoid tumor. Despite extensive surgery removing both tumors, the patient showed locoregional relapse by the sarcoma, followed by multimetastatic progression, then death 25 months after the surgery. The arising of a soft tissue sarcoma in a desmoid tumor is an exceptional event since our case is the fourth one reported so far in literature. It reinforces the need for timely and accurate diagnosis when a new mass develops in the region of a preexisting desmoid tumor, and more generally when a desmoid tumor modifies its clinical or radiological aspect.

  4. 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.

  5. Early wound site seeding in a patient with CNS high-grade neuroepithelial tumor with BCOR alteration: A case report.

    Science.gov (United States)

    Kirkman, Matthew A; Pickles, Jessica C; Fairchild, Amy R; Avery, Aimee; Pietsch, Torsten; Jacques, Thomas S; Aquilina, Kristian

    2018-05-30

    Advances in molecular profiling have facilitated the emergence of newly defined entities of central nervous system tumor, including CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR). Relatively little is known about the clinical behaviour of these newly-characterized tumors. We describe a pediatric male patient with CNS HGNET-BCOR who developed seeding of the tumor into the site of the surgical wound within months of surgery for resection of a residual posterior fossa tumor. This case emphasises three important points. First, CNS HGNET-BCOR can be aggressive tumors that necessitate close clinical and radiological surveillance. Second, surveillance imaging in such cases should incorporate the surgical incision site into the field of view, and this should be closely scrutinised to ensure the timely detection of wound site seeding. Third, wound site seeding may still occur despite the use of meticulous surgical techniques. Copyright © 2018. Published by Elsevier Inc.

  6. Guide for the recovery of high grade waste paper from federal office buildings through at-source separation

    Energy Technology Data Exchange (ETDEWEB)

    1978-01-01

    This guide is intended to serve as a manual for organizing and managing office waste paper recovery programs in Canadian federal buildings. Waste paper generated in such buildings is of particular interest for recycling as it is produced in sufficiently large amounts, and contains large amounts of high-grade waste paper which obtain good prices from paper mills. The key to successful recovery of such paper is separation, at the source of waste generation, from other less-valuable papers and non-paper materials. In recommending ways to do this, the manual covers assessment of the viability of a collection program in a particular building, estimating the quantities of waste generated, calculating storage space necessary, marketing the paper collected, using proper collection and storage containers, promoting employee awareness, and administering and monitoring the program. A sample cost-benefit analysis is given for a general office building with 1,000 employees. Includes glossary. 14 refs., 10 figs., 5 tabs.

  7. Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility.

    Science.gov (United States)

    Wrensch, Margaret; Jenkins, Robert B; Chang, Jeffrey S; Yeh, Ru-Fang; Xiao, Yuanyuan; Decker, Paul A; Ballman, Karla V; Berger, Mitchel; Buckner, Jan C; Chang, Susan; Giannini, Caterina; Halder, Chandralekha; Kollmeyer, Thomas M; Kosel, Matthew L; LaChance, Daniel H; McCoy, Lucie; O'Neill, Brian P; Patoka, Joe; Pico, Alexander R; Prados, Michael; Quesenberry, Charles; Rice, Terri; Rynearson, Amanda L; Smirnov, Ivan; Tihan, Tarik; Wiemels, Joe; Yang, Ping; Wiencke, John K

    2009-08-01

    The causes of glioblastoma and other gliomas remain obscure. To discover new candidate genes influencing glioma susceptibility, we conducted a principal component-adjusted genome-wide association study (GWAS) of 275,895 autosomal variants among 692 adult high-grade glioma cases (622 from the San Francisco Adult Glioma Study (AGS) and 70 from the Cancer Genome Atlas (TCGA)) and 3,992 controls (602 from AGS and 3,390 from Illumina iControlDB (iControls)). For replication, we analyzed the 13 SNPs with P RTEL1 had discovery P = 1.5 x 10(-7), replication P = 0.00035 and combined P = 3.40 x 10(-9). For both SNPs, the direction of association was the same in discovery and replication phases.

  8. A Pilot Study of Hypofractionated Stereotactic Radiation Therapy and Sunitinib in Previously Irradiated Patients With Recurrent High-Grade Glioma

    International Nuclear Information System (INIS)

    Wuthrick, Evan J.; Curran, Walter J.; Camphausen, Kevin; Lin, Alexander; Glass, Jon; Evans, James; Andrews, David W.; Axelrod, Rita; Shi, Wenyin; Werner-Wasik, Maria; Haacke, E. Mark; Hillman, Gilda G.; Dicker, Adam P.

    2014-01-01

    Purpose/Objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG). Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acute toxicity, and response was assessed via serial magnetic resonance imaging. Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%. Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival

  9. 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.

  10. Human papillomavirus (HPV) persistence and HPV 31 predict the risk of recurrence in high-grade vaginal intraepithelial neoplasia.

    Science.gov (United States)

    Bogani, Giorgio; Martinelli, Fabio; Ditto, Antonino; Taverna, Francesca; Lombardo, Claudia; Signorelli, Mauro; Chiappa, Valentina; Leone Roberti Maggiore, Umberto; Fontanella, Caterina; Sabatucci, Ilaria; Borghi, Chiara; Recalcati, Dario; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

    2017-03-01

    High-grade vaginal intraepithelial neoplasia (vaginal HSIL) represents an uncommon entity. Here, we sought to identify predictors for recurrence and risk factor for developing genital cancers after primary treatment for vaginal HSIL. Data of consecutive 5104 women who had human papillomavirus (HPV) DNA test were searched for identify women with histological confirmed vaginal HSIL. Disease-free interval and the risk of developing HPV-related gynecological cancers were assessed using Kaplan-Meier and Cox proportional hazard models. Overall, 77 patients were included. After a mean (SD) follow-up of 69.3 (33.0) months, 11 (14%) and 4 (5%) patients experienced vaginal HSIL recurrence and the occurrence of HPV-related gynecological cancers, respectively. Via multivariate analysis factors predicting for vaginal HSIL recurrence were infection from HPV31 at diagnosis (HR: 5.0 (95%CI:1.17, 21.3); p=0.03) and persistence of HPV infection after treatment (HR: 7.0 (95%CI:1.54, 31.6); p=0.01). Additionally, patients who had LASER ablation experienced a trend toward a lower risk of recurrence in comparison to medical treatment (HR: 0.20 (95%CI:0.03, 1.09); p=0.06). Considering the occurrence of HPV-related gynecological cancers, we observed that no factors independently correlated with this risk; while, a trend towards higher risk was observed for women with HIV infection (HR:16.4 (95%CI:0.90, 300.1); p=0.06) and persistence of HPV infection (HR: 13.3 (95%CI:0.76, 230.2); p=0.07). Patients affected by vaginal HSIL experienced a relatively high risk of recurrence. Persistence of HPV after treatment and pretreatment HPV-31 infection predicts for high-grade vaginal intraepithelial neoplasia recurrence. Further investigations are warranted in order to corroborate our data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Predicting Factors for High-Grade Cervical Dysplasia in Women With Low-Grade Cervical Cytology and Nonvisible Squamocolumnar Junction.

    Science.gov (United States)

    Bogani, Giorgio; Taverna, Francesca; Lombardo, Claudia; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Leone Roberti Maggiore, U; Mosca, Lavinia; Sabatucci, Ilaria; Scaffa, Cono; Lorusso, Domenica; Raspagliesi, Francesco

    2018-01-01

    To assess the risk of developing high-grade cervical dysplasia among women with low-grade cervical cytology and nonvisible squamocolumnar junction (SCJ) at colposcopic examination. Data of consecutive women with low-grade intraepithelial lesion(≤LSIL) undergoing colposcopic examination, which was unsatisfactory (due to the lack of the visualization of the entire SCJ), were retrospectively reviewed. The risk of developing high-grade cervical intraepithelial neoplasia (CIN2+) was assessed using Kaplan-Meier and Cox models. Data of 86 women were retrieved. Mean (standard deviation [SD]) age was 36.3 (13.4) years. A total of 71 (82.5%) patients had high-risk human papillomavirus (HR-HPV) at the time of diagnosis. Among the 63 patients undergoing repetition of HPV testing, 15 (24%) and 48 (76%) women had positive and negative tests for HR-HPV at 12 months, respectively. We observed that 5 (33%) of 15 patients with HPV persistence developed CIN2+, while only 1 (2%) patient of 48 patients without HPV persistence developed CIN2+ (odds ratio [OR]: 23.5; 95% confidence interval [CI]: 2.46-223.7; P < .001). The length of HR-HPV persistence correlated with an increased risk of developing CIN2+ ( P < .001; P for trend). High-risk HPV persistence is the only factor predicting for CIN2+ (hazard ratio: 3.19; 95% CI: 1.55-6.57; P = .002). High-risk HPV persistence predicts the risk of developing CIN2+ in patients with unsatisfactory colposcopic examination. Further studies are warranted in order to implement the use of HPV testing in patients with unsatisfactory colposcopy.

  12. 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.

  13. 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.

  14. A Pilot Study of Hypofractionated Stereotactic Radiation Therapy and Sunitinib in Previously Irradiated Patients With Recurrent High-Grade Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Wuthrick, Evan J., E-mail: evan.wuthrick@osumc.edu [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Curran, Walter J. [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Camphausen, Kevin [Department of Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland (United States); Lin, Alexander [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Glass, Jon; Evans, James; Andrews, David W. [Department of Neurological Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Axelrod, Rita [Department of Medical Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Shi, Wenyin; Werner-Wasik, Maria [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Haacke, E. Mark [Department of Radiology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Department of Biomedical Engineering, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Hillman, Gilda G. [Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Dicker, Adam P. [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-10-01

    Purpose/Objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG). Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acute toxicity, and response was assessed via serial magnetic resonance imaging. Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%. Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival.

  15. High success rate with new modified endoscopic treatment for high-grade VUR: A pilot study with preliminary report.

    Science.gov (United States)

    Asgari, S A; Asl, A S; Safarinejad, M R; Ghanaei, M M

    2016-04-01

    Despite the benefits of the minimally invasive endoscopic treatment for vesicoureteral reflux (VUR) it has a major drawback which is low success rate in high grade VUR. For overcoming this problem, we introduce a new modified technique of endoscopic treatment called periureteral injection technique (PIT). In a prospective study a total of 37 ureters in 19 boys and 14 girls were treated, including 3 bilateral cases. Of 37 units, 30 (81.1%) had grade IV and 7 (18.9%) had grade V primary VUR (18 right, 13 left and 3 bilateral units). Subureteral injection of Vantris(®) was done at the 5-o'clock and 7-o'clock positions in which the direction of injecting needles were almost parallel. Pre- and post-operative evaluation included urinalysis, urinary tract ultrasonography, voiding cystourethrography (VCUG), dimercaptosuccinic acid scan and urodynamic studies. The median age was 38 months (range 8-125). At 6 months follow up period confirmed with VCUG, the VUR has been disappeared in 34 (91.8%) units and 3 units [2 (5.4%) grade II and 1 (2.7%) had grade III)] had downgraded VUR. Complications included early fever due to urinary tract infection in 1 children, transient dysuria in 2 patients and low back pain in one patient (Summary Table). The success rate of PIT for treatment of high grade VUR is high. However, further studies with more patients and longer follow up periods are needed to draw final conclusion. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  16. Serous tubal intraepithelial carcinoma upregulates markers associated with high-grade serous carcinomas including Rsf-1 (HBXAP), cyclin E and fatty acid synthase.

    Science.gov (United States)

    Sehdev, Ann Smith; Kurman, Robert J; Kuhn, Elisabetta; Shih, Ie-Ming

    2010-06-01

    Serous tubal intraepithelial carcinoma (STIC) has been proposed as a precursor for many pelvic high-grade serous carcinomas. Our previous analysis of the ovarian cancer genome identified several genes with oncogenic potential that are amplified and/or overexpressed in the majority of high-grade serous carcinomas. Determining whether these genes are upregulated in STICs is important in further elucidating the relationship of STICs to high-grade serous carcinomas and is fundamental in understanding the molecular pathogenesis of high-grade serous carcinomas. In this study, 37 morphologically defined STICs were obtained from 23 patients with stage IIIC/IV high-grade serous carcinomas. Both STICs and the high-grade serous carcinomas were analyzed for expression of Rsf-1 (HBXAP), cyclin E, fatty acid synthase (FASN) and mucin-4. In addition, they were examined for expression of established markers including p53, Ki-67 and p16. We found that diffuse nuclear p53 and p16 immunoreactivity was observed in 27 (75%) of 36 and 18 (55%) of 33 STICs, respectively, whereas an elevated Ki-67 labeling index (>or=10%) was detected in 29 (78%) of 37 STICs. Cyclin E nuclear staining was seen in 24 (77%) of 35 STICs, whereas normal tubal epithelial cells were all negative. Increased Rsf-1 and FASN immunoreactivity occurred in 63%, and 62% of STICs, respectively, compared with adjacent normal-appearing tubal epithelium. Interestingly, only one STIC showed increased mucin-4 immunoreactivity. Carcinomas, when compared with STICs, overexpressed p16, Rsf-1, cyclin E and FASN in a higher proportion of cases. In conclusion, STICs express several markers including Rsf-1, cyclin E and FASN in high-grade serous carcinomas. In contrast, mucin-4 immunoreactivity either did not change or was reduced in most STICs. These results suggest that overexpression of Rsf-1, cyclin E and FASN occurs early in tumor progression.

  17. A Systematic Review and Meta-analysis of the Diagnostic Accuracy of Prostate Health Index and 4-Kallikrein Panel Score in Predicting Overall and High-grade Prostate Cancer.

    Science.gov (United States)

    Russo, Giorgio Ivan; Regis, Federica; Castelli, Tommaso; Favilla, Vincenzo; Privitera, Salvatore; Giardina, Raimondo; Cimino, Sebastiano; Morgia, Giuseppe

    2017-08-01

    Markers for prostate cancer (PCa) have progressed over recent years. In particular, the prostate health index (PHI) and the 4-kallikrein (4K) panel have been demonstrated to improve the diagnosis of PCa. We aimed to review the diagnostic accuracy of PHI and the 4K panel for PCa detection. We performed a systematic literature search of PubMed, EMBASE, Cochrane, and Academic One File databases until July 2016. We included diagnostic accuracy studies that used PHI or 4K panel for the diagnosis of PCa or high-grade PCa. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Twenty-eight studies including 16,762 patients have been included for the analysis. The pooled data showed a sensitivity of 0.89 and 0.74 for PHI and 4K panel, respectively, for PCa detection and a pooled specificity of 0.34 and 0.60 for PHI and 4K panel, respectively. The derived area under the curve (AUC) from the hierarchical summary receiver operating characteristic (HSROC) showed an accuracy of 0.76 and 0.72 for PHI and 4K panel respectively. For high-grade PCa detection, the pooled sensitivity was 0.93 and 0.87 for PHI and 4K panel, respectively, whereas the pooled specificity was 0.34 and 0.61 for PHI and 4K panel, respectively. The derived AUC from the HSROC showed an accuracy of 0.82 and 0.81 for PHI and 4K panel, respectively. Both PHI and the 4K panel provided good diagnostic accuracy in detecting overall and high-grade PCa. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. 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.

  19. Crack blunting, cleavage fracture in transition area and stable crack growth - investigated using the nonlinear fracture mechanics method

    International Nuclear Information System (INIS)

    Heerens, J.

    1990-01-01

    A procedure is developed which allows to estimate crack tip blunting using the stress-strain curve of the material and the J-integral. The second part deals with cleavage fracture in a quenched and tempered pressure vessel steel. It was found that within the ductile to brittle transition regime the fracture toughness is controlled by cleavage initiated at 'weak spots of the material' and by the normal stresses at the weak spots. In the last part of the paper the influence of specimen size on J-, Jm- and δ 5 -R-curves for side grooved CT-specimens under fully plastic condition is investigated. In order to characterize constraint-effects the necking of the specimens was measured. For specimens having similar constraint the parameters Jm and δ 5 yielded size independent R-curves over substantial larger amounts of crack extension than the J-integral. (orig.) With 114 figs., 10 tabs [de

  20. Exploring the multidimensional nature of stock structure: a case study on herring dynamics in a transition area

    DEFF Research Database (Denmark)

    Worsøe Clausen, Lotte

    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 passively by drifting eggs and larvae following ocean currents, or actively by migration of juveniles...... will aid a sustainable aggregated management of a fishery on a mixed herring stock. It will facilitate protecting the weaker populations from over harvesting in a mixed fishery and thus maintain the diversity and in turn the resilience of the stock to a fishery...

  1. Z-LASIK and Trans-PRK for correction of high-grade myopia: safety, efficacy, predictability and clinical outcomes.

    Science.gov (United States)

    Gershoni, Assaf; Mimouni, Michael; Livny, Eitan; Bahar, Irit

    2018-03-12

    The aim of the study was to examine the outcomes of transepithelial photorefractive keratectomy (Trans-PRK) and Femtosecond Laser-assisted in situ keratomileusis (Z-LASIK) for the correction of high myopia. A retrospective cohort study design was used. The study group included 792 eyes with high-grade myopia (- 6.0 diopters or higher) or high-grade myopia with astigmatism that were treated with Z-LASIK or Trans-PRK in 2013 through 2014 in an optical outpatient clinic of a large private medical service. The Trans-PRK group comprised of 674 eyes with a spherical equivalent (SE) of - 7.87 ± 1.46 and the Z-LASIK group comprised of 118 eyes with a SE of - 7.19 ± 0.81 (P PRK group was - 0.06 and - 0.02 in the Z-LASIK group (P = 0.545). Efficacy index values were 0.92 in the Trans-PRK group and 0.95 in the Z-LASIK group (P = 0.083), and corresponding safety index values were 0.95 and 0.97 (P = 0.056). An UCVA of 20/40 or better was achieved in 94.20% of eyes in the Trans-PRK group, and 98.31% in the Z-LASIK group (P = 0.063). The majority of eyes in both the Trans-PRK and Z-LASIK groups were within ± 0.5D of attempted correction: 59.35 and 64.71%, respectively (P = 0.271). Both Trans-PRK and Z-LASIK demonstrated excellent efficacy, safety and predictability profiles, with results comparable and in some cases superior to the current literature. Results of Z-LASIK were slightly better than those of Trans-PRK, though the preoperative SE of the latter was higher.

  2. 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

  3. A Comparative Study of Survival Rate in High Grade Glioma Tumors Being Treated by Radiotherapy Alone Versus Chemoradiation With Nitrosourea.

    Science.gov (United States)

    Houshyari, Mohammad; Hajalikhani, Farzaneh; Rakhsha, Afshin; Hajian, Parastoo

    2015-03-25

    In adults, malignant glioma (high-grade glioma) is one of the most common brain tumors. In spite of different types of treatment, the outcome is still not likely to be favorable. The aim of this study was to determine the difference between survival rate in adult patients with high grade glioma treated by radiotherapy only and those treated by a combination of radiotherapy and nitrosurea-based chemotherapy. This study was conducted using the records of 48 patients with grade 3 or 4 of glial brain tumor referred to the radiation-oncology ward of Shohada-e-Tajrish Hospital in Tehran, Iran from 2005 to 2012. The patients had undergone radiotherapy alone or adjuvant chemoradiation with nitrosourea. The median survival of patients after receiving the different types of treatment were evaluated using the Kaplan-Meier method and the log -rank exam. Data were analyzed using univariate analysis for median survival regarding to the patients' age, gender, extent of surgery, Karnofsky performance status (KPS) with the Kaplan-Meier method, and the log-rank exam. We used the Cox-model for multivariate analysis. Records of 48 patients were studied (34 men and 14 women). The mean survival were 18 months for men and 15.2 months for women (P=0.05). Around 58% (28 patients) were more than 50 years old, and 42% (20 patients) were less than 50, and mean survival for the two age groups were 13 and 20 months, respectively (P<0.001). Then, the patients were divided into three groups according to the extent of surgery, i.e., excisional biopsy (11 patients), stereotactic biopsy (22 patients), and resection (15 patients), and the mean survival for the three groups were 14.7, 17.3, and 18.8 months, respectively. There was no significant statistical difference for mean survival between the three groups (P=0.23). The KPS was greater than 70% in 23 patients and less than 70% in 21 patients, and the mean survival for the former and latter groups were 17.6 and 16 months, respectively (P=0

  4. Response of three instruments devoted to surface-area for monodisperse and polydisperse aerosols in molecular and transition regimes

    International Nuclear Information System (INIS)

    Bau, Sebastien; Witschger, Olivier; Gensdarmes, Francois; Thomas, Dominique

    2011-01-01

    An increasing number of experimental and theoretical studies focus on airborne nanoparticles (NP) in relation with many aspects of risk assessment. Indeed, our understanding of the hazards, the actual exposures in the workplace and the limits of engineering controls and personal protective equipment with regard to NP are still under development. Several studies have already identified surface-area as an important determinant of low solubility nanoparticles toxicity. As a consequence, the concept that surface-area could be a relevant metric for characterizing exposure to low solubility airborne NP has been proposed [1]. To provide NP surface-area concentration, some direct-reading instruments have been designed, based on diffusion charging. The actual available instruments providing airborne NP surface-area concentration are studied in this work: LQ1-DC (Matter Engineering), AeroTrak T M 9000 (TSI) and NSAM (TSI model 3550). Their performances regarding monodisperse carbon NP have been investigated by Bau et al.. This work aims at completing the instruments characterization regarding monodisperse NP of other chemical composition (aluminium, copper, silver) and studying their performances against polydisperse aerosols of NP.

  5. Response of three instruments devoted to surface-area for monodisperse and polydisperse aerosols in molecular and transition regimes

    Energy Technology Data Exchange (ETDEWEB)

    Bau, Sebastien; Witschger, Olivier [Institut National de Recherche et de Securite (INRS), Laboratoire de Metrologie des Aerosols, Rue du Morvan, CS 60027, 54519 Vandoeuvre Cedex (France); Gensdarmes, Francois [Institut de Radioprotection et de Surete Nucleaire (IRSN), Laboratoire de Physique et de Metrologie des Aerosols, BP 68, 91192 Gif-sur-Yvette (France); Thomas, Dominique, E-mail: sebastien.bau@inrs.fr [Laboratoire Reactions et Genie des Procedes (LRGP), groupe SAFE, 1 rue Grandville, BP 20041, 54001 Nancy Cedex (France)

    2011-07-06

    An increasing number of experimental and theoretical studies focus on airborne nanoparticles (NP) in relation with many aspects of risk assessment. Indeed, our understanding of the hazards, the actual exposures in the workplace and the limits of engineering controls and personal protective equipment with regard to NP are still under development. Several studies have already identified surface-area as an important determinant of low solubility nanoparticles toxicity. As a consequence, the concept that surface-area could be a relevant metric for characterizing exposure to low solubility airborne NP has been proposed [1]. To provide NP surface-area concentration, some direct-reading instruments have been designed, based on diffusion charging. The actual available instruments providing airborne NP surface-area concentration are studied in this work: LQ1-DC (Matter Engineering), AeroTrak{sup TM} 9000 (TSI) and NSAM (TSI model 3550). Their performances regarding monodisperse carbon NP have been investigated by Bau et al.. This work aims at completing the instruments characterization regarding monodisperse NP of other chemical composition (aluminium, copper, silver) and studying their performances against polydisperse aerosols of NP.

  6. Classifying low-grade and high-grade bladder cancer using label-free serum surface-enhanced Raman spectroscopy and support vector machine

    Science.gov (United States)

    Zhang, Yanjiao; Lai, Xiaoping; Zeng, Qiuyao; Li, Linfang; Lin, Lin; Li, Shaoxin; Liu, Zhiming; Su, Chengkang; Qi, Minni; Guo, Zhouyi

    2018-03-01

    This study aims to classify low-grade and high-grade bladder cancer (BC) patients using serum surface-enhanced Raman scattering (SERS) spectra and support vector machine (SVM) algorithms. Serum SERS spectra are acquired from 88 serum samples with silver nanoparticles as the SERS-active substrate. Diagnostic accuracies of 96.4% and 95.4% are obtained when differentiating the serum SERS spectra of all BC patients versus normal subjects and low-grade versus high-grade BC patients, respectively, with optimal SVM classifier models. This study demonstrates that the serum SERS technique combined with SVM has great potential to noninvasively detect and classify high-grade and low-grade BC patients.

  7. Early planning and transition management from operation into decommissioning - Vision of future work in the area of human and organisational factors based on experience

    International Nuclear Information System (INIS)

    Almeida, P.; Gil, B.; Lekberg, A.; Hansson, B.; Frischknecht, A.; Pyy, Pekka; )

    2005-01-01

    Full text: Decommissioning commercial nuclear power plants with their employees and stakeholders leads to a range of safety management, socio-technical and societal challenges. These aspects need to be taken into account in order to assure smooth end-of -operation and decommissioning. The focus of this paper is especially in the planning and transition period into decommissioning. The areas found as critical as a conclusion of the workshop organised by Committee on Safety of Nuclear Installations (CSNI) in 1999 are used as the starting point of the evaluation. The topic is discussed based on experiences from mainly two countries with different cultural and regulatory frameworks: Spain and Sweden. The discussion is completed by information about the accomplishments of Special Expert Group on Human and Organisational Factors (SEGHOF) in the area. The area of treating human and organisational factors in planning and transition is broken down into five sub-areas. Each topic ends up with a view of the situation and visions for future, of which the most important are elaborated more in the concluding remarks. Decommissioning commercial nuclear power plants leads to a broad range of safety management, socio-technical and societal challenges. Organisational aspects are fundamental to any successful decommissioning process. Organisations must provide support for the management of change and must assure that resource and competence needs are appropriately specified, that uncertainty of personnel is minimised and staff morale is maintained. Furthermore, many new technical challenges must be met. The organisations too often have to address all these challenges with little guidance or experience, with reduced resources and surrounded by societal pressures. During the planning and transition into decommissioning, an organisation needs to determine and implement a range of organisational processes: management of change, work planning and management, safety management, and

  8. 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.

  9. The first report of a microdiverse anammox bacteria community in waters of Colombian Pacific, a transition area between prominent oxygen minimum zones of the eastern tropical Pacific.

    Science.gov (United States)

    Castro-González, M; Molina, V; Rodríguez-Rubio, E; Ulloa, O

    2014-12-01

    Anaerobic ammonium oxidizers contribute to the removal of fixed nitrogen in oxygen-deficient marine ecosystems such as oxygen minimum zones (OMZ). Here we surveyed for the first time the occurrence and diversity of anammox bacteria in the Colombian Pacific, a transition area between the prominent South and North Pacific OMZs. Anammox bacteria were detected in the coastal and oceanic areas of the Colombian Pacific in low oxygen (Chile and Arabian Sea) within Candidatus ‘Scalindua spp’. Moreover, some anammox bacteria OTUs shared a low similarity with environmental phylotypes (86–94%). Our results indicated that a microdiverse anammox community inhabits the Colombian Pacific, generating new questions about the ecological and biogeochemical differences influencing its community structure.

  10. PA03.13. Effect of triphaladi rasayana along with yoga therapy on low grade non hodgkins lymphoma and resistant intermediate and high grade non hodgkins lymphoma

    Science.gov (United States)

    Soumya, MS Surya; Sarasa, TP

    2013-01-01

    Purpose: 1. To find out the effect of Thriphaladi Rasayana along with Yoga Therapy on low grade Non Hodgkins Lymphoma and resistant intermediate and high grade NonHodgkins Lymphoma. 2. To apply a less costly, less morbid, well accepted method of treatment on NHL. 3.To find a simple method to increase the immunity. 4.To try a drug which is easy to prepare? Method: Purposive sampling technique was used for the study. Sample of 30 patients age range 25 75 years with histologicaly proven NonHodgkins lymphoma, attending the M.O.I.O.P of the regional cancer centre during a period of 18 months. Groups1) Low grade NonHodgkins Lymphoma 2) Resistant intermediate &High grade NonHodgkins lymphoma (failed chemotherapy) were taken. Procedure : 2 groups were given Triphaladhi Rasayana (15 grams of powder with ghee and honey) twice dailymorning& at bed time with milk as anupana for period of 1month along with selected yoga asanas and niyama? Result: Symptoms included were fever, night sweats, weight loss, lymph nodes enlargement, splenomegaly, and hepatomegaly. In low grade symptom relief was noted in almost all cases. Lymph node changes notedLow grade5 2% (complete remission), 38% (partial remission), 10% (no change), intermediate35% (CR), 52% (PR) & 13% (NC), High grade67% (CR), 33%(PR). Hepatomegaly changes :ve in low grade92.86%, intermediate 90.9% & high grade100%. Splenomegaly changes :ve in low grade92.86%, intermediate72.72% & high grade80% Over all remission status of 30 patientscomplete remission30%, partial remission 30% & no change30%? Conclusion: Thriphaladirasayana along with Yoga therapy is very effective in Low grade NonHodgkins lymphoma and resistant intermediate and high grade Non hodgkins Lymphoma?

  11. Comparison of Utility of Histogram Apparent Diffusion Coefficient and R2* for Differentiation of Low-Grade From High-Grade Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Zhang, Yu-Dong; Wu, Chen-Jiang; Wang, Qing; Zhang, Jing; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin

    2015-08-01

    The purpose of this study was to compare histogram analysis of apparent diffusion coefficient (ADC) and R2* for differentiating low-grade from high-grade clear cell renal cell carcinoma (RCC). Forty-six patients with pathologically confirmed clear cell RCC underwent preoperative BOLD and DWI MRI of the kidneys. ADCs based on the entire tumor volume were calculated with b value combinations of 0 and 800 s/mm(2). ROI-based R2* was calculated with eight TE combinations of 6.7-22.8 milliseconds. Histogram analysis of tumor ADCs and R2* values was performed to obtain mean; median; width; and fifth, 10th, 90th, and 95th percentiles and histogram inhomogeneity, kurtosis, and skewness for all lesions. Thirty-three low-grade and 13 high-grade clear cell RCCs were found at pathologic examination. The TNM classification and tumor volume of clear cell RCC significantly correlated with histogram ADC and R2* (ρ = -0.317 to 0.506; p histogram ADC and R2* indexes, 10th percentile ADC had the highest accuracy (91.3%) in discriminating low- from high-grade clear cell RCC. R2* in discriminating hemorrhage was achieved with a threshold of 68.95 Hz. At this threshold, high-grade clear cell RCC had a significantly higher prevalence of intratumor hemorrhage (high-grade, 76.9%; low-grade, 45.4%; p Histogram analysis of ADC and R2* allows differentiation of low- from high-grade clear cell RCC with high accuracy.

  12. Historiographical reflections on local and transit trade relations on the Prut-Dniester area and the Lower Danube (late 13th - 14th century

    Directory of Open Access Journals (Sweden)

    Silvia Barcari

    2013-12-01

    Full Text Available Due to the geographical position of the Prut-Dniester and the Lower Danube regions, there were lying the important trade routes and the important transit trade was carried out that in some ways contributed to their economic development. Through Transylvania and Wallachia there passed trade route linking the Western and Central Europe with the Black Sea region and the Balkan Peninsula and reaching the cities of the Adriatic coast; through the area of future Moldova there passed a road connecting the Baltic and the Black Seas. In transit trade there were involved Italian merchants from the Levant, Armenian merchants of Poland, and Transylvanian Saxons, who traded here "overseas goods": from the East - pepper, spices, from Western and Central Europe - cloth, linen, weapons, agricultural tools. In return, foreign merchants were buying in these areas cattle, horses, hides, wax, grain, etc. Need in money, especially the fractional coins often needed in small business transactions, has led to cutting coins into equal parts and stamping local imitations of foreign coins. In the 14th century in the mouth of the Danube there is attested the existence of "banks" and "bankers" engaged in exchange of money. Trading activity was stimulated by the transit of goods on major trade routes of Europe, as well as the opening of the local market for high-quality goods of the European market. The expansion of trade exchange contributed to the economic prosperity of the independent Romanian states and increasing of their military power that brought them to the international political arena.

  13. Simulation of ridesourcing using agent-based demand and supply regional models : potential market demand for first-mile transit travel and reduction in vehicle miles traveled in the San Francisco Bay Area.

    Science.gov (United States)

    2016-01-01

    In this study, we use existing modeling tools and data from the San Francisco Bay Area : (California) to understand the potential market demand for a first mile transit access service : and possible reductions in vehicle miles traveled (VMT) (a...

  14. 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.

  15. Long-term results of exclusive low-dose rate curie-therapy for a high-grade vaginal intraepithelial neoplasia

    International Nuclear Information System (INIS)

    Blanchard, P.; Monnier, L.; Dumas, I.; Azoury, F.; Mazeron, R.; Haie-Meder, C.

    2010-01-01

    The authors report the results of an exclusive low dose rate curie therapy for female patients treated for a grade 3 vaginal intraepithelial neoplasia. They reviewed the medical files of patients treated since 1983, i.e. 28 women. They analysed demographic characteristics, the clinic description of lesions, possible treatments which occurred before this high-grade vaginal intraepithelial neoplasia, possible previous history of cervical or endometrial cancer, curie therapy detailed data, presence of tumorous relapse. According to that, they conclude that a 60 Gy exclusive low- vaginal dose-rate curie-therapy is an efficient and well tolerated treatment for high-grade vaginal intraepithelial neoplasia. Short communication

  16. An innovation on high-grade CNC machines tools for B-spline curve method of high-speed interpolation arithmetic

    Science.gov (United States)

    Zhang, Wanjun; Gao, Shanping; Cheng, Xiyan; Zhang, Feng

    2017-04-01

    A novel on high-grade CNC machines tools for B Spline curve method of High-speed interpolation arithmetic is introduced. In the high-grade CNC machines tools CNC system existed the type value points is more trouble, the control precision is not strong and so on, In order to solve this problem. Through specific examples in matlab7.0 simulation result showed that that the interpolation error significantly reduced, the control precision is improved markedly, and satisfy the real-time interpolation of high speed, high accuracy requirements.

  17. Pediatric and Adult High-Grade Glioma Stem Cell Culture Models Are Permissive to Lytic Infection with Parvovirus H-1.

    Science.gov (United States)

    Josupeit, Rafael; Bender, Sebastian; Kern, Sonja; Leuchs, Barbara; Hielscher, Thomas; Herold-Mende, Christel; Schlehofer, Jörg R; Dinsart, Christiane; Witt, Olaf; Rommelaere, Jean; Lacroix, Jeannine

    2016-05-19

    Combining virus-induced cytotoxic and immunotherapeutic effects, oncolytic virotherapy represents a promising therapeutic approach for high-grade glioma (HGG). A clinical trial has recently provided evidence for the clinical safety of the oncolytic parvovirus H-1 (H-1PV) in adult glioblastoma relapse patients. The present study assesses the efficacy of H-1PV in eliminating HGG initiating cells. H-1PV was able to enter and to transduce all HGG neurosphere culture models (n = 6), including cultures derived from adult glioblastoma, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Cytotoxic effects induced by the virus have been observed in all HGG neurospheres at half maximal inhibitory concentration (IC50) doses of input virus between 1 and 10 plaque forming units per cell. H-1PV infection at this dose range was able to prevent tumorigenicity of NCH421k glioblastoma multiforme (GBM) "stem-like" cells in NOD/SCID mice. Interestingly NCH421R, an isogenic subclone with equal capacity of xenograft formation, but resistant to H-1PV infection could be isolated from the parental NCH421k culture. To reveal changes in gene expression associated with H-1PV resistance we performed a comparative gene expression analysis in these subclones. Several dysregulated genes encoding receptor proteins, endocytosis factors or regulators innate antiviral responses were identified and represent intriguing candidates for to further study molecular mechanisms of H-1PV resistance.

  18. Preoperative evaluation and monitoring chemotherapy in patients with high-grade osteogenic and Ewing's sarcoma: review of current imaging modalities

    International Nuclear Information System (INIS)

    Woude, H.-J. van der; Bloem, J.L.; Hogendoorn, P.C.W.

    1998-01-01

    Diagnostic imaging is pivotal in the initial detection, characterization, staging and post-treatment follow-up of patients with high-grade osteogenic and Ewing's sarcoma. In the present review article, conventional and new imaging modalities are discussed with regard to the monitoring of the effect of neoadjuvant chemotherapy in such patients. Presurgical monitoring of response to chemotherapy may have an impact on modification of neoadjuvant treatment protocols, on patient selection for the performance and timing of limb-salvage surgery and on planning of radiation therapy (in non-operated Ewing's sarcomas) and selection of postoperative chemotherapy regimens. Dynamic contrast-enhanced MR imaging, as part of a routine MR protocol, assists in the detection of the most viable parts of the tumour and serves as an initial standard for follow-up of the metabolic activity of the tumour during and after chemotherapy, both in small intraosseous tumours and in tumours with an associated soft tissue mass. In combination with selected morphological features, dynamic imaging parameters are therefore advocated for monitoring the effect of neoadjuvant chemotherapy in patients with osteogenic and Ewing's sarcoma. (orig.)

  19. Paclitaxel poliglumex, temozolomide, and radiation for newly diagnosed high-grade glioma: a Brown University Oncology Group Study.

    Science.gov (United States)

    Jeyapalan, Suriya; Boxerman, Jerrold; Donahue, John; Goldman, Marc; Kinsella, Timothy; Dipetrillo, Thomas; Evans, Devon; Elinzano, Heinrich; Constantinou, Maria; Stopa, Edward; Puthawala, Yakub; Cielo, Deus; Santaniello, Alyson; Oyelese, Adetokunbo; Mantripragada, Kalyan; Rosati, Kayla; Isdale, Debora; Safran, Howard

    2014-10-01

    Paclitaxel poliglumex (PPX), a drug conjugate that links paclitaxel to poly-L-glutamic acid, is a potent radiation sensitizer. Prior studies in esophageal cancer have demonstrated that PPX (50 mg/m/wk) can be administered with concurrent radiation with acceptable toxicity. The primary objective of this study was to determine the safety of the combination of PPX with temozolomide and concurrent radiation for high-grade gliomas. Eligible patients were required to have WHO grade 3 or 4 gliomas. Patients received weekly PPX (50 mg/m/wk) combined with standard daily temozolomide (75 mg/m) for 6 weeks with concomitant radiation (2.0 Gy, 5 d/wk for a total dose of 60 Gy). Twenty-five patients were enrolled, 17 with glioblastoma and 8 with grade 3 gliomas. Seven of 25 patients had grade 4 myelosuppression. Hematologic toxicity lasted up to 5 months suggesting a drug interaction between PPX and temozolomide. For patients with glioblastoma, the median progression-free survival was 11.5 months and the median overall survival was 18 months. PPX could not be safely combined with temozolomide due to grade 4 hematologic toxicity. However, the favorable progression-free and overall survival suggest that PPX may enhance radiation for glioblastoma. A randomized study of single agent PPX/radiation versus temozolomide/radiation for glioblastoma without MGMT methylation is underway.

  20. 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.

  1. Safety and Efficacy of Stereotactic Body Radiation Therapy in the Treatment of Pulmonary Metastases from High Grade Sarcoma

    Directory of Open Access Journals (Sweden)

    Niraj Mehta

    2013-01-01

    Full Text Available Introduction. Patients with high-grade sarcoma (HGS frequently develop metastatic disease thus limiting their long-term survival. Lung metastases (LM have historically been treated with surgical resection (metastasectomy. A potential alternative for controlling LM could be stereotactic body radiation therapy (SBRT. We evaluated the outcomes from our institutional experience utilizing SBRT. Methods. Sixteen consecutive patients with LM from HGS were treated with SBRT between 2009 and 2011. Routine radiographic and clinical follow-up was performed. Local failure was defined as CT progression on 2 consecutive scans or growth after initial shrinkage. Radiation pneumonitis and radiation esophagitis were scored using Common Toxicity Criteria (CTC version 3.0. Results. All 16 patients received chemotherapy, and a subset (38% also underwent prior pulmonary metastasectomy. Median patient age was 56 (12–85, and median follow-up time was 20 months (range 3–43. A total of 25 lesions were treated and evaluable for this analysis. Most common histologies were leiomyosarcoma (28%, synovial sarcoma (20%, and osteosarcoma (16%. Median SBRT prescription dose was 54 Gy (36–54 in 3-4 fractions. At 43 months, local control was 94%. No patient experienced G2-4 radiation pneumonitis, and no patient experienced radiation esophagitis. Conclusions. Our retrospective experience suggests that SBRT for LM from HGS provides excellent local control and minimal toxicity.

  2. Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era

    Science.gov (United States)

    Perry, Christina; Agarwal, Devika; Abdel-Fatah, Tarek M.A.; Lourdusamy, Anbarasu; Grundy, Richard; Auer, Dorothee T.; Walker, David; Lakhani, Ravi; Scott, Ian S.; Chan, Stephen; Ball, Graham; Madhusudan, Srinivasan

    2014-01-01

    Deregulation of multiple DNA repair pathways may contribute to aggressive biology and therapy resistance in gliomas. We evaluated transcript levels of 157 genes involved in DNA repair in an adult glioblastoma Test set (n=191) and validated in ‘The Cancer Genome Atlas’ (TCGA) cohort (n=508). A DNA repair prognostic index model was generated. Artificial neural network analysis (ANN) was conducted to investigate global gene interactions. Protein expression by immunohistochemistry was conducted in 61 tumours. A fourteen DNA repair gene expression panel was associated with poor survival in Test and TCGA cohorts. A Cox multivariate model revealed APE1, NBN, PMS2, MGMT and PTEN as independently associated with poor prognosis. A DNA repair prognostic index incorporating APE1, NBN, PMS2, MGMT and PTEN stratified patients in to three prognostic sub-groups with worsening survival. APE1, NBN, PMS2, MGMT and PTEN also have predictive significance in patients who received chemotherapy and/or radiotherapy. ANN analysis of APE1, NBN, PMS2, MGMT and PTEN revealed interactions with genes involved in transcription, hypoxia and metabolic regulation. At the protein level, low APE1 and low PTEN remain associated with poor prognosis. In conclusion, multiple DNA repair pathways operate to influence biology and clinical outcomes in adult high grade gliomas. PMID:25026297

  3. 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.

  4. Radiotherapy in the management of high-grade gliomas diagnosed in Western Australia: a patterns of care study

    International Nuclear Information System (INIS)

    Jackson, Melanie; Taylor, Mandy; Bydder, Sean; Maujean, Eric; Nowak, Anna

    2012-01-01

    Radiotherapy (RT) plays an integral role in the management of high-grade glioma (HGG). However, there is little information on the patterns of care in unselected Australian patients with HGG. This prospective cohort study collected information on patients with a diagnosis of HGG managed in Western Australia over a 25-month period from 2006 to 2008. RT treatment and survival data were analysed. 86% of Western Australian patients with HGG were treated at the study site over this period. Of these, 80% were reviewed by a radiation oncologist with RT recommended in 88% of cases. One hundred eighty-seven patients proceeded to have RT, with most receiving 60 Gy in 30 fractions with limited field external beam radiotherapy (LFRT). Median survival from diagnosis was 13.6 months for all patients and 15.4 months for those planned for treatment with 60 Gy in 30 fractions. The median time from surgery to the start of RT was 41 days. Longer waiting times were not predictors of poor survival. Failure to receive all planned treatment (13% of patients) predicted for poor survival (hazard ratio 0.38). Dose and fractionation practices show concordance with published data and guidelines. Survival is also consistent with clinical trial data for patients planned for aggressive therapy. Nevertheless, a substantial number of patients are not suited to aggressive therapy or fail to complete planned therapy, and these patients have poor outcomes. Treatment delays did not affect survival outcomes but are confounded by earlier treatment of those unsuited to LFRT.

  5. The natural limb is best: joint preservation and reconstruction by distraction osteogenesis for high-grade juxta-articular osteosarcomas.

    Science.gov (United States)

    Tsuchiya, Hiroyuki; Abdel-Wanis, Mohamed E; Kitano, Shinji; Sakurakichi, Keisuke; Yamashiro, Teruhisa; Tomita, Katsuro

    2002-01-01

    This paper introduces an innovative technique of highly conservative limb-saving surgery for juxta-articular osteosarcoma. This technique consists of marginal tumour excision, joint preservation and reconstruction by distraction osteogenesis. Ten patients, with a mean age of 19.5 years and high-grade osteosarcoma, underwent this procedure. The distal femur and proximal tibia were affected in five patients each. After effective pre-operative chemotherapy, the tumour was excised with preservation of the epiphysis, the articular surface and the maximun amount of healthy soft tissue. This was followed by application of an external fixator. Bone transport was performed for seven patients and shortening-distraction for three. The limb function was rated excellent in seven patients, good in one and fair in two. At the final follow-up, three patients were dead after a mean of 25.3 months while seven patients remained free of disease with a mean follow-up of 55.4 months. Joint preservation and biological reconstruction through distraction osteogenesis can produce excellent and long-lasting functional results.

  6. PHASE ANALYSES OF URANIUM-BEARING MINERALS FROM THE HIGH GRADE ORE, NOPAL I, PENA BLANCA, MEXICO

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. 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.

  8. Nano-mineralogy and -geochemistry of high-grade diasporic karst-type bauxite from Parnassos-Ghiona mines, Greece

    DEFF Research Database (Denmark)

    Gkamaletsos, Platon; Godelitsas, Athanasios; Kasama, Takeshi

    2017-01-01

    and electron microscopy in microscale and mesoscale (SEM-EDS including STEM mode), proved the presence of “Fe-Cr-Ti-containing diaspore”, anatase and minor rutile. The study by means of 57Fe Mössbauer spectroscopy, in correlation with magnetic susceptibility measurements and, complemented, with Synchrotron......In the present work, a combination of various techniques is utilized for the study of nano-mineralogy and -geochemistry of high-grade karst-type bauxite (Al-rich and Fe-depleted samples; Al2O3 ca. 80 wt.%) from the Parnassos-Ghiona mines located in Greece. Initial characterization using PXRD......-based spectroscopies at the microscale (SR micro-XRF and micro-XANES/-EXAFS), indicated that Fe3+, in contrast to [6]Cr3+, is not exclusively a component of the diaspore structure. While Cr3 + substitutes Al3 + in octahedral sites of diaspore ([6]Cr3+ ↔ [6]Al3+), the electron microscopy in nanoscale (TEM-EDS & EELS...

  9. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer.

    Science.gov (United States)

    Lawrenson, Kate; Li, Qiyuan; Kar, Siddhartha; Seo, Ji-Heui; Tyrer, Jonathan; Spindler, Tassja J; Lee, Janet; Chen, Yibu; Karst, Alison; Drapkin, Ronny; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Baker, Helen; Bandera, Elisa V; Bean, Yukie; Beckmann, Matthias W; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Chen, Anne; Chen, Zhihua; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T; Edwards, Robert P; Eilber, Ursula; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; James, Paul; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kruger Kjaer, Susanne; Kelemen, Linda E; Kellar, Melissa; Kelley, Joseph L; Kiemeney, Lambertus A; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Nevanlinna, Heli; McNeish, Ian; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Narod, Steven A; Nedergaard, Lotte; Ness, Roberta B; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schildkraut, Joellen M; Schwaab, Ira; Sellers, Thomas A; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Sucheston, Lara; Tangen, Ingvild L; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S; van Altena, Anne M; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Monteiro, Alvaro; Pharoah, Paul D; Gayther, Simon A; Freedman, Matthew L

    2015-09-22

    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 associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.

  10. DNA Repair Alterations in Children With Pediatric Malignancies: Novel Opportunities to Identify Patients at Risk for High-Grade Toxicities

    International Nuclear Information System (INIS)

    Ruebe, Claudia E.; Fricke, Andreas; Schneider, Ruth; Simon, Karin; Kuehne, Martin; Fleckenstein, Jochen; Graeber, Stefan; Graf, Norbert; Ruebe, Christian

    2010-01-01

    Purpose: To evaluate, in a pilot study, the phosphorylated H2AX (γH2AX) foci approach for identifying patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging cancer therapy. Methods and Materials: The DSB repair capacity of children with solid cancers was analyzed compared with that of age-matched control children and correlated with treatment-related normal-tissue responses (n = 47). Double-strand break repair was investigated by counting γH2AX foci in blood lymphocytes at defined time points after irradiation of blood samples. Results: Whereas all healthy control children exhibited proficient DSB repair, 3 children with tumors revealed clearly impaired DSB repair capacities, and 2 of these repair-deficient children developed life-threatening or even lethal normal-tissue toxicities. The underlying mutations affecting regulatory factors involved in DNA repair pathways were identified. Moreover, significant differences in mean DSB repair capacity were observed between children with tumors and control children, suggesting that childhood cancer is based on genetic alterations affecting DSB repair function. Conclusions: Double-strand break repair alteration in children may predispose to cancer formation and may affect children's susceptibility to normal-tissue toxicities. Phosphorylated H2AX analysis of blood samples allows one to detect DSB repair deficiencies and thus enables identification of children at risk for high-grade toxicities.

  11. 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...

  12. 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.

  13. 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.

  14. Metronomic cyclophosphamide-induced long-term remission after recurrent high-grade serous ovarian cancer: A case study.

    Science.gov (United States)

    de Boo, Leonora Wijnandina; Vulink, Annelie Johanna Elisabeth; Bos, Monique Elisabeth Martina Maria

    2017-12-01

    Metronomic oral cyclophosphamide has gained increasing interest in recent years as a promising maintenance therapy in advanced, platinum-sensitive, high-grade serous ovarian cancer (HGSOC). Metronomic treatment with cyclophosphamide refers to the frequent, usually daily, administration of a low (oral) dose of cyclophosphamide with no prolonged drug-free breaks. Main advantages of this treatment are the effective reduction of tumour activity, oral administration in an outpatient setting, low cost and the low toxicity profile. Metronomic oral cyclophosphamide can benefit patients suffering from types of cancer known to be sensitive to alkylating agents, such as platinum-sensitive HGSOC. In recent years, several publications have underlined the advantage of this regimen and possible explanations were explored. We here present a patient with multiple recurrences of metastasized HGSOC, platinum-sensitive, with an on-going complete response to monotherapy with oral cyclophosphamide. This observation supports that patients with relapsing HGSOC who responded to platinum-based chemotherapy and cannot continue platinum-based chemotherapy because of toxicity, can be offered a course of metronomic cyclophosphamide. This case may serve as a reminder that old drugs can be used successfully even in the age of new upcoming therapy such as anti-angiogenic agents (VEGF inhibitors) and poly-ADP-ribose polymerase (PARP) inhibitors.

  15. Separation and recovery of high grade Dy2O3 by solvent extraction process with DEHPA in kerosene

    International Nuclear Information System (INIS)

    Mishra, S.L.; Thakur, N.V.; Koppiker, K.S.

    1993-01-01

    During the solvent extraction (SX) fractionation of rare earths chloride obtained from monazite, a heavy RE (HRE) fraction assaying 60% Y 2 O 3 is produced. This is purified further to 93% Y 2 O 3 by another SX cycle. During this step most of Dy and Tb get separated to yield a concentrate assaying >50% Dy 2 O 3 . An attempt has been made to process this Dy rich concentrate to obtain a high grade Dy 2 O 3 by a SX route using DEHPA in kerosene. The distribution data (D vs H i + ) of Dy have been generated experimentally at various metal concentrations and similar data for other metals present (Gd, Tb, Y, Er and Ho) have been derived using a mathematical expression developed in our laboratory. Based on this information mathematical models for extraction behaviour of these HRE have been derived and used in a computer program developed for multicomponent system. This program has been utilised to optimise the process parameters to obtain 95-97% pure Dy 2 O 3 at about 90% recovery. The parameters have been experimentally confirmed and Dy 2 O 3 95.5% pure w.r.t. Tb was obtained at about 90% recovery, thus confirming the validity of the program. This paper presents data obtained during these investigations. (author). 6 refs., 5 tabs

  16. Treatment of symptomatic high-grade intracranial stenoses with the balloon-expandable Pharos stent: initial experience

    International Nuclear Information System (INIS)

    Kurre, W.; Berkefeld, J.; Mesnil de Rochemont, R. du; Sitzer, M.; Neumann-Haefelin, T.

    2008-01-01

    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.)

  17. Limb sparing approach: Adjuvant radiation therapy in adults with intermediate or high-grade limb soft tissue sarcoma

    International Nuclear Information System (INIS)

    Merimsky, Ofer; Soyfer, Vjacheslav; Kovner, Felix; Bickels, Jacob; Issakov, Josephine; Flusser, Gideon; Meller, Isaac; Ofer, Oded; Kollender, Yehuda

    2005-01-01

    Background: Limb soft tissue sarcomas (STS) are currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). Patients and methods: Between October 1994 and October 2002, 133 adult patients with intermediate or high-grade limb STS were approached by LSS+RT. Results: RT related toxicity was manageable, with a low rate of severe effects. At 4-year median follow-up, there were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic spread w/o local failure. DFS and OS were influenced by disease stage II vs I, primary site in the upper limb vs lower limb, MPNST vs other types, induction therapy vs no induction, adequate resection vs marginal resection or involved margins, and good response to induction therapy vs bad response. DFS and OS were Patient's age and sex, tumor depth, acute or late toxicity of RT, or the interval of time between the date of definitive surgery and the start of RT did not affect DFS and or OS. Conclusions: The RT protocol is applicable in the era of complicated, expensive and time-consuming 3D therapy. Our results of LSS+RT in adults with limb HG STS are satisfactory

  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. Progesterone Prevents High-Grade Serous Ovarian Cancer by Inducing Necroptosis of p53-Defective Fallopian Tube Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Na-Yiyuan Wu

    2017-03-01

    Full Text Available High-grade serous ovarian carcinoma (HGSOC originates mainly from the fallopian tube (FT epithelium and always carries early TP53 mutations. We previously reported that tumors initiate in the FT fimbria epithelium because of apoptotic failure and the expansion of cells with DNA double-strand breaks (DSB caused by bathing of the FT epithelial cells in reactive oxygen species (ROSs and hemoglobin-rich follicular fluid (FF after ovulation. Because ovulation is frequent and HGSOC is rare, we hypothesized that luteal-phase progesterone (P4 could eliminate p53-defective FT cells. Here we show that P4, via P4 receptors (PRs, induces necroptosis in Trp53−/− mouse oviduct epithelium and in immortalized human p53-defective fimbrial epithelium through the TNF-α/RIPK1/RIPK3/MLKL pathway. Necroptosis occurs specifically at diestrus, recovers at the proestrus phase of the estrus cycle, and can be augmented with P4 supplementation. These results reveal the mechanism of the well-known ability of progesterone to prevent ovarian cancer.

  20. 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.

  1. High-definition fiber tractography for the evaluation of perilesional white matter tracts in high-grade glioma surgery.

    Science.gov (United States)

    Abhinav, Kumar; Yeh, Fang-Cheng; Mansouri, Alireza; Zadeh, Gelareh; Fernandez-Miranda, Juan C

    2015-09-01

    Conventional white matter (WM) imaging approaches, such as diffusion tensor imaging (DTI), have been used to preoperatively identify the location of affected WM tracts in patients with intracranial tumors in order to maximize the extent of resection and potentially reduce postoperative morbidity. DTI, however, has limitations that include its inability to resolve multiple crossing fibers and its susceptibility to partial volume effects. Therefore, recent focus has shifted to more advanced WM imaging techniques such as high-definition fiber tractography (HDFT). In this paper, we illustrate the application of HDFT, which in our preliminary experience has enabled accurate depiction of perilesional tracts in a 3-dimensional manner in multiple anatomical compartments including edematous zones around high-grade gliomas. This has facilitated accurate surgical planning. This is illustrated by using case examples of patients with glioblastoma multiforme. We also discuss future directions in the role of these techniques in surgery for gliomas. © 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.

  2. Revisit the Candidacy of Brain Cell Types as the Cell(s of Origin for Human High-Grade Glioma

    Directory of Open Access Journals (Sweden)

    Fangjie Shao

    2018-02-01

    Full Text Available High-grade glioma, particularly, glioblastoma, is the most aggressive cancer of the central nervous system (CNS in adults. Due to its heterogeneous nature, glioblastoma almost inevitably relapses after surgical resection and radio-/chemotherapy, and is thus highly lethal and associated with a dismal prognosis. Identifying the cell of origin has been considered an important aspect in understanding tumor heterogeneity, thereby holding great promise in designing novel therapeutic strategies for glioblastoma. Taking advantage of genetic lineage-tracing techniques, performed mainly on genetically engineered mouse models (GEMMs, multiple cell types in the CNS have been suggested as potential cells of origin for glioblastoma, among which adult neural stem cells (NSCs and oligodendrocyte precursor cells (OPCs are the major candidates. However, it remains highly debated whether these cell types are equally capable of transforming in patients, given that in the human brain, some cell types divide so slowly, therefore may never have a chance to transform. With the recent advances in studying adult NSCs and OPCs, particularly from the perspective of comparative biology, we now realize that notable differences exist among mammalian species. These differences have critical impacts on shaping our understanding of the cell of origin of glioma in humans. In this perspective, we update the current progress in this field and clarify some misconceptions with inputs from important findings about the biology of adult NSCs and OPCs. We propose to re-evaluate the cellular origin candidacy of these cells, with an emphasis on comparative studies between animal models and humans.

  3. 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.)

  4. Child restraint use in low socio-economic areas of urban Sydney during transition to new legislation.

    Science.gov (United States)

    Keay, Lisa; Hunter, Kate; Brown, Julie; Bilston, Lynne E; Simpson, Judy M; Stevenson, Mark; Ivers, Rebecca Q

    2013-01-01

    Child restraints protect a young child against injury in crashes but best practice child restraint use is low in Australia, particularly among lower socio-economic groups. We investigated factors associated with restraint use to inform the development of education and distribution programmes to support new Australian legislation on child passengers among families in low socio-economic areas of metropolitan Sydney. We interviewed a parent or carer of 1160 children aged 2-5 years enrolled at one of 28 early childhood centres in low socio-economic areas of urban Sydney. Appropriate child restraint use was defined as a forward facing child restraint (FFCR) for 2-3 year olds and a FFCR or booster seat for children aged 4 years or more. Predictors of self-reported appropriate use were explored using logistic regression. Analysis was conducted on one child from each family in the target age range (2-5 years): 586 (51%) were male and the mean age was 3.5 (Standard Deviation 0.8) years. There were 432 (45%) families with annual income below $60,000, 248 (22%) spoke a language other than English at home and 360 (33%) had 3 or more children. Fifty-four percent of carers indicated that their 2-3 year old children travelled in a FFCR. Inappropriate use among children in this age group was more likely when the carer was law and poorer knowledge of safety benefits of child restraints. They also had lower household incomes and more concerns about cost of child restraints and booster seats. These findings can inform development of interventions to promote best practice child restraint use, which will reach non-English speaking families in this region. They also confirm the importance of economic and logistic barriers to best practice child restraint use. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium

    NARCIS (Netherlands)

    Fleshner, N.E.; Kapusta, L.; Donnelly, B.; Tanguay, S.; Chin, J.; Hersey, K.; Farley, A.; Jansz, K.; Siemens, D.R.; Trpkov, K.; Lacombe, L.; Gleave, M.; Tu, D.; Parulekar, W.R.

    2011-01-01

    PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is a putative precursor of invasive prostate cancer (PCa). Preclinical evidence suggests vitamin E, selenium, and soy protein may prevent progression of HGPIN to PCa. This hypothesis was tested in a randomized phase III double-blind

  6. A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (Types 6/11/16/18) vaccine against high-grade cervical and external genital lesions

    DEFF Research Database (Denmark)

    Kjaer, Susanne K; Sigurdsson, Kristján; Iversen, Ole-Erik

    2009-01-01

    Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18-related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions bas...

  7. 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.

  8. Poor results of 5-aminolevulinic acid-photodynamic therapy for residual high-grade dysplasia and early cancer in barrett esophagus after endoscopic resection

    NARCIS (Netherlands)

    Peters, F.; Kara, M.; Rosmolen, W.; Aalders, M.; ten Kate, F.; Krishnadath, K.; van Lanschot, J.; Fockens, P.; Bergman, J.

    2005-01-01

    BACKGROUND AND STUDY AIMS: The aim of the study was to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of residual high-grade dysplasia or early cancer (HGD/EC) after endoscopic resection in Barrett esophagus. PATIENTS AND METHODS: Study patients were separated into group A,

  9. 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

    Background 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.

  10. 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

  11. Stepwise circumferential and focal ablation of Barrett's esophagus with high-grade dysplasia: results of the first prospective series of 11 patients

    NARCIS (Netherlands)

    Gondrie, J. J.; Pouw, R. E.; Sondermeijer, C. M. T.; Peters, F. P.; Curvers, W. L.; Rosmolen, W. D.; Krishnadath, K. K.; ten Kate, F.; Fockens, P.; Bergman, J. J.

    2008-01-01

    BACKGROUND AND STUDY AIMS: Stepwise circumferential and focal ablation of nondysplastic Barrett's esophagus has proven safe and effective. This study assessed the efficacy and safety of ablation for Barrett's esophagus with high-grade dysplasia (HGD), and residual Barrett's esophagus with dysplasia

  12. Changes in the Extracellular Matrix Are Associated With the Development of Serous Tubal Intraepithelial Carcinoma Into High-Grade Serous Carcinoma

    NARCIS (Netherlands)

    Steen, S.C.H.A. van der; Bulten, J.; Vijver, K.K. Van de; Kuppevelt, T.H. van; Massuger, L.F.

    2017-01-01

    OBJECTIVE: The identification of a marker for early progression of preinvasive lesions into invasive pelvic high-grade serous carcinoma (HGSC) may provide novel handles for innovative screening and prevention strategies. The interplay between cancer cells and the extracellular matrix (ECM) is one of

  13. 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

  14. 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...

  15. Measuring health-related quality of life in high-grade glioma patients at the end of life using a proxy-reported retrospective questionnaire

    NARCIS (Netherlands)

    Sizoo, E.M.; Dirven, L.; Reijneveld, J.C.; Postma, T.J.; Heimans, J.J.; Deliens, L.; Pasman, H.R.W.; Taphoorn, M.J.B.

    2014-01-01

    To develop, validate, and report on the use of a retrospective proxy-reported questionnaire measuring health-related quality of life (HRQoL) in the end-of-life (EOL) phase of high-grade glioma (HGG) patients. Items relevant for the defined construct were selected using existing questionnaires,

  16. Economic analysis of continuous antibiotic prophylaxis for prevention of urinary tract infections in infants with high-grade hydronephrosis.

    Science.gov (United States)

    Tu, H Y V; Pemberton, J; Lorenzo, A J; Braga, L H

    2015-10-01

    For infants with hydronephrosis, continuous antibiotic prophylaxis (CAP) may reduce urinary tract infections (UTIs); however, its value remains controversial. Recent studies have suggested that neonates with severe obstructive hydronephrosis are at an increased risk of UTIs, and support the use of CAP. Other studies have demonstrated the negligible risk for UTIs in the setting of suspected ureteropelvic junction obstruction and have highlighted the limited role of CAP in hydronephrosis. Furthermore, economic studies in this patient population have been sparse. This study aimed to evaluate whether the use of CAP is an efficient expenditure for preventing UTIs in children with high-grade hydronephrosis within the first 2 years of life. A decision model was used to estimate expected costs, clinical outcomes and quality-adjusted life years (QALYs) of CAP versus no CAP (Fig. 1). Cost data were collected from provincial databases and converted to 2013 Canadian dollars (CAD). Estimates of risks and health utility values were extracted from published literature. The analysis was performed over a time horizon of 2 years. One-way and probabilistic sensitivity analyses were carried out to assess uncertainty and robustness. Overall, CAP use was less costly and provided a minimal increase in health utility when compared to no CAP (Table). The mean cost over two years for CAP and no CAP was CAD$1571.19 and CAD$1956.44, respectively. The use of CAP reduced outpatient-managed UTIs by 0.21 infections and UTIs requiring hospitalization by 0.04 infections over 2 years. Cost-utility analysis revealed an increase of 0.0001 QALYs/year when using CAP. The CAP arm exhibited strong dominance over no CAP in all sensitivity analyses and across all willingness-to-pay thresholds. The use of CAP exhibited strong dominance in the economic evaluation, despite a small gain of 0.0001 QALYs/year. Whether this slight gain is clinically significant remains to be determined. However, small QALY gains

  17. Altered expression of MGMT in high-grade gliomas results from the combined effect of epigenetic and genetic aberrations.

    Directory of Open Access Journals (Sweden)

    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.

  18. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib

    International Nuclear Information System (INIS)

    Kinsella, Paula; Howley, Rachel; Doolan, Padraig; Clarke, Colin; Madden, Stephen F.; Clynes, Martin; Farrell, Michael; Amberger-Murphy, Verena

    2012-01-01

    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. -- Highlights: ► Non-responders had low EGFR expression, high PDGFR-β, and a low proliferation rate. ► PTEN is not indicative of response to a TKI. ► Erlotinib response was not associated with expression of the proteins examined. ► Imatinib-response correlated with expression of PDGFR-α. ► Gefitinib response correlated with increased expression of EGFR.

  19. Microsatellite instability in pediatric high grade glioma is associated with genomic profile and differential target gene inactivation.

    Directory of Open Access Journals (Sweden)

    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.

  20. IGF2BP3 as a potential tissue marker for the diagnosis of esophageal high-grade intraepithelial neoplasia

    Directory of Open Access Journals (Sweden)

    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

  1. A Tissue Systems Pathology Test Detects Abnormalities Associated with Prevalent High-Grade Dysplasia and Esophageal Cancer in Barrett's Esophagus.

    Science.gov (United States)

    Critchley-Thorne, Rebecca J; Davison, Jon M; Prichard, Jeffrey W; Reese, Lia M; Zhang, Yi; Repa, Kathleen; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory G; DeMarshall, Maureen; Foxwell, Tyler; Jobe, Blair A; Zaidi, Ali H; Duits, Lucas C; Bergman, Jacques J G H M; Rustgi, Anil; Falk, Gary W

    2017-02-01

    There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC. We performed a multi-institutional case-control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days). The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test. A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240-8. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. 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.

  3. [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.

  4. Behavior of the PCA3 gene in the urine of men with high grade prostatic intraepithelial neoplasia.

    Science.gov (United States)

    Morote, Juan; Rigau, Marina; Garcia, Marta; Mir, Carmen; Ballesteros, Carlos; Planas, Jacques; Raventós, Carles X; Placer, José; de Torres, Inés M; Reventós, Jaume; Doll, Andreas

    2010-12-01

    An ideal marker for the early detection of prostate cancer (PCa) should also differentiate between men with isolated high grade prostatic intraepithelial neoplasia (HGPIN) and those with PCa. Prostate Cancer Gene 3 (PCA3) is a highly specific PCa gene and its score, in relation to the PSA gene in post-prostate massage urine (PMU-PCA3), seems to be useful in ruling out PCa, especially after a negative prostate biopsy. Because PCA3 is also expressed in the HGPIN lesion, the aim of this study was to determine the efficacy of PMU-PCA3 scores for ruling out PCa in men with previous HGPIN. The PMU-PCA3 score was assessed by quantitative PCR (multiplex research assay) in 244 men subjected to prostate biopsy: 64 men with an isolated HGPIN (no cancer detected after two or more repeated biopsies), 83 men with PCa and 97 men with benign pathology findings (BP: no PCa, HGPIN or ASAP). The median PMU-PCA3 score was 1.56 in men with BP, 2.01 in men with HGPIN (p = 0.128) and 9.06 in men with PCa (p = 0.008). The AUC in the ROC analysis was 0.705 in the subset of men with BP and PCa, while it decreased to 0.629 when only men with isolated HGPIN and PCa were included in the analysis. Fixing the sensitivity of the PMU-PCA3 score at 90%, its specificity was 79% in men with BP and 69% in men with isolated HGPIN. The efficacy of the PMU-PCA3 score to rule out PCa in men with HGPIN is lower than in men with BP.

  5. A prediction model for treatment decisions in high-grade extremity soft-tissue sarcomas: Personalised sarcoma care (PERSARC).

    Science.gov (United States)

    van Praag, Veroniek M; Rueten-Budde, Anja J; Jeys, Lee M; Laitinen, Minna K; Pollock, Rob; Aston, Will; van der Hage, Jos A; Dijkstra, P D Sander; Ferguson, Peter C; Griffin, Anthony M; Willeumier, Julie J; Wunder, Jay S; van de Sande, Michiel A J; Fiocco, Marta

    2017-09-01

    To support shared decision-making, we developed the first prediction model for patients with primary soft-tissue sarcomas of the extremities (ESTS) which takes into account treatment modalities, including applied radiotherapy (RT) and achieved surgical margins. The PERsonalised SARcoma Care (PERSARC) model, predicts overall survival (OS) and the probability of local recurrence (LR) at 3, 5 and 10 years. Development and validation, by internal validation, of the PERSARC prediction model. The cohort used to develop the model consists of 766 ESTS patients who underwent surgery, between 2000 and 2014, at five specialised international sarcoma centres. To assess the effect of prognostic factors on OS and on the cumulative incidence of LR (CILR), a multivariate Cox proportional hazard regression and the Fine and Gray model were estimated. Predictive performance was investigated by using internal cross validation (CV) and calibration. The discriminative ability of the model was determined with the C-index. Multivariate Cox regression revealed that age and tumour size had a significant effect on OS. More importantly, patients who received RT showed better outcomes, in terms of OS and CILR, than those treated with surgery alone. Internal validation of the model showed good calibration and discrimination, with a C-index of 0.677 and 0.696 for OS and CILR, respectively. The PERSARC model is the first to incorporate known clinical risk factors with the use of different treatments and surgical outcome measures. The developed model is internally validated to provide a reliable prediction of post-operative OS and CILR for patients with primary high-grade ESTS. LEVEL OF SIGNIFICANCE: level III. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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

  7. Integrated analyses of microRNAs demonstrate their widespread influence on gene expression in high-grade serous ovarian carcinoma.

    Science.gov (United States)

    Creighton, Chad J; Hernandez-Herrera, Anadulce; Jacobsen, Anders; Levine, Douglas A; Mankoo, Parminder; Schultz, Nikolaus; Du, Ying; Zhang, Yiqun; Larsson, Erik; Sheridan, Robert; Xiao, Weimin; Spellman, Paul T; Getz, Gad; Wheeler, David A; Perou, Charles M; Gibbs, Richard A; Sander, Chris; Hayes, D Neil; Gunaratne, Preethi H

    2012-01-01

    The Cancer Genome Atlas (TCGA) Network recently comprehensively catalogued the molecular aberrations in 487 high-grade serous ovarian cancers, with much remaining to be elucidated regarding the microRNAs (miRNAs). Here, using TCGA ovarian data, we surveyed the miRNAs, in the context of their predicted gene targets. Integration of miRNA and gene patterns yielded evidence that proximal pairs of miRNAs are processed from polycistronic primary transcripts, and that intronic miRNAs and their host gene mRNAs derive from common transcripts. Patterns of miRNA expression revealed multiple tumor subtypes and a set of 34 miRNAs predictive of overall patient survival. In a global analysis, miRNA:mRNA pairs anti-correlated in expression across tumors showed a higher frequency of in silico predicted target sites in the mRNA 3'-untranslated region (with less frequency observed for coding sequence and 5'-untranslated regions). The miR-29 family and predicted target genes were among the most strongly anti-correlated miRNA:mRNA pairs; over-expression of miR-29a in vitro repressed several anti-correlated genes (including DNMT3A and DNMT3B) and substantially decreased ovarian cancer cell viability. This study establishes miRNAs as having a widespread impact on gene expression programs in ovarian cancer, further strengthening our understanding of miRNA biology as it applies to human cancer. As with gene transcripts, miRNAs exhibit high diversity reflecting the genomic heterogeneity within a clinically homogeneous disease population. Putative miRNA:mRNA interactions, as identified using integrative analysis, can be validated. TCGA data are a valuable resource for the identification of novel tumor suppressive miRNAs in ovarian as well as other cancers.

  8. Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. 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.

  11. Diffusion Profiling via a Histogram Approach Distinguishes Low-grade from High-grade Meningiomas, Can Reflect the Respective Proliferative Potential and Progesterone Receptor Status.

    Science.gov (United States)

    Gihr, Georg Alexander; Horvath-Rizea, Diana; Garnov, Nikita; Kohlhof-Meinecke, Patricia; Ganslandt, Oliver; Henkes, Hans; Meyer, Hans Jonas; Hoffmann, Karl-Titus; Surov, Alexey; Schob, Stefan

    2018-02-01

    Presurgical grading, estimation of growth kinetics, and other prognostic factors are becoming increasingly important for selecting the best therapeutic approach for meningioma patients. Diffusion-weighted imaging (DWI) provides microstructural information and reflects tumor biology. A novel DWI approach, histogram profiling of apparent diffusion coefficient (ADC) volumes, provides more distinct information than conventional DWI. Therefore, our study investigated whether ADC histogram profiling distinguishes low-grade from high-grade lesions and reflects Ki-67 expression and progesterone receptor status. Pretreatment ADC volumes of 37 meningioma patients (28 low-grade, 9 high-grade) were used for histogram profiling. WHO grade, Ki-67 expression, and progesterone receptor status were evaluated. Comparative and correlative statistics investigating the association between histogram profiling and neuropathology were performed. The entire ADC profile (p10, p25, p75, p90, mean, median) was significantly lower in high-grade versus low-grade meningiomas. The lower percentiles, mean, and modus showed significant correlations with Ki-67 expression. Skewness and entropy of the ADC volumes were significantly associated with progesterone receptor status and Ki-67 expression. ROC analysis revealed entropy to be the most accurate parameter distinguishing low-grade from high-grade meningiomas. ADC histogram profiling provides a distinct set of parameters, which help differentiate low-grade versus high-grade meningiomas. Also, histogram metrics correlate significantly with histological surrogates of the respective proliferative potential. More specifically, entropy revealed to be the most promising imaging biomarker for presurgical grading. Both, entropy and skewness were significantly associated with progesterone receptor status and Ki-67 expression and therefore should be investigated further as predictors for prognostically relevant tumor biological features. Since absolute ADC

  12. Long-term Outcomes With Planned Multistage Reduced Dose Repeat Stereotactic Radiosurgery for Treatment of Inoperable High-Grade Arteriovenous Malformations: An Observational Retrospective Cohort Study.

    Science.gov (United States)

    Marciscano, Ariel E; Huang, Judy; Tamargo, Rafael J; Hu, Chen; Khattab, Mohamed H; Aggarwal, Sameer; Lim, Michael; Redmond, Kristin J; Rigamonti, Daniele; Kleinberg, Lawrence R

    2017-07-01

    There is no consensus regarding the optimal management of inoperable high-grade arteriovenous malformations (AVMs). This long-term study of 42 patients with high-grade AVMs reports obliteration and adverse event (AE) rates using planned multistage repeat stereotactic radiosurgery (SRS). To evaluate the efficacy and safety of multistage SRS with treatment of the entire AVM nidus at each treatment session to achieve complete obliteration of high-grade AVMs. Patients with high-grade Spetzler-Martin (S-M) III-V AVMs treated with at least 2 multistage SRS treatments from 1989 to 2013. Clinical outcomes of obliteration rate, minor/major AEs, and treatment characteristics were collected. Forty-two patients met inclusion criteria (n = 26, S-M III; n = 13, S-M IV; n = 3, S-M V) with a median follow-up was 9.5 yr after first SRS. Median number of SRS treatment stages was 2, and median interval between stages was 3.5 yr. Twenty-two patients underwent pre-SRS embolization. Complete AVM obliteration rate was 38%, and the median time to obliteration was 9.7 yr. On multivariate analysis, higher S-M grade was significantly associated ( P = .04) failure to achieve obliteration. Twenty-seven post-SRS AEs were observed, and the post-SRS intracranial hemorrhage rate was 0.027 events per patient year. Treatment of high-grade AVMs with multistage SRS achieves AVM obliteration in a meaningful proportion of patients with acceptable AE rates. Lower obliteration rates were associated with higher S-M grade and pre-SRS embolization. This approach should be considered with caution, as partial obliteration does not protect from hemorrhage. Copyright © 2017 by the Congress of Neurological Surgeons

  13. Terminal area automatic navigation, guidance, and control research using the Microwave Landing System (MLS). Part 2: RNAV/MLS transition problems for aircraft

    Science.gov (United States)

    Pines, S.

    1982-01-01

    The problems in navigation and guidance encountered by aircraft in the initial transition period in changing from distance measuring equipment, VORTAC, and barometric instruments to the more precise microwave landing system data type navaids in the terminal area are investigated. The effects of the resulting discontinuities on the estimates of position and velocity for both optimal (Kalman type navigation schemes) and fixed gain (complementary type) navigation filters, and the effects of the errors in cross track, track angle, and altitude on the guidance equation and control commands during the critical landing phase are discussed. A method is presented to remove the discontinuities from the navigation loop and to reconstruct an RNAV path designed to land the aircraft with minimal turns and altitude changes.

  14. 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.

  15. 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

  16. Improving contrast enhancement in magnetic resonance imaging using 5-aminolevulinic acid-induced protoporphyrin IX for high-grade gliomas.

    Science.gov (United States)

    Yamamoto, Junkoh; Kakeda, Shingo; Yoneda, Tetsuya; Ogura, Shun-Ichiro; Shimajiri, Shohei; Tanaka, Tohru; Korogi, Yukunori; Nishizawa, Shigeru

    2017-03-01

    Magnetic resonance imaging (MRI) with a gadolinium-based contrast agent is the gold standard for high-grade gliomas (HGGs). The compound 5-aminolevulinic acid (5-ALA) undergoes a high rate of cellular uptake, particularly in cancer cells. In addition, fluorescence-guided resection with 5-ALA is widely used for imaging HGGs. 5-ALA is water soluble, while protoporphyrin IX (PpIX) is water insoluble. It was speculated whether converting from 5-ALA to PpIX may relatively increase intracellular water content, and consequently, might enhance the T2 signal intensity in HGG. The aim of the present study was to assess whether 5-ALA-induced PpIX enhances the T2 signal intensity in patients with HGGs. A total of 4 patients who were candidates for HGG surgical treatment were prospectively analyzed with preoperative MRI. Patients received oral doses of 5-ALA (20 mg/kg) 3 h prior to anesthesia. At 2.5 h post-5-ALA administration, T2-weighted images (T2WIs) were obtained from all patients. Subsequently, tumors were evaluated via fluorescence using a modified operating microscope. Fluorescent tumor tissues were obtained to analyze the accumulation of 5-ALA-induced PpIX within the tumors, which was confirmed quantitatively by high-performance liquid chromatography (HPLC) analysis. The MRI T2 signal intensity within the tumors was evaluated prior to and following 5-ALA administration. Three glioblastoma multiformes (GBMs) and 1 anaplastic oligodendroglioma (AO) were included in the analysis. Intraoperatively, all GBMs exhibited strong fluorescence of 5-ALA-induced PpIX, whilst no fluorescence was observed in the AO sample. HPLC analysis indicated a higher accumulation of 5-ALA-induced PpIX in the GBM samples compared with the AO sample. In total, 48 regions of interest were identified within the tumors from T2-WIs. In the GBM group, the relative T2 signal intensity value within the tumors following 5-ALA administration was significantly increased compared with the T2 signal

  17. Inhibitors of GLUT/SLC2A Enhance the Action of BCNU and Temozolomide against High-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    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.

  18. EORTC 22972-26991/MRC BR10 trial: Fractionated stereotactic boost following conventional radiotherapy of high grade gliomas

    International Nuclear Information System (INIS)

    Baumert, Brigitta G.; Brada, Michael; Bernier, Jacques; Kortmann, Rolf D.; Dehing-Oberije, Cary; Collette, Laurence; Davis, J. Bernard

    2008-01-01

    Background and purpose: The EORTC trial No. 22972 investigated the role of an additional fractionated stereotactic boost (fSRT) to conventional radiotherapy for patients with high grade gliomas. A quality-assurance (QA) programme was run in conjunction with the study and was the first within the EORTC addressing the quality of a supposedly highly accurate treatment technique such as stereotactic radiotherapy. A second aim was to investigate a possible relation between the clinical results of the stereotactic boost arm and the results of the QA. Materials and methods: The trial was closed in 2001 due to low accrual. In total, 25 patients were randomized: 14 into the experimental arm and 11 into the control arm. Six centres randomized patients, 8 centres had completed the dummy run (DR) for the stereotactic boost part. All participating centres (9) were asked to complete a quality-assurance questionnaire. The DR consisted of treatment planning according to the guidelines of the protocol on 3 different tumour volumes drawn on CT images of a humanized phantom. The SRT technique to be used was evaluated by the questionnaire. Clinical data from patients recruited to the boost arm from 6 participating centres were analysed. Results: There was a full compliance to the protocol requirements for 5 centres. Major and minor deviations in conformality were observed for 2 and 3 centres, respectively. Of the 8 centres which completed the DR, one centre did not comply with the requirements of stereotactic radiotherapy concerning accuracy, dosimetry and planning. Median follow-up and median overall survival were 39.2 and 21.4 months, respectively. Acute and late toxicities of the stereotactic boost were low. One radiation necrosis was seen for a patient who has not received the SRT boost. Three reported serious adverse events were all seizures and probably therapy-related. Conclusions: Overall compliance was good but not ideal from the point of view of this highly precise radiation

  19. High-grade serous carcinomas arise in the mouse oviduct via defects linked to the human disease.

    Science.gov (United States)

    Zhai, Yali; Wu, Rong; Kuick, Rork; Sessine, Michael S; Schulman, Stephanie; Green, Megan; Fearon, Eric R; Cho, Kathleen R

    2017-09-01

    Recent studies have suggested that the most common and lethal type of 'ovarian' cancer, i.e. high-grade serous carcinoma (HGSC), usually arises from epithelium on the fallopian tube fimbriae, and not from the ovarian surface epithelium. We have developed Ovgp1-iCreER T2 mice in which the Ovgp1 promoter controls expression of tamoxifen-regulated Cre recombinase in oviductal epithelium - the murine equivalent of human fallopian tube epithelium (FTE). We employed Ovgp1-iCreER T2 mice to show that FTE-specific inactivation of several different combinations of tumour suppressor genes that are recurrently mutated in human HGSCs - namely Brca1, Trp53, Rb1, and Nf1 - results in serous tubal intraepithelial carcinomas (STICs) that progress to HGSC or carcinosarcoma, and to widespread metastatic disease in a subset of mice. The cancer phenotype is highly penetrant and more rapid in mice carrying engineered alleles of all four tumour suppressor genes. Brca1, Trp53 and Pten inactivation in the oviduct also results in STICs and HGSCs, and is associated with diffuse epithelial hyperplasia and mucinous metaplasia, which are not observed in mice with intact Pten. Oviductal tumours arise earlier in these mice than in those with Brca1, Trp53, Rb1 and Nf1 inactivation. Tumour initiation and/or progression in mice lacking conditional Pten alleles probably require the acquisition of additional defects, a notion supported by our identification of loss of the wild-type Rb1 allele in the tumours of mice carrying only one floxed Rb1 allele. Collectively, the models closely recapitulate the heterogeneity and histological, genetic and biological features of human HGSC. These models should prove useful for studying the pathobiology and genetics of HGSC in vivo, and for testing new approaches for prevention, early detection, and treatment. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of

  20. Impact of MRI on high grade Ductal Carcinoma Insitu (HG DCIS) management, are we using the full scope of MRI?

    Science.gov (United States)

    Hajaj, Mohamad; Karim, Ahmed; Pascaline, Sana; Noor, Lubna; Patel, Shivali; Dakka, Mahmoud

    2017-10-01

    Preoperative assessment of pure Ductal Carcinoma Insitu (DCIS) is essential in the surgical planning. The role of Magnetic resonance imaging (MRI) has long been debated. The impact of MRI on the management of High Grade (HG) DCIS was assessed, whether it accurately captures the true size of this entity in comparison to conventional imaging, and, if MRI use would reduce the number of re-excision surgery. Ninety-one consecutive patients with HG DCIS, who were identified from a prospectively collected data at Kettering General Hospital between April 2011 and December 2015. All patients had preoperative MRI scan in addition to the standard breast imaging. This was compared to a control group of consecutive patients (n=52) which was obtained from a period just before 2011. Impact on surgical planning and number of surgeries for each patient was compared. The size of HG DCIS estimated by MRI was compared to the final histological size. Secondary outcomes included change of initial surgical plan and detection of occult contralateral breast cancer. MRI group had 91 patients with median age of 63. Seventy percent of which presented through the screening program. The overall sensitivity of MRI to detect HG DCIS was 77% (70/91) with a false negative rate FNR of 23% (21/91). Therefore, 70 patients only were included in the data analysis. The control group included 52 screening patients with comparable baseline characteristics. Re-excision (or completion mastectomy) rates were higher in the control group 26% compared to 8% in the MRI group (P-value 0.012). MRI use correctly converted the initial plan of breast conservation to mastectomy in 9 patients (13%). Five patients had additional ipsilateral malignant features (7%).Occult contra lateral disease, was diagnosed in 2 patients (3%). This study suggests that MRI could be an important tool in reducing the re-excision rates in the surgical management of HG DCIS. Although still controversial, selective MRI imaging can be useful

  1. The Impact of Adjuvant Radiation Therapy for High-Grade Gliomas by Histology in the United States Population

    Energy Technology Data Exchange (ETDEWEB)

    Rusthoven, Chad G., E-mail: Chad.Rusthoven@ucdenver.edu [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Carlson, Julie A.; Waxweiler, Timothy V. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Dally, Miranda J.; Barón, Anna E. [Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora, Colorado (United States); Yeh, Norman; Gaspar, Laurie E.; Liu, Arthur K. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Ney, Douglas E.; Damek, Denise M. [Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado (United States); Lillehei, Kevin O. [Department of Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado (United States); Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States)

    2014-11-15

    Purpose: To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. Results: The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were

  2. PCI is Not Predictive of Survival After Complete CRS/HIPEC in Peritoneal Dissemination from High-Grade Appendiceal Primaries.

    Science.gov (United States)

    Votanopoulos, Konstantinos Ioannis; Bartlett, David; Moran, Brendan; Haroon, Choudry M; Russell, Greg; Pingpank, James F; Ramalingam, Lekshmi; Kandiah, Chandrakumaran; Chouliaras, Konstantinos; Shen, Perry; Levine, Edward A

    2018-03-01

    Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment option in patients with carcinomatosis from high-grade appendiceal (HGA) primaries. It is unknown if there is a Peritoneal Carcinomatosis Index (PCI) upper limit above which a complete CRS/HIPEC does not assure long-term survival. Retrospective analysis from three centers was performed. The PCI was used to grade volume of of disease. Survival in relation to PCI was studied on patients with complete cytoreduction. Overall, 521 HGA patients underwent CRS/HIPEC from 1993 to 2015, with complete CRS being achieved in 50% (260/622). Mean PCI was 14.8 (standard deviation 8.7, range 0-36). Median survival for the complete CRS cohort was 6.1 years, while 5- and 10-year survival was 51.7% (standard error [SE] 4.6) and 36.1% (SE 6.3), respectively. Arbitrary cut-off PCI limits with 5-point splits (p = 0.63) were not predictive of a detrimental effect on survival as long as a complete CRS was achieved. A linear effect of the PCI on survival (p = 0.62) was not observed, and single-point PCI cohort splits within a PCI range of  10 were not predictive of survival for complete CRS patients. The PCI correlated with the ability to achieve a complete CRS, with a mean PCI of 14.7 (8.7) for completeness of cytoreduction (CC)0, 22.3 (7.8) for CC1 and 26.1 (9.5) for CC2/3 resections (p = 0.0001, hazard ratio 1.12, 95% confidence interval 1.09), with an HR of 1.15 for each 1-unit increase in the PCI score. Only 21% of the cohort achieved a complete CRS with a PCI ≥ 21. The PCI correlates with the ability to achieve a complete CRS in carcinomatosis from HGA. PCI is not associated with survival as long as a complete CRS can be achieved.

  3. The health care burden of high grade chronic obstructive pulmonary disease in Korea: analysis of the Korean Health Insurance Review and Assessment Service data

    Directory of Open Access Journals (Sweden)

    Kim JH

    2013-11-01

    Full Text Available JinHee Kim,1 Chin Kook Rhee,2 Kwang Ha Yoo,3 Young Sam Kim,4 Sei Won Lee,5 Yong Bum Park,6 Jin Hwa Lee,7 YeonMok Oh,5 Sang Do Lee,5 Yuri Kim,8 KyungJoo Kim,8 HyoungKyu Yoon9 1Office of Health Service Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Korea; 2Department of Internal Medicine, Seoul St Mary’s Hospital, Catholic University of Korea College of Medicine, Seoul, Korea; 3Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea; 4Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; 5Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 6Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea; 7Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, Korea; 8Department of Clinical Research Support, National Strategic Coordinating Center for Clinical Research, Seoul, Korea; 9Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, Catholic University of Korea College of Medicine, Seoul, Korea Background: Patients with high grade chronic pulmonary obstructive disease (COPD account for much of the COPD-related mortality and incur excessive financial burdens and medical care utilization. We aimed to determine the characteristics and medical care use of such patients using nationwide data from the Korean Health Insurance Review and Assessment Service in 2009. Materials and methods: Patients with COPD were identified by searching with the International Classification of Diseases–10th Revision for those using medication. Patients with high grade COPD were selected based on their patterns of tertiary institute visits and medication use. Results: The numbers of patients with high grade COPD increased rapidly

  4. Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL Nephrometry score.

    Science.gov (United States)

    Kutikov, Alexander; Smaldone, Marc C; Egleston, Brian L; Manley, Brandon J; Canter, Daniel J; Simhan, Jay; Boorjian, Stephen A; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

    2011-08-01

    Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology. We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features. We retrospectively queried Fox Chase Cancer Center's prospectively maintained database for consecutive renal masses where a Nephrometry score was available. All patients in the cohort underwent either partial or radical nephrectomy. The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors. Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p renal mass. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  5. Association mapping of the high-grade myopia MYP3 locus reveals novel candidates UHRF1BP1L, PTPRR, and PPFIA2

    DEFF Research Database (Denmark)

    Hawthorne, Felicia; Feng, Sheng; Metlapally, Ravikanth

    2013-01-01

    PURPOSE: 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. METHODS: We performed a genetic association study...... 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 Independently conducted whole genome expression array analyses identified...... protein tyrosine phosphatase genes PTPRR and PPFIA2, which are in the same gene family, as differentially expressed in normal rapidly growing fetal relative to normal adult ocular tissue (confirmed by RT-qPCR). CONCLUSIONS: In an independent high-grade myopia cohort, an intronic SNP in UHRF1BP1L, rs...

  6. Overexpression of long non-coding RNA TUG1 predicts poor prognosis and promotes cancer cell proliferation and migration in high-grade muscle-invasive bladder cancer.

    Science.gov (United States)

    Iliev, Robert; Kleinova, Renata; Juracek, Jaroslav; Dolezel, Jan; Ozanova, Zuzana; Fedorko, Michal; Pacik, Dalibor; Svoboda, Marek; Stanik, Michal; Slaby, Ondrej

    2016-10-01

    Long non-coding RNA TUG1 is involved in the development and progression of a variety of tumors. Little is known about TUG1 function in high-grade muscle-invasive bladder cancer (MIBC). The aims of our study were to determine expression levels of long non-coding RNA TUG1 in tumor tissue, to evaluate its relationship with clinico-pathological features of high-grade MIBC, and to describe its function in MIBC cells in vitro. TUG1 expression levels were determined in paired tumor and adjacent non-tumor bladder tissues of 47 patients with high-grade MIBC using real-time PCR. Cell line T-24 and siRNA silencing were used to study the TUG1 function in vitro. We observed significantly increased levels of TUG1 in tumor tissue in comparison to adjacent non-tumor bladder tissue (P TUG1 levels were significantly increased in metastatic tumors (P = 0.0147) and were associated with shorter overall survival of MIBC patients (P = 0.0241). TUG1 silencing in vitro led to 34 % decrease in cancer cell proliferation (P = 0.0004) and 23 % reduction in migration capacity of cancer cells (P TUG1 silencing on cell cycle distribution and number of apoptotic cells. Our study confirmed overexpression of TUG1 in MIBC tumor tissue and described its association with worse overall survival in high-grade MIBC patients. Together with in vitro observations, these data suggest an oncogenic role of TUG1 and its potential usage as biomarker or therapeutic target in MIBC.

  7. High-grade acute organ toxicity as positive prognostic factor in primary radio(chemo)therapy for locally advanced, inoperable head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wolff, Hendrik Andreas; Bosch, Jan; Hennies, Steffen; Hess, Clemens F.; Christiansen, Hans [Dept. of Radiotherapy and Radiooncology, Univ. Medicine Goettingen (Germany); Jung, Klaus [Dept. of Medical Statistics, Univ. Medicine Goettingen (Germany); Overbeck, Tobias [Dept. of Haematology and Oncology, Univ. Medicine Goettingen (Germany); Matthias, Christoph; Roedel, Ralph M. [Dept. of Otorhinolaryngology, Univ. Medicine Goettingen (Germany)

    2010-05-15

    Purpose: to test for a possible correlation between high-grade acute organ toxicity during primary radio(chemo)therapy and treatment outcome in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Patients and methods: from 05/1994 to 01/2009, 216 HNSCC patients were treated with radio(chemo)therapy in primary approach. They received normofractionated (2 Gy/fraction) irradiation including associated nodal drainage sites to a cumulative dose of 70 Gy. 151 patients received additional concomitant chemotherapy (111 patients 5-fluorouracil/mitomycin C, 40 patients cisplatin-based). Toxicity during treatment was monitored weekly according to the Common Toxicity Criteria (CTC), and any toxicity grade CTC {>=} 3 of mucositis, dysphagia or skin reaction was assessed as high-grade acute organ toxicity for later analysis. Results: a statistically significant coherency between high-grade acute organ toxicity and overall survival as well as locoregional control was found: patients with CTC {>=} 3 acute organ toxicity had a 5-year overall survival rate of 4% compared to 8% in patients without (p < 0.01). Thereby, multivariate analyses revealed that the correlation was independent of other possible prognostic factors or factors that may influence treatment toxicity, especially concomitant chemotherapy and radiotherapy technique or treatment-planning procedure. Conclusion: these data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, as high-grade acute organ toxicity during radio(chemo)therapy showed to be an independent prognostic marker in the own patient population. However, the authors are aware of the fact that a multivariate analysis in a retrospective study generally has statistical limitations. Therefore, their hypothesis should be further analyzed on biomolecular and clinical levels and other tumor entities in prospective trials. (orig.)

  8. LASER treatment for women with high-grade vaginal intraepithelial neoplasia: A propensity-matched analysis on the efficacy of ablative versus excisional procedures.

    Science.gov (United States)

    Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Mosca, Lavinia; Chiappa, Valentina; Rossetti, Diego; Leone Roberti Maggiore, Umberto; Sabatucci, Ilaria; Lorusso, Domenica; Raspagliesi, Francesco

    2018-05-14

    To investigate the long-term effectiveness of LASER treatment in women affected by high-grade vaginal intra-epithelial neoplasia. Data of consecutive women treated for high-grade vaginal intra-epithelial neoplasia were retrieved. Efficacy and long-term effectiveness of ablative and excisional procedures were tested using a propensity-matched algorithm. Risk of recurrence over the time was assessed using Kaplan-Meier and Cox models. Overall, 204 patients met the inclusion criteria. LASER ablation and exicision were performed in 169 (82.8%) and 35 (17.2%) patients. A total of 41 (20%) patients developed high-grade vaginal intraepithelial neoplasia at a median follow-up of 65 (range, 6-120) months. We observed that only HPV persistence (HR: 2.37 [95%CI:1.03, 5.42]; P = 0.04) was associated with the risk of recurrence at multivariate analysis. Seven (3.4%) invasive cancers of the lower genital tract were observed in our population. Considering the efficacy of type of procedure (after we applied the propensity-matched analysis), we observed that type of procedure did not influence persistence of HPV infection (22.8% after excision and 15.7% after ablation; P = 0.424). Similarly, recurrence (17.1% vs. 18.6%; P = 1.00) and lower genital tract (2.8% vs. 1.4%; P = 1.00) rates were similar between groups. Women affected by high-grade vaginal intra-epithelial neoplasia are at high risk of recurrence. LASER ablation seems to be equivalent to excision in term of long-term effectiveness. Lasers Surg. Med. 9999:1-7, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  9. Trajectories of Symptom Clusters, Performance Status, and Quality of Life During Concurrent Chemoradiotherapy in Patients With High-Grade Brain Cancers.

    Science.gov (United States)

    Kim, Sang-Hee; Byun, Youngsoon

    Symptom clusters must be identified in patients with high-grade brain cancers for effective symptom management during cancer-related therapy. The aims of this study were to identify symptom clusters in patients with high-grade brain cancers and to determine the relationship of each cluster with the performance status and quality of life (QOL) during concurrent chemoradiotherapy (CCRT). Symptoms were assessed using the Memorial Symptom Assessment Scale, and the performance status was evaluated using the Karnofsky Performance Scale. Quality of life was assessed using the Functional Assessment of Cancer Therapy-General. This prospective longitudinal survey was conducted before CCRT and at 2 to 3 weeks and 4 to 6 weeks after the initiation of CCRT. A total of 51 patients with newly diagnosed primary malignant brain cancer were included. Six symptom clusters were identified, and 2 symptom clusters were present at each time point (ie, "negative emotion" and "neurocognitive" clusters before CCRT, "negative emotion and decreased vitality" and "gastrointestinal and decreased sensory" clusters at 2-3 weeks, and "body image and decreased vitality" and "gastrointestinal" clusters at 4-6 weeks). The symptom clusters at each time point demonstrated a significant relationship with the performance status or QOL. Differences were observed in symptom clusters in patients with high-grade brain cancers during CCRT. In addition, the symptom clusters were correlated with the performance status and QOL of patients, and these effects could change during CCRT. The results of this study will provide suggestions for interventions to treat or prevent symptom clusters in patients with high-grade brain cancer during CCRT.

  10. Dextranomer/hyaluronic acid endoscopic injection is effective in the treatment of intermediate and high grade vesicoureteral reflux in patients with complete duplex systems.

    Science.gov (United States)

    Hunziker, Manuela; Mohanan, Nochiparambil; Puri, Prem

    2013-05-01

    Endoscopic subureteral injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis or surgical treatment for vesicoureteral reflux. We evaluated the effectiveness of endoscopic injection of dextranomer/hyaluronic acid in intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems. A total of 123 children underwent endoscopic correction of intermediate or high grade vesicoureteral reflux using injection of dextranomer/hyaluronic acid into complete duplex systems between 2001 and 2010. Vesicoureteral reflux was diagnosed by voiding cystourethrogram, and dimercapto-succinic acid scan was performed to evaluate the presence of renal scarring. Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure and renal ultrasound thereafter every 2 years. Mean followup was 6.7 years. Complete duplex systems were unilateral in 110 patients and bilateral in 13. Reflux severity in the 136 refluxing units was grade II in 1 (0.7%), III in 52 (38.2%), IV in 61 (44.9%) and V in 22 (16.2%). Dimercapto-succinic acid scan revealed renal functional abnormalities in 63 children (51.2%). Vesicoureteral reflux resolved after the first endoscopic injection of dextranomer/hyaluronic acid in 93 ureters (68.4%), after a second injection in 35 (25.7%) and after a third injection in 8 (5.9%). Febrile urinary tract infection developed in 5 patients (4.1%) during followup. No patient required ureteral reimplantation or experienced significant complications. Our results confirm the safety and efficacy of endoscopic injection of dextranomer/hyaluronic acid in eradicating intermediate and high grade vesicoureteral reflux in patients with complete duplex systems. We recommend this minimally invasive, 15-minute outpatient procedure as a viable option for treating intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems

  11. Single center experience with endoscopic subureteral dextranomer/hyaluronic acid injection as first line treatment in 1,551 children with intermediate and high grade vesicoureteral reflux.

    Science.gov (United States)

    Puri, Prem; Kutasy, Balazs; Colhoun, Eric; Hunziker, Manuela

    2012-10-01

    In recent years the endoscopic injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis and the surgical management of vesicoureteral reflux. We determined the safety and effectiveness of the endoscopic injection of dextranomer/hyaluronic acid as first line treatment for high grade vesicoureteral reflux. Between 2001 and 2010, 1,551 children (496 male, 1,055 female, median age 1.6 years) underwent endoscopic correction of intermediate and high grade vesicoureteral reflux using dextranomer/hyaluronic acid soon after the diagnosis of vesicoureteral reflux on initial voiding cystourethrogram. Vesicoureteral reflux was unilateral in 761 children and bilateral in 790. Renal scarring was detected in 369 (26.7%) of the 1,384 patients who underwent dimercapto-succinic acid imaging. Reflux grade in the 2,341 ureters was II in 98 (4.2%), III in 1,340 (57.3%), IV in 818 (34.9%) and V in 85 (3.6%). Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure, and renal ultrasound was performed annually thereafter. Patients were followed for 3 months to 10 years (median 5.6 years). Vesicoureteral reflux resolved after the first, second and third endoscopic injection of dextranomer/hyaluronic acid in 2,039 (87.1%), 264 (11.3%) and 38 (1.6%) ureters, respectively. Febrile urinary tract infections developed during followup in 69 (4.6%) patients. None of the patients in the series needed reimplantation of ureters or experienced any significant complications. Our results confirm the safety and efficacy of the endoscopic injection of dextranomer/hyaluronic acid in the eradication of high grade vesicoureteral reflux. We recommend this 15-minute outpatient procedure as the first line of treatment for high grade vesicoureteral reflux. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  12. Impact of [F-18]-fluoro-ethyl-tyrosine PET imaging on target definition for radiation therapy of high-grade glioma

    DEFF Research Database (Denmark)

    af Rosenschold, Per Munck; Costa, Junia; Engelholm, Svend Aage

    2015-01-01

    BACKGROUND: We sought to assess the impact of amino-acid (18)F-fluoro-ethyl-tyrosine (FET) positron emission tomography (PET) on the volumetric target definition f